Systemic Veterinary Pharmacology and Clinical Toxicology

PHYSIOLOGY OF DOMESTIC ANIMALS:
SHRIKANT KULKARNI
AN OVERVIEW
The normal functions of the body-the study of bodys muscle, and different organ systems and the interrelationships among them, overall the normal physiology is essential to be understood if one is to understand the mechanisms of disease and subsequently to treat the diseases. Physiological functions of different organs and organ systems in domestic animals are summarized in brief. CIRCULATORY SYSTEM The circulatory system is an organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases and help to stabilize body temperature and pH to maintain homeostasis. Two types of fluids move through the circulatory system: blood and lymph. The blood, heart, and blood vessels form the cardiovascular system. The lymph, lymph nodes, and lymph vessels form the lymphatic system. The cardiovascular system and the lymphatic system collectively make up the circulatory system. The main components of the cardiovascular system are the heart, blood, and blood vessels. It includes: the pulmonary circulation, a "loop" through the lungs where blood is oxygenated; and the systemic circulation, a "loop" through the rest of the body to provide oxygenated blood. Pulmonary circulation: The pulmonary circulatory system is the portion of the cardiovascular system in which oxygen-depleted blood is pumped away from the heart, via the pulmonary artery, to the lungs and returned, oxygenated, to the heart via the pulmonary vein. Oxygen deprived blood from the vena cava, enters the right atrium of the heart and flows through the tricuspid valve (right atrioventricular valve) into the right ventricle, from which it is then pumped through the pulmonary semilunar valve into the pulmonary artery to the lungs. Gas exchange occurs in the lungs, whereby CO2 is released from the blood, and oxygen is absorbed. The pulmonary vein returns the now oxygen-rich blood to the heart.
________________________________________________________________________________________________ Karnataka Veterinary Council, Bengaluru sponsored CVE training programme titled: An Update on Systemic Pharmacology and Clinical Toxicology organized by the Dept.of Pharmacology and Toxicology,Veterinary College,Bidar,from 12th to 17th December, 2011 for the Officers of Dept. of A.H&V.S, Govt. of Karnataka
108
Systemic circulation: Systemic circulation is the portion of the cardiovascular system which transports oxygenated blood away from the heart, to the rest of the body, and returns oxygen-depleted blood back to the heart. Systemic circulation is, distance-wise, much longer than pulmonary circulation, transporting blood to every part of the body. Coronary circulation: The coronary circulatory system provides a blood supply to the heart. As it provides oxygenated blood to the heart, it is by definition a part of the systemic circulatory system. Heart: The heart pumps oxygenated blood to the body and deoxygenated blood to the lungs. In heart there is one atrium and one ventricle for each circulation, and with both a systemic and a pulmonary circulation there are four chambers in total: left atrium, left ventricle, right atrium and right ventricle. The right atrium is the upper chamber of the right side of the heart. The blood that is returned to the right atrium is deoxygenated (poor in oxygen) and passed into the right ventricle to be pumped through the pulmonary artery to the lungs for reoxygenation and removal of carbon dioxide. The left atrium receives newly oxygenated blood from the lungs as well as the pulmonary vein which is passed into the strong left ventricle to be pumped through the aorta to the different organs of the body. DIGESTION The primary difference in ruminants over non-ruminants (monogastrics, such as humans, dogs, and pigs) is the four-compartment stomach: rumen, reticulum, omasum, and abomasum. In the the rumen and the reticulum, the food is mixed with saliva and separates into layers of solid and liquid material. Solids clump together to form the cud or bolus. The cud is then regurgitated, chewed slowly to completely mix it with saliva and to break down the particle size. Fiber, specially cellulose and hemi-cellulose, is primarily broken down into the three volatile fatty acids, acetic acid, propionic acid and betahydroxybutyric acid, in these chambers by microbes (bacteria,archaea, protozoa, and fungi). Protein and non-structural carbohydrate (pectin, sugars, starches) are also fermented. Even though the rumen and reticulum have different names they represent the same functional space as digesta can move back and
108
forth between them. Together these chambers are called the reticulorumen. The degraded digesta, which is now in the lower liquid part of the reticulorumen, then passes into the next chamber, the omasum, where water and many of the inorganic mineral elements are absorbed into the blood stream. After this the digesta is moved to the true stomach, the abomasum. The abomasum is the direct equivalent of the monogastric stomach (for example that of the human or pig), and digesta is digested here in much the same way. Digesta is finally moved into the small intestine, where the digestion and absorption of nutrients occurs. Microbes produced in the reticulorumen are also digested in the small intestine. Fermentation continues in the large intestine in the same way as in the reticulorumen. Almost all the glucose produced by the breaking down of cellulose and hemi-cellulose is used by microbes in the rumen, and as such ruminants usually absorb little glucose from the small intestine. Rather, ruminants' requirement for glucose (for brain function and lactation if appropriate) is made by the liver from propionate, one of the volatile fatty acids made in the rumen. RESPIRATION Respiration (often mistaken with breathing) is defined as the transport of oxygen from the outside air to the cells within tissues, and the transport of carbon dioxide in the opposite direction. This is in contrast to the biochemical definition of respiration, which refers to cellular respiration : the metabolic process by which an organism obtains energy by reacting oxygen with glucose to give water, carbon dioxide and ATP (energy). Although physiologic respiration is necessary to sustain cellular respiration and thus life in animals, the processes are distinct: cellular respiration takes place in individual cells of the animal, while physiologic respiration concerns the bulk flow and transport of metabolites between the organism and the external environment. The respiratory system works in concert with a circulatory system to carry gases to and from the tissues.In air-breathing vertebrates respiration of oxygen includes four stages:

Ventilation, moving of the ambient air into and out of the alveoli of the lungs. Pulmonary gas exchange, exchange of gases between the alveoli and the pulmonary capillaries.
108
Gas transport, movement of gases within the pulmonary capillaries through the circulation to the peripheral capillaries in theorgans, and then a movement of gases back to the lungs along the same circulatory route. Peripheral gas exchange, exchange of gases between the tissue capillaries and the tissues or organs, impacting the cells composing these and mitochondria within the cells.
Ventilation and gas transport require energy to power a mechanical pump (the heart) and the muscles of respiration, mainly the diaphragm. In heavy breathing, energy is also required to power additional respiratory muscles such as the intercostal muscles. The energy requirement for ventilation and gas transport is in contrast to the passive diffusion taking place in the gas exchange steps. Respiratory behavior is correlated to the cardiovascular behavior to control the gaseous exchange between cells and blood. Both behaviors are intensified by exercise of the body. However, respiratory activity is highly voluntary compared to cardiovascular activity which is totally involuntary. EXCRETION : The excretory system is a passive biological system that removes excess, unnecessary or dangerous materials from an organism, so as to help maintain homeostasis within the organism and prevent damage to the body. It is responsible for the elimination of the waste products of metabolism as well as other liquid and gaseous wastes. Kidney : Removes metabolic and liquid toxic wastes as well as excess water from the organism. Within each kidney there are millions of microscopic nephrons, where blood filtration takes place. Each nephron contains a cluster of capillaries called a glomerulus. A cup-shaped sac called a bowmans capsule surrounds each glomerulus. The blood that flows through the glomerulus is under great pressure. This causes water, glucose and urea to enter the bowmans capsule. White blood cells, red blood cells and proteins remain in the blood. As the blood continues in the excretory system, it passes through the renal tubule. During this time, reabsorption occurs: glucose and chemicals such as potassium, sodium, hydrogen, magnesium and calcium are reabsorbed into the blood. Almost all the water removed during filtration returns to the blood during the reabsorption phase. The kidneys control the amount of liquid in our bodies. Now only wastes are in the nephron. These wastes are called urine and include urea, water and inorganic salts. The cleansed blood goes into veins that carry the blood from the kidneys and back to the heart.
108
Kidneys perform several homeostatic functions: 1. Maintain volume of extracellular fluid 2. Maintain ionic balance in extracellular fluid 3. Maintain pH and osmotic concentration of the extracellular fluid. Skin : Though the sweat may contain a trace amount of metabolic wastes, sweating is an active process of secretion not excretion, specifically for temperature control and pheromone release. Therefore, its role as a part of the excretory system is minimal at best. Specifically, the skin secretes a fluid waste called sweat, or perspiration. Lungs: The lungs constantly secrete gaseous wastes from the bloodstream as a regular part of respiration. Defecation : Organisms eliminate solid, semisolid or liquid waste material (feces) from the digestive tract via the anus during the process of defecation. Waves of muscular contraction known as peristalsis in the walls of the colon move fecal matter through the digestive tract towards the rectum. Undigested food may also be expelled this way; this process is called egestion. NERVOUS SYSTEM The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous system contains the brain, spinal cord, and retina. The peripheral nervous system consists of sensory neurons, clusters of neurons called ganglia, and nerves connecting them to each other and to the central nervous system. These regions are all interconnected by means of complex neural pathways. The enteric nervous system, a subsystem of the peripheral nervous system, has the capacity, even when severed from the rest of the nervous system through its primary connection by the vagus nerve, to function independently in controlling the gastrointestinal system. Neurons send signals to other cells as electrochemical waves travelling along thin fibers called axons, which cause chemicals called neurotransmitters to be released at junctions called synapses. A cell that receives a synaptic signal may be excited, inhibited, or otherwise modulated. Sensory neurons are activated by physical stimuli impinging on them, and send signals that inform the central nervous
108
system of the state of the body and the external environment. Motor neurons situated either in the central nervous system or in peripheral ganglia, connect the nervous system to muscles or other effector organs. Central neurons, which in vertebrates greatly outnumber the other types, make all of their input and output connections with other neurons. The interactions of all these types of neurons form neural circuits that generate an organism's perception of the world and determine its behavior. Along with neurons, the nervous system contains other specialized cells called glial cells (or simply glia), which provide structural and metabolic support. REPRODUCTION The reproductive system is a system of organs within an organism which work together for the purpose of reproduction. Many non-living substances such as fluids, hormones, and pheromones are also important accessories to the reproductive system. The major organs of the reproductive system include, the external genitalia (penis and vulva) as well as a number of internal organs including the gamete producing gonads (testicles and ovaries). Diseases of the reproductive system are very common and widespread. Production of gametes The production of gametes takes place within the gonads through a process known as gametogenesis. Gametogenesis occurs when certain types of germ cells undergo meiosis to split the normal diploid number of chromosome into haploids cells. In males this process is known as spermatogenesis and takes place only after puberty in the seminiferous tubules of the testes. The immature spermatozoon or sperm are then sent to the epididymis where they gain a tail and motility. Each of the original diploid germs cells or primary spermatocytes forms four functional gametes . In females gametogenesis is known as oogenesis which occurs in the ovarian follicles of the ovaries. This process does not produce mature ovum until puberty. In contrast with males, each of the original diploid germ cells or primary oocytes will form only one mature ovum, and three polar bodies which are not capable of fertilization ENDOCRINE SYSTEM Endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The
108
endocrine system is an information signal system like the nervous system, yet its effects and mechanism are classifiably different. The endocrine system's effects are slow to initiate, and prolonged in their response, lasting for hours to weeks. The nervous system sends information very quickly, and responses are generally short lived. Hormones are substances (chemical mediators) released from endocrine tissue into the bloodstream where they travel to target tissue and generate a response. Hormones regulate various physiological functions, including metabolism, growth and development, tissue function, and behavior.
*****
NUTRACUETICALS AS THERAPEUTICS IN LIVESTOCK HEALTH

THIRUMALESH.T
108
There is a drastic reduction in the use of antibiotics and other medicinal products in livestock industry largely due to development of bacterial resistance and presence of their residues in the livestock products like meat, milk and egg. Hence any alternative to antibiotics in health maintenance, disease avoidance in addition to as a source of nutrients will help in antibiotic residue free animal products and reduce the cost of production. In this regard,Nutraceuticals/ Neutracueticals are used to enhance health by providing a physiological benefit beyond the provision of basic nutrients and these are now one of the exciting trends in food technology. Neutracueticals are any substances that are food or a part of food that provides medical or health benefits, including prevention and treatment of diseases. Neutracueticals range between isolated nutrients, dietary supplements and genetically engineered designed foods, herbal products and processed foods (cereals,--and beverages).These include safe feeds (protein hydrolysates, predigested/hydrolyzed carbohydrates and fats), enzymes, acids, phytogenic additives, 8mmunostimulants etc. Properties of nutraceuticals 1. It must improve performance effectively and economically 2. It must have little therapeutic use and must not cause cross resistance to other antibiotics 3. It must not involve with transferable (Infectious drug resistance) 4. It must not cause deleterious disturbances of the normal gut flora
5. It must not absorb from the gut into edible tissue, must not
permute salmonella shedding

6. It
must not give rise to environmental pollution, biodegradable, non toxic to animal and human handlers
readily
7. It must not be mutagenic or carcinogenic Classification 1. Antioxidants, vitamin-C, E, -carotene, omega fatty acids 2. Chondro-protective agent- glucosamine, chandriotin sulphate 3. Herbs or botanicals: garlic, milk thistle etc. 4. Enzymes and minerals
108
Neutracueticals and their functions 1. Organic acid mould and bacterial inhibitors, antioxidants maintain feed quality and hygiene 2. Flavors, antioxidants, enzymes improve voluntary feed intake 3. Enzymes and phospholipids enhance digestion and absorption of nutrients 4. Organic acids, oligosaccharides, probiotics help in modulation of gastrointestinal tract 5. Carotenoids, -glucans, herbal extracts promote modulation of immune system 6. Antioxidants prevent oxidative stress and non-infectious diseases Use of neutracueticals in livestock and poultry Cattle and buffaloe: 1. Many herbal preparations are used to treat the various diseases of cattle a. Turmeric (Curcuma longa) b. Amahaldi (Curcuma amola) c. Ashwagandha (Withania somanifera) d. Adalsa (Adhatoda vasica) e. Sitaphal (Annona squamosa) These are used to treat various diseases, injury and used as antioxidant and anti-inflammatory substances. 2. Supplementation of polyunsaturated fatty acids can enhance the reproductive efficiency by influencing ovarian follicular growth, luteal function and postpartum reproductive performance 3. Mixture of bamboo leaves and ajwana are used for the treatment of retention of placenta 4. Mixture of alum and marigold is used for wound healing Dairy neutracuetical ingredients and their properties: Category Ingredients Properties Prebiotics Lactulose Replacement of sugar, fat, calorie reduction Lactitol Fiber enrichment Lactobionic acid Reduction of tooth decay Galacto oligo Increasing of colonic bifidus saccharides Milk proteins Milk proteins Stimulation fo immune system Whey proteins Antioxidant effect Casein Antithrombic and
108
Purified fractions
milk Alpha-lactalbumin Beta-lactalbumin Lactoferrin
immunomodulator Immune system defense
Bioactive peptides
Others
Provitamin-A/ rich in cystein Body fortification, immune system defense Lactoperoxidase Intestinal comfort, body defense Protease peptone Antitoxin, calcium obsorption Caseinopeptides Body fortification, nervous system and behavior, intestinal transit Glutamine peptide Energy/wound healing/critical ill neonates Growth factors Repair process/bone healing/cancer Colostrum/IgG Immune system/ GI damage Phosphopeptides Osteoporosis Conjugated linoleic Antiatherogenic/obesity/immu acid nologic Oligonucleotides GI/immune system Milk calcium Body fortification
PIGS: 1. Enzymes: Amylase, protease and lipase addition improve post weaning growth and minimize digestive disturbances. -glucanose and xylanose are beneficial when high fibre diet is given. 2. Fructo-oligosaccharide (FOS): These are derivative of inulin, secreted by intestinal flora. Inulinase which are secreted by intestinal flora breakdown this linkage and resultant fructose and glucose act as probiotic. 3.Mannose-oligosaccharide (MOS): Adding indigestible oligosaccharides having fructans and mannose sugar in the feed attract the pathogenic bacteria to attach to feed particles and bacteria are then passed out of gut. Oligosaccharides stimulate the secretion of cytokine and enhance the immune system. 4. Miscellaneous: -glucans, derivatives of inner cell wall of yeast improve the immune system; potentiates response to vaccinations. Porcine plasma supplementation improves feed intake, faster growth and lower incidence of scour and weaning pigs shed rotavirus. Equines:
108
1. Superoxide dismutase (SOD): It is an enzyme required for
revitalizing the cells and reduce the rate of cell destruction. SOD destroys free radicals and used as antioxidants along with vitamin-C and E.
2. Dimethyl Glycine (DMG): It is an amino acid derivative, helps to
produce phosphocreatine in muscles and brain where it reduces lactic acid production after exercise. It is also used to treat epilepsy.
3. Octacosanol: It is a natural food substance in most of the
vegetables, oil, alfalfa leaves and wheat. It improves stamina, strength and cardiovascular function.
4. Methyl sulfanyl methane (MSM): It is derivative of dimethyl
sulfoxide (DMSO). It acts as a source of sulfur to the horse and helps in cross linking in collagen fibers. It acts antioxidants, antiallergic, analgesic and antiparasitic. It is rich in milk. Canine: Polysulfated glycosaminoglycans (PSGAG), glucosamine, chondroitin sulfate and hyaluronic acid are used to treat disease like chronic degenerative disease and osteoarthritis. It also act as antiinflammatory and support anabolic repair process in cartilage, bone and synovium. Supplementation of chondroitin sulfate inhibits the enzymatic destruction of cartilage. Poultry: 1. Probiotics: These are live microbial feed supplements which beneficially affects the host animals by improving its intestinal balances. All most all the probiotics in the market contain Lactobacilli and /or Streptococci and few contain Bifidobacteria, yeast and fungi also. The microbial species used in probiotic preparations include Lactobacillus acidophilus, L.bulgaricus, L.planatarum, L.casei, Streptococcus faecium, S.lactis, S.thermophilus, S.diacetilactus, Bifidofacterium bifidum, Aspergillus oryzae and Saccharomyces cervisiae. Intensive system of poultry rearing causes stress on the birds. Probiotics can counteract the stress in addition to beneficial effects on live weight gain, feed conversion efficiency and decreased mortality in chicks. Mode of action of probiotics: a.They maintain beneficial microbial population in the alimentary tract b. They improve feed intake and digestion
108
c. They alter bacterial metabolism system
d. They stimulate immune
2. Prebiotics: These are non-digestible food ingredients that beneficially affect the host by stimulating the growth and activity of one or limited number of bacteria in the colon and thus improve host health. Among food ingredient, prebiotics include non-digestible carbohydrate like oligo and polysaccharides, some peptides and proteins, certain lipids. These compounds , because of their chemical nature, are not absorbed in the upper part of the GIT. When enter into the caecum/colon, it serve as a substance for the endogenous bacteria, thus indirectly providing the host with energy, metabolic substrates and essential micronutrients. Mode of action of prebiotics: They lower pH through lactic acid production by inhibiting colonization of pathogen and producing systemic effect on utilization of feed ingredient. They stimulate immunity and neutralize the toxins. Prebiotic that has elicited great interest to intestinal health and productivity in livestock is fructo-oligosaccharide (FOS). It stimulates the growth of Bifido bacteria and inhibits pathogenic bacteria such as enterobacteria, clostridia and salmonella. 3. Synbiotics: It is a combination of probiotics and prebiotics. This combination improve the survival of probiotic organism. For example, combinations of FOS and Bifidobacteria, Lactotol and Lactobacilli reduce the colonization of salmonella.
Beneficial effect of probiotics and prebiotics:

Probiotics Modify intestinal microbiota Stimulate immune system Reduce inflammatory reaction Prebiotics Increase production of VFAs Increase biomass and stool bulking Increase Vitamin-B synthesis
108
Prevent pathogen colonization Improve mineral absorption Enhance animal performance Prevents cancer Decrease carcass contamination Lower serum cholesterol Decrease ammonia and urea excretion
2.
Enzymes: Nutritive value of cereals is affected by the presence of certain non-starch polysaccharides (NSP). These are partially soluble in water and from viscous gel solution which increases gut viscosity leading to improvement in the function of digestive enzymes, decrease digesta flow and absorption of nutrients and finally causes sticky droppings. Hence feed enzymes are added to the diet to improve the nutritive value and also for economic poultry production.
In poultry feed ingredients rich in phytic acid which makes phosphorus unavailable to poultry as they lack enzyme phytase to hydrolyze phytate into inorganic phosphorous and inositol. This limits the ability of the birds to utilize phytate phosphorous. The phytate also decreases protein digestibility and inhibit the activity of alpha amylase. Hence, supplementation of diet with microbial phytase improves the availability of phytate phosphorus and other nutrients like energy and amino acids.
3. Organic acids: These are widely used in feed hygiene programmes
as they destroy pathogenic bacteria like Salmonella and Escherichia coli. Mode of action: Organic acids decrease pH below 6 which makes the condition less favorable for bacterial growth and also act directly against specific organisms. For example, 2% lactic acid addition increases weight gain and FCR while addition of propionic acid inhibits mycotoxin production in feeds. However, higher level of formic or propionic acids lead to irritation of the esophagus and intestine leading to poor performance.
4. Phytogenetic/herbal products: The part of many herbal plant s
such as bark, fruit, seed, leaf and root etc. and their extracts are utilized to cure different diseases in animals. Because these are considered as safe, cost effective and environment friendly with no side effects. These products enhance the performance, improve feed utilization, maintain health, alleviate adverse effects of
108
environmental stress and prevent respiratory infection in birds.For example, certain mushroom and herb polysaccharides as immune enhancers prevent bacterial and parasitic disease. These are used as either adjuvant of vaccines, therapeutic agents or feed supplements.
5. Antioxidants: The lipid or fat component of feed reacts with
atmospheric oxygen and suffers deterioration in the process of auto-oxidation. It can be checked by chelating metal ions or by scavenging free radicals. Vitamin-E, ethoxyquin, butylated hydroxyl toluene (BHT), propyl gallate, calcium ascorbate, sodium ascorbate, lecithins are commercially available antioxidants. These maintain potency of dietary energy and vitamins (A,D,E and biotin), stimulates body immunity and protect sources of xanthophylls and other pigments for egg yolk and shank coloration.
6. Carotenoids: are widely distributed in nature, found in both plants
and animals. Carotenoids (xanthophylls) play a role as pigments and provide camouflage. It also possess provitamin activity, antioxidative activity and immune stimulating effects. Neutraccuetical eggs: Eggs supplies about 6.5g of protein of high biological value, 5.8g of emulsified fat and rich in essential amino acids, minerals and vitamins. In spite of this nutritional superiority and low cost, egg consumption is not to the recommended level of ICMR due to high cholesterol content. To increase consumption of eggs as a part of healthy eating, fatty acid composition and level of vitamins and minerals and certain non-nutrient chemicals (pigments and antioxidants) can be manipulated by dietary means. This concept of modifying eggs is called designer or functional food or neutracueticals eggs. The common neutracueticals used are omega 3-fatty acid, Carotenoids, tocotrienols, minerals, vitamins and herbal extracts. Inclusion of these substances in the layer feed decreases the serum cholesterol (LDL cholesterol). The other natural sources of omega 3fatty acids like flax seed, rapeseed, fish, algae and pearl millet lower the serum cholesterol. Challenges: 1. Neutracueticals, also called functional foods, are blur the traditional dividing lines between feeds and medicine. 2. No separate legal category for functional foods as with other foods.
108
3. Manufacturers are not allowed to make a claim that they can prevent, treat or curediseases. For example providing calcium is important for strong bones is health claim and is acceptable but providing calcium prevents osteoporosis is medicinal claim that is illegal. 4. Although there is no legal definition of functional food, most of the parties agree that they are foods marketed as having specific health effects. 5. Necessary to examine, verify active ingredients in the herbs for desired results. 6. The dose mentioned must be verified through the clinical trials. 7. No regulatory authorities to ensure the proper use, pricing and advertising *****
PROTOCOLS OF DRUGS FOR VETERINARY PATIENTS UNDERGOING SURGERY

SHIVAPRAKASH.B.V
Protocol refers to proper planning of drugs and procedure required for successful and complete recovery of surgical patient. A safe and cost effective drug therapy is important in veterinary practice. Protocol of drugs is planned for following period when surgery is planned.
1. 2. 3.
When drug protocol is required? Drug therapy during : preoperative period. Drug therapy during : intra operative period. Drug therapy during : post-operative period. Drug therapy during : perioperative period. 1. Prophylactic antibiotics & therapeutic antibiotics 2. Fluid and electrolyte therapy 3. Perioperative analgesia 4. Pre anesthetics and anethetics
PROPHYLAXIS OF ANTIMICROBIAL AGENTS
Definition: Prophylaxis of antimicrobial agents strictly means administration of antimicrobials before any contamination or infection is present at the surgical site.
1. Strictly it should be given before 30 minutes and not later than 60

minutes before surgery. 2. Antimicrobial therapy may involve either bacteriostats or bacteriocidals. 3. Bacteriostat drugs should not be combined with bacteriocidal drugs.
108
4. Dosage depends on minimum inhibitory concentration of a drug at the site. 5. The interval of repeating a drug is based on half life of a drug. 6. Its interaction with other drugs, anesthetics should be kept in mind 7. Its side effects and toxicity should be kept in mind. 8.Its distribution in the operated site and elimination should be kept in mind. 9.Prophylactic antibiotic should be given intravenously. 10.It should be repeated during surgery until closure of wound if half life of drug is short. 11. Prophylactic antibiotic is not recommended for each and every case as it may lead to development of drug resistance. 12. It is indicated if gross contamination is expected or surgery takes more than 2 hours. Drugs: Dogs: Cefazolin is the most commonly used antimicrobial for dogs in western countries because of its excellent efficacy against pathogens, reasonable cost, low toxicity and prolonged duration of action. It is given at the dose of 22 mg/kg every 3 hours for soft tissue surgery and every 90 minutes for orthopaedic surgery. Other drugs: penicillins, cephalosporins, aminoglycosides, fluroquinolones, metronidazole, trimethoprim-sulfonamide are in use for prophylaxis. Ruminants : any of the above can be administered. I recommend(because of cost) Combination of amoxicillin- cloxacillin, or streptomycin-procaine penicillin or ceftriaxone before and after most of the surgeries such as caesarean, oesophagotomy, open fracture repair. Costly preparations such as tazobactum or clavunalate are rarely required. Postoperative antibiotics It is common practice in India to administer antibiotics after surgery rather than before surgery. Research done in humans undergoing surgery showed that infection rate is same for who receive antimicrobials for the first 24 hours and also for those who receive a 5day course of postoperative antimicrobials. At this time, there is no clinical evidence to support that antibiotic are required beyond the operative period(Dellinger et al. 1994; Rosin et al., 1993). I recommend post operative antibiotics for more than 4 days for cases such as caesarean, oesophagotomy in cows, orthopaedic procedures. Elective surgeries such as ovariohysterectomy in dogs and rumenotomies done for acidosis or impaction due to plastics may not require prolonged antibiotics. Topical antibiotics: These are included in drug protocol for topical treatment of wounds including surgical wounds. Triple antibiotic
108
ointment: Bacitracin-polymixin-neomycin : wide spectrum of activity, not effective against pseudomonas. Nitrofurazone: spectrum of activity, slowes wound re-epitheliazation. Silver sulfadiazine: Broad spectrum, effective against pseudomonas. Specific for burn wounds.Gentamycin sulfate: effective against gram negative bacteria.
PROTOCOLS IN FLUID AND ELECTROLYTE TREATMENT
Fluid therapy should be planned in following 3 stages of surgery for better outcome, 1.Preoperative fluid therapy 2. Intraoperative fluid therapy 3. Post- operative fluid therapy Fluid therapy should be given as following in all above 3 stages: 1. Replacement therapy 2. Maintenance therapy 3.Therapy for ongoing/ continuous fluid loss Water is the main constituent of the body and constitutes about 60 % of the body weight and 40% is present in ICF and 20% in ECF. Water is essential for metabolism, chemical reaction and thermoregulation. Electrolytes such sodium, potassium, bicarbonate and chloride are essential for cell metabolism. In addition, energy is required to meet nutritional demand. Hence all the three components (fluids, electrolytes and nutrition) are taken care before and after surgical procedure . Preoperative fluid therapy Step 1: Diagnose the fluid & electrolyte imbalance : by clinical signs & lab. Tests. Sodium, potassium, chloride, bicarbonate estimation Step 2: Calculate fluid requirement 1. Replacement therapy: Fluid(ml) required = % dehydration x BW x 1000 Rate of administration: 90 ml/kg/hr.Fluid deficit is corrected during first 4 to 6 hours. Electrolyte imbalance will take more time than this for correction. 2. Maintenance : 40 to 60 ml/kg/day : A dog or cat requires 50 to 100 ml of fluids/per kg per day to maintain hydration depending upon its activity and environmental temperature. An animal suffering from a disease and anorexia might require less fluid. 3. Ongoing loss: depends on extent of blood loss, vomition, diarrhea Fluid therapy during surgery(Intraoperative) Anaesthetics result in compromised cardiopulmonary function and hence the need of fluid therapy. Surgical stress releases ADH to conserve fluid but anaesthetics will combat this mechanism. Additional blood loss during surgery also requires fluid therapy.
108
Dose Of fluids during surgery: 10 ml/kg/hr. . But depends on length of surgery and complexity of surgery. Type of fluid : isotonic crystalloid solution Fluid therapy during post operative period Fluid therapy has to be continued during postoperative period if animal do not take feed and water voluntarily The dose depends upon type of disease and extent of dehydration Fluids are not required if animal resumes feeding. Crystalloids or colloids? In most of the cases crystalloids are administered as they are readily available and are economic. They diffuse through the compartments and reach from ECF to ICF quickly. Colloids stay in intravascular compartment and are preferred if hypovolemia requires rapid volume replacement.It is also required to correct hypoalbuminemia. Colloids are costly and can be given if crystalloids requirement is reduced. Fluid & electrolyte therapy for specific disorders
Abnormality Type of Acid-base dehydration status Simple dehydration, Hypertonic stress, exercise Anorexia, starvation Vomiting Hypertonic Isotonic/hypert onic Fluid therapy Half strength or Balanced electrolyte / 5% glucose Mild metabolic Half acidosis strengthfollowed by Balanced electrolyte Metabolic Ringers/ 0.9% NaCl alkalosis, chronic: metabolic acidosis metabolic Balanced acidosis electrolyte, HCO3metabolic 0.9% NaCl followed acidosis by Balanced electrolyte metabolic 0.9% NaCl initially alkalosis metabolic acidosis metabolic acidosis Balanced electrolyte Balanced electrolyte, blood colloid,
Diarrhea Urethral obstruction(dogs) Urethral obstruction(ruminan t) Acute/chronic renal failure Hemorrhagic shock
Isotonic/hypert onic Isotonic/hypert onic Isotonic/hypert onic Isotonic/hypert onic isotonic
PERIOPERATIVE ANALGESIA Control of pain is most essential part of surgical management. Most veterinarians consider it more casually and survey has shown that only 19% of dogs received analgesics for more than 8 hours after surgery.
108
In a survey with British veterinarians 95% agree that perioperative analgesia is beneficial to the patient. It is divided into 3 phases. 1. Prepoerative analgesia(Preemptive analgesia) 2. Operative analgesia 3. Postoperative analgesia Preemptive analgesic protocol: Preemptive analgesia refers to administration of analgesic drugs before the start of surgery. Whether or not it reduces pain during surgery or at postoperative period is controversial. Opioid analgesics, ketamine, alpha 2 agonists, nonsterodial antiinlammatory agents and local anesthetics are used with following guidelines.
Drug Morphine Oxymorphon e Medetomidin e Xylazine Bupivacaine Ketamine Ketoprofen Acepromazin e Diazepam ANESTHETIC OPERATIONS Species Dog Dog Dog, cat Dog, cat Dog Dog Dog, cat Dog, cat Dog, cat PROTOCOL Dose 0.05-1.0 0.2-2.0 0.02-01 0.05-0.2 0.001-0.002 0.1-0.2 0.1-05 2-3 0.5-1.5 0.25=0.5 1-2 0.01-0.03 0.1-0.5 FOR Route IV IV.,SQ IV IM, Sq IV IV IM, SQ Local block Epidural IV IV, IM, SQ IV IV AND Duration(h r) 1-2 2-6 1-2 2-6 0.5-1 0.5-1 0.5-2 2-6 4-6 Loading dose 12-24 1-2 0.5-1 UNCOMPLICATED
ELECTIVE
Eg. Castration, overiohysterectomy in dogs 1. Xylazine (1mg/kg, IM15 mts before) + thiophental sodium (12.5 mg/kg IV) 2. Xylazine (1 mg/kg IM ) + Ketamine(8-10mg/kg IV, IM) 3. Triflupromazine 0.5-1mg/kg) + Thiophental sodium 4. Triflupromazine + Thiophental sodium+ Halothane/isoflurane 5. Triflupromazine + Propofol(4-6mg/kg, IV)
ANAESTHESIA FOR SHOCK /CRITICALLY ILL PATIENTS (DOGS)
1. 2. 3. 4.
Oxymorphone(0.1mg/kg IV) + Diazepam to effect Thiophental _ should not be used Propofol (4-6 /kg IV) Diazepam(0.27/kg) + ketamine(5.5 mg/kgIV) Small doses
108
5.
Etomidate(0.5-2 mg/kgIV)
FOR PATIENTS WITH CNS/ OPTAHLMIC
ANAESTHETIC PROTOCOL PROBLEM
Avoid ketamine( as it produces excitement) Avoid acepromazine as it causes seizures Use Drugs: Opioids + inhalant anesthetics(isoflurane) Donot use nitrous oxide
ANESTHETIC PROTOCOLS IN RUMINANTS
Xylazine sedation (0.05-0.11mg/kg ) + lignocaine(infiltration/nerve block) Xylazine (0.05-0.11 mg/kg) + ketamine (2 mg/kg) Xylazine (0.05-0.11 mg/kg) + ketamine (2 mg/kg) + halothane/isoflurane
*****
108
TRANQUILIZERS, INTRAVENOUS ANAESTHETICS AND DISSOCIATIVES IN VETERINARY PRACTICE

DILIPKUMAR.D
Tranquilizers are basically employed as preanesthetics primarily for smooth induction of anaesthesia or to deliver reduced dosage of aanesthetic agent in question. Tranquilizers belonging to phenothiazine class cause sedation, reduce spontaneous motor activity through antagonism of central neurotransmission of dopamine by preventing its interaction with the excitatory D1(++) and D2(+++) receptors. Pharmacologically phenothizene tranquilizers possesses antiseratonergic, anticholinergic,hyperglycemic antiarrythemic (quinidine like depressant on myiocardium) properties. Additionally, they block alpha-adrenergic, H1 and 5HT2 receptors in the CNS and cause . Benzodiazepins like diazepam,midazolam, flurazepam etc. exert sedative effect through potentiating the action of ingibitory neurotransmitter(GABA) by binding with GABAA receptors. These drugs do not have no significant effect on cardiovascular and respiratory system at sedative or tranquilizer doses. Intravenous anaesthetics: Advantages of IV anesthesia include rapid and smooth induction of anesthesia, little equipment requirement (syringes, needles, catheters), and easy administration of drugs. Disadvantages include difficult retrieval of drug once administered, less control of depth and duration of anesthesia, lack of ventilatory support, and poor tolerability in debilitated, dehydrated or toxicated animals. Details of pharmacokinetics and uptake and metabolism of these agents are beyond the scope of this lecture, but brief pharmacokinetic knowledge is essential for safe use of these agents.Response to administration of IV anesthetic induction agents depends on: a. Dose, concentration and speed of administration b. Blood volume between injection site and brain c. Ionization d. Protein binding e. Redistribution to non-nervous tissue f. Metabolism and excretion of the drug and metabolites.
108
Barbiturates: Mechanism of action of barbiturates and nonbarbiturates intravenous anesthetics is mediated via CNS depression by modulation of GABA-mediated neurotransmission. Barbiturates are classified according to duration of action: o Long acting: phenobarbital o Short acting: pentobarbital and o Ultra-short acting: thiopental, thiamylal, methohexital. Primary factors determining the plasma levels of the barbiturates are dose, concentration and speed of administration, blood volume between injection site and brain, ionization, degree of protein binding, redistribution to non nervous tissue, and metabolism and excretion of the drug and metabolites. Major clinical properties include good hypnosis, poor to moderate analgesia and dose-related respiratory and cardiovascular depression. However, at light levels of anesthesia, cardiovascular depression is minimal unless the patient is hypovolemic. There can be marked recovery excitement, but this is reduced or removed by premedication. Barbiturates will cross the placenta, and will affect the fetus. Adult ruminants metabolize barbiturates faster than do cats and dogs. Thus they may be shorter acting and less cumulative in ruminants. Neonates do not have the necessary enzymes, and prolonged effect may be seen. Although theoretically the horse also has the ability to metabolize barbiturates faster than the dog, this is not so in the clinical circumstances, and recovery from cumulative doses of barbiturates may be prolonged and violent. Treatment of overdose of barbiturates should be aimed at removal of respiratory depression (NB: analeptics do not last as long as the barbiturate) and fluid therapy to increase renal excretion. In small animals, general anesthesia is induced by administering part of pre-calculated dose until the desired anesthetic depth (usually just deep enough for endotracheal intubation) is reached - referred to as titrating to effect. Pentobarbital (Saggital, Nembutal) Anesthetic concentration is 60 mg/ml. (NB: euthanasia solutions contain a higher concentration, and various stabilizing agents sometimes cause cardiac arrest). No longer used routinely for anesthetic induction due to its prolonged rough recovery. Pentobarbital is mainly used for seizure control in the animal. Intravenous dose for healthy unpremedicated dogs and cats is 20-30 mg/kg, given to effect. It has a slower onset of action than thiopental (minutes). Pentobarbital is metabolized by the liver. Administered IV (slow response, give very slowly) or IP (laboratory rodents). In single stomached animals, full anesthetic doses produce about 1 hour surgical anesthesia, but recovery takes up to 24
108
hours. Recovery is also violent (dogs howl and paddle) unless premedication is used. Small animals become very hypothermic. Ruminants, however, recover quietly and very much faster, and the drug still has a place to play in farm animal anesthesia. Contraindicated in neonates and animals with liver failure, respiratory disease, porphyria, requiring cesarean section, hypovolemia and emaciation. Ultra-short acting Methohexital barbiturates: Thiopental, Thiamylal,
Ultra-short acting barbiturates are often used in the clinic for inducing general anesthesia in both small and large animals. Advantages of ultra-short-acting barbiturates for induction of anesthesia: o They are the least expensive of the injectable anesthetics. o Need no specialized equipment for administration (vs inhalant anesthetics). o These drugs have a rapid onset of action, provide a predictable response, and rapid recovery following single dose administration. Patients that benefit from thiobarbiturates induction include:o Patients with raised intracranial pressure - thiobarbiturates decrease intracranial pressure. Patients with seizure history - thiobarbiturates decrease seizure activity. Patients with corneal lacerations or glaucoma - thiobarbiturates decrease intraocular pressure. Patients for examination of laryngeal function - thiobarbiturates does not depress laryngeal reflexes at the light dose. Patients with hyperthyroidism - thiobarbiturates have antithyroid effect In large animals, ultra-short acting barbiturates are usually used in combination with glycerol guaiacolate (also called guaifenesin). When compared to using ultra-short acting barbiturates alone, the total dose of ultra-short acting barbiturates is decreased when it is given with guaifenesin. This results in less cardiovascular depression and smoother inductions and recoveries from anesthesia Precautions when using ultra-short acting barbiturates for induction of anesthesia: The drug must be given intravenously because of its highly alkaline pH (= 11); perivascular injection will cause tissue necrosis. The drug must not be used when venous access is not possible or questionable
108
Small margin of safety between an effective dose and a lethal dose - especially in debilitated patients Apnea and profound respiratory depression following IV bolus injection often occur. Cardiac arrhythmia often presents ventricular bigeminy and other ventricular arrhyhthmias (PVCs) Thiobarbiturates should not be used alone in sighthounds (Greyhounds, Whippets, Salukis, Afghan, Borzoia etc.); recovery is 2-4 times longer than in non-Sighthounds, and may be very rough. Methohexital is acceptable for use in Sighthounds; recovery time is not prolonged Thiobarbiturates induce splenic engorgement, which makes surgical manipulation and removal of the spleen more difficult. Other induction agents should be used in patients requiring a splenectomy. Thiopental (Thiopentone) (Pentothal:): The most widely used barbiturate. Presented as powder and dissolved in water to required concentration. Limited shelf life of solution. Only for IV use. Very acidic; causes severe necrosis in accidental extra-vascular administration. Inject through catheters to avoid this. The lowest concentration practicable should be used (1.25% cats; 2.5% dogs; up to 10 % for large horses and cattle). High concentrations cause thrombophlebitis in the vein. Treat accidental extravascular injection by injecting sterile saline with either the enzyme hyaluroniclase or local anesthetic without epinephrine. Volumes needed depend on concentration and quantity of thiopental but may be very large (e.g., 500 mls in a horse). In most unpremedicated domestic animals, doses of 10 mg/kg thiopental will cause rapid onset and short duration (5 minutes) unconsciousness. However, effect depends on concentration and speed of injection. Recovery is by redistribution. Further doses become cumulative; each dose delaying recovery, until at the maximum licensed cumulative dose (30 mg/kg) (NB, anesthetists consider that a cumulative total of 30 mg/kg in single stomached animals is a gross overdose; do not exceed a total dose of 15 mg/kg). Recovery is identical to that seen with pentobarbital. Respiratory depression is marked, so except at the very lowest doses, oxygen supplementation is needed. At 10 mg/kg in the majority of fit animals, there is little cardiovascular depression (although by 30 mg/kg this may be marked). Premedication reduces dose (4-8 mg/kg IV in cats or dogs), and increases duration. Acepromazine, opioids, benzodiazepines or alpha 2 agonists decrease
108
thiopental dose in a dose-related manner. Premedication usually results in a smoother recovery. Thiopental is highly protein bound; thus hypoproteinemic and anemic animals are very sensitive to its effects (keep doses very low). Similarly hypovolemia increases sensitivity. Contraindicated in neonates and animals with liver failure, porphyria and emaciation. Phenol derivatives: Propofol (Rapinovet; Diprivan): Propofol (2, 6 diisopropylphenol) is a phenolic compound unrelated to any other general anesthetics. Propofol is a non-barbiturate, non-dissociative intravenous anesthetic agent, and very widely used in dogs and cats. Propofol is not water soluble, and is prepared as a milky white emulsion of containing 10 mg propofol, 100 mg soybean oil, 12 mg egg lecithin, and 22.5 mg glycerol per ml. Propofol contains no preservative and the emulsion supports bacterial growth and endotoxin production. Once exposed to the air the contents in the vial must be used within 8 hours or discarded thereafter. New formulation of Propofol resistant to microbial contamination is under current development. Not a controlled substance, a major advantage over other scheduled agetns. Propofol is for intravenous use only (non irritant, but too rapidly metabolized for other routes). Propofol is very respiratory depressant (worse than thiopental). Maximal effects are a little slower than a circulation time so beware of delayed respiratory depression about 2 minutes after induction. Some animals become cyanotic without stopping breathing. Circulatory effects at equipotent doses are similar to thiopental (some hypotension and direct cardiac depression).Muscle relaxation is usually fair. Quality of anesthesia (smoothness) is usually good. Quality of recovery is usually excellent (very complete). Convulsive twitching or muscle rigidity is seen following induction at times but usually resolves spontaneously. Propofol is rapidly metabolized by hepatic and extra-hepatic metabolic pathways. Recovery depends on this rather than on redistribution away from highly perfused tissues (eg, brain). Propofol is, in general, non cumulative. Thus it can be used for prolonged anesthesia by intermittent injection or by continuous infusion (NB, in neonatal children problems occurred when it was
108
used by continuous infusion for several days to obtain sedation in intensive care. It is probable that the toxicity was due to accumulation of the carrier in patients whose enzymes were sufficiently undeveloped to cope. It can be used safely for anesthesia in neonates). Propofol has extensive protein binding over 90 %. Propofol should be administered slowly titrate to effect for endotracheal intubation. Single induction dose of propofol in healthy non-sighthound dogs makes no clinically significant difference in terms of awakening time from induction to recovery compared to thiobarbiturates anesthesia. A distinct difference exists between propofol and thiopental for anesthesia induction. Propofol is more hypnotic, so can be given slowly (over a period of 60 seconds), as subclinical doses of propofol, unlike thiopental, are unlikely to induce excitement. So propofol alone can be given slowly as a sedative at lower doses (0.5- 1 mg/kg). The slow IV administration is also helpful to minimize propofol induced apnea by titrating the dose just enough for intubation. On the other hand, the first half of the calculated doses of thiopental is typically administered relatively fast so as to avoid excitement. Since propofol provides no analgesia, a high dose is required (to maintain unconsciousness) when performing painful procedures. These high doses produce apnea and intubation with positive ventilation is required. It is recommended to combine propofol with an analgesic agent (opioids or alpha2 agonists) for painful procedures. Propofol has become very popular, particular following price drop after the patent expiration, for use in dogs and cats, both for induction prior to gaseous anesthesia [NB: may need more volatile agent than after thiopental, and for more prolonged procedures (by intermittent injection or by continuous infusion)]. Propofol is often used to maintain anesthesia during those procedures where gaseous anesthesia is not possible, eg bronchoscopy, transtracheal aspiration, MRI Dose depends on premedication. e.g., in dogs, IV induction dose after no premedication is 6-8mg/kg; after acepromazine 2-4mg/kg; after
108
medetomidine a dose related reduction, so after 40 mcg/kg medetomidine IV doses of propofol of l mg/kg are adequate. Overdose causes apnea. In dogs, single dose just enough for intubation gives about 10-20 minute recumbency. Prolonged anesthesia, using continual injection (constant infusion pump) is commonly used in man, and is practicable in animals. In man, computer programs based on EEG and other physiologic monitoring results may be used to control infusion and maintain a constant depth of anesthesia. Imiazole anesthesia: Etomidate/Metomidate Etomidate (Amidate; Hypnomidate): Etomidate is a carboxylated imidazole derivative.Etomidate is an intravenous, ultrashort-acting, nonbarbiturate hypnotic drug. Etomidate is quite widely used in man as an induction agent and by continuous infusion. In man, the IV induction dose is 0.3mg/kg, but higher dose is needed in dogs and cats (2- 4 mg/kg). Prolonged infusion suppresses adrenocortical function. Etomidate, then, undergoes rapid hepatic metabolism resulting in rapid recovery and does not accumulate when repeated boluses or an infusion is given. Major advantages are minimal cardiopulmonary depression. It produces minimal change in heart rate, mean arterial blood pressure, or myocardial performance. The respiratory effects of etomidate are similar to thiopental and propofol it will induce respiratory depression and apnea in animals. Etomidate has not gained popularity as a regular anesthetic induction agent in veterinary medicine because: o It is the most expensive (vs propofol and thiopental) o Sneezing, retching, and myoclonic twitching are often observed at induction (these side effects can be minimized with a premedication) o Etomidate inhibits adrenocortical function o Hemolysis and hematuria also have been reported in dogs and cats following either induction or infusion of etomidate o It is painful upon injection due to its propylene glycol preparation and perivascular njection of etomidate does not cause tissue irritation. Metomidate (Hypnodil): Metomidate has been used over two decades as a hypnotic agent in the pig. Given IV (irritant), its advantages are minimal respiratory or cardiovascular depression
108
with good quality hypnosis. Analgesia is very poor. Recovery time is of moderate length (about 1 hour). It has been withdrawn and is currently not available. Dissociatives Tiletamine: (Phencycline derivatives): Ketamine and
Dissociative anesthesia implies dissociation from the surrounding with only superficial sleep mediated by interruption of neuronal transmission from unconscious to conscious parts of the brain. During dissociative anesthesia, the animal maintains its pharyngeal, laryngeal, corneal, palpebral, and swallowing reflexes. The eyes also remain open. Dissociative anesthetic agents increase muscle tone, spontaneous involuntary muscle movement (occasionally seizures are seen in some species). Salivation, lacrimiation are also increases and somatic analgesis is good. Ketamine and tiletamine (combined with zolazepam in Telazol) are the two dissociative anesthetics currently available in veterinary practice. Cardiovascular effects of dissociatives are dose dependent. At clinical doses, ketamine (and tiletamine) centrally stimulate the sympathetic system resulting in tachycardia, increased blood pressure and increased cardiac output. Large doses of ketamine depress the myocardium directly and may produce hypotension. Ketamine and Telazol produce less respiratory depression than other intravenous anesthetic agents (propofol, etomidate, barbiturates); however, clinically effective dose of ketamine or Telazol may induce apnea in some susceptible animals. In most species, ketamine and Telazol are metabolized by the liver. In cats, a significant amount (50%) of ketamine is excreted unchanged by the kidney. This difference may account for differing responses seen in dogs and cats receiving dissociatives. Dogs tend to have slow and stormy recoveries (head shaking, salivating, muscle rigidity, vocalization, defecation) from ketamine and Telazol, while cats tend to have faster and smoother recoveries. Ketamine and Telazol reliably produce anesthesia following either IM or IV administration.The effectiveness of these drugs following IM administration is an important reason for the popularity of these agents in cats, many exotic species, and intractible patients. Ketamine HCl: Ketamine possesses better somatic analgesia than visceral analgesia. Its analgesic effect is partly mediated by N-methyl-D-aspartate (an excitatory neurotransmitter) antagonistic activity. In dogs and horses, ketamine should be used in combination with or after premedication
108
(xylazine, detomidine, medetomidine, diazepam, midazolam, and acepromazine) with a sedative or a tranquilizer - violent involuntary movements (muscle rigidity and/or seizures) will occur if ketamine is given alone. In dogs, ketamine is often combined with diazepam, midazolam, or medetomidine, whereas as in horses, xylazine or detomidine is used. Ketamine has been used in combination with guaifenesin as an induction agent in large animals (horses, cattle). Eyes remain wide open with nystagmus at times, and, therefore protective eye lubrication is indicated to protect the damage of the eye during anesthesia. Emergence hallucination and delirium can be prevented with concurrent use of sedatives/tranquillizers. Increased muscle rigidity is counteracted by use of sedative possessing good muscle relaxant effect (e.g. benzodiazepines). Both hypothermia and hyperthermia is observed. Hypothermia,due toeffect on thermoregulatory centers, and hyperthermia on increased muscle activity or hyperactive behavioral change. Tiletamine (in Telazol): Telazol consists of equal parts (weight to weight) of tiletamine, a dissociative anesthetic and zolazepam, a benzodiazepine derivative. The pharmacologic actions of these two drugs are complementary with tiletamine providing analgesia and immobilization and zolazepam providing muscle relaxation and tranquilization. Telazol comes as a powder and needs to be reconstituted with 5 ml solution of sterile water or other liquid solution of choice (e.g., ketamine, xylazine). Following reconstitution with sterile water, each ml of solution contains 100 mg of Telazol (50 mg of tiletamine and 50 mg of zolazepam) per ml. Telazol is a product similar to ketamine and diazepam (Ket-Val) combination. In the dog, the plasma half life of zolazepam is 1 hour and that of tiletamine is 1.2 hours. Therefore, the effect of tiletamine outlasts that of zolazepam, and may result in emergence delirium associated with dissociative anesthesia recovery. On the other hand, in the cat, the plasma half life of zolazepam is 4.5 hours and that of tiletamine is 2.5 hours. This longer lasting effect of zolazepam over tiletamine may partly explain the smoother recovery characteristics in this species compared to that in the dog. Telazol has been used extensively in exotic large animal (large cats, pigs, and hoof-stock) as a darting agent for immobilization. Steroid anesthesia: Historically, hydroxydione and minaxolone were available. One of the most widely used steroid anesthetic in current veterinary use in Europe is Saffan (alphaxalone solubilized by Cemorphor EL). The product is
108
not available in the US. There has been a renewed interest in the use of steroid anesthetic with different formulation (alphaxalone solubilized by cyclodextrins) in the US. Alphaxalone (Saffan): Alphaxalone, a potent steroid anesthetic has been used in veterinary medicine for 30 years in Europe. It is not available in the US for clinical use. Alphadolone, a weak steroid anesthetic is added to increase solubility. As alphaxalone is poorly water soluble it has been formulated in 20 % polyoxyethylated castor oil (Cremophor EL) and saline (Saffan) to make 12 mg total steroid per ml. It is licensed for use in cats and non-human primates in Europe. The agent is metabolized by the liver; non - cumulative. Alphaxalone is non-irritant, so can be given IM (volume limited) or IV. Respiratory depression is minimal in cats. At clinically applicable doses, hypotension is seen through peripheral vasodilation, but cardiac depressant effects is minimal, so circulatory state is well maintained (unless hypovolemic). Analgesia is fairly good. Quality of anesthesia is good during deep anesthesia, but muscle twitching is seen at light level of anesthesia, with convulsive type behavior in recovery. Recovery convulsions are increased by stimulation but can still occur in quiet surroundings. IM use can induce twitching during induction. Major side effects are swollen ears and paws - this is very frequent although variable in degree. Less frequent occurrence is edema of lungs or larynx (can be fatal). Post-operatively there are occasional reports of ear tips or paw tips sloughing, presumably as a result of swelling. More serious side effect can be occasional deaths through postoperative necrosis of larynx. Nevertheless, reports showed that Saffan was three times safer in cats than was any other regimens (presumably because of lack of respiratory depression). The popularity of Saffan in the cat is because, without causing apnea, a large enough dose can be given as a single IV bolus to enable an ovariohysterectomy to be performed. In the unpremedicated cat IV doses of 9 mg/kg gives 20-30 min surgical anesthesia (enough for an ovariohysterectomy). Top up doses (1-3 mg/kg) can be given to lengthen anesthesia if required or volatile agents may be used. Smaller doses may be used for induction only. Acepromazine premedication does not reduce the dose but improves quality of anesthesia and reduces paw/ear swellings. Alpha 2 agonists greatly reduce the dose, but must be combined with great care. Do not use in dogs! It has not a license in this species in Europe because the Cremophor EL formulation would induce high incidences of allergic reaction in this species, fatal at times. Histamine release causes
108
severe hypotension, broncho-constriction, rashes and vomiting. It has been used in a variety of species. Occasional aberrant reactions occur, presumably through histamine release. Large animal use is limited by volume and the poor quality of recovery. Propanidid (Epontol): Propanidid, a eugenol derivative, is highly water soluble and onset of induction and recovery are rapid, the rapid recovery being due to both redistribution and metabolism. This induction agent was though used in humans, but fell into disrepute as it was solubilized in Cremophor EL and has high incidence of allergic reactions. The future of its use in veterinary medicine is uncertain at this point, and will largely depend on its success in human anesthesia. *****
THERAPEUTIC MANAGEMENT OF PRODUCTION DISEASES OF RUMINANTS

N.A. PATIL
Ruminants, dairy animals in particular undergo a remarkable
metabolic change during periparturient period which extends from 3-4 weeks before parturition to 3-4 weeks post-partum period. Good care of dairy animals during this phase is important preventive strategy for control of production oriented diseases. Milk fever and downer cow syndrome are the most commonly occurring production diseases in dairy animals. PARTURIENT PARESIS (MILK FEVER) Aetiology : Depression of levels of ionized calcium in tissue fluids is the major biochemical defect in parturient paresis. The onset of lactation results in a sudden large demand of calcium. Most of the recently calved animals adopt to the demand (23 grams of calcium is drained in single milking in a dairy animal giving about 10 kg of colostrums, which needs to be replaced by intestinal absorption and bone resorption)with the help of parathyroid hormone (PTH) and 1,25dihydroxy vitamin D. The cows which do not adopt to this develop milk fever. Risk Factors: High calcium diet ( >100 gm /day) during the pregnancy depresses the calcium homeostatic mechanism. Therefore ,
108
such animals are unable to initiate calcium resorption from bone or intestinal absorption making them more susceptible to severe hypocalcaemia immediately after parturition. Prepartum diets high in phosphorus (>80 gm/day) inhibits renal enzyme which catalyses production of 1,25-(OH)2 D which when decreased reduces intestinal calcium absorption. Recent Studies indicate that prepartum diets high in cations like sodium and potassium are associated with increased incidence of milk fever and diets high in anions like chloride and sulfur decrease the incidence. The high anion content of the diet induces metabolic acidosis which help in calcium resorption from bones. High oxalate content in plants and soil in certain geographical area also predisposes for hypocalcaemia due to formation of unabsorbable calcium oxalate complex. Pathogenesis: Normal calcium level in bovines ranges between 8-12 mg/dl. The clinical signs are evident when the level falls below 5.5 mg/dl. The hypocalcaemia exerts its effect on skeletal, cardiac and smooth muscles. Effect on skeletal muscles is indicated by fatigue, muscular weakness, hypothermia and recumbency. Decrease in cardiac output, decreased stroke volume, decreased, amplitude of pulse, decreased tissue perfusion and hypoactivity of the vital organs, alimentary stasis, decreased amplitude and contractions of rumen are other effects of hypocalcaemia. There may be concurrent hypophosphataemia. Clinical findings :The disease is seen in three arbitrary stages. First stage (Stage of excitement): This is a brief stage and many a times goes unnoticed . Hypersensitivity, muscle tremor of the head and limbs, grinding of the teeth, normal to slightly above normal rectal temperature, ataxia is noticed in this stage. Second stage (Stage of Sternal recumbency): Majority of the cases are seen in this stage. The animal is seen in sternal recumbency with a typical posture of lateral kink in the neck and head resting over the flank. Subnormal temperature, cold extremities, dialated pupil unresponsive to light, relaxed anal spincture, increase in rate (80/min) but decreased intensity of heart sounds, weak pulse, ruminal stasis are important findings in this stage. Third stage (Stage of lateral recumbency): The animal is almost comatose and lies in lateral recumbency. Heart sounds are almost inaudible,the rate is high (up to 120/min). It is almost impossible to raise the jugular pulse indicating venous collapse. Spontaneous recovery is very rare;untreated cases deteriorate and die in about 12 to 24 hours.
108
Diagnosis: The history of recent calving and classical clinical signs are indicative of the condition. Negative Sulcowitch test on urine is preliminary indication of hypocalcaemia. Hypocalcaemia ( 5.5 mg/dl), elevated Creatinine phosphakinase in blood/serum are important biochemical changes indicative of the condition. Marginal hypermagnesaemia (> 3 mg/dl ) and hypophosphataemia ( 1.3 - 3 mg/dl) can be seen in few cases. Eosinopenia, lymphopenia and neutrophilia are some haematological findings indicative of adrenocortical hyperactivity in the cases of parturient paresis Treatment : Standard treatment of milk fever comprises supplementation of parenteral calcium preparations. Adult dairy animals require about 8-12 gms of calcium as a total dose. Commercial preparations usually contain 20-25% of calcium borogluconate. Boric acid in this type of preparations make calcium gluconate complex more stable. The requirement of such preparations in a dairy animal weighing 300-400 kgs is about 400-500ml. Underdosing is the main reason for incomplete recovery and relapse. 50% of the calculated dose is administered by intra-venous, route and remaining 50% is administered by subcutaneous route. The subcutaneous calcium acts as a depot for steady calcium level maintenance. Composite solutions containing calcium, magnesium, phosphorus and glucose are recommended to non-responsive and relapse cases with initial calcium therapy. Prevention and Control: Feeding of high phosphorus/low calcium ration (3.3:1) in the last month of pregnancy prevents the occurrence. Addition of chloride and sulfur in excess during prepartum period improves the intestinal absorption of calcium and also mobilization from bone. It can be achieved by adding ammonium chloride @ 100 gms/head per day. Prophylactic feeding of 150 gms of calcium gel given at 24 hours, 1-2 hours before and 10-14 hours after calving is effective. Administration of vitamin D and its metabolites also helps in the prevention. 1, 25 -Dihydroxyvitamin D3 is given in 200 g orally 45 days prior to calving. 1-Alpha hydroxyvitamin D3 given @ 350 g as a total dose intramuscularly 72 and 24 hours before calving is more effective. KETOSIS It is a production disease resulting due to negative energy balance and represent incomplete combustion of fatty acids which results in
108
accumulation of ketone bodies. characterized by Ketonemia, Ketonuria, hypoglycemia and low hepatic glycogen. Aetiology :Recent classfication etiopathogenesis is as follows: of the disease based on
1. Alimentary ketosis: It is due to exclusive feeding of silage which is rich not only in butyrate, a highly ketogenic substance, but also decrease the feed intake due to poor palatability. 2. Starvation Ketosis: Poor quality of food stuffs which are low in proprionate and proteins are the causative factors. Famines and drought conditions also contribute in certain area due to non availability of fodder.
3. Production Ketosis (primary ketosis0: Most common form;.
High yielding animals have constant drain of lactose in milk which should be appropriately replaced by dietary input of glucose precursors like propionate and amino acids. This deficiency compounds during the peak of lactation which accelerates the rate of gluconeogenesis which contributes for accumulation of ketone bodies. 4. Secondary Ketosis: The disease conditions like traumatic reticulitis, metritis, mastritis displacement of abomasum cause decrease in apetite thereby resulting in a state of hypoglycemia which triggers gluconeogenesis ultimately leading to accumulation of ketone bodies. Epidemiology: The incidence is high during first two months postpartum. Mature cattle in their 3rd to 4th lactation are highly susceptible as they attain maximum milk yield at this stage. The disease is more commonly seen during the winter as the animal is in need of extra energy. Cross-bred cattle and buffaloes are more susceptible. Pathogenesis: Ruminants mainly depend on hepatic gluconeogenesis. The ingested carbohydrates are fermented into volatile fatty acids. In this propionate is the important glucose precursor whereas acetate and butyrate are long chain fatty acids precursor. High yielding dairy animals are usually in negative energy balance in first few weeks of lactation. The dietary inadequate glucose precurcors create a state of hypoglycemia which triggers accelerated gluconeogenesis. Miobilization of fat for this purpose results in accumulation of Acetyl coA which is normally oxidized via TCA cycle. But its oxidation depends on adequate oxaloacetate for which propionate is precursor. Therefore, deficiency of propionate and
108
resultant inadequate oxaloacetate limit the aceyl coA oxidation via TCA cycle. The accumulated acetyl coA combines to form acetoacetate which is referred as parent ketone body. Acetoacetate further breaks down to form -OH butyrate, acetone and isopropyl alcohol. The nervous signs in ketosis are presumed to be due to the damage caused by isopropyl alcohol to the brain. The rapid loss of body weight (wasting) in ketosis is due to the mobilization of sub-cutaneous fat for the purpose of gluconeogenesis. Clinical Findings It occurs in two forms. Majority of the cases show the wasting form of the disease. Wasting Form: characterized by sudden, severe drop in milk yield, refusal of concentrate (selective appetite for roughages), licking of inanimate objects, passing of hard pelleted faeces covered with mucus, woody appearance with prominent rib cage. The animals have pronounced sweetish odour due to presence of acetone in the breath. The temperature, pulse and respiratory rates are usually in normal range. Nervous Form:About 5% of the cases of ketosis show this form. Nervous signs like walking in circles, salivation, Vigorous licking of skin and inanimate objects, hyperasthesia, aimless wandering, convulsive episodes are commonly encountered. Diagnosis : The tentative diagnosis can be made on history of recent calving and important clinical signs. The laboratory diagnosis can be made by urine analysis. Rothera's Test is employed for the detection of ketone bodies in the urine. The urine is saturated with ammonium chloride in which 2 - 3 drops of 5% sodium nitro-prusside is added. Ammonium hydroxide or strong ammonia solution is added over this urine nitro-prusside conjugate. The development of purple colour at the junction is positive test. The intensity of purple colour indirectly reflects the amount of ketonuria. Alternatively, the test can also be performed on milk. Hypoglycemia ( 40 mg %), ketonemia (upto 100 mg %), elevated levels of free fatty acids, triglycerides are important biochemical changes associated with ketosis. Differential Diagnosis: Postparturient hypocalcaemia may be confused due to its sudden onset and drop in milk yield but can be differentiated by its clinical picture like typical posture, hypocalcaemia and negative Rothera's test. The disease associated with secondary ketosis like metritis, left displacement of abomasum and mastitis should also be taken into account for differentiation. The hypoglycaemia and
108
ketonemia are marginal in these diseases and the reaction to Rothera's test is also mild. Traumatic reticulitis doesnot have relationship to recent calving and recurrent tympany, pain on deep palpation at xiphoid region are characteristics of Traumatic reticulitis. Abomasal displacement is characterized by passing of small amount pasty faeces and abomasal sounds are audible over lower left abdomen. The nervous form of ketosis should be differentiated from Rabies and Listeriosis. Constant bellowing, tenesmus, knuckling, hypersalivation, attacking complex are characteristic of Rabies and the disease is always fatal. Walking in circles unilateral facial paralysis, abortion in pregnant animals and demonstration of Listeria monocytogenes in blood will help in the differentiation from listeriosis. Treatment: Supplementation of glucose is the preliminary concept in the treatment of ketosis. Hypertonic solutions (10-50%) of glucose at the rate of 0.5 gm/kg body weight by intravenous route are used. As there is a concurrent hypoinsulinemia in ketosis supplementation of insulin has proved more efficacious. Short acting insulin at the rate of 0.5 units/kg body weight is injected subcutaneously after 10-15 minutes of initiation of intravenous hypertonic glucose. Alternatively,oral supplimentation of propionate precursors is also effective. Sodium propionate @ 110 gms along with 8 gms nicotinic acid or6 gms of DL-methionine by oral route for 7 days. Propylene glycol @ 125 ml can be a replacement for Sodium propionate. Glucocorticoids @ 0.05 mg/kg body weight alone or along with insulin is also effective. Preferential breakdown of proteins for gluconeogenesis by glucocorticoids reduces the acetyl coA accumulation. Prevention & Control: Avoid fattening during pregnancy. The body score should be maintained between 3.5 - 4.0 on 5 point scale. The animal should be kept on the balanced diet. The concentrate should not be more than 1 lb/150 lbs body weight. The ration should have a minimum of 20% crude fibre along with supplementation of essential vitamins and minerals. Feeding of ground maize which contains polymerized glucose escapes rumen fermentation and is absorbed directly in the intestine. Prophylactic feeding of sodium propionate @ 110 gms/cow daily from first week upto 6 weeks postpartum. Incorporation of ionophore antibiotic like monensin @ 25 mg/cow daily upto 4 - 6 weeks after calving increases propionate to acetate ratio in rumen. Sub clinical ketosis is gaining importance in the recent days. The animals though showing ketonuria, do not show any clinical signs of ketosis. The ketonemia, hypoglycemia and ketonuria is mild in these
108
cases. Early detection of such cases prevents clinical form of the ketosis thereby preventing economic loss to the farmers. *****
A NOTE
ON: DRUGS ACTING ON HAEMATOPOIETIC SYSTEM

SUNILCHANDRA.U
Clinical and pharmacological aspects of commonly used drugs in animals acting on the haematopietic system has been discussed in this article HAEMATINICS/ANTIANAEMIC DRUGS: the agents that help in the formation of blood, used clinically for the treatment and prevention of anaemias that occurs with blood loss, pregnancy, newborn animals (piglets). 1.Minerals: Iron, Cobalt and Copper 2.Vitamins:VitaminB12,Folicacid,Pyridoxine, Ascorbicacid 3. Anabolic steroids: Nandrolone decanoate, stanozolol etc IRON: Oral iron preparations are available as : Ferrous ( - sulphate, fumarate, succinate, gluconate) and Ferric (-ammonium citrate, hydroxide and glycerophosphate). Ferrous sulphate and ferrous fumarate salts are preferred as they are better absorbed rapidly. Common adverse effects of oral iron therapy include nausea, epigastric discomfort, abdominal cramps, constipation, and diarrhea. These effects are usually dose-related and can often be overcome by lowering the daily dose of iron or by taking the tablets immediately after or with meals Parenteral preparations are available as: Iron-carbohydrate complexes( Iron dextran and iron sorbitol) and are indicated when oral preprations can not be tolerated or in severe anaemia. Iron dextran, given by both IM and IV routes. Iron sorbitol is used clinically only by IM route,. Iron-sucrose complex and iron sodium gluconate complex are newer, alternative preparations, given deep intramuscular injection or by intravenous infusion. Adverse effects of parenteral iron therapy: local pain,tissue staining (brown discoloration of the tissues overlying the injection site), fever, arthralgias, flushing, urticaria, bronchospasm, and, rarely, anaphylaxis and death.
108
Overdose: can cause necrotizing gastroenteritis, vomiting, abdominal pain, bloody diarrhea, followed by shock, lethargy, and dyspnea. Subsequently, improvement is often noted, but this may be followed by severe metabolic acidosis, coma, and death. Activated charcoal, does not bind iron and thus is ineffective. Deferoxamine, a potent iron-chelating compound, can be given systemically (Dose: ) to bind iron and to promote its excretion in urine and feces. Appropriate supportive therapy for gastrointestinal bleeding, metabolic acidosis, and shock must also be provided. Dose: Ferrous sulphate: dog-100-300mg(Total), PO, once daily for 2 weeks; cats: 50-100mg (Total) PO, Once daily for 2 weeks; Cattle-815g(Total), PO, once daily for 2 weeks; Sheep, goats: -0.5-2g (Total) PO, Once daily for 2 weeks Dose: Iron dextran: dog-10-20mg/kg. IM, once daily ; cats: 50mg (Total) IM, piglets: 100-200mg(total)IM, once daily VITAMIN B12 : .Deficiency of vitamin B12, rare in animals, leads to anemia, gastrointestinal symptoms, and neurologic abnormalities: that usually begins with paresthesias,weakness in peripheral nerves ;progresses to ataxia, and other central nervous system dysfunctions. parenteral injection available as cyanocobalamin or Hydroxocobalamin. Cyanocobalamine- available in pure form, combination with other vitamins, minerals for injection or oral administration,given as feed additive, by IM or SC route. Dose: dog-0.1-0.2mg(total), PO, once daily; Cats: 0.050.1mg(total), PO, Once daily; Cattle::1-3mg(total), IM, SC 1-2 times a week; Calves and foals :0. 5 -1.5 mg 1 -2 times weekly Pigs, Sheep, Goats: 0.25-0.75mg (total), IM, SC 1-2times/week. FOLIC ACID: Rarely Deficiency in animals, caused by drugs that interfere with folate absorption or metabolism: Phenytoin, other anticonvulsants, oral contraceptives ,methotrexate and sulphonamides, trimethoprim and pyrimethamine., by IM cattle- 10mg ; Dose; dog5mg(total), PO, once daily; cat: 2.5mg(total), PO VITAMIN C (ASCORBIC ACID): antioxidant, in deficiency conditions: bleeding, delayed wound healing, impaired bone formation, anaemia, growth retardation, infertility in cattle; as adjunct in poisoning of paracetamol, copper, acidification of urine. Dose; Dogs- 100-500mg(total), PO, once daily; cat-100mg(total);PO; for paracetamol txy- 30mg/kg, PO/SC q6h. COBALT AND COPPER: Cobalt defeiciency in young growing ruminants (sheep, cattle) results in Vit B12 deficiency; with emaciation, loss of body weight, anaemia. Cobalt sulphate (- oxide, -chloride salts) in trace mineral premixes and salt blocks or incorporated as feed concentrates. ANABOLIC STEROIDS: are synthetically produced variants of the naturally occurring male hormone testosterone. These promote the
108
growth of skeletal muscle, and the androgenic effects promote the development of male sexual characteristics, which is responsible for the majority of their side effects. Nandrolone and Stanozolol, are commonly used in animals; have been indicated in: 1) Convalescence: Following surgical operations and febrile diseases;Debilitating, wasting diseases, catabolic states, major acute illness, immunosuppressive states,trauma, -conditions where there is negative nitrogen balance 2)osteoporosis in elderly, to remove tissue depleting processes in young ones , in diseases like CD, heavy parasitism, hypoproteinaemia etc. 3) To hasten the tissue repair (tendon, bone damage) after major surgery and to promote the healing and reunion in fracters 4) To counteract glucocorticoid induced catabolism and negative effects 5) To stimulate erythropoiesis in hypolplastic, hemolytic anemia and malignancy conditions 6) Testosterone deficiency conditions male hypogonadism, andropause Nandrolone decanoate (laurate): Dose : 1 mg/kg bodyweight,IM,SC at three week intervals, monthly up to 50 mg (Dogs); 25mg (cat); 200mg(horse). Stanozolol : has appetite stimulant action in cats. Dose: 0.25-3 mg/kg, PO, SID; 2-10 mg/kg, IM, once weekly . Contraindications: Pregnancy, prostate or breast carcinoma in male. They may improve glucose tolerance and decrease the need for insulin or other antidiabetic medicines in diabetics. Side Effects:fluid retention, gynaecomastia, increased aggression, epistaxis, reduced sperm count,prostate enlargement,sterility(long term), reproductive failure, suppressive effect on sexual development in young male animals, libido reduction, appetite stimulation, and hair loss. HAEMOSTATICS: Topical haemostatics: Thromboplastin, Thrombin, Fibrin foam and Fibrinogen have been used singly or in combination as local haemostatic in capillary bleeding , dental sockets, epistaxis, surgery of nose , throat and glandular tissues. Oxidised cellulose is suitable fro surface haemostatsi only, also interferes with healing of wound. It must be neyutralised with sodium bicarbonate, if used with thrombin solution. Gelatine sponge ( Absorbable) moistened with saline or thrombin is left in bleeding area, which is completely absorbed within 4 weeks. Calcium alginate dressing may also be left at bleeding site in the same manner. Feracrylum : is another topical haemostatic solution applied as spray/ gel for capillary bleeding, surface bleeding. Adrenaline and Noradrenaline induce localized haemostasis by virtue of their vasocconstrictive effects. They are applied intranasally(1%) to decrease capillary bleeding, epistaxis. Styptics (Astringents) that arrest bleeding by precipitation of proteins of blood and soft tissues; should not be used in high concentration as they irrite and can damage the surrounding tissue. Examples include:
108
ferric sulphate,ferric chloride, silver nitrate, tannic acid, alum, zinc chloride, zinc oxide Systemic Haemostatics: Other than the Fresh blood, fresh plasma, fresh frozen plasma, platelet rich plasma are the blood/ blood components administered as haemostatics, following are some of the systemic haemostatics used in animals. Adrenochrome monosemicarbazone (carbazochrome salicylate): is an oxidation product of adrenaline; used for systemic control of capillary bleeding associated with increased capillary permeability. It is used both orally and parenterally , and is often given in combination with vitamin K for variety of bleeding disorders like: epistaxis, haematuria, secondary haemorrhage from wounds etc. Ethamsylate: reduces capillary bleeding by correcting abnormal platelet adhesion leading to the repair of capillary wall. It is used for capillary haemorrhage, haematemesis, epistaxis, post partum haemorrhage etc. Rutin: is a a plant glycoside that improves capillary fragility, used orally in combination with vitamin C and vitamin K. Protamine sulphate : used clinically (slow IV) as an antagonist for heparin overdosage associated bleeding only. Bothrops venom: Desmopressin acetate (arginine vasopressin) : is a synthetic analogue of vasopressin used as haemostatic. Cryoprecipitate is a plasma protein fraction obtainable from whole blood. It is used to treat deficiencies or qualitative abnormalities of fibrinogen, such as that which occurs with disseminated intravascular coagulation and liver disease. Fibrinolytic inhibitors: Epsilon Aminocaproic Acid: (EACA), Tranexamic acid and Aprotinin are primarily used as therapy for bleeding from fibrinolytic therapy, and as prophylaxis for rebleeding postsurgical gastrointestinal bleeding and postprostatectomy bleeding and bladder hemorrhage secondary to radiation- and drug-induced cystitis and intracranial aneurysms. Vitamin K : is used therapeutically in the prophylaxis and treatment of bleeding disorders due to deficiency of vitamin K dependent clotting factors as in warfarin rodenticide poisoning. Used as haemostatic agent in the oral anticoagulant rodenticide (Coumarin derivatives- warfarin, dicoumarol, acenocoumarol) poisoning,indanedione derivatives rodenticide(phenindione, diphenadione, anisindione) and sweet clover poisoning . Available as: the natural plant form-Phytomenadione (vitamin K1) , Synthetic vitamin K compounds; Menaquinones (vitamin K2 ) and Menadione (vitamin K3).
108
Phytomenadione (vitamin K1) is mainly used in acute conditions as it acts more rapidly than other synthetic forms. It is usually administered for 7 days in case of warfarin poisoning and may be continued for several weeks(4-8 weeks) in case of long acting oral anticoagulant riodenticides(eg:brodifacoum,bromadiolone, difenacoum) poisoning Dose: dos, cats: 2.5-5mg/kg/day, Slow IV/IM/ SC( several sites) in divided doses for 1-3 days, followed by oral administration. . 0.25-2.5mg/kg/day, PO, in 2-3 divided doses, Cattle, sheep, goat, swine: 0.5-1mg/kg/day, IM/SC(several sites) in divided doses Menadione takes longer time to act, can be used fro chronic therapy, after resolving acute condition. It is irritating to skin and mucous membranes. ANTICOAGULANTS: drugs are much less frequently used in veterinary medicine than in human patient because atherosclerotic disease and prolonged postoperative recumbency are not common veterinary problems. Anticoagulants are part of the management of disseminated intravascular coagulation, but most commonly used to maintain patency of vascular catheters. Oxalates( sodium potassium, ammonium, lithium), Sodium fluoride, , ethylene diamine tetra acetic acid, sodium citrate, acid citrate dextrose are the invitro anticoagulants used for laboratory blood diagnostic , analytical purposes and blood transfusion. Heparin sulphate ( invivo an dinvitro anticoagulant) and low molecular weight heparinoids are used for the prevention or treatment of acute venous or pulmonary embolism, disseminated intravascular coagulopathy. Dose: dogs and cats- 40-80units/ kg, SC , tid.; 100-200 Units/ kg, IV( initial) ; followed by 50units/ kg, q3h
Antithrombotics/Antiplatelet drugs like aspirin, dipyridamole, ticlopidine, useful in the prevention of arterial thrombosis, thus inhibiting the growth/ reoccurrence of thrombus formation as in conditions of feline cardiomyopathy, canine heart worm infection etc are less commonly used *****
AN UPDATE ON
DRUGS ACTING ON EYE AND EAR

VIJAY KUMAR.M
108
Routes of drug administration: The 3 primary methods of delivery of ocular medications to the eye are : Topical, Local ocular (ie, subconjunctival, intravitreal, retrobulbar, intracameral) and Systemic. The most appropriate method of administration depends on the area of the eye to be medicated - extraocular structures, cornea, anterior segment (anterior chamber and iris), posterior segment (ciliary body, retina, vitreous), and retrobulbar or orbital tissues. The conjunctiva, cornea, anterior chamber, and iris are usually best treated with topical therapy. In contrast, the eyelids can be treated with topical therapy but more frequently require systemic therapy. The posterior segment always requires systemic therapy, as most topical medications do not penetrate to the posterior segment. 1. Topical-most common route of administration :Degree of penetration of topically applied medications depends on integrity of normal defense mechanisms of the eye. Drug absorption is greatly enhanced by ocular inflammation. Medications put in the conjunctival sac can penetrate the cornea, conjunctiva, or be absorbed systemically via the nasolacrimal system It is also affected by the Vehicle, molecular size of the drug, drug concentration, pH, electrolyte composition and preservatives. Corneal epithelium is the main site of resistance to drug penetration.. As a result, the epithelium and endothelium are relatively impermeable to electrolytes but are readily penetrated by fat-soluble substances. Drugs that have the ability to exist in equilibrium in solution as ionized (water soluble; polar) and unionized (lipid soluble;nonpolar) forms are ideal for topical use, i.e., chloramphenicol, fluoroquinolones. Topical administration is used for treatment of eyelids, conjunctiva, cornea, iris, and anterior uvea. Following which , up to 80% of the applied drug(s) is absorbed systemically across the highly vascularized nasopharyngeal mucosa. Because absorption via this route bypasses the liver, there is no large first-pass metabolism seen after administration PO. 2. Subconjunctival (bulbar conjunctiva): This technique requires only topical anesthesia and a tuberculin syringe with a 25- or 27-gauge needle. Volumes should not exceed 0.25 ml in cats and dogs and 1.0 ml in horses and cows. Subconjunctival medication reaches the cornea by slowly leaking out of the injection site. Intraocular drug levels are attained by diffusion through the cornea and sclera. This is used for
108
diseases of the cornea, anterior, uvea, anterior vitreous, and sclera.Drugs with low solubility such as corticosteroids may provide a repository of drug lasting days to weeks. Appropriate amounts must be used, as large amounts, especially of long-acting salts, can cause a significant inflammatory reaction. For sub-Tenons injections, 0.5 ml/site is usually safe and effective in small animals and 1 ml in large animals such as the horse and cow. 3.Retrobulbar medications:are used infrequently for therapeutics. In cattle, the retrobulbar tissues can be anaesthetized with local anesthetic (lidocaine) for enucleations. Whenever any medication is placed into the orbit, extreme care must be taken to ensure that the medication is not inadvertently injected into a blood vessel, the optic nerve, or one of the orbital foramen. Retrobulbar injection has a high risk of adverse effects and should not be used unless the clinician is experienced and the animal is appropriately restrained. 4. Intravitreal-used infrequently: Antibiotics,antifungal drugs have been effectively used in microgram dosages. Generally injected at the pars plana for infectious endophthalmitis. 5. Systemic-P.O., I.V. or I.M: Systemic administration is required for treatment of diseases of the retina, optic nerve, and vitreous., for posterior segment therapy and to complement topical therapy for the anterior segment. The blood-ocular barriers can limit absorption of less lipophilic drugs, but inflammation initially allows greater drug concentrations to reach the site. As the eye starts to heal, these barriers become more effective and can limit further drug penetration. This should be considered when treating posterior segment disease, eg, blastomycosis in small animals with hydrophilic drugs such as itraconazole. Ocular dosage forms : Topical ophthalmic drugs are formulated as ointments, suspensions and solutions. Deciding which formulations to be used depends on the several practical considerations.Ocular contact time of ointment is longer than solutions or suspensions,so they are more practical when the owner cannot follow a frequent administration regimen.avoid ointments on penetrating wounds or descemetocele,and prior to intraocular surgery,as their petroleum base elicits severe granulomatous reaction when in direct contact with intraocular tissue. The frequency of topical application depends on disease and formulation.One drop of an antimicrobial solution applied four times
108
daily is usally sufficient in uncomplicated corneal ulcers and bacterial conjunctivitis.When ointment is used a , 5mm strip is applied to the conjunctiva a minimum of three times a day. If more than one drug is involved in the therapeutic regimen,then 3 to 5 minutes should be allowed between application of each medication to avoid dilution or chemical incompatability.antimicrobial therapy is typically continued for seven days or until the ocular infection is resolved.
ANTIBACTERIAL DRUG THERAPY ; Topical antibiotics are indicated for
the treatment of corneal ulcers, corneal perforations, conjunctivitis,and blepharitis.. Ideal choice of appropriate therapy begins with identification of the organism and its sensitivity. Culture or cytologic examination of material from the affected area is necessary.Minor bacterial conjunctivitis infection may not justify routine culture and may be amendable to initial therapy with broad spectrum antibiotics. Normal ocular flora is predominantly gram positive;a predominance of gram negative organisms is indicative of an abnormal condition. Chloramphenicol: Broad spectrum, bacteriostatic. Soluble in both water and fat so it penetrates intact cornea with topical administrationthus may be considered for initial treatment of intraocular infections (penetrates the cornea).it is good first choice antimicrobial for corneal ulcers and bacterial conjunctivitis.it is having poor efficacy against gram negative bacteria and pseudomonas spp. Aminoglycosides: a.. Neomycin: Usually found in combination with other antibiotics. Broad spectrum-bacteriocidal impairs protein synthesis.Frequency of administration-BID-TID. Toxicity- Topicallocalized sensitivity; conjunctival irritant.Systemic-ototoxicity-possible head tilt. b. Gentamicin: Broad spectrum bactericidal activity including Streptococcus, Staphylococcus, Proteus spp, and Pseudomonas aeruginosa. Effective topically and subconjunctivally for external ocular infections. It is available as solution and ointment because of its chemical characteristics does not readily cross lipid membranes,but readily enters the stroma when the corneal epithelium is damaged. Renal toxicity with concurrent oral therapy, may be toxic to surface epithelium. c. Tobramycin.: Two to four times more effective against Pseudomonas spp. and betalactamase producing staphylococci than gentamicin and effective against gentamicin-resistant microbes. Polypeptides:a.Bacitracin: Bactericidal, active against gram positive microorganisms. Used in combination with other antibiotics. Poor
108
corneal penetration. b. Polymyxin B: Poor penetration. Bactericidal. Effective mainly against gram-negative bacilli and Pseudomonas spp. Should not be given subconjunctivally. Cephalosporins: a.Cefazolin: Broad spectrum, first generation cephalosporin.Topical use for gram + cocci resistant to other antimicrobials. Can be administered subconjunctivally-does penetrate intact cornea. Usually diluted to 50 - 100 mg/ml concentration. Mix with artificial tears to a concentration of 33 mg/ml for treatment of meibomitis Fluoroquinolones: Eg: Ciprofloxacin ,Levofloxacin, Ofloxacin etc. Broad spectrum, active against gram positive and gram negative microorganims. Drug of choice for betalactamase producing staphylococcus and aminoglycoside resistant pseudomonas spp. Generally preferred in corneal, conjunctival, and intraocular infections. Excellent corneal penetration.not effective against streptococci spp. Because of their spectrum of activity these agents should never be used as empirical treatment.
ANTIVIRAL DRUG THERAPY: The topical antiviral agents are static in
action and topically irritating,so frequent dministration is necessary and client compliance and patient tolerance are issues. Idoxuridine: Frequency of administration is 1 drop every 4hrs until corneal re-epithelialization occurs. Doesnot penetrate the cornea unless the epithelial barrier is broken. Vidarabine: 3%Ointment-it is poorly lipid soluble,so corneal penetration is minimal unless ulceration is present.Penetrates the cornea better than Idoxuridine. Frequency of administration is to apply small amount of ointment 5 times daily until corneal re-epithelialization is complete,the every 12 hours for 7 days. Trifluridine: 1%Solution-Current drug of choice for feline herpetic keratitis. Antiviral potency reported as over twice that of idoxuridine and 5 times greater than Vidarabine. s.penetrates the intact cornea,and ulceration and uveitis increase its intraocular penetration.; administered 4-8 times/day for 2 days, and reduced over next 2-3 weeks. Topical antifungal agents are used more commonly to treat fungal keratitis in horses than in small animals. Penetration of the intact cornea is poor with all antifungals.
ANTIFUNGAL DRUG THERAPY :
108
Polyenes : Natamycin : Used against Candida spp. and Fusarium spp. Amphotericin B: Fungistatic. Generally used systemically for fungal endophthalmitis. May be given as an intravitreal injection in mcg dosages. Imidazoles. Miconazole 1%: the drug of choice for most veterinary fungal keratitis.Tolerated well as subconjunctival injection. 1 ml SID x 3-5 days if tolerated. Treatment frequency of a fungal keratitis may warrant 1 to 4hour treatment intervals.lotions or sprays that contain ethyl alcohol should not be applied to the eye. .Fluconazole is the synthetic triazole, fungistatic.currently drug of choice for topical use, subpalpebral lavage unit, and intracameral (100 g) injection. Treatment for fungal keratitis may warrant 2 to 4hour treatment intervals. Corticosteroids: Subconjunctival injection of corticosteroids provide a greater local antiinflammatory effect than can be achieved by topical or systemic administration. Posterior segment inflammation requires systemic corticosteroid therapy. In general, topical therapy should be continued two weeks beyond resolution of clinical signs. Local side effects of corticosteroid use include delayed corneal healing, increased corneal collagenase activity, and an increased incidence of bacterial and mycotic keratitis. In addition, topical corticosteroids may result in systemic changes. These include reduced baseline cortisol levels, suppression of the adrenocorticotropic hormone response curve, and altered carbohydrate metabolism. Frequency of administrationdependent on clinical signs and the type of steroid used..
ANTI-INFLAMMATORY OCULAR DRUG THERAPY:
Nonsteroidal anti-inflammatory ocular drugs : Some degree of GI intolerance may occur such as gastroduodenal ulceration and hemorrhage-when NSAIDs are used systemically. Aspirin: dog-10 to 20 mg/kg, BID; cat-10 mg/kg, q 48 hours. Carprofen :. May have fewer side effects.Do not use in Labrador retrievers - may cause liver disease. Dosages: 2.2mg/kg BID. Not approved for use in cats. Etodolac :: dog-10 - 15 mg/kg, PO SID. Should not be used in dogs < 5 kg in the horse and dog , although not currently approved for use in dogs.: dog-0.75 to 1.20 mg/kg, IV, SID, not to exceed 2 days. Commonly given 30 minutes prior to surgery to minimize postoperative swelling and inflammation .; Not to be used. In cat. Flurbiprofen: Used topically preoperatively to stabilize the blood________________________________________________________________________________________________ Karnataka Veterinary Council, Bengaluru sponsored CVE training programme titled: An Update on Systemic Pharmacology and Clinical Toxicology organized by the Dept.of Pharmacology and Toxicology,Veterinary College,Bidar,from 12th to 17th December, 2011 for the Officers of Dept. of A.H&V.S, Govt. of Karnataka
108
aqueous barrier in inflammation (in diabetes mellitus), decrease production of ocular prostaglandins and maintain pupil size. Used to treat anterior uveitis and in the presence of corneal ulceration. Ocular topical Anesthetics : To be effective, local anesthetics must have properties similar to drugs that penetrate the cornea. They must be capable of existing in ionized (water-soluble) and nonionized (lipid soluble) forms. Local anesthesia is less effective in inflamed tissue which has more acidic pH than normal. Most topical anesthetics are effective within 30 seconds to 3 minutes to facilitate procedures such as tonometry, corneal and conjunctival scrapings, and subconjunctival injections. Microbial cultures should be taken prior to application of topical anesthetics as inhibition of microorganisms has been attributed to topical anesthetic agents. The agents used are Proparacaine 0.5%, . Tetracaine - 0.5% to 2%.. Topical anesthetics should not be used on a regular basis with painful eyes because: Animal may scratch off corneal epithelium (feels no pain) and may inhibit mitosis (thus healing) in corneal cells. a. Osmotic Agents (topical) : 2-5% NaCl (hypertonic saline). Indicated primarily for treatment of severe chronic corneal edema originating from superficial epithelial disruption and for severe cornea bullae formation. Side effect-localized irritation. b.Tear Film Supplements : Many tear film supplements currently exist today. All are indicated to control keratitis sicca. May provide temporary comfort to corneal irritation resulting from distichia, entropion, or sutures, and as a vehicle for delivery of medications. Tear supplements are available in solution and ointment form and are intended to replace the aqueous or lipid layer of the tear film. Preservative-free products generally recommended. c.Lacrimogenics: These are drugs potentially capable of stimulating tear secretion. 1. Pilocarpine: May be effective in the rare case of neurogenic KCS. Prescribed as 2 drops of 2% Pilocarpine per 4.5kg body weight added to the food twice daily. 2. Cyclosporine A 0.2% ointment : Cyclosporine is a potent suppressor of T-cell growth factor and of the cytotoxic T-cell response to this growth factor.3. Tacrolimus 0.02%, 0.03% ointment or solution : Effective alternative to cyclosporine. T-cell surpressor with a distinct receptor site to cyclosporine.
108
Anticollagenase/Mucolytic Agents :Collagenase inhibitors are indicated for the treatment of melting corneal ulcers. Acetylcysteine : Diluted from 10 to 20% with artificial tears to a 5 to 8% concentration. Administered every 1 to 4 hours until desired effect is achieved. *****
THERAPEUTIC MANAGEMENT OF DERMATOLOGICAL DISORDERS

SANDEEP HALMANDGE
Skin is the largest organ in the body, dermatological disorder in animals are numerous and therapeutic management depend upon the understanding of the nature and possible causes of the disease, some of the important frequently encountered diseases in animals are included in this section. General diagnostic approach to the dermatological cases As the diagnosis plays an integral part of successful treatment, we have to follow the diagnostic strategy in dermatology. It includes, a) History: Vaccination, Husbandry practice, feeding practices, primary complaint, exposure to the different animals, previous therapies if any, how long the animal had skin problems. Etc because, many skin diseases can be differentiated based on the history and clinical signs. b) Physical examination: Dermatological examination requires a close examination of animals/ lesions under sufficient light. Primary lesions include : Macule, papule, pustule, wheal, vesicle, and bulla.
108
Secondary lesion include : scales, crusts, erosion, ulcer, excoriation, Lichinification, and epidermal collorates. c) Laboratory examination: includes skin scraping, hair combing, hair examination, Cytology, Bacterial culture, Fungal culture, Skin biopsy and Intra dermal / Allergic testing. BACTERIAL SKIN DISEASE (PYODERMA) Bacterial infection of the skin is generally termed as pyoderma, it invariably involves lot of causes, but most important are like Staphylococcus intermedius S. aureus, Cornybacterum, Pseudomonas and Propionibacterium. It usually occurs due to some other secondary underlying causes. Lesions: Lesions in pyoderma are small inflammatory papule or pustule with hair protruding from the center. If the condition is severe the folliculitis may appear as moth eaten alopecia, with epidermal collorates, scales and crusts. Pustular lesions are often erythematous, hot to touch, exudative, very moist and extremely painful. According to the depth of infection bacterial infection of skin are classified into Surface pyoderma, superficial pyoderma and deep pyoderma. Distribution of lesions: Lesions in pyoderma restricted to trunk, neck, back, rump, face, leg, tail, and ventral aspect of the abdomen, lateral aspect of hind leg, axillary region, and inguinal region, Diagnosis is based on skin lesions and laboratory confirmation of the pyoderma is based on the bacterial culture from the affected lesions. Treatment: As pyoderma is due to some other underlying cause, for this reason specific therapy for correcting underlying cause is instituted. Topical therapy is employed in managing localized lesions of pyoderma, Shampoos containing chlorhexidine, ethyl lactate and benzyol peroxide can be used for 2 to 3 times along with topical application of gel or cream containing antimicrobial agents. However, in severe cases, along with topical therapy systemic administration of antibiotics for a minimum period of 3 weeks is necessary. Some of the drugs recommended for use in dogs for treating pyoderma include:
Erythromycin Lincomycin Amoxicillin + acid Enrofloxacin Cephelexin Cefadroxil Cepharidine 10-15 mg/kg, 8 h, orally 22 mg/kg , 12 h, inj Clauvulenic 12.5 - 25 mg/kg, 12 hr, oral/inj 2.5 - 5 mg/kg, 12 24 h, oral/inj 22 mg/kg, 12 h, oral 22 mg/kg, 8-12 h, inj 22 mg/kg, 12 h, oral
108
Azithromycin
5 mg/kg, 24 h, orally
FUNGAL SKIN DISEASE (DERMATOPHYTOSIS) Fungal infections involving the keratinized layers of the skin and its appendages like hoof, nails, and horns by a group of mycelial keratinophilic fungi called derrnatophytes. The term dermatophytosis indicates the relationship of the disease with dermatophytes as etiological agents. Dermatophytes mainly belong to T. mentagrophytes, M. canis, M. gypseum. Signs/Lesions: Lesions are circular and discrete/irregular and vary from scaly patches of alopecia to inflammed to nodular erythematous patch of alopecia. Hairs partially broken/ fallen with bran like scales and crusts, signs like erythema, scales, crusts, thinning of hairs frequently in the form of broken hairs with secondary folliculitis with pruritus are usually observed. Diagnosis: Based on clinical signs, skin scraping examination, examination of hairs by wood's lamp and finally by fungal culture on Saborauds dextrose agar or dermatophyte test medium. Treatment: Many researchers are of the opinion that topical along with systemic therapy will hasten the recovery in animals. Thick scales and crusts on the animal body should be removed by brushing with mild detergent soap solution (Chlorhexidine), or shampoo like selenium sulphide, bezyol peroxide containing shampoos, swabbing of the lesions with Iodine application or topical antifungal agents. i) Iodine solution ii) Cotrimazole cream iii) Ketoconazole iv) Miconazole cream Systemic treatment involves administration of the anti fungal drugs for a minimum period of 3 to 4 weeks, with simultaneous monitoring of animal for serum profile for liver & kidney functions, as many of these drugs are potential hepatotoxic as well as nephrotoxic.
Griseofulvin Ketokonazole Itraconazole Fluconazole Terbinafine Amphotericin-B Miconazole Clotrimaxazole 25 mg/kg, oral for 1 month 10 mg/kg, oral for 1 month 5-10 mg/kg, oral for 1 month 2.5-5 mg/kg, oral for 1 month 2.5 - 5 mg/kg, oral for 1 month 0.1-0.4 mg/kg, iv 3 times a week, in bolus dosing with 500-1000 ml of 5% dextrose (Oint, cream) Topical application (Oint, powder) Topical application
PARASITIC SKIN DISEASES

108
Parasitic infestations are usually uncomfortable and distressing to the patient. Parasitic dermatitis probably accounts major share among the other dermatological diseases of small animals. Mange: i. Cheyletiellosis (walking dandruff): They live on layers of the epidermal debris and feeds on tissue fluids. Young once are commonly affected. Here typical lesions like scaling over the dorsal midline which may spread up to back to head. Coat of the affected dog is usually oily in nature with variable pruritus. ii. Canine Demodicosis: is an inflammatory skin disease caused by D. canis which are considered to be a normal habitat of the canine skin, immunosuppression presumed to be the reason for turning into pathogenic for these mites.
Localized demodicosis : less than 1 year old affected, alopecia with erythema, hyperpigmentation, scaling frequently on perioccular skin, muzzle, mouth commisure, pinnae with secondary pyoderma. Generalized demodicosis: Adult dogs are commonly affected, initial alopecia spread over the body becoming patchy or diffuse in nature. Scaling, erythematous lesions along with peripheral lymphadenopathy complicated with pyoderma are frequently observed. Pododemodicosis: affects feet, usually swollen, erythematous and painful.
iii. Otodectus Cynotis : (ear mite) This mite infestation contributes 50 % of the otitis externa cases in cats and 10 % in dogs, caused by Otobius cynotis, young animals with pruritic ears, head shaking, ear canal filled with reddish brown/ black debris with dermatitis may be present on head, neck and perioccular region. iv. Sarcoptic mange/Scabies: Non seasonal and intensely pruritic skin disease, caused by Sarcoptes scabei var canis affecting dogs, cats and human beings. Irritation is due to secreting of allergic substances like saliva, faecal matter etc. Lesions typically noticed on pinnae margin, elbow, hock which spread rapidly and appear alopecic, erythematous papular eruptions with yellow colored crusts and secondary pyoderma. Diagnosis is based on history of exposure to other dogs/cats, clinical signs, penna-pedal reflex, Microscopic observation of skin scrapings or debris collected either by vacuum cleaning or by adhesive tape method and skin biopsy.
108
Treatment is by frequent using of acaricidal dips like Pyrithroids, Carbamates, OPC's and Amitraz. It involves clipping of hairs then animal should be bathed with benzoyl peroxide shampoo/ anti saborrhoeic shampoo which flushes out the follicle/ removes scales or crusts and also it has antimicrobial activity. i) Amitraz dip: 6 ml/ lit water diluted and applied once a week. ii) Milbemycin Oxime: 0.5 mg/kg once daily for 2-3 months. iii) Ivermectin: 200-300 g/kg bw, S.C. twice or thrice 1-2 week apart. iv) Doramectin: 200-300 g/kg bw, S.C. twice or thrice 1-2 week apart v) Moxidectin: Topical application or injection at 200-300 g/kg bw, S.C Institute a course of antibiotic for controlling secondary bacterial infection for 2 weeks along with other supportive treatment. Also, stress has to be minimized by providing high nutrition diet along with eliminating internal and external parasites.
FLEA BITE ALLERGY/ FLEA BITE DERMATITIS:
Ctenocephalides felis is the common flea of dogs and cats. These mini creatures can transmit other diseases like tape worm infestation, plague and tularemia. One adult female flea can lay 1000 eggs for up to 4 months. Flea bite dermatitis is simply because of mechanical irritation of frequent bites or by active migration of fleas, where as flea bite allergy is due to the allergic nature of the saliva which causes hypersensitivity. Lesions range from mild irritation to pruritic papular eruptions, alopecia, lichinification & hyperpigmentation usually noticed on posterior one third of the body, tail head, flank, caudo-medial aspect of the thigh and abdomen. Diagnosis is based on history of exposure to other animals, clinical signs, demonstration of flea excreta on a blotting paper, by visualization, or even by allergic patch test. Many classes of drugs are available for controlling fleas namely; Pyrethrins, Pyrethroids, Carbamates, Organophosphate compounds, Organochlorine compounds, Insect Growth regulators and Insect Development Inhibitors. Many products are available for the treatment of flea infestation, some of them include; Capster (Nitenpyran) and Program (Lufenuron) are oral products which results in flea death after administration. Frontline (Fibronil), Advantage (Imidocloprid) are topical products and are placed directly in skin which result in killing of fleas. Revolution (Salamectin) a topical product that prevents flea and heart worm in canines.
ALLERGIC SKIN DISEASE (CANINE ATOPY)
108
Atopy is an inherited tendency of an animal to develop hypersensitivity reaction to the environmental allergen. Common in young animals < 1 year old, breeds like GSD, Labrodor, and Cocker spaniel are prone for this. Usually there will be a chronic relapsing dermatitis will be there. Itching starts then followed by rashes but in remaining diseases it is vice versa. Scratching, rubbing discoloration of hair coat, lesions will be on face, forearms, axilla, groin, conjunctivitis, respiratory problems like coughing, sneezing, secondary problems like pyoderma which may persist or last for month to year, irregular heat cycle are some of the manifestations of the disease. Diagnosis is by history, clinical signs and confirmation can be done by intra dermal skin test. Treatment involves administration of Antihistamines like Polaramine, 1 tab bid, Atarax, oral 1 tsp bid, Allegra tab Sid, CPM injections for 2-3 weeks, Antipruritic dose of Prednisalone (0.5 mg/kg) for 2-3 weeks by tapering this has to be withdrawn. Supplement essential fatty acids containing tonics like Evening Prime Roseoil capsules, Nutricoat syrup. Applying cold water bath are some of the considerations while treating such cases.
ANTIMICROBIAL, ANTISEBORRHEIC AND ANTIPRURITIC SHAMPOO THERAPY
Ingredient Chlorhexidine Benzoyl peroxide Triclosan Povidone iodine Acetic Boric acid Ketoconazole/ Miconazole Sulphur/
Therapeutic effects Anitbacterial, Antifungal, Antiviral Antibacterial, Follicular flushing, Degreasing, Keratolytic Antibacterial
Usage Mild shampoo with antimicrobial acitivity excellent
Potent degreasing, follicular flushing shampoo with excellent antibacterial effects Moderately effective antibacterial ingredient added to shampoos Mild shampoo with excellent antimicrobial activity but limited duration of effect Good therapy for Malassezia dermatitis Mild shampoo with good antifungal acitivity Moderately well tolerated
Antibacterial, Antifungal, Antiviral acid/ Antimicrobial Antifungal Keratolytic
108
Salicylic acid
Selenium sulfide Diphenhydrami ne Hydrocortisone L-rhamnose Aloe vera
Keratolytic, Keratoplastic, Degreasing Antipruritic
shampoo with good antiseborrheic activity. Good for crusting or dry seborrheic disorders Potent degreasing shampoo with good antiseborrheic activity.
Humectants: Propylene glycol, Urea, Lactic acid, Glycerin Emollients: Oils, Moisturizers Lanolin, Paraffin, Waxes
Mild shampoo with moderate antipruritic activity Anti inflammatory, Mild shampoo with moderate Antipruritic antipruritic activity Anti allergic Mild shampoo that helps prevent allergen penetration Anti inflammatory, Added to many products for mild Antibacterial anti inflammatory effects Moisturizers Hygroscopic agents that actively pull water into the skin
Occlusive agents that decrease transepidermal water loss
*****
108
EXPLORING THE RUMEN AND ITS MICROBES FOR THERAPEUTIC BENEFITS

THIRUMALESH.T
In the newborn ruminant, the fore stomach is nonfunctional and poorly developed. The normal anatomic position of the ruminoreticulum and omasum is attained at 2 months and the relative size by about 3 months. With access to grasses and forage, calves will start developing the adult population by 3-6 weeks and the process is complete by 9-13 weeks. Cellulolytic bacteria are ingested with feed and airborne seeding is an established possibility. Ciliate protozoa established when they have direct contact with animals harboring mixed populations. Initiation of fermentation process is necessary for development of normal sized papillae in ruminoreticum. Butyrate is the most effective in promoting papillary growth. Reticular groove reflex: Beneficial use of the reticular groove reflex has been neglected in practical veterinary medicine. Oral administration of medicaments intended for local intestinal effect (Eg. Purgatives, antidiarrheals, contrast media and some anthelmintics) should always be preceded by administration of an appropriate salt solution to close the groove. But this reflex response is not as unreliable in the older animals. Although after 2 years of age in cattle and 18 months in sheep, closure is somewhat irregular and may be absent. In cattle, closure of the groove can be elicited with 5% copper sulphate, 5% zinc sulphate and 10% sodium bicarbonate or sodium sulphate where as in sheep 1-2% copper sulphate is effective. Closure of the groove takes place in about 5-10 seconds and it remains closed for up to 60 seconds. Suckling remains a very strong closure stimulus even in the full grown adult. It is better to allow sick calves and lambs to drink medicated milk from a nipple to assume delivery to abomasum and rapid absorption of the drug. Biochemical alteration of drugs within the rumen:The biochemical reactions in the rumen lead to either activation or inactivation. The major transformations of anutrient compounds by ruminal microflora
108
include hydrolytic reactions, reductive reactions, decarboxylation, dealkylation, dehalogenation, deamination and ring fission. Examples of xenobiotic inactivation in rumen include: 1. Chloramphenicol: reduces the nitro group to amine. 2. Digitalis glycosides and thioglucosides: These are destroyed in rumen 3. Parathion: reduces nitro group into primary amine. 4. Ruminal fluid contains oxalose which destroys oxalate in the diet. Thus ruminants are not susceptible to oxalate poisoning. 5 Gossypol is bound by protein with disappearance of 2--amino group. 6. Phytooestrogenic isoflavones: These are inactivated as estrogens in rumen. Example of drug activation in rumen: 1.Microbial glycosidase release cyanide from cyanogenic glucosides in rumen. 2.Some inorganic salts are reduced. Eg: nitrate is reduced to ammonia in the rumen. 3.Tryptophan and indoleacetic acid are converted to 3-methylindole, a toxic metabolite cause pulmonary edema and emphysema in cattle. 4. Polioencephalomalacia (or cerebrocortical necrosis), caused by thiamine deficiency , associated with production of high levels of thiaminase by ruminal microbes. Effect of drugs on ruminal microflora: Certain substances are highly detrimental and others may be beneficial to ruminal microflora. The most harmful effects can be expected from broad-spectrum antibacterial and antiprotozoal agents. Antibiotics reduce the total volatile fatty acids production and increase the acetic acid-propionic acid ratio. Sulfonamides are also potentially deleterious, only a temporary interference with normal ruminal function and microfloral activity occurs and spontaneous recovery is likely. Certain compounds on the ruminal microflora are beneficial in therapeutics. For example, use of antibiotics to control bloat and acidosis. Chloral hydrate depresses cellulose digestion, with a consequent fall in total VFA production but relative increase in propionic acid fraction. This effect is used in treatment of acetonemia where these are necessary to increase ruminal propionic acid and blood glucose. Some compounds modify ruminal fermentation and improve digestive efficiency in the ruminant. Monensin-sodium, lasalocid and salinomycin are polyether antibiotics and avoparcin is a glycopeptides antibiotic; these are capable of altering the population of ruminal microbes and their metabolism to produce more propionic acid and less
108
acetic and butyric acid. These antibiotics temporarily depress synthesis of microbial protein but this effect is overcome after the 3rd week when the animal adapts to them. These can decrease production of methane, improves energy balance of the ruminant. Other feed additives such as diphenyliodonium salts prevent degradation of amino acids, increasing the amount of free amino acids that can reach the abomasum. Absorption of drugs from the ruminoreticulum: About 600 kg cow has a ruminoreticulum content of about 100-150 liters of ingesta and fluid. Such a large fluid volume will dilute any orally administered drug and thus prolong its absorption due to small ratio of surface area to volume of contents. The ruminoreticular epithelium is permeable to lipid-soluble compounds but impermeable to ions. The transfer process involved a simple non-ionic diffusion. Since, the pH of the rumen lies within the range of 5.5 to 6.8, ion trapping would be concentrate weak bases. Important factors affecting absorption: Diet; Ruminal motility (stasis depresses the absorption rate of drugs); Blood flow to the ruminoreticulum is limiting factor, it increases upon feeding due to increased carbon dioxide tension and VFAs concentration in rumen ; water molecules diffuse across the ruminal epithelium rapidly. Distribution of drugs into the ruminoreticulum: Drugs may or may not diffuse into the ruminoreticulum from the blood stream. 1. Dilution of drug into an additional fluid space will reduce its concentration within tissues and plasma. 2. Distribution into rumen fluid result in a potential drug reservoir. 3. Passage of antibacterial or antiprotozoal agents into forestomach may have deleterious effect on rumen microflora. 4. Up to 20% of body weight is ruminal content; ruminoreticulum may or may not constitute a distribution compartment for a drug. Distribution of drugs into rumen follows simple non-ionic diffusion of free drug. Ion trapping because of pH differences between plasma and ruminal fluid may occur. Drugs like antipyrine, aminopyrine, sulfanilamide, sulfadimidine, sulfapyridine, ephedrine, quinine, pentobarbital, benzoic acid and salicylate diffuse into rumen water. In contrast, tetracyclines donot pass into ruminal fluid from the systemic circulation. Agents affecting functions of the forestomach: 1. Appropriate substrates for microbial fermentation (solube sugars, NPN compounds) and Co-factors necessary for microbial fermentation process. 2. Removal of soluble end products, undigested residues and gas. 3.Maintenance of continual flow culture of ruminal microorganisms.
108
4.Fluid medium: ruminal atony can be treated by water, saline, ringers solution, artificial saliva and ruminal fluid itself may be used. 5. Optimal ruminal pH and temperature range 6.Mixing cycles and eructation. Parasympathomimetic agents like neostigmine, phyostigmine and carbachol are used to promote forestomach motility. Nuxvomica and strychnine are regarded as ruminatonic action, even antimony potassium tartorate and barium chloride are used. Metaclopromide is useful agent to promote motility. Antibiotic susceptibility of anaerobic ruminal bacteria: Among seventeen anaerobic ruminal bacteria tested for their susceptibility, fifteen viz. Bacteroides amylophilus(starch), B. melaninogenicus, B.ruminicola brevis(starch), B. ruminicola ruminicola, B.succinogenes(cellulose), Butytrivibrio fibrisoolvens(xylan, starch), Eubacterium ruminantium, Lachnospira multiparus(pectin), Peptostreptococcus elsdenii(lactate), Eubacterium limosum(cellulose), Ruminococcus albus(cellulose, xylan), R. flavefaciens(cellulose, xylan), Selenomonas ruminantium(lactate, starch), Spirillum sp, Streptococcus bovis(starch), Succinimonas amylolytica(starch), Succinivibrio dextrinosolvens(starch) were very susceptible for bacitracin, chloramhenicol, chlortetracycline, erythromycin, novobiocin, oleandomycin, oxytetracycline, pencillin, tetracycline, tylosin and vancomycin where as kanamycin, neomycin, polymyxin-B and streptomycin have not inhibited the microbial activity in the rumen. *****
AN UPDATE ON HORMONES OF THERAPEUTIC UTILITY IN ANIMAL REPRODUCTION

M.K TANDLE
Reproductive endocrinology: The GnRH secreted from hypothalamus is transported by the portal system to the pituitary where it increases secretion of the gonadotrophins FSH and LH in both sexes. Frequent administration of GnRH may result in decreased LH and FSH secretion via down-regulation of pituitary GnRH receptors. The gonadotrophins stimulate the secretions of gonadal steroids (testosterone in male and estrogen and progesterone in females). During the oestrous cycle, ovarian follicles produce estradiol and estrogen, predominantly in response to pulsatile secretion of the gonadotrophins. Following ovulation mediated by a surge secretion of LH, progesterone is secreted from one corpus luteum or several corpora lutea. The CL requires pituitary hormones for
108
support (luteotrophic factors). The luteotrophic factors LH and prolactin and estradiol are species specific. A decrease in luteotrophic factors secretion will result in decreased CL function and abortion in the pregnant animals. The life span of the CL is lengthened with pregnancy, resulting in continued progesterone secretion which is necessary for pregnancy maintenance. Late in diestrus in the cycling large animals, PGF2 alpa released from the endometrium mediates CL regression. Estrus shows CL regression within a few days. Such utero-ovarian relationships whereby uterine PGF2 alpa results in luteolysis do not exist in bitch. The estrogen and progesterone have prominent stimulatory effects upon the endometrium and the mammary gland. While increased circulating concentrations may result in pathological changes in target organs. Gonadal steroids mediate reproductive behaviour and gametogenesis in both sexes. Ovarian steroids generally decrease gonadotrophin secretion (negative feedback). The exception to this is a positive feedback effect on estradiol, in the relative absence of progesterone, upon gonadotrophin secretion immediately prior to ovulation that results in a surge secretion of both gonadotrophins. LH mediates ovulation. Exogenous administered gonadal steroids may inhibit gonadotrophin secretion result in uterine and mammary gland pathology and interrupt gonadal function. Testosterone in the male mediates behaviour and stimulates male sex accessory glands. Increased circulating testosterone from either an exogenous or endogenous source may result in prostatic hypertrophy and hyperplasia. Additionally, testosterone administration results in decreased gonadotrophin secretion and interruption of spermatogenesis. Induction of ovarian activity in the sows: A combination of 400 IU of PMSG and 200 IU of hCG is used to induce estrus in pre-pubertal gilts 7 and 28 days after treatment. A single injection of 725 or 1088 IU IM was effective in induction of puberty in gilts in the adverse environment condition. A single dose of PMSG 1200 IU given to sows the day after weaning was effective in bringing about a return to estrus. Melatonin to advance breeding season in ewes, does and deer: A melatonin implant (18 mg) advanced the breeding season in ewes, does and deer with an increased ovulation rate. Introduction of the ram has the similar effect of hastening the onset of the breeding season. Use of Testosterone in the cow to shorten interval from calving to estrus: Testosterone 2 g (2 weeks) before use and booster at 2 week intervals in the cow to shorten interval from calving to estrus. In addition, 200 mg of testosterone propionate IM on alternate days for 20 days and testerone enanthate 1 g every 2 weeks in cows is used to detect estrus in other cows.
108
Altrenogest in mares to induce estrus: Altrenogest 0.044 mg/kg feeding for 15 days during the breeding season resulted in estrus in most mares within 3.5 to 5 days and ovulation 9-11 days after treatment. Altrenogest in sows to induce estrus: When the gilts that had been previously observed in estrus were fed 15-20 mg altrenogest daily for 18 days, approximately 95% expressed estrus 4-7 days after treatment. Progestins: 1. Synchro-Mate B in cattle: The treatment is composed of an ear implant containing the progestin norgestomet (6 mg) for 9 days and solution of norgestomet (3 mg) and estradiol valerate (5 mg) injected at the time of implantation. This treatment synchronizes estrus in heifers and post partum cows and insemination 48 hours after implant removal with exhibition of estrus in 77-100% cattle with 33-68% conception rate. 2. Controlled Internal Drug Release (CIDR): The CIDR-B is intravaginal progesterone device kept for 7- 15 days and with PGF2 alpa removal in cycling animals and 400 IU PMSG in anoestrus animals with 87% mated by 96 hours and pregnancy rates were 50%. 3. Progesterone Releasing Intra-vaginal device (PRID): It is composed of stainless steel coils coated with silicone rubber containing 6.75% progesterone. Estradiol benzoate (10 mg) in a gelatine capsule is attached to it. PRID is efficacious in synchronizing estrus and ovulation in cattle. PRID is kept in situ for 7-12 days and after its removal resulted in good estrus synchrony and pregnancy rates in heifers. Puberty induction in lambs has utilized a progestin sponge for 10-14 days followed by 400-600 IU of PMSG. The same is utilized in seasonally anoestrus ewes with 500-800 IU of PMSG at the time of progestin withdrawal. GnRH: 1. Fertility improvement in cows: The use of GnRH around the time of insemination to increase fertility in cattle has yielded mixed results whereas pregnancy rates were significantly improved when buserelin was given 12 days post insemination. 2. Follicular cyst in cows: It may be treated with 100 mcg GnRH results in luteinization of the cystic structure with estrus occurring in 18021 days. The administration of PGF2 alpa 9 days after GnRH will often shorten the interval to estrus. 3. Anoestrus in mares: Twice daily SC injections of buserelin (10 mcg) beginning midwinter for a maximum of 28 days with 2500 IU hCG IV given when follicle size was more than 35 mm resulted in estrus in 72% of the mares. Pregnancy rate and mortality were not altered. PGF2 alpha: PGF2 alpha is being used for estrus synchronization of estrus in cows and buffaloes as a breeding management tool successfully. PGF2 alpa
108
given twice 10-12 days apart to a herd will result in the majority of the animals expressing estrus 3-5 days after the second injection. 1. Mares: Two injections of PGF2 alpha 14-18 days apart results in good estrus synchrony in mares. 2. Goats: Two injections of 8 mg PGF2 alpha 11 days apart during the breeding season resulted in good synchrony of estrus and fertility. Induction of parturition: Parturition may be induced 1-2 weeks prematurely in cows by a single dose of glucocorticoids or PGF2 alpa. Dexamethasone 20-30 mg or Flumethasone 8-10 mg or Cloprostenol 500 mcg IM is effective in parturition induction with calving occurring 24-72 hours post treatment. Oxytocin is the most widely used drug for induction of parturition in the mare. Delivery is usually complete within 10-90 minutes of administering oxytocin. Farrowing is induced by oxytocin 16-24 hours after PGF2 alpa. Post partum use of Oxytocin, estrogen and PGf2 alpa: Oxytocin 20 IU IM given immediately after calving and repeated 2-4 hours late reduces the incidence of RFM. Oxytocin doses for RFM in the mares are 3-40 IU at 60-90 minute intervals. Alternatively, 80-100 IU oxytocin may be added to 500 mL normal saline and given IV according to the mares reaction in terms of abdominal pain. In uterine infections in the cow and mare, 20 IU oxytocin IM 3-4 times daily for 2-3 days has been recommended. The dose for small ruminants and sows is 5-10 IU of oxytocin. Estrogen doses for the cows are 3-10 mg of estradiol benzoate, valerate or cypionate to prevent and to treat uterine infections. Administration of PGF2 alpa once or twice between days 14-40 post partum may reduce the incidence of uterine infection and improve the subsequent fertility. Estrogens: Natural estrogens include oestradiol, estrone and oestriols. They have low bioavailability following postoperative administration. Simple esters of steroidal estrogens such as benzoates or valerate are used in therapeutics as they release parent molecule on hydrolysis. Potency of estrogen is enhanced adding ethinyl groups to the molecule. Indications: Misalliance (Post coitus), urinary incontinence in old / spayed bitches, uterine infections, anal adenoma and to induce estrus in bitches; Dosage: Dog 1-3 mg daily orally / 0.5 1 ml, IM. Precautions: Polydypsia, polyuria, GI upsets, suppression of red cell production, chronic use may lead to hypogonadism and cystic ovary in females. Products: Tab Evalon, 30 s (Infar); Tab Progynon-C30s(German Remedies);Inj. Progynon Depot 1 ml amp. (German Remedies) Conjugated estrogens: To prevent conception in small animal (misalliance) as it delays transport of zygote from oviduct into the uterus. In uterine infections, estrogens facilitate uterine drainage through cervix provided cervix is dilated. Indications: Misalliance (within one week following breeding), urinary incontinence in spayed / old bitches, anal adenoma, lactation, suppression and uterine infectionsPrecaution: Pregnancy, feminization in male and large doses may cause aplastic anemia Products: Premarin (Wyeth
108
lederle) injection
Dosage: Dog, Cat 3 tabs daily for 3 days, 1 ml IM as bolus Tab 0.625 mg; Inj. 25 mg / ml)
Hormones of reproduction in Small animals: GnRH dose of 2.2 mcg/kg IM once weekly is given for a month in male dog to improve libido and same dose in bitches to treat cystic ovaries. DES 5 mg/day is given orally in anestrus bitches until proestrus with treatment continuing for 2 additional days. The following three regimes were effective: 0.1 mg/kg every 8 hours; 0.25 mg/kg every 12 hours; or 0.1 mg/kg every 8 hours for 2 days and then 0.2 mg/kg every 8 hours afterward are most effective for inducing abortion (30-35 days) in bitches. Pregnancy has been terminated in queens after days 40 of pregnancy following either 0.50 or 1 mg/kg PGF2 alpa once or twice. Abortion followed 8-24 hours post PGF2 alpa. Doses of PGF2 alpa (25-1000mcg/kg S/Q or IM is recommended twice daily for 3-5 days or until the vaginal discharge is scant and uterine size is considerably reduced. Antibiotics are also used. Administration of Mifepristone (5-10 mg/kg) IM during the second half of pregnancy for 5-7 days resulted in abortion 5-7 days later. Bitches given 20-30 mcg/kg Bromocriptine orally twice daily for 4 days beginning day 42 of pregnancy aborted 3-5 days later. The hormones are also indicated in other reproductive problems like pseudo pregnancy, uterine inertia, cryptochidism and prostatic hypertrophy. In future some more hormones or similar preparations or drugs will be available to achieve desirable therapeutic results in animals. *****
108
AN UPDATE ON :
DRUGS ACTING ON DIGESTIVE SYSTEM

SUNILCHANDRA.U
The major groups of drugs acting on digestive system in monogatsrics include: emetics, antiemetics, antiulcer drugs, appetite stilmulants, prokinetics, antidiarrhoeal agents, laxatives and in ruminants include: stomachics, sialics, antisialogogues, antispasmodics, rumenotorics, rumenoreticular motolity modifying agenst, antifoaming sgents, rumenoreticular acidifying and alkalinizing agents. RUMINORETICULAR ANTACIDS/ ALKALISERS : Indicated in ruminal acidosis. Magnesium hydroxide (cattle: 100-300 g; sheep: 10-30 g); Magnesium carbonate (cattle: 10-80 g; sheep: 1-8 g). ; Mixed in10 L of warm water to ensure adequate dispersion through the ruminoreticular contents. Activated charcoal (2 g/kg) to protect the ruminoreticular mucosa from further injury by inactivating toxins RUMINORETICULAR ACIDIFYING AGENTS/ ACIDIFIERS: Indicated in ruminal alaklosis as in conditions of urea/ acute ammonia poisoning. Administration of weak acids in cold water returns the pH of ruminoreticular content toward physiologic levels, promotes the uptake of volatile fatty acids. Acetic acid (4-5%) or vinegar (cattle: 4-8 L; sheep: 250-500 mL), or 13ml glacial acetic acid RUMENOTORICS. Indictaed in ruminal indigestion, ruminal. Atony, Impaction, loss of appetite. Fresh ruminal fluid is considered to be the best available ruminotoric as it contains viable ruminal bacteria and protozoa as well as many useful fermentation factors .Formulations that contain glucogenic substrates, minerals, cofactors, and bitters (eg, nux vomica) ,antimony potassium tartarate, Cobalt sulphate, Cobalt chloride, ferrous sulphate, Copper sulphate, Thiamine, Manganese sulphate, Dried yeast, sodium acid phosphate,. Zinc sulphate, brassica, antihistaminics, and prokinetics. Mineral oil (1-2 L) or dioctyl sodium sulfosuccinate (DSS, 90-120 mL in 1-2 L of water) administered PO or via nasogastric tube followed by gentle ruminal massage- helpful in promoting the dissolution and passage of impacted fibrous ruminal contents.
SALIVARY STIMULANTS/SIALICS/ SIALOGOGUES: Increase the volume and fluidity of saliva, with the intention iof thereby increasing the appetite or digestibility of food.Eg: Bitters: gentian, quassia, calumba, cascara, nux vomica, cinchona, calumba, ; Turpentine
108
oil;Cholinergics:cholineesters(carbachol),cholinomimeticalkaloids(piloca rpine),cholinesteraseinhibitors(physostigmine, neostigmine); alpha adrenergic drugs; nicotine; mercurials, iodine, alcohol etc
ANTISIALOGOGUES:Antimuscarinics(atropine, hyoscyamine, glycopyrrolets), neuroleptics (chlorpromazine, trifluperazine, prochlorpromazine), anticonvulsants (carbamazepine), antihistaminics (promethazine, diphenhydramibne, dimenhydrinate) and astringents (alum, potassium sulphate) )are the examples. Indicated mainly as preanaesthetic medicants and in some poisoning cases
CARMINATIVES (ANTIFLATULENTS): Agents which cause expulsion of gases from the stomach, indicated in treatment of free gas bloat/tympany. Examples: pure volatile oils (turpentine oil, peppermint oil, eucalyptus oil; Ginger, powdered aniseed/anise; volatile compounds( alcohol, ethr, chloroform,ammonia,)s camphor, menthol; cardamom, cinnamom, coriander, pepper, dill seeds, nutmeg, sodium bicarbonate, asafoetida, simethicone, dimethylpolysiloxane etc
ANTIZYMOTICS: Agents which prevent or reduce the bacterial/enzymatic fermentation in rumen. Mainly used for the prevention of further gas production in the rumen in conditions of frothy bloat in ruminants and flatulent colic in horses. Eg: turpentine oil, linseed oil, formalin, phenolic compounds, chloroform, surfactants/ antifoaming/antifrothing agents: a) organic silicones Poloxalene, methyl silicone, Polymerized methyl silicone, PMS, dimethyl poly siloxane, silica in dimethicone (SIMETHICONE); b) Docusate sodium in emulsified soybean oil (6-12 fl oz containing 240 mg/mL) ; c) Vegetable oils such as peanut oil, sunflower oil, or soybean oil (cattle: 60 mL; sheep: 10-15 mL); d) Ionophores (such as monensin sodium ) in the ration Antifoaming substances may be included in the feed, drinking water, or sprayed on the crops. Poloxalene Oral suspension, 830mg/ml, 55%,
25g/30ml Dose. Oral liquid, poloxalene 830mg /ml, for cattle;(up to 227kg body weight) 30ml diluted in 500 ml water;(more than 227kg body-weight) 60ml diluted in 500ml water Premix, poloxalene 530 mg /g, for cattle; 22 mg of poloxalene /kg body weight daily. May be increased to 44mg of
108
poloxalene/kg;Dimethicone Oral suspension, 1 %, 2%. Dose. Cattle: 100 ml, sheep: 25 ml
ALIMENTARY DEMULCENTS: The agents coat, protect, lubricate and soothen the inflamed oral, pharyngeal, esophageal, gastric mucosa; are used to lessen the irritation of the abraded mucosa. Also indicated to mask the unpleasant taste/odor of the medicines. Eg: syrups (syrup of squill, jaggery syrup); honey , starch, glycerol, Gums (gum tragacanth, gum acacia, gum arabica, guargum,) ; methyl cellulose, agar, Glycerrhiza (liquorice), liquid paraffin , linseed oil, sesame oil APPETITE STIMULANTS (in monogastrics): include Cyproheptadine (antihistaminic), vitamin B complex preparations ,glucocorticoids, benzodiazepines(diazepam,oxazepam) and megestrol acetate, a synthetic progestin EMETICS: Apomorphine is an opiate drug administered PO, IV,SC, In case of over dose symptoms like :CNS depression; restlessness;respiratory depression, administration of antagonist ( e.g. naloxone 0.04mg/kg ) is useful. Xylazine is an 2 -adrenergic agonist, a reliable emetic, particularly in cats (IV route is preferred over IM). Syrup of ipecac produces vomiting by acting as a stomach irritant. Hydrogen peroxide (3%) in cats, aspiration of foams may cause aspiration pneumonia. Salt (1-3 tsp) in warm water / Sod. carb. (washing soda) applied on the posterior side of pharynx induce emesis ANTIEMETICS: Phenothiazine tranquilizers: also have antihistaminic and weak anticholinergic action. Affect almost all centrally origin emesis except those of labrynithitis . The agents are acepromazine, triflupromazine, chlorpromazine, and prochlorperazine perphenazine, trifluoperazine etc. Potential side effects: sedation, hypotension needing fluid therapy. Anticholinergic (antimuscarinics )drugs:. Alone, they are less effective than the other emetics. The agents are methscopolamine., glycopyrrolate, dicyclomine, propantheline, and isopropamide. The last two are commonly used in small animals for the control of motion sickness. They ameliorate spasm of the gastrointestinal smooth muscles, inhibition of entro-gastric secretions, dont cross blood brain barrier ,delays gastric emptying and should not be used more than 3 days . Side effects: drowsiness, xerostomia. Methoscopolmine is contraindicated in cat.
108
Antihistaminics: include diphenhydramine, dimenhydrinate, promethazine (a phenothiazine with H1 -blocking effects), cyclizine, and meclizine; preferred for controlling motion sickness related vomition, associated with journey; cause sedation. Cyclizine,meclizine are teratogenic. Metoclopramide: controls emesis induced by chemotherapy, nausea and vomiting associated with delayed gastric emptying, reflux gastritis, and viral enteritis. It readily crosses the blood-brain barrier causes adverse effects known collectively as extrapyramidal signs: involuntary muscle spasms, motor restlessness, and inappropriate aggression. Concurrent use of phenothiazine and butyrophenone tranquilizers to be avoided since they increases the potential for extrapyramidal reactions, can be reversed by antihistaminic:diphenhydramine hydrochloride 1.0 mg/kg,IV.GI obstruction(intussusception),hemorrhages, perforationto be excluded before therapy. Serotonin (5-HT3) antagonists: Ondansetron,palonosetron dolasetron: specific inhibitors of 5-HT 3 (serotonin) receptors in the CTZ; are effective antiemetics used in patients undergoing radiation and anticancerous therapy, not effective for motion sickness. Domperidone : is devoid of the extrapyramidal side effects seen with metoclopramide. Maropitant and casopitant are newer antiemetics, with potent and selective oral neurokinin 1 receptor antagonist activity; are useful in preventing /treating nausea and vomition caused by variety of conditions. Midazolam is a short-acting benzodiazepine with a rapid onset of action efficacious as antiemetic in postoperative emesis resistant to the usual treatments ANTIULCER DRUGS : Acetylcholine M1 Receptor antagonists(anticholinergics) : Pirenzepine and telenzepine(more potent), selective M1 cholinergic antagonists. Others: hyoscine (scolpolamine) ,dicyclomine.HCl, isopropamide iodide. They potentiate effects of H2 blockers. Antacids: neutralize gastric acid to form water and a neutral salt. Usually not absorbed systemically. Common antacid preparations are combinations of aluminum hydroxide, magnesium oxide or hydroxide, and calcium carbonate. Antacids frequently interfere with the GI absorption of concurrently administered drugs. As a general guideline, it is best not to give antacids within 2 hours of other oral medications. Used in adjunctive treatment of oesophagitis, gastric hyperacidity, peptic ulcer and gastritis. In ruminants, magnesium hydroxide is used to increase rumen pH and as a laxative in the treatment of rumen overload syndrome (acute rumen engorgement, rumen acidosis, grain overload).
108
Sodium bicarbonate is systemic, rapid and short acting antacid, may cause metabolic alkalosis in high dose or in renal insufficiency. Mainly indicated for : metabolic acidosis, alkalization of urine and as adjunctive therapy in hypercalcemic,hyperkalemic crisis. Contraindicated in metabolic or respiratory alkalosis. Incompatible with: ,5%dextrose,injectableVit C,codeine,epinephrine, glycopyrrolate ,regular insulin, oxytetracycline etc. Magnesium containing antacids: Mg hydroxide ( milk of magnesia), Mg oxide, and Mg silicate. Repeated administration which may leads to hyper magnesia; are contraindicated in patients with renal disease. Aluminum-containing antacids may deplete phosphate, causes muscular weakness, bone resoption and hypocalcaemia. (Rapid onset of action (less than 30 minutesDue to short duration of action should beadministered ever 3-4 hours).Adverse effects like constipation with aluminum- and calcium-containing antacids, and diarrhea or frequent loose stools with magnesium containing antacids.; hypophosphatemia with aluminum antacids or hypermagnesemia with magnesiumcontaining antacids; hypercalcemia, hypophosphatemia and gastric acid rebound phenomenon with calcium carbonate are possible. Histamine (H2)-receptor Antagonists: effectively block pepsin and gastric acid secretion from parietal cells by blocking the H 2 receptor. Cimetidine, ranitidine, nizatidine and famotidine are the commonly used H2-receptor antagonists. Potencywise: . famotidine > nizatidine >ranitidine >cimetidine.They strengthen the gastric mucosal defenses against ulceration and enhances cytoprotection. Among these agents, Cimetidine reduces the metabolism of other drugs by inhibiting hepatic microsomal enzyme systems.and has got adverse effects like antiandrogenic, effects: gynecomastia , azospermia and decreased libido, skin rashes, and diarrhea . Proton-pump inhibitors (H+ K+ ATPase Inhibitors): These agents (e.g., omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole) inhibit the sodium/potassium proton pump (H+ K + ATPase) at the luminal surface of the parietal cell that secretes hydrogen ions into the gastric lumen. Omeprazole, inhibits gastric acid secretion in dogs for at least 24 hours after a single oral dose and is as effective as cimetidine in healing mechanically-induced gastric ulcers, and more effective than cimetidine in healing aspirin-induced gastritis. It is also a microsomal enzyme inhibitor; decreases metabolism of :Diazepam,Phenytoin,warfarin Increases gastric PH and decreases absorption of drugs that need low PH for absorption : Ketoconazole, ester and metal salts of ampicillin. Cytoprotective drugs : Sucralfate is an alkalinizing aluminium hydroxide complex with sucrose, reacts with gastric HCl, forming a
108
insoluble pasty complex that binds to exudate protein of the damaged tissue (GIT epithelium) forming a barrier and thus protecting the damaged tissue from more injuries by acid, bile and pepsin. Prostaglandin E1 analogues: Misoprostol , prostaglandin E1 analogue, is the adjunctive drug in treatment/prevention of peptic ulcers related to NSAIDs but is less efficacious than H2-blockers in peptic ulcers not associated with NSAIDs therapy. PROKINETICS: increase movement of ingested material through the GI tract by inducing coordinated motility patterns, are useful in the treatment of GI motility disorders Metoclopramide stimulates and coordinates esophageal, gastric, pyloric, and duodenal motor activity. It increases lower esophageal sphincter (LES) tone and stimulates gastric contractions; while relaxing the pylorus and duodenum. speeds gastric emptying of liquids, but may slow the emptying of solids. Its prokinetic action is negated by narcotic analgesics and anticholinergic drugs, such as atropine. Due to accelerated food absorption, metoclopramide therapy may increase the insulin dose required in diabetics. Indications: i) gastric emptying disorders-delayed gastric emptying, an important cause of upper gastrointestinal tract signs, (anorexia and vomiting, in dogs and cats) dilatation, volvulus, gastroesophageal reflux, infectious and inflammatory gastric diseases. ii) small bowel motility disorders-. ess effective in the distal small intestine and colon iii) free gas bloat and ruminal impaction in ruminants iv) in disorders of ruminoreticular motility. Cisapride,Mosapride and Itopride are with broadest spectrum and potency of prokinetic activity, but without antidopaminergic effects (antiemetic action) or extrapyramidal effects (do not cross blood brain barrier). Indications:i).gastric stasis, idiopathic constipation, gastroesophageal reflux, chronic constipation with megacolon, postoperative ileus and intestinal pseudo-obstruction in dogs and cats. ii) in dogs with idiopathic megaesophagus that continue to regurgitate frequently despite a carefully managed, elevated feeding program. Domperidone is superior to metoclopramide in stimulating antral contractions in dogs, with no effect on colon motility and dont cross blood brain barrier as readily as metoclopramide. Antacids and H2 blockers decrease absorption of drug. It is a good anti emetic and prokinetic agent in small animal, to be used cautiously in collie dogs. Acetylcholinesterase Inhibitors: Ranitidine and nizatidine -histamine H2-receptor antagonists with prokinetic action. Neostigmine is recommended for use in large animals for treatment of paralytic ileus
108
ANTIDIARRHOEAL AGENTS Mucosal Protectants and Adsorbents : . Absorbents bind physically with chemicals and hinder their absorption.Kaolin-pectin formulations absorb toxins and make protective layer which prevent gastric mucosa from further injuries; are used for the symptomatic treatments of acute diarrhea. It may change the consistency of the feces but neither decreases the fluid or electrolyte loss, nor shortens the duration of the illness. Nevertheless, it is often administered to small animals, foals, calves, lambs, and kids. used every 4-6 hours. Kaolin-pectin products may adsorb or bind other drugs administered PO and reduce bioavailability. Activated charcoal is the broadest spectrum,rapid acting absorbentuseful in the emergency treatment of intoxications It forms stable complexes with noxious agents& enhances Administration every 6 h for 1-2 days increases elimination of systemic absorbed toxins their excretion. It also adsorbs many drugs and toxins and prevents GI absorption, so it is a common nonspecific treatment for intoxications. Bismuth salts: Bismuth sub salicylate, bismuth sub nitrate, bismuth sub carbonate. Bismuth subsalicylate is the absorbent, anti endotoxin,weak antibacterial, which adsorbs bacterial enterotoxins and endotoxins to have a GI protective effect; salicylate has antiprostaglandin activity to control secretory diarrhea..By making a protective lining layer and formation of insoluble complexes with noxious agents, it can be useful in improving indigestion, useful in the treatment of flatulence. Salicylate toxicosis is possible, especially in cats. Motility-modifying Drugs: Anticholinergic drugs themselves have profound systemic pharmacologic effects. and these drugs may actually worsen the diarrhea . Side effects : severe ileus, xerostomia, urine retention, cycloplegia, tachycardia, CNS excitement and intestinal atony. Atropine ,because of its systemic effects, is not used for an antidiarrhoeal effect. To avoid CNS excitement, hyoscine, aminopentamide, isopropamide, propantheline and dicyclomine are preferred since they do not cross the blood-brain barrier; are used for the treatment of acute abdominal spasm, tenesmus, pylorospams, gastritis and related emesis, emesis & diarrhea in dogs and cats. Opiates have both antisecretory and antimotility effects. Diphenoxylate and Loperamide are two synthetic opiates that have specific action on the GI tract, without other systemic effects is used in small animals and neonates. They are generally used for the symptomatic treatment of acute diarrhea and are contraindicated in infectious diarrhea, hepatic diseases and obstruction of the GIT and urinary tract . Loperamide In dogs adverse effects: abnormal pupillary
108
response to light, circling, constant or increased vocalization, head pressing, mydriasis and constipation cats and collie dogs: paralytic ileus, toxic megacolon, pancreatitis, and CNS stimulation.. Non steroidal Anti-inflammatory Drugs (NSAID): These (meloxicam )may directly inhibit fluid and electrolyte hypersecretion by the intestinal cells, can be used in calf scours. Theyare administered cautiously due to the adverse GI, hepatic, and renal effects. Glucocorticoids: Prednisolone, prednisone, hydrocortisone, are generally used for the treatment of moderate inflammatory intestinal diseases that involve rectum or colon. LAXATIVES (CATHARTICS): They increase the motility of the intestine or increase the bulk of feces. Clinically, these are administered to increase passage of gut contents associated with intestinal impaction, to cleanse the bowel before radiography or endoscopy, to eliminate toxins from the GI tract, and to soften feces after intestinal or anal surgery. Stimulant (irritant) laxatives: The vegetable oils - Castor oil cathartic, used in nonruminants and preruminant calves. Raw linseed oil (cooked linseed oil is toxic) in smaller doses and olive oil is a mild lubricant laxative and a source of fatty acids for horses. Oils are contraindicated in intestinal obstruction and non diagnosed rectal hemorrhage . Phenolphthalein is effective in primates and pigs. Bisacodyl administered by mouth or by enema in dog and cat and only 5% of any dose is absorbed. Osmotic (Saline) laxatives: Adequate water intake must be assured. Magnesium salts(sulphate): Mg. sulfate containing compounds often not to be used in horses. Sodium salts: - sodium biphosphate or sodium phosphate enemas. Not to be used in cats because of fatal hyperphosphatemia, hypocalcemia, and hypernatremia. Sugar alcohols, such as mannitol and sorbitol, are poorly absorbed and fermented in the terminal ileum and large intestine. Lactulose is a synthetic disaccharide is used to treat chronic constipation in cats. Hydrophilic Colloids (Bulk) laxatives: Cellulose and hemi cellulose undergo bacterial fermentation in large intestine, make volatile fatty acids which precipitate laxative effect by osmotic character. Examples include methylcellulose, carboxy methyl cellulose , psyllium, prunes, wheat bran, and canned pumpkin. Emollient (Mechanical or lubricant) laxatives: Mineral oil ( Liquid paraffin) or white petroleum. Long term use: interference with absorption of the fat soluble vitamins, nutrients and coadministered drugs, decrease sensitivity and irritability of intestinal mucosa which
108
can leads to constipation, intestinal and lymphoid absorption which lead to granulomatous enteritis. They are not suitable for diagnosis or treatment of GIT obstruction. Fecal Softeners (Surfactants): Docusate sodium, docusate calcium, and docusate potassium are salts that decrease surface tension and allow water to accumulate in feces. Neuromuscular purgatives are the fast acting muscarinic cholinergic agents acting at small intestine; to be used cautiously in physical obstruction. Eg: neostigmine,physostigmine, bethanechol,carbachol. Neostigmine,used for ruminal atony, to enhance urination, stimulation of skeletal muscles contraction and peristaltic activity in cows, horses, sheep and swine. DIGESTANTS: These agents promote the digestion of food especially in monogastric animals. A number of proteolytic, amylolytic and lipolytic enzymes are used as appetite stimulant , health tonics and digestants.Eg: Proteolytic enzymes (papain, trypsin, chymotrypsin, enterokinase, carboxypeptidase);amylolytic enzymes (diastase, takadiastase); Pancreatic enzymes (pancreatin (mixture of amylase, trypsin and lipase), pancreolipase) indicated in chronic pancreatitis, exocrine pancreatic insufficiency HEPATOPROTECTIVE DRUGS AND CHOLAGOGUE/ CHOLERETICS: The substances which cause gall bladder contraction are cholagogues; and the substances which increase the bile secretion are choleretics. They are indicated in gall bladder disease, cholestasis, biliary fistula, gall bladder stones, biliary cirrhosis. Ursodeoxycholic acid (ursodiol): is a naturally occurring bile acid, used in the dogs with chronic hepatitis and cats with lymphocytic plasmacytic cholangitis..The hepatoprotective effect may, however, be less in cats and dogs than in humans as the major circulating bile acid in dogs and cats is taurocholate.Dose: dog, cats- 1015 mg/kg q.24 h or divided and given q.12 hIt is recommended that ursodeoxycholic acid be administered for 34 months. Aluminum-containing antacids may bind to it, thus reducing efficacy. Administration with food, thus improving absorption is recommended. Colchicine: the antigout drug, has been used in the management of amyloidosis and chronic hepatic fibrosis. Dogs: 0.0250.03 mg/kg/d. it is teratogenic . NSAIDs increase the risk of thrombocytopenia, bone marrow suppression ,if used concurrently. S-adenosyl methionine (SAMe): is an endogenous molecule which is synthesized, from methionine, by many cells in the body. It is most frequently used as adjunctive therapy for a variety of hepatic disorders (canine chronic hepatitis,hepatic lipidosis, cholangiohepatitis, etc.). It may also be beneficial in the treatment of certain hepatotoxic disorders. The dosing : 5.5 kg- 90 mg POq.24 h; 5.51 kg: 180 mg PO
108
q.24 h; 1116 kg: 225 mg POq.24 h; 1629.5 kg: 450 mg PO q.24 h; 29.541 kg: 675 mgPO q.24 h; 41 kg, 900 mg PO q.24 h, on an empty stomach Silymarin: Source-Milk thistle, Silybum marianum, has been traditionally used in the treatment of liver disease. It may:control hepatic cell membrane permeability and thus prevent toxin penetration; inhibit the cytotoxic, inflammatory and apoptotic effects; reduce hepatic collagen formation and increase hepatic glutathione content. in the chronic hepatopathies, acute hepatic disease and as a hepatoprotective agent against a variety of hepatotoxic substances.Increase the clearance of drugs which undergo hepatic glucuronidation, e.g.paracetamol (acetaminophen), diazepam and morphine. Dogs and cats 2050 mg/kg PO q.24 h *****
DOSAGES OF DRUGS ACTING ON DIGESTIVE SYSTEM OF ANIMALS.

APPETITE STIMULANTS Drug Prednisone Stanozolol Oxazepam EMETICS Apomorphine Xylazine Dogs: 4 mg/kg, PO; 0.02 mg/kg, IV; 0.3 mg/kg, SC; 0.25 mg in the conjunctival sac Cats: 0.4-0.5 mg/kg, IV or Syrup of ipecac 3-6 mL/kg, PO IM Hydrogen peroxide Dogs: 5-10 mL, PO 0.025-0.2 mg/kg, IV, IM, SC, max. 3 mg; 1-3 mg/kg, PO 0.5 mg/kg, IV, IM, SC, 0.1 mg/kg, IM, PO, BID 0.25 mg/kg, PO, 4-8 mg/kg, PO,
TID; TID TID-QID
Dosage 1 mg/kg, other day PO, every Boldenone undecylenate Diazepam Cyproheptadine 2.5mg/kg, IM,
Cats: 0.005-0.4 mg/kg, IM or IV, SID; 1 mg/kg, PO, SID
0.25-3 mg/kg, PO, SID; 2-10 mg/kg, IM, once weekly Cats: 2 mg, PO,
BID
Cat PO,
1-4mg,
BID
ANTIEMETICS Acepromazine Chlorpromazine Prochlorperazin e Propantheline Dimenhydrinat e
Isopropamide Diphenhydramine Cyclizine Meclizine
1 mg/kg,
0.2-1.0 mg/kg, PO, BID 2-4 mg/kg, PO, TID 4 mg/kg, PO,
TID
TID
4 mg/kg, PO,
SID
108
Butorphanol Ondansetron
0.2-0.4 mg/kg, IM, 0.1-0.2 mg/kg, PO,
SID-BID SID-BID
Dolasetron ; 0.22 mg/kg, IV,

TID; BID-TID
0.6 mg/kg, IV,

SID
Metoclopramid 0.1-0.5 mg/kg, IM, SC, PO, e ANTI ULCER DRUGS Ranitidine Famotidine Sucralfate Omeprazole
0.01-0.02 mg/kg/hr, IV infusion
Dogs, cattle : 0.5 mg/kg, PO, SC, or IV, BID Horses: 1.3 mg/kg, IV, BID; 11 mg/kg, PO, BID Dogs: 0.5-1 mg/kg, PO or IV, SID Horses: 0.4 mg/kg, IV, BID; 3 mg/kg, PO, BID Cats: 250 mg, BID-TID Dogs: 500 mg to 1 g, TID-QID Foals: 1-2 g, QID
SID
Dogs: 0.5-1 mg/kg, PO, mg/kg, PO, SID PROKINETIC DRUGS Metoclopramid e Domperidone Cisapride Ranitidine Neostigmine
Horses: 4 mg/kg, PO,
SID
for treatment; 2
Dogs and cats: 0.2-0.5 mg/kg, PO or SC, TID; 0.01-0.02 mg/kg/hr, IV infusion Horses: 0.125-0.25 mg/kg, diluted in 500 mL of polyionic solution 0.1-0.5 mg/kg, IM; 0.5-1.0 mg/kg, PO Dogs: 0.1 mg/kg, PO, TID Cats: 2.5 mg/cat, TID for cats <5 kg, and 5.0 mg/cat for cats >5 kg Horses: 0.1 mg/kg, PO, TID 1-2 mg/kg, PO, BID Nizatidine 2.5-5 mg/kg, PO, BID 0.02 mg/kg, SC, as needed Erythromycin 0.5-1.0 mg/kg, PO,
BID-TID
Lidocain Horses: 1.3 mg/kg as a iv bolus followed by a continuous infusion of 0.05 e mg/kg/min ANTIDIARRHOEAL DRUGS Kaolin1-2 mL/kg, PO, QID Diphenoxylate 0.05-0.1 mg/kg, PO, QID pectin Activated 2-8 g/kg, PO LAXATIVES:Cast Dogs: 5-25 mL, PO Foals: 25-50 charcoal or oil mL, PO Bismuth 1-3 mL/kg/day Bisacodyl Dogs: 5-20 mg, PO, SID- BID Cats: subsalicyla in divided doses, 2.5-5.0 mg, PO, SID- BID te PO Aminopentami 0.1-0.4 mg, Mag.sulfate(Epso Dogs: 5-25 g, PO Cats: 2-5 g, PO de IM, SC, pO, m salt) Horses: 30-100 g, Cattle-250BID 400g, PO Isopropami 0.2-1.0mg/kgPO, Magnesiumhydro Dogs: 5-10 mL, PO Cats: 2-6 mL, de BID xide (milk of PO Horses: 1-4 L, PO magnesia) Propanthelin 0.25-0.5mg/kg,PO, BID Lactulose Dogs: 5-15 mL, PO, TID Cats: 2-3 e mL, PO, TID Loperamid 0.08 mg/kg, PO, TID e
*****THERAPEUTIC PROTOCOLS IN HEPATIC AND RENAL IMPAIRMENTS

VIJAY KUMAR.M
108
Liver disorder should always be considered when nonspecific clinical signs, such as depression, weight loss, intermittent fever, and recurrent colic, are present without an apparent cause. Differentiation between acute and chronic hepatitis or failure based on the duration of clinical signs before presentation may be misleading because the disease process is often advanced before clinical signs are evident.Liver biopsy to determine the type of pathology, degree of hepatic fibrosis present, and the regenerative capabilities of the liver parenchyma is necessary for developing a treatment plan and giving an accurate prognosis. Chronic hepatitis patients sometimes need to use antibiotics for unrelated infections and various other procedures and many are not sure about the possible harmful effects some antibiotics may cause their liver. The effect is difficult to predict and almost impossible to quantify. There are no tests for hepatic function that will reliably predict drug clearance. Changes in hepatic function due to disease that may affect drug clearance are described by: :i) decreased intrinsic clearance caused by loss of functional hepatic mass ii) Increased fraction unbound of protein-bound drugs. Decreased drug protein binding caused by decreased albumin; this may increase clearance of drugs that are highly protein bound iii) decreased hepatic blood flow resulting in decreased drug clearance. Drugs that accumulate in this manner could become toxic to the body and its functions can change drastically from its original purpose. For the most part in treating patients with preexisting liver disease who develop infections outside the liver, one should use caution in prescribing drugs known to be dependent on liver for inactivation or excretion. Usually a safer substitute drug can be found. One should also take care to avoid use of hepatotoxic non-antibiotic drugs concomitantly. On the other hand, drugs metabolized and/or excreted by the liver are theoretically ideal for treatment of acute infections of liver and biliary tract. Tetracyclines: Used in larger doses, cause jaundice, fever, and fatty liver. Hepatitis patients should not be administered with these agents. All tetracyclines are concentrated in liver and excreted via bile into intestine, where they are reabsorbed. Variable amounts of each member of this drug family are thereafter eliminated in urine.; have prolonged half-lives in the serum because of slower renal clearance than that of tetracycline or oxytetracycline. With excess parenteral
108
dose, liver toxicity progresses to acidosis, shock, coma and death.Other organs which may suffer simultaneous toxicity are pancreas, kidneys and brain. Pregnancy and chronic renal disease seem to predispose patients to this type of hepatotoxicity. Dosage adjustment is necessary, avoid exceeding a blood level of 10mcg/ml. Tetracyclines have adverse effects on several hepatic enzymes. Inactivated chlortetracycline causes same toxic hepatic changes as the active drug, so hepatic toxicity appears not related to antibacterial activity; thus to be avoided completely in liver disease Macrolides : Erythromycin: It causes damage to the liver via cholestasis (bile retention) and jaundice. The harmful effects usually start to show after 10 to 14 days use and the incidence rate is approximately 5 to 10%. Clinically, patients may develop abdominal pain, nausea, vomiting, jaundice, and elevation of liver enzymes. These conditions are often considered allergic reactions since the incidence rate is not very high Liver toxicity is caused by only estolate form. Avoid estolate form in liver disease and other forms in usual dosage. Estolate-induced hepatitis is a dose dependent. hypersensitivity reaction. Lincosasmides: Lincomycin: is excreted and re-excreted via enterohepatic circulation. Bile levels are high upto 10-20x the serum level. Occasional jaundice and/or abnormal liver function tests which clear rapidly, sometimes even while drug is continued. Half-life of drug is doubled in liver disease accordingly drug dose should be reduced, or drug avoided entirely. Kanamycin : Not Metabolised by liver.No change in dose in case of parenteral liver disease.in case of oral dose kanamycin at 8 Gm/day eventually builds serum levels to therapeutic range. This effect is even greater with hepatic disease and azotemia. Accordingly, such patients on gut sterilization with kanamycin should be watched for deafness and increasing nephropathy. Neomycin: Not metabolised by liver. No more than 6 Gm P.o in liver disease for gut sterilization. If azotemia also present,kanamycin is preferred. Chloramphenicol: When metabolized in the liver, they combined with glucoronic acid and lose their anti-microbial effects. This combination of antibiotics and glucoronic acid can accumulate in the bloodstream, which can cause bone marrow inhibition. As a result, WBC and RBC counts can drop and patients with hepatitis should try to avoid this
108
group if they can. Metabolism by liver. 85-95% is conjugated in liver to monoglucuronide and 3% is further converted to aryl amines and aryl nitro derivatives.Most of above is secreted then by kidney tubules. Significant concentration in liver tissue levels and average bile levels,that of plasma. Liver toxicity is rare. Use with caution in liver disease. If ascites or jaundice is present, use under 25 mg/kg/ day or another drug. Newborns are vulnerable to "grey syndrome"due to immature hepatic and renal function. Penicillins: These antibiotics cause the least liver damage and only patients who are allergic may experience some side effects. Generally, antibiotics in the penicillin family are the most "liver friendly" and safe for chronic hepatitis patients to use. Penicillin G: . Metabolism by liver: Only minor fraction is ordinarily handled by liver, but in impaired renal function the liver may be a major excretion route via bile. Attains significant liver tissue levels and also bile levels.Liver toxicity is rare, as part of a generalized hypersensitivity reaction. No change in dose in liver diseases if renal function is good and reduce dose in circumstances of combined kidney and liver disease. Generally the information for penicillin G applies also for Alphaphenoxy-peniclllins Methicillin., Oxacillin methicillin. Cloxacillin and broad spectrum penicillins: ampicillin, hetacillin, carbenicillin and nafcillin. Streptomycin and Dihydrostreptomycin: Metabolism by liver.Small fraction is secreted into bile. Bile levels up to 10-20mcg/ ml on high doses. Liver toxicity is rare and also may aggravate existing liver disease. No change in dose in liver disease. Cephalosporins: Cephalothin: Metabolism by liver, 70-80% usually excreted unchanged in urine. However, it can be inactivated by deacetylation (presumably in liver), then excreted in urine. Advisable to decrease in presence of combined renal-hepatic disease. Nitrofurantoin: Metabolism by liver: 50-60% is metabolized at unknown site. Rarely, causes a hypersensitivity hepatitis with cholestasis, focal necrosis, infiltrates,eosinophils. Sulphonamides: Metabolism is significantly, but not solely by liver (acetylation, glucuronidation, and/or oxidation), then excreted into
108
urine. Not influenced by dose: direct hepatotoxicity and hypersensitivity. Either may go on to acute yellow atrophy. Best to avoid dose in liver disease. Pre-existing nutritional liver disease may predispose to sulfonamide hepatotoxicity. Kidneys appear to be more susceptible to damage by sulfas in patients with chronic liver disease.Neonate require less dose for therapeutic blood levels. Metronidazole and related drugs (tinidazole, ronidazole): are sometimes used in patients with hepatic disease because of the anaerobic spectrum. The most serious problem caused by high dose of metronidazole has been attributed to CNS toxicity and include seizures, ataxia, nystagmus, tremors, and rigidity.4 These signs have been attributed to inferring with the inhibitory neurotransmitter GABA. Because animals with hepatic disease also may be prone to CNS disorders that also share these clinical signs, veterinarians should understand the risks of metronidazole, and become familiar with the signs associated with toxicity. Fluoroquinolones: The fluoroquinolones (enrofloxacin, marbofloxacin, orbifloxacin, difloxacin) have had a good safety record and increased risk of toxicity in animals with hepatic disease has not been documented. Although some of these drugs are metabolized, the clearance is low and probably not affected unless there is substantial loss of hepatic function. These drugs are also cleared by the kidneys A common dilemma for veterinarians is which nonsteroidal antiinflammatory drug (NSAID) to administer to a patient with hepatic disease. The six approved NSAIDs for dogs: carprofen, etodolac, Meloxicam (cats), tepoxalin, deracoxib, and firoxixib. Because studies have not been conducted in animals with hepatic disease, there is no single drug shown to be safer than another. However, All NSAIDs have the potential to: (1) induce liver injury. (2) Pre-existing elevations in liver enzymes has not been shown to increase an animals risk for NSAID-induced liver injury, but a sharp increase in liver enzymes and/or bilirubin after instituting NSAID therapy is cause for alarm. (3) cause gastrointestinal injury, including erosions, ulcers, and bleeding. Patients with hepatic disease have an increased risk of these problems. (4) There is no NSAID yet to be shown safe for long-term administration for cats and hepatic reactions have been one of the problems associated with NSAID administration in cats. Tramadol and opiate analgesic drugs have high clearance and their metabolism is not likely to be affected by
108
a loss in hepatic function or changes in hepatic enzymes. These drugs have a high safety margin and can be used safely in patients with hepatic disease. RENAL IMPAIREMENTS: The excretory function involves elimination of toxins from the body by way of glomerular filtration and tubular secretion. Elimination of urea, creatinine, and other nitrogenous waste products of protein catabolism are excretory functions. Excretory failure is often recognized as azotemia.Loss of these renal functions results in a narrowing of the physiologic range over which the kidneys are able to adapt. For example, loss of urine concentrating ability (regulatory failure) leads to obligatory increases in water intake. The failing kidneys have impaired ability to adapt to extremes (high or low) in electrolyte intake. This limited ability of the failing kidneys to adapt to variations in intake directly relates to therapeutic plans. CONSERVATIVE MEDICAL MANAGEMENT OF RENAL FAILURE: Conservative medical management of CKD consists of supportive and symptomatic therapy designed to correct deficits and excesses in fluid, electrolyte, acid-base, endocrine, and nutritional balance and thereby minimize the clinical and pathophysiological consequences of reduced renal function. Goals of conservative medical management of patients with chronic primary renal failure are to: (1) ameliorate clinical signs of uremia, (2) minimize disturbances associated with excesses or losses of electrolytes, vitamins, and minerals, (3) support adequate nutrition by supplying daily protein, calorie, and mineral requirements, and (4) modify progression of renal failure. Conservative medical management is most beneficial when combined with specific therapy directed at correcting the primary cause of renal disease. PHARMACOLOGIC CONSIDERATIONS Renal insufficiency can markedly alter one or more of the pharmacokinetic parameters of a drug including oral bioavailability, volume of distribution, drug binding to plasma proteins, and most importantly the rates of metabolism and excretion, i.e., drug clearance. To minimize drug toxicity and maximize therapeutic benefits, it is often necessary to adjust drug dosage in proportion to the degree of renal efficiency Dose adjustment may involve one or a combination of the following measures:
108
1. Extension of the dosing interval. dose.
2. Reduction of the maintenance
3. Administration of a loading dose. 4. Monitoring serum drug levels. To maintain a therapeutic level and, at the same time, avoid drug accumulation and toxicity in a patient with reduced renal function, the clinician must consider reducing the size of the maintenance dose or the dosing frequency or both. In general, this reduction should also be proportional to the degree of renal impairment but should also take into account adaptive or compensatory changes in the metabolism and excretion of the drug through non renal routes. Conservative Medical Management of Renal Failure in Dogs and Cats
Clinical or Laboratory Treatment Options Abnormality Progression of CKD Diet therapy Azotemia/uremia Diet therapy Polyuria and polydipsia Free access to water Consider diet therapy Dehydration Free access to water Avoidstress (prophylaxis) CannedFood Supplemental fluid therapy (?) Metabolic acidosis Therapeutic alkalinization Anemia of CKD ErythropoietintherapySupplementalIron Transfusiontherapy Androgen therapy Hyperphosphatemia Diet therapy Intestinal phosphate binding agents Hypocalcemia Oral calcium supplements Calcitriol therapy Renal osteodystrophy Minimizehyperphosphatemia (prophylaxis/treatment) Oral calcium supplements Calcitriol therapy Systemic hypertension Sodiumrestriction Antihypertensive drug therapy Drug Avoid nephrotoxic drugs reactions/overdosage Adjust dosages according to renal function Urinary tract infection Monitor for infection Antibiotic therapy
Ameliorating clinical consequences of excretory failure: Reducing protein intake:Controlled reduction of non-essential proteins wil result in decreased production of nitrogenous wastes with consequent amelioration of clinical signs of uremiaIndications of diet therapy:
108
Dietary Component Protein quantity Protein quality Phosphorus Sodium Fatty acids Caloric density Fiber
Change from typical maintenance diets Reduced Increased Reduced Reduced Enhanced omega 3:omega 6 PUFA ratio Enhanced Enhanced
Enhancing diet palatability: Changes in the diet: changes in the diet should be made gradually over a period of one two weeks.Warming of food improves palatability.warm water should be added to dry feed.fresh aromatic feed should be offered. Food aversion : occurs if nauseated patients are force fed.If painful sample collection or drug administration is associated with feeding unpalatable drugs should not be mixed with regular feed or water.Flavoring agents: agents like animals fat, butter,dehydrated cottage cheese,garlic etc.enhance palatability Modifying feeding patterns and environment: Animal should be fed frequently with small quantities of food, placing palatable food in the patients mouth or paws may stimulate a licking response Pharmacological appetite stimulants Anabolic steroids: even though these drugs are claimed to improve the appetite, no data is available to support this in renal failure Corticosteroids: there is no data to support longterm beneficial effect in ureamic dogs and cats Benzodiazepenes: diazepam stimulates appetite in various species.But only marginal success in renal failure patients. Diazepam : 0.2mg/kg i.v with a maximum of 5mg/kg/patient,given twice a day,PO or i.m can also be givenOxazepam: used only for oral administration.2.5mg/patient,not suitable for longterm usage Modification of drug dosages: nephrotoxic drugs that require renal excretion should be avoided in patients with renal failure Hyperphosphatemia is managed by restricting dietary phosphorus intake , oral administration of intenstinal phosphorous binding agents or a combination of these methods . The ultimate aim is phosphoros restriction . Modified protein diets designed for dogs with renal failure may contain as little as 0.13 to 0.28 % phosphorous on a dry matter basis and provide about 0.3 to 0.5 mg/kg phosphorous (Typical commercial dog food contain 1 to 2 % phosphorous on DM basis and 2.7 mg/Kcal phosphorous ) Modified protein diet for cats contains 0.5 % phosphorous on DM basis and 0.9 mg/Kcal of phosphorous ( Typical
108
commercial food contains 1-4 % phosphorous on DM basis and 2.9 mg/Kcal phosphorous). Intestinal binding agents : These render ingested phosphorous contained in the saliva , bile and intestinal juices unabsorable. These agents are administered by mixing food or just before meal. Aluminium containing intestinal phosphorous binding agent include aluminum hydroxide, aluminum carbonate and aluminum oxide, Dose 30 to 90 mg/kg/day . Available as antacid preparation in liquid, tablet or capsule forms, Sucralfate, a complex polyaluminium hydroxide salt of sulfate used primarily for gastro intestinal ulceration is also effective than aluminum based agents, excess usage may lead to hypercalcaemia Calcium acetate is the most effective and given at a dose rate of 60 90 mg/kg/day. Calcium carbonate is given at a dose rate of 90250mg/kg, calcium based agents must be administred with feed both to enhance phosphorous binding and to minimize absorption of calcium. Hypokalemia : Potassium replacement therapy is indicated for cats with hypokalemia (serum potassium concentration less than 4 mEq/1r) even in the absence of clinical signs of hypokalemia .Potassium gluconate 2-6 mEq/cat/day as powder , tablet , gel or elixir .Patassium citrate can also be given. Routine supplementation of low oral doses of potassium (2 meq/day ) has been recommended for all cats with chronic renal disease. Diets that are acidifying and restricted in magnesium content may promote hypokalemia and hence be avoided in cats with chronic renal failure .Fluid should be administred such as potassium is delivered intravenously at a rate less than 0.5 meq/kg/hr Metabolic acidosis : Alkalinization therapy designed to correct metabolic acidosis is an important component in the management of patients with CRF. Oral alkalinization therapy is indicated when serum bicarbonate concentration decline to or below 17 mEq/1r. Oral sodium bicarbonate 8-12 mg/kg 8-12 hrs is commonly used Dehydration: Fresh clean unadulterated water should be available in adequate quantities at all times. The composition of fluids selected for chronic parentral administration should provide free water as well as electrolytes for maintenance (Lactated ringers solution supplemented with KCL).
108
Arterial hypertension : Blood pressure may be measured directly by cannulation of an artery or indirectly by doppler ultrasonography or oscillometry . Hypertension exists when mean arterial blood pressure exceeds 152mm of Hg in dogs and 139mm in cats.160/95 in dogs and 180/120 in cats warrant a diagnosis of hypertension. Therapy should be directed at counteracting the effect of extracellular fluid volume and vasoconstrictor effects of angiotension II and not epiephrine which is important in arterial hypertension associated with CRF. There are non pharmacologic and pharmacological therapies to reduce hypertension. Non Pharmacologic therapy:Dietary sodium restriction: Daily sodium intake should be reduced to 0.1 to 0.3 percent of the diet on a dry matter basis ( 10-40 mg/kg/day) without reduction of sodium intake administration of some anti hypertensive drugs such as beta adrenergic receptor antagonists and arteriolar vasodilators ; may lead to sodium retention extra cellular fluid volume expansion attenuation of anti hypertensive effects . Protein restriction : May limit or prevent renal hypertensive injury by reducing intraglomerullar capillary pressures. Commonly used drugs in the treatment of renal failure : Class Angiotensin converting enzyme inhibitor Appetite stimulant Calcium channel blocker Dopamine antagonist Gastric protectant Generic name Enalapril Oxazepam Amlodipin e Metaclopr opamide Sucralfate Dosage Indications
0.25mg/kg PO q Systemic 12-24 h (D) hypertension 0.2-0.4mg/kg PO,q12-24 h (D,C) 0.625-1.25mg PO q 24 h (C) 0.2-0.4mg/kg q 6-8h SQ,PO (D,C) 0.5-1.0g q 8-12 h PO (D) Appetite stimulant Systemic hypertension Antiemetic/gas trokinetic Uremic gastropathy/ph osphate binding agent
H2 receptor Cimetidine 5mg/kg q 8-12 h Uremic antagonists PO,IV (D,C) gastropathy Ranitidine 2-2.5g/kg q 2 h Uremic PO (D,C) gastropathy
108
Famotidin e Intestinal Aluminium phosphate hydroxide binders gel,Al.carb onate gel Calcium acetate Calcium carbonate Iron supplements Ferrous sulphate Potassium Potassium supplements gluconate, potassium citrate Proton pump Omeprazol inhibitor e Sertonergic Cisapride agonist Synthetic Misoprosto prostaglandin l Vitamin D Calcitrol
0.5mg/kg q 24h Uremic IV,PO (D,C) gastropathy 10-30mg/kg q Phosphate 8h ,PO (D,C) binding agents 20-30mg/kg q 8h ,PO (D,C) 30-50mg/kg q 8h ,PO (D,C) 100-300mg/d PO,(D) 2-6mEq/d PO,(C) Phosphate binding agents Phosphate binding agents
0.7mg/kg q 24h PO (D,C) 0.1-0.5mg/kg PO q 8-12h (D,C) 2-5g/kg q 8h PO(D) 2.5-3.5ng/kg q 24h PO *****
Ureic gastropathy Antiemetic/Gas troprokinetic Uremic gastropathy
AN UPDATE ON : DRUGS ACTING ON RESPIRATORY SYSTEM

SUNILCHANDRA.U
108
Anomalies of the respiratory system may result in a number of clinical signs such as: sneezing, reverse sneezing, coughing, gagging, nasal discharge, noisy breathing, increased , rate of breathing, increased or decreased depth of breathing, lethargy and exercise intolerance. The drugs acting on respiratory system discussed in this article , have been employed as supportive remedies along with other agents: suitable antimicrobials/ antiinflammatories as required. BRONCHODILATORS: A bronchodilator is a drug used to relieve bronchospasm/bronchial narrowing due to excessive bronchial secretion or bronchoconstriction associated with respiratory disorders, such as bronchial asthma, chronic bronchitis, mild tracheobronchitis, mild recurrent airway obstruction , bronchopneumonia and chronic pulmonary interstitial disease and emphysema. They are often used, with or without concurrent corticosteroid therapy, for the control of chronic bronchitis in dogs and asthma syndrome in cats. Hypoxaemia is a possible complication of bronchodilator therapy caused by ventilationperfusion mismatching; this may be an important consideration in severe pneumonia especially in young animals such as calves and foals. Adrenergic agonists (sympathomimetics): Adrenoceptor stimulants cause bronchodilation by stimulation of beta2-receptors in the large and small airways. Beta2- receptors are also found in vascular beds and the uterus . Nonselective beta receptor agonists such as isoprenaline(isoproterenol) or mixed alpha and beta receptor agonistssuch as adrenaline (epinephrine) are more likely to produce cardiovascular side effects than similarly administered selective beta -agonists. Consequently, drugs with preferential affinity for beta2receptors: such as clenbuterol, salbutamol, pirbuterol and fenoterol ,pirbuterol and terbutaline are direct-acting sympathomimetic drugs. are likely to provide more effective bronchodilation with fewer side effects.In addition to bronchodilation these drugs increase ciliary beating of the respiratory mucosal cells and have a mucolytic action, which may contribute to their therapeutic effect. The two principal beta2-agonists currently used in small animals: terbutaline sulfate and salbutamol (albuterol) sulfate. Terbutaline sulfate: produces relaxation of smooth muscle found principally in bronchial, vascular and uterine tissues.Terbutaline is available as a tablet, an elixir and an injectable preparation suitable for
108
subcutaneous or intramuscular use. The dose rate has 0.01 mg/kg SC, IM; 0.10.2 mg/kg/8 h for the dog and cat, PO. Salbutamol (albuterol) sulfate:. 0.02 mg/kg/12 h,PO. This dose should be maintained for 5 days and if there has been no improvement and no adverse effects, the dose may be increased to 0.5 mg/kg/812 h. In animals that respond at this higher dose, the dose should be reduced progressively until the lowest effective dose has been determined Both drugs to be used with care in increased sensitivity to adrenergic agents in particular, patients with pre-existing cardiac disease, diabetes mellitus, hyperthyroidism, hypertension and seizure disorders. Or with other sympathomimetics which increases the risk of adverse cardiovascular effects, as does its concurrent use with digoxin, tricyclic antidepressants and monoamine oxidase inhibitors All beta2-agonists may lower plasma potassium; patients receiving longterm therapy, it may be prudent to monitor plasma potassium levels. METHYL XANTHINES:They relax smoothmuscle, particularly bronchial smooth muscle, stimulate the central nervous system and are weakly positive chronotropes and inotropes(cardiac stimulanats), as well as mild diuretics. Eg: Theophylline, aminophylline , etamphylline, diprophylline They induce bronchodilation of the smaller airways, have little effect on larger airways. also increase tidal volume by stimulating the respiratory centre The bronchodilation is severely impaired by pathological changes in both the airway walls and pulmonary interstitium. This accounts for the wide variability of response seen with these drugs and individual animal treatment is often determined on a trial-and-error basis. They are also CNS and myocardial stimulants and diuretics. The therapeutic index is low and they are erratically absorbed from the gastro-intestinal tract At therapeutic doses they cause increased alertness and activity. Signs of toxicity include restlessness, tachycardia, tachypnoea, and convulsions. Inhibit calcium mobilization in smooth muscle, inhibit prostaglandin production, augment the release of catecholamines from storage granules, and increase the availability of calcium to contractile proteins of the heart and diaphragm. Decrease the release of inflammatory mediators from mast cells and increase mucociliary
108
transport. However, in small animal practice the methylxanthines have been used primarily as bronchodilators Fo Undergo enterohepatic recirculation, activated charcoal is recommended if toxicity clinical signs are present Their metabolism is inhibited by erythromycin, , propranolol, and fluoroquinolones; concomitant therapy can result in toxicity . Their use for the treatment of both cardiac and respiratory diseases in dogs and cats has been replaced by -agonist bronchodilators.The use of theophylline in cattle; suggested that it is a poor bronchodilator in this species Administered together with sympathomimetic drugs- additive CNS and cardiovascular effects may occur. Certain foods contain xanthine (eg, coffee, colas, or chocolate) and may increase the risk of cardiac and CNS adverse reactions. A chronopharmacokineticstudy in cats showed that evening administration is associated with better bioavailability and fewer fluctuations in plasma drug levels. Dosage: Aminophylline: By PO/IM or slow IV .Dogs, cats: 10 mg/kg bid/tid Etamiphylline camsylate: respiratory stimulation of neonates, myocardial stimulation. Dogs, cats: by PO, (310 kg body-weight) 100 mg; (11 20 kg body-weight) 200 mg; (2130 kg body-weight) 300 mg; (3140 kg body-weight) 400 mg. May be repeated up to 3 times daily if required. Reduce to lowest effective dose after 2 weeks; by SC,IM : (3 5 kg bodyweight) 70 mg; (610 kg body-weight) 140 mg; (1120 kg body-weight) 280 mg; (2130 kg body-weight) 420 mg; (3140 kg bodyweight) 700 mg. Dose may be repeated up to 3 times daily if required Propentofylline : Contra-indications. Pregnant,breeding animals;dogs-25 mg/5 kg body-weight twice daily,PO, on an empty stomach 30 minutes before feeding : Theophylline: Indications: Bronchitis; congestive heart failure; care with concurrent macrolides, fluoroquinolones, phenobarbital, phenytoin, ketamine, halothane; Dose. Dogs: by 20 mg/kg once daily,PO, given in the morning; Theophylline : Dogs: 10 mg/kg, IV (slow) or IM Horses: 15 mg/kg, IV (slow); 5-7 mg/kg, PO, TID Cats: 3 mg/kg, PO, BID Horses: 10-15 mg/kg, PO, BID; Aminophylline : Dogs: 10 mg/kg, IV (slow) Cats, horses: 5 mg/kg, IV (slow); Dogs: 10 mg/kg, PO, TID Cats: 5 mg/kg, PO, BID . Antimuscarinic bronchodilators: The antimuscarinic drug atropine may be used for bronchodilation in recurrent airway obstruction. However it causes significant side-effects including decreased
108
mucociliary clearance, tachycardia, mydriasis, ileus, and excitement that limit its routine use. Although atropine may be administered by aerosol, it is rapidly absorbed and has systemic effects. The antimuscarinic bronchodilator ipratropium has a quaternary ammonium structure, and does not inhibit mucociliary clearance. Dose. Horses: by inhalation, (75 micrograms/mL solution) 23 micrograms/kg up to 4 times daily ANTITUSSIVES The agents directly suppress the cough center in the medulla oblongata to reduce the incidence/ frequency of coughing. Coughing as a result of bronchoconstriction may be relieved by bronchodilators acting simply to dilate airways, while other antitussive agents act primarily on the peripheral or central nervous system components of the cough reflex. Coughing should normally be viewed as a protective physiological process resulting in clearance of thick and tenacious secretions produced by chronic airway inflammation. Thus, cough suppression as a single therapeutic agent is relatively contraindicated when cough is associated with mucus production. However, once mucus production is diminished or resolved, cough suppression may be desirable. Chronic coughing tends to increase airway inflammation, increasing the risk of a vicious cycle in which the cough causes mucosal irritation. This can result in further coughing. Consequently, cough suppression may be particularly helpful for patients, with tracheobronchial collapse or dogs recovering from acute phase ofkennel-cough complex. Cough suppressants are only beneficial where coughing is persistent and unproductive, interferes with the animals sleep and rest, or causes muscular fatigue and exhaustion. They should not be used where there are excess secretions in the tracheobronchial tree, as in chronic bronchitis or bronchopneumonia. In general, the use of antitussives is restricted to dogs. Drugs used to suppress coughing are categorized as i) Peripherally acting antitussives including mucosal anesthetics, mucolytics, demulcents, and bronchodilators. And ii) Centrally acting antitussives: Narcotic (opioid) such as morphine, codeine, hydrocodone, butorphanol and non-narcotic drugs: dextromethorphan.
108
Morphine though an effective antitussive at doses lower than the doses that produce analgesia and sedation is not commonly used for antitussive activity due to adverse effects. Dextromethorphan is the a semisynthetic nonopioid antitussive; safest antitussive for use in cats and is reported to be more efficacious in cats than codeine; It does not have addictive,analgesic or sedative action and in usual doses does not produce respiratory depression or inhibit ciliary activity. It is generally marketed in over-the-counter formulations (usually syrups or lozenges) combined with various antihistamines, bronchodilators and mucolytics. A dose of approximately 2 mg/kg PO has been suggested, although, as with most of the antitussive agents, higher doses are often required. It is used for relief of non-productive cough; it has a central action on the cough centre in the medulla. It is structually similar to opioids but has no analgesic and limited sedative properties. Codeine: Codeine phosphate and codeine sulfate are found in many preparations, including tablets, liquids, and syrups as well as being present in many mixed analgesic preparations. Codeine has analgesic effects that are about one-tenth that of morphine, but its antitussive potency is about equal to that of morphine. The side effects of codeine are significantly less than those seen with morphine at antitussive doses. Toxicity (especially in cats) is exhibited as excitement, muscular spasms, convulsions, respiratory depression, sedation, and constipation. Codeine should not be used after GI tract surgery. Dogs: 0.52.0 mg/kg twice daily, PO; The starting antitussive dose has been as low as 0.10.3 mg/kg/812 h and as high as 12 mg/kg/612 h. Generally well tolerated, although adverse effects are possible especially at higher dose rates. Sedation is the most common side effect in the dog. CNS stimulation may be seen in cats. Constipation is common if given more than few weeks. Hydrocodone-used with caution in cats, increased antitussive properties compared to codeine. eThe starting dose in dogs is 0.22 mg/kg/612 h PO. Butorphanol, an opioid agonist-antagonist, is used as an analgesic and antitussive in dogs. It is more potent than morphine as an analgesic and more potent than codeine or dextromethorphan as an antitussive , but with sedation. Because butorphanol has poor bioavailability, the oral dose in dogs is 10 times the SC dose. Its use in cats is controversial It is
108
most helpful as an antitussive given parenterally to treat acute intractable cough.Dogs: by mouth, 500 micrograms/kg 24 times daily for up to 14 days. MUCOLYTICS Mucolytics alter the structure of mucus ( a normal protective coating of the respiratory system from the nasal cavity through to the larger bronchioles, is produced by submucosal glands and goblet cells within the surface epithelium of airways and acts as a barrier to infectious and irritating particles) to decrease its viscosity and therefore facilitate its removal by ciliary action and expectoration. Expectorants increase the volume of secretions in the respiratory tract and therefore assist in removal by ciliary action and coughing They reduce mucus viscosity in the tracheobronchial tree and are often prescribed for chronic bronchitis in dogs, bronchopneumonia in cattle, and chronic coughing in horses. Therationale for their use is that mucus of lower viscosity is more easily carried up the tracheobronchial tree by themucociliary clearance mechanism and expectorated during coughing. theoretical value in facilitating resolution of the infl ammatory airway disease. It is also worth remembering that normal saline, directly administered to the airways by nebulization, is an effective mucolytic and expectorant. Bromhexine hydrochloride: is a synthetic derivative of the alkaloid vasicine.; decreases mucus viscosity by increasing lysosomal activity, which over time (23 d) results in a signifi cant increase in immunoglobulin concentrations and a decline in albumin and globulin oncentrations in respiratory secretions. The increased immunoglobulins are IgA and IgG; IgM levels remain unchanged. It has been hypothesized that because of these effects concurrent administration of bromhexine and an antimicrobial agent will facilitate treatment of infectious tracheobronchitis.Dose.: Horses: 200400 micrograms/kg once daily, PO; Cattle: 500 micrograms/kg once daily, PO.IM; Pigs: 200500 micrograms/kg once daily, PO.IM; Dogs: 2 mg/kg, PO,bid; Cats: 1 mg/kg, PO, sid. Ambroxol, a metabolite of bromhexine and Dembrexine has similar actions. Acetylcysteine: Aerosolization of acetylcysteine can cause reflex bronchoconstriction due to irritant receptor stimulation, so its use should be preceded by bronchodilator therapy. It is also used to
108
detoxify an intermediate paracetamol metabolite that is present in paracetamol overdosageFormulatis and dose rates For effective mucolytic activity, an acetylcysteine solution should be nebulized and administered directly to the respiratory mucosa as an aerosol. The dose rate in dogs and cats is 510 mg/kg for 30 min every 12hr. 10% and 20% solutions of the sodium salt in various sized vials, solution can be readily used in a nebulizer undiluted, although dilution with sterile saline will reduce the risk of reactive bronchospasm.an As it appears to irritate respiratory tract epithelium and many dogs and cats develop cough and/or bronchoconstriction If administered directly into the respiratory tract. Consequently,its use in animals with bronchoconstrictive airway disease must be carefully monitored. Solutions of acetylcysteine are incompatible with :ampicillin sodium, tetracycline and Oxytetracycline. EXPECTORANTS : drugs used to produce an increased volume of respiratory secretions that can theoretically be coughed out more easily. Expectorants and mucolytic drugs are used to increase the output of bronchial secretions, enhance the clearance of bronchial exudate, and promote a productive cough. Saline expectorants : stimulate bronchial mucous secretions via a vagally mediated reflex action on the gastric mucosa.Eg: ammonium chloride, ammonium carbonate, potassium iodide, calcium iodide, and ethylenediamine dihydroiodide. Iodinecontaining products should not be administered to pregnant, hyperthyroid, or milk-producing animals Direct stimulants of respiratory secretions include the volatile oils, such as eucalyptus oil and oil of lemon. Their efficacy in animals is unknown Guaiphenesin (Gllycerol guaiacolate): is a centrally acting muscle relaxant with expectorant,mucolytic , antitussive effect. It is a common component of human cold remedies in combination with dextromethorphan. Dose:
108
Expectorants containing small doses of ipecacuanha, squill, and ammoniumn salts are claimed to aid removal of mucus from the airways by a mild irritant effect on the mucous membrane; their efficacy is unproven. DRUGS FOR ALLERGIC AND INFLAMMATORY DISORDERS ANTIHISTAMINES: acting on respiratory system are H1-receptor antagonists- used to counteract the effects of histamine on body organs and structures . They provide symptomatic relief of allergic signs caused by histamine release, including pruritus and anaphylactic reactions. The release of histamine produces an inflammatory response. Histamine is also released in allergic reactions or hypersensitivity reactions, such as anaphylactic shock. H1RECEPTORANTAGONISTS:Firstgeneration(Sedative,withanticholiner giceffects:Eg:clemastine,dimenhydrinate,diphenhydramine,doxylamine, pheneramine,chlorpheneramine,pyrilamine,tripelennamine,cyproheptad ine,promethazine,alimemazine,hydroxyzine,bromopheniramine and the behavior-modifying tricyclic antidepressants: amitriptyline,clomipramine, doxepin) and Second generation (Nonsedative,with non anticholinergic, lesser antiprutitic action; Eg:oxatomide terfenadine, azatadine cetirizine, loratadine, astemizole) antihistamines. The Indications are : adjunct therapy for the management of systemic anaphylaxis ( allergens, insect stings, drug induced), with adrenaline and fluids. management of pruritus, given in conjunction with glucocorticoid, and when pruritus is controlled (generally within 5 days) the glucocorticoid is withdrawn synergistically with NSAID,glucocorticoids, -6/-3 (omega-6/3) fatty acid supplements and may allow dosages of these agents to be reduced in some cases Used in acute septic gangrenous mastitis, septic metritis, retained placenta, myoglobinuria, ruminal atony conditions in ruminants. Some ( eg: promethazine,meclizine,cyclizine, diphenhydramine) are used as antiemetic during travelling (motion sickenss) cyproheptadine, an antihistamine with serotonin-antagonist and calcium-channel blocking properties, used for prophylaxis in feline asthma and as the appetite stimulant in dogs and cats. Dose: Cats: asthma, 300500 micrograms/kg 3 times daily anxiety disorders in dogs and cats :inappropriate urination associated with anxiety, excessive nocturnal activity such as pacing,vocalization and pruritus associated with anxiety.Doxepin, topically has proved more useful than others for the treatment of anxiety-related pruritus. Adverse effects: CNS depression (lethargy, depression, drowsiness,somnolence); Anticholinergic effects (dry mouth, throat, noseand eyes; urinary retention or dysuria; intestinalatony) An increase
108
in pruritus occasionally with higher dosages of the drugs . OverdosageExcitement (restlessness, nervousness, tremors,hyperactivity),;Gastrointestinal effects (anorexia, vomiting, diarrhea,constipation); Cardiovascular effects (tachycardia, arrhythmia,hypertension). Contraindications and Precautions: Avoiding the concurrent administration of : monoamine oxidase inhibitors (e.g.selegiline,amitraz), or CNS depressans.; Astemizole or terfenadine with ketoconazole, itraconazole, fluconazole,clarithromycin; phenothiazine antihistamines, diphenhydramine with antidiarrheal mixtures (e.g.kaolin/pectin),antacids, adrenaline. Not recommended in animals with hepatic, cardiovascular disease, glaucoma, hyperthyroidism , history of seizures,urinary retention , intestinal atony. No detailed information on safety of administration during pregnancy except buclizine and cyclizine which are teratogenic. Treatment of toxicosis:Induction of Emesis, Activated charcoal, useful for recent ingestion. Diazepam to control seizures Physostigmine to counteract the CNS anticholinergic effect . Dose: Amitriptyline:12 q.12 h (dog); 510 q.1224 h (cat); Astemizole : 1mg/kg q.1224 h (dog); Azatadine- 1 mg/dog q.24 h (dog); Brompheniramine- 0.52, q.12 h (dog); Cetirizine- 0.51, q.24 h(dog);Chlorpheniramine-0.22 q.812 h (dog)24,q.1224h(cat); Clemastine-0.051.5 q.12 h(dog);0.68 q.12 h (cat);Clomipramine 13, q.24 h; Cyproheptadine- 0.12, q.812 h(dog) 2q.12 h (cat); Dimenhydrinate-8,q.8 h (dog);Diphenhydramine- 14q.8 h (dog)2 4,q.12h(cat); Horses, cattle: 60 mL as necessary; foals, calves: 10 20 mL 23 times daily; Dogs: 1520 mL every 23 hours.Doxepin-0.51 ,q.812 h(dog); Doxylamine-12, q.8 h(dog); Hydroxyzine 27 q.8 h (dog); 510 q.812 h; Ketotifen- 24 mg/dog q.12 h; Loratadine -0.5 q.24 h(dog); Oxatomide 0.52 q.12 h (dog) ,1530 q.12 h (cat); Promethazine 12.5 q.12 h(dog)5 q.24 h (cat); Pyrilamine 12 q.812 h(dog); Terfenadine 0.2510 q.1224 h (dog); Trimeprazine 0.55 q.8 12 h(dog); tripelennamine 1 q.12 h (dog). ANTILEUKOTRIENES: Leukotrienes belong to a family of inflammatory mediators that are derived from arachidonic acid, which is metabolized to various prostaglandins and thromboxanes through the action of cyclo-oxygenase as well as various leukotrienes (LTA4, LTB4, LTC4,LTE4)through the action of the lipoxygenase systems. LTs play an important role in airway inflammation,producing mucus hypersecretion, increased vascular permeability,mucosal edema, potent bronchoconstriction and act as chemoattractants to inflammatory cells, particularly eosinophils and neutrophils.
108
Zafirlukast, montelukast, zileuton: are competitive, highly selective and potent oral inhibitors of production or function of LTC4, LTD4 and LTE4. Absorbed orally, although the presence of food can reduce absorption by up to 60%..aFeline asthma has been treated with zafirlukast (12 mg/kg BID) and montelukast (0.51.0 mg/kg SID).s In cats, current advice is that they should be used to complement glucocorticoid or bronchodilator therapy, but should not be used singly. CORTICOSTEROIDS: counteract the symptoms of respiratory disease by: reducing airway inflammation due to histamine and prostaglandin release, prevent inflammatory mediator-induced bronchoconstriction.In emergency situations intravenous corticosteroids such as dexamethasone or betamethasone should be used, followed by oral prednisolone for long-term maintenance To reduce the risk of side effects, administered by mouth or nebulisation. Oral prednisolone on an alternate day regime. An initial dose of 1 to 2 mg/kg is administered every morning. After two weeks of therapy, response to treatment should be assessed and the dosage reduced until the minimum effective dose is reached. Cats in respiratory distress, Reversal of severe bronchoconstriction can be achieved with intravenous aminophylline (2 to 5 mg/kg), intravenous atropine (20 to 40 micrograms/kg), or epinephrine 20 micrograms/ kg by subcutaneous, intramuscular, or intravenous injection using epinephrine 100 micrograms/mL. The intravenous injection should be given with extreme caution. Fluticasone is the most potent of the commercially available aerosolised Inhaled corticosteroid preparations. It is highly lipophilic, and consequently has the longest pulmonary residence time. Flunisolide is the least potent of the synthetic, topically active corticosteroids. NSAIDs: The NSAIDs : flunixin meglumine, meloxicam and ketoprofen, may be used in the adjuvant treatment of acute bovine pulmonary emphysema and oedema with antimicrobials. RESPIRATORY STIMULANTS: The drugs used (analeptics) are central nervous system stimulants and the therapeutic dose is close to that which causes convulsions. Their use must therefore be carefully monitored. They are administered, at doses below the convulsive threshold, to stimulate respiration.
108
Their main uses: to promote respiration in apnoeic newborn, neonates, and preterm animals and to reverse respiratory depression associated with general anaesthetic, sedative, or hypnotic drugs. Doxapram is selective as a respiratory stimulant.. Dose: Foals, calves: 40100 mg , SC,IM,IV; Lambs: 510 mg SC,IM,IV; Puppies: 15 mg SC,IM,IV; Kittens: 12 mg SC,IM,IV; Post-anaesthetic use.Horses: 0.5 1.0 mg/kg, IV; Dogs, cats: 12 mg/kgIV, following inhalational anaesthetic; 25 mg/kg IV, following intravenous anaesthetic Methylxanthines such as aminophylline, diprophylline,etamiphylline, increase respiratory drive and are non-specific CNS stimulants.Etamiphylline camsylate: . Calves: 700 mg PO, q 34 hrs if required; Lambs: (<2.5 kg body-weight) 140 mg; (>2.5 kg bodyweight) up to 280 mg. Dose may be repeated after 34 hours if required ****
AN UPDATE ON : DRUGS ACTING ON GENITOURINARY SYSTEM

SUNILCHANDRA.U
The drugs acting on uterus and cervix includes: Myometrial stimulants, relaxants and the cervical dilators which are mainly used in obstetrical cases. Myometrial Stimulants (ECBOLICS): stimulate contraction of the oestrogen-sensitised uterine myometrium and mammary myoepithelial cells. Indications: 1. In dystocia due to secondary uterine inertia. However, should not be used when dystocia is due to malpresentation or obstruction. 2. Control of postpartum hemorrhage in all species in the control of postpartum haemorrhage, to hasten uterine involution immediately after parturition in all species, to aid clearance of uterine discharge in mares, and to remove retained fetal membranes in mares, sows, bitches, and queens; they have no effect on separation of the placenta in ruminant species 3. To reduce the size of a uterine prolapse after replacement in cattle and occasionally mares. 4. agalactia due to failure of milk let down . Oxytocin: mediates contractility of the endometrium which has been prestimulated with estradiol. It stimulates contractility of the myoepithelial cells that surround mammary alveoli. Oxytocin facilitates
108
some milk let-down without having galactopoietic ability. It is mildly antidiuretic. Inappropriate use of oxytocin can lead to uterine rupture, anaphylactoid and other allergic reactions, and possibly maternal death. Prolonged stimulation of uterine contractions can result in the following fetal adverse reactions: persistent uteroplacental insufficiency, sinus bradycardia, premature ventricular contractions, other arrhythmias, and fetal death. Given by intravenous infusion (e.g., labor induction), intramuscular injection (e.g., control of postpartum bleeding), To promote contraction of uterine smooth muscle to assist vaginal birth, to induce uterine evacuation in metritis and to assist uterine contraction following reduction of uterine prolapse. To promote milk let-down in bitches with adequate milk production. Doses recommended have ranged from 0.254 IU or 15 IU per bitch to 520 IU per bitch, repeated up to three times. In the queen, 2 IU maximum per queen and per injection IM or by IV infusion. It is important to use calcium gluconate 10% solution (1 mL/5.5 kg SC q.46 h) minimum 15 min before oxytocin even in eucalcemic bitches. If one treatment of oxytocin for dystocia is unsuccessful, repeated use must be questioned, given the likelihood of inducing tetanic uterine contraction and fetal death Contraindications and precautions: Obstructive dystocia.; Any contraindication for vaginal delivery (e.g.relative or absolute oversize); Maternal toxemia.; Underlying causes of dystocia (e.g. hypocalcemia) should be treated before use of oxytocin. Adverse effects Use in obstructive dystocia can cause uterine rupture.; Overdose, either single large doses or multiple doses, will cause spastic, hypertonic or tetanic uterine muscle contraction with lack of orchestration of contractions. This may induce placental separation or damage without delivery, fetal distress or death and uterine rupture. Incompatible with fibrinolysin, noradrenaline (norepinephrine) bitartrate, prochlorperazine edisylate and warfarin sodium. If used with sympathomimetic agents, can result in postpartum hypertension.
108
Dose: Cattle: uterine inertia, agalactia due to failure of let down, to promote uterine involution: 1040 units SC.IM;, 2.510.0 units of diluted solution slow IV; Mastitis: initial dose 80 units, SC.IM before stripping out and initial intramammary treatment, then 20 units, SC,IM before each stripping out and concurrent intramammary treatment Uterine prolapse:, 2.510 units,IM. Sheep, goats, pigs, dogs: uterine inertia, agalactia due to failure of let down, to promote uterine involution: 2 10 units, SC,IM; 0.52.5 units of diluted solution slow IV; Cats: uterine inertia, agalactia due to failure of let down to promote uterine involution, 25 units SC,IM; , 0.51.25 units, slow IV. Prostaglandin F2alpha and derivatives: Alfaprostol, cloprostenol, dinoprost, etiproston, luprostiol and tiaprost are synthetic prostaglandin F2 alpha analogues . The prostaglandins used as ecbolics: in obstetrics are dinoprostone (PGE2), carboprost (15methyl PGF2) cloprostenol, and gemeprost or misoprostol (PGE1 analogues). In veterinary practice, they are used to control cyclical ovarian activity in polyoestrous species, for termination of pregnancy, or for induction of parturition. In addition, prostaglandins are used to treat a number of pathological conditions including mummified fetus, pyometra, and luteal cysts in cattle, and pseudopregnancy in goats, Abortion induction in the bitch and queen.; Treatment of pyometra in the bitch and queen. Reduction of the duration of interestrus intervals. Adverse effects: abdominal pain, emesis, defecation, urination, pupillary dilation followed by constriction, tachycardia, restlessness and anxiety, fever, hypersalivation, restlessness and panting. On occasion some prostaglandins may produce severe reactions at the site of intramuscular injections, severe cellulitis, and systemic reactions sometimes leading to death Prior atropine ( or Butylscopolamine) administration may attenuate adverse effects. Concurrent administration of atropine, 1520 minutes prior to prostaglandins administration has been proposed, to reduce side effects. Contraindications and precautions: during pregnancy or in animals with hepatic, renal or systemic disease.Not to be administered intravenously.Pregnant women or people with bronchial disease,including asthma, should not handle or administer these drugs. Indications: Abortion in the bitch: Natural or synthetic PGF2s rarely capable of inducing luteolysis in early pregnancy (before day 1520).
108
However, high doses (150250 g/kg q.12 h for 45 d) may be successfully used around day 1525 of pregnancy. Lower doses (20 g/kg q.8 h) around 2021 d after ovulation induced abortion in 5/5 bitches However, side effects (emesis, salivation, defecation, respiratory distress) are often induced when using a high dose from the start of the treatment period. To avoid this a suggested protocol is repeated injections q.812 h, for 7 d or longer, initially using low doses (25 g/kg) for 1 or 2 d, increasing to doses of 50 g/ kg and then increasing again to doses of 100 g/kg after 4 d if higher doses are well tolerated by the bitch. Prostaglandins of the F2 type can be absorbed through the skin and may cause bronchospasm or miscarriage. Care to be taken when handling the product to avoid self-injection or skin contact. Women of child-bearing age, asthmatics, and persons with bronchial or other respiratory problems should avoid contact with, or wear disposable gloves when administering, the product. Accidental spillage on the skin should be washed off immediately with soap and water. Cloprostenol has been proved to be an efficient abortive agent: 2.5 g/kg 3 injections at 48-h intervals after d25 of pregnancy. Abortion in the queen: Dinoprost 0.51.0 mg/kg SC once and repeated in 48 h will result in abortion (after d40) within 824 h. Natural prostaglandins are better tolerated by queens than by dogs. Doses of up to 0.5 mg/kg q.812 h for 5 d may be used Treatment of pyometra in the bitch: Dinoprost (0.010.1 mg/kg q.812 h SC) until both uterine evacuation has occurred and serum progesterone is basal. The dose of dinoprost may be reduced by including cabergoline (5 g/kg/d PO) in the regimen.Concurrent use of progestins may reduce the effi cacy of prostaglandins. Concurrent use of other ecbolic agents may have additional myotonic effects. Dinoprostone, synthetic preparation of PGE2, is administered vaginally for oxytocic use. stimulates the contraction of the uterus throughout pregnancy. directly affects the collagenase of the cervix, resulting in softening. For the induction of labor, dinoprostone is available either as a gel (0.5 mg PGE2) For softening of the cervix at term, the preparations used are either a single vaginal insert containing 10 mg PGE2 or a vaginal gel containing 0.5 mg PGE2
108
administered every 6 hours. The softening of the cervix for induction of labor substantially shortens the time to onset of labor ERGOT ALAKALOIDS: These compounds stimulate uterine smooth muscle directly, thereby increasing muscular tone and enhancing the rate and force of rhythmical contractions. Examples: Ergometrine (ergonovine) maleate and Methylergometrine (methyl ergonovine) maleate. Both are commonly used for the routine expulsion of the placenta after delivery and in postpartum and postabortal atony and hemorrhage. Ergonovine also stimulates cervical contractions. These drugs are capable of inducing a sustained tetanic contraction, which can shorten the final stage of labor and aid in the reduction of postpartum blood loss should not be used with sympathomimetics, ergotamine or dopaminergic drugs. No adverse effect has been observed with the concomitant use of oxytocin. It should not be given during pregnancy. Oral methylergometrine maleate (0.5 mL PO, q.8 h) has been proposed as an adjuvant therapy in cases of uterine hemorrhage after parturition. May induce arterial vasoconstriction.,transient severe hypertension. Excreted in milk, and, should not be administered longer than necessary,since prolonged use can lead to ergot poisoning (ergotism), including gangrene, in the young one. These alkaloids should not be used in cases of threatened spontaneous abortion . Dopamine agonists : Cabergoline, Bromocriptine; Antiserotoninergic compounds: Metergoline.directly inhibits prolactin by its action of D2 pituitary receptors. Clinical applications Galactostasis: dopamine agonists will prevent prolactin secretion and indirectly impede milk production. Overt pseudocyesis or pseudopregnancy: bitches exhibiting these signs have high peripheral prolactin concentrations, which can be treated with dopamine agonists. Cabergoline: 5 g/kg/d PO for 510 d; Bromocriptine: 50100 g/kg PO for 1014 d. To reduce sideeffects, the dose can be given q.812 h. . The emetic effect can be attenuated by gradually increasing the dose Pregnancy termination: during pregnancy, after day 3040 postLH surge, may induce abortion. Oral cabergoline or bromocriptine
108
may be combined with cloprostenol (a synthetic prostaglandin analog) in the bitch and queen. Cabergoline (5 g/kg/day PO for 10 d) plus cloprostenol (1 g/kg/48 h SC for fi ve injections) from day 28 post-LH surge will induce abortion in bitches Bromocriptine at doses of 50100 g/kg PO twice a day for at least 5 ,up to 10 d is not consistently effective in inducing abortion beforeday 40; but not before 30d Estrus induction in bitches:Cabergoline-induced cycles have follicular development and ovulatory rates similar to those observed at natural cycles. Fertile estrus is more reliably obtained if the bitch is treated during late anestrus. Bromocriptine (250 g/kg/d until proestrus occurred);Cabergoline 5 g/kg/d induces estrus within 30 d, with 7585% whelping rate. Treatment of pyometra in bitches: Combination treatment with oral cabergoline (5 g/kg daily) and cloprostenol (5 g/kg every third day) has been used to treat pyometra medically (in addition to appropriate antibacterial therapy) in bitches. Resolution was achieved in 21 of 22 treated bitches within 13 d. 11/21 bitches were mated at the next estrus and conceived. Treatment of pyometra in queens:Cabergoline (5g/kg PO daily) and cloprostenol (1 g/kg SC daily) until complete uterine emptying (in addition to appropriate antibacterial therapy) has been recommended Pretreatment of mammary tumors: Treatment with cabergoline 57 d before surgery will facilitate the surgical procedure because there is reduced risk of a postsurgical reaction as milk does not contaminate the surgical site Adverse effects: mild emesis and nausea. prolonged treatments reversible coat color changes may occur due to tonic suppression of pituitary secretion of melanocytestimulating hormone ( Contraindications and precautions: pregnancy liver disease and hypertension.Phenothiazines, reserpine and butyrophenones (e.g. haloperidol) increase prolactin concentrations MYOMETRIAL RELAXANTS( Tocolytics): are the drugs that inhibit uterine contraction or result in relaxation of uterus are used to aid obstetrical manoeuvres during dystocia and to facilitate handling of the uterus during caesarean operation. They can be used to delay parturition so that it may occur when greater observation and care are available. In addition, when
108
used in heifers, calving can be delayed sufficiently to allow better relaxation of the birth canal and perineum. Also used in the treatment of incomplete cervical dilation (ringwomb) in sheep, although their effect is questionable Must be used with extreme care, since pulmonary edema, myocardial infarction, respiratory arrest, cardiac arrest, and death can occur during tocolytic therapy. Newborns of mothers given tocolytics have had respiratory depression, intraventricular hemorrhage, and necrotizing enterocolitis. Absolute contraindications to tocolysis include: acute fetal distress (except during intrauterine resuscitation), chorioamnionitis, eclampsia or severe preeclampsia, fetal demise (of a singleton pregnancy), fetal maturity, and maternal hemodynamic instability, Concurrent administration of atropine, adrenoceptor stimulants, vasodilators, or general anaesthetics, oxytocin, prostaglandins; hypersensitivity to the product Transient vasodilation, tachycardia and muscle tremors with high dosage Selective 2-adrenoceptor agonists, such as clenbuterol( Cattle: 300 micrograms as a single dose, IM,IV) terbutaline, isoxsuprine, ritodrine or salbutamol, cause direct relaxation of vascular and uterine smooth muscle; inhibiting spontaneous or oxytocin-induced contractions of the pregnant uterus Magnesium sulfate prevents convulsions in preeclampsia and directly uncouples excitationcontraction in myometrial cells. Magnesium toxicity can be life threatening..Respiratory depression can occur with respiratory paralysis. Higher levels cause cardiac arrest. Toxicityavoided by noting urine output and checking patellar reflexes in patients receiving magnesium. Indomethacin given orally or rectally for 24 or 48 hours to delay premature labor. Indomethacin use also can decrease amniotic fluid volume and cause oligohydramnios through its ability to decrease fetal urinary output. Long-term use of maternal indomethacin is associated with primary pulmonary hypertension and an increased incidence of intraventricular hemorrhage in the newborn.
108
Nifedipine, calcium channel blocking agent, is one of the more recent drugs examined as a tocolytic agent. It acts by impairing the entry of Ca _ into myometrial cells via voltagedependent channels and thereby inhibits contractility. Hydroxyprogesterone has been used prophylactically for the 12th to 37th week of pregnancy, particularly in the high-risk category for premature delivery (e.g., those with a history of premature delivery or spontaneous abortion).Hydroxyprogesterone as a tocolytic agent requires further evaluation before its routine prophylactic administration DIURECTICS Diuretics increase urine flow by increasing renal plasma flow or by altering nephron function ar indicated to reduce oedema in cases of heart failure, hepatic disease, cerebral oedema, hypoproteinaemia, inflammation, and trauma. Diuretics are usually classified according to their site of action. In general, agents that act on the loop of Henle are the most potent. Majorly three classes of diuretics are used clinically: Loop diuretics: furosemide, bumetanide, ethacrynic acid Thiazide diuretics: hydrochlorothiazide, chlorothiazide Potassium-sparing diuretics: spironolactone, triamterene,amiloride Thiazides: Thiazides reduce urinary calcium excretion.; are used to treat cardiac or hypoproteinaemic oedema and may also be used as an adjunct to hormonal therapy in pseudopregnancy. Thiazides are primarily used in canines that have developed furosemide resistance. Dogs in heart failure are considered resistant to furosemide therapy when chronic oral furosemide at 45 mg/kg q.8 h fails to relieve clinical signs of congestion. In these cases the addition of a thiazide diuretic results in a synergistic drugdrug interaction as a result of sequential nephron blockade. Dietary sodium restriction can potentiate their benefi cial effects in this setting. In addition to their effects on sodium and chloride, the thiazides also increase potassium excretion Chlorothiazide: Dose. Dogs, cats: 10-20 mg/kg daily; PODruginteraction.Acetazolamide, antidiabetic drugs, beta-blockers, corticosteroids, lignocaine, quinidine
108
Hydrochlorothiazide: Indications. Oedema; inhibition of lactation in pseudopregnancy in the bitch; diabetes insipidus Dose. Dogs, cats: 1-2 mg/kg daily,PO Loop diuretics: Loop diuretics are the most potent group of diuretics, with a rapid onset of effect but a short duration of action. These drugs block sodium reabsorption in the loop of HenleThey increase magnesium excretion and, as with thiazides, may cause severe potassium loss. May potentiate the ototoxic effects of aminoglycoside antibiotics. Frusemide (Furosemide): is used to decrease oedema in conditions such as cardiovascular and pulmonary oedema, hepatic and renal dysfunction, hydrothorax, ascites, and non-specific oedema. inhibiting sodium, potassium and chloride reabsorption in the loop of Henle, also decreases reabsorption of sodium and chloride in the distal renal tubule. results in enhanced excretion of sodium, chloride, potassium, hydrogen, calcium,magnesium and possibly phosphate. Enhanced hydrogen ion excretion without a concomitant increase in bicarbonate excretion can result in metabolic alkalosis in dog acts as a bronchodilator in humans, horses and guinea-pigs. Its bronchodilatory effects in dogs and cats are unknown. Cats (Dose-12 mg/kg q.1224 h PO) are more sensitive to furosemide than dogs. Used chronically for the treatment of pulmonary edema. The potential for ototoxicity: can potentiate the ototoxic and nephrotoxic effects of other drugs such as the aminoglycosides. Injection can be mixed with weakly alkaline and neutral solutions having a pH of 710, such as 0.9% saline or Ringers solution. A precipitate may form if the injection is mixed with strongly acidic solutions such as those containing ascorbic acid, tetracycline, adrenaline (epinephrine) or noradrenaline (norepinephrine). Injection should also not be mixed with most salts of organic bases, including lidocaine, alkaloids, antihistamines and morphine. Contraindications.: renal failure with anuria, acute glomerular nephritis, concurrent dosing with aminoglycosides antibiotics. Dose.Horses:0.5-1.0 mg/kg1-2 times daily,IM,IV; cattle: 2-5 mg/kg, PO: 0.5-1 mg/kg,IM,IV; Pigs: 5 mg/kg,IM,IV; Dogs, cats: 5 mg/kg,PO,
108
1-2 times daily, may be reduced to 1.2 mg/kgtwice daily for maintenance;2.5- 5 mg/kg,IM,IV, bid Drug interactions. Acetazolamide, aminoglycoside, antidiabetic drugs, beta-blockers, captopril, cardiacglycosides, cephalothin and other cephalosporins, corticosteroids, lignocaine, quinidine, Osmotic Diuretics: include hypertonic solutions of mannitol, urea, glycerol Administration of mannitol causes water retention with in the nephron,which dilutes urinary sodium and opposes its reabsorption in the proximal tubule used to promote urine output, as in acute renal failure, or to reduce cellular oedema in cerebral oedema. Not suitable for the mobilization of general or local oedema because it may lead to cardiac overload. Excessive administration of mannitol can produce severe hypovolaemia and maintenance of extarcellular fulid volume may require administration of an electrolyte solution such as compound of sodium lactate intravenous infusion. Mannitol:Indications.:Cerebral oedema, forced osmotic dieresis.Extravasation causes inflammation and thrombophlebitis. Dose. Dogs: 250-500 mg/kg,IV. Potassium sparing diuretics E X A M P L E S Act by inhibiting the action of aldosterone on distal tubular cells or blocking sodium reabsorption in the latter regions of the distal tubule and collecting tubules. Weak diuretics when used alone as diuretics and thus should never be used as sole agents In a patient, refractory to other diuretics. When potassium-sparing diuretics are administered with other diuretics, potassium loss is decreased, representing an additional benefit. Spironolactone: used in combination with other diuretics, primarily furosemide, to produce additional diuresis (generally a mild increase) or to decrease potassium excretion. used in the management of fluid retention associated with noncardiac disease such as hepatic disease and nephrotic syndrome. Diuretics Interactions: ACE inhibitors, potassium supplements increased risk of hyperkalaemia with potassium sparing diuretics Acetazolamide increased risk of hypokalaemia with loop and thiazide diuretics Aspirin antagonism of diuretic effect of spironolactone
108
Beta-adrenoceptor blocking drugs increased risk of ventricular arrhythmias in the presence of hypokalaemia Calcium salts increased risk of hypercalcaemia with thiazide diuretics Cardiac glycosides increased toxicity if hypokalaemia occurs; enhanced effect of digoxin with furosemide or spironolactone Cephalosporins increased risk of nephrotoxicity with loop diuretics Corticosteroids, corticotropin antagonism of diuretic effect; increased risk of hypokalaemia with loop and thiazide diuretics Insulins possible increase in insulin requirement with thiazide diuretics Lidocaine lidocaine effect antagonised by hypokalaemia with loop and thiazide diuretics Mannitol decreased effect of loop diuretics NSAIDs antagonism of diuretic effect; increased risk of hyperkalaemia with potassiumsparing diuretics Oestrogens antagonism of diuretic effect Sulphonamides increased risk of sulphonamide allergy with loop diuretics Adverse effects Primarily electrolyte disturbances, dehydration and prerenal and renal azotemia. The relative risks of azotemia are heightened when they are used concurrently with ACE inhibitors and/or NSAIDs and other potential renal toxins. Cats appear to be more susceptible than dogs to becoming electrolyte depleted and dehydrated with diuretic therapy. Hypokalemia , hypomagnesema, Hyponatremia may occur in patients on high dose diuretic therapy. URINARY ACIDIFIERS Ascorbic acid (Horses: 2 g/kg daily,PO; Dogs: 100500 mg 3 times daily,PO; Cats: 100 mg 3 times daily), ammonium chloride (Dogs: 100 mg/kg 12 times daily,PO; Cats: 400 mg/4.5 kg body-weight twice daily with food. Adjust dose until desired urinary pH change achieved) ; , ammonium sulfate (Horses: 175 mg/kg daily,PO); ethylenediamine, arginine HCl, Calcium chloride , methionine and sodium acid phosphate may be used to acidify the urine. Acidifiers are used in the dissolution and prevention of struvite calculi . Ascorbic acid is inconsistent in lowering urinary pH and is usually unpalatable at the recommended dosages. Ammonium sulfate is more palatable than ammonium chloride and has proved effective at the recommended dose. It should not be given to patients with impaired renal or hepatic function. URINARY ALKALINISERS:
108
Alkalinisation is important in preventing certain drugs, such as some sulfonamides, from crystallising out in the urine; it also decreases the formation of uric acid and cystine stones Sodium bicarbonate, sodium citrate, and potassium citrate are used for urine alkalinisation. Alkalinisers are also used to manage some forms of urolithiasis This may have some antibacterial effects, as well as decreasing irritation or inflammation in the urinary tract. They also increase the excretion of drugs that are weak acids (e.g. salicylates and some barbiturates) by alkalinising the urine and reduces irritation of an inflamed urinary tract, discourages the growth of certain organisms, e.g.Escherichia coli Potassium citrate: Indications. Urine alkalinisation, for treatment of urinary tract infections; management of calcium oxalate, cystine, and urate urolithiasis. Dose: . Dogs, cats: 75 mg/kg , PO, twice daily or 2mmol/kg twice daily Sodium bicarbonate: Dose. Dogs, cats: 1050 mg/kg 23 times daily,PO; Adjust dose until desired urinary pH change achieved DRUGS FOR URINARY RETENTION AND INCONTINENCE Urinary incontinence may be caused by hypercontractility or decreased accommodation of the urinary bladder, flaccidity of the urethral sphincter, or urethral incompetence. Bladder wall irritability leading to frequent micturition, which may be confused with incontinence, may be caused by cystitis . Propantheline reduces urinary urgency and frequency by diminishing unstable muscle contractions but has a negligible effect on urethral sphincter pressure. Drugs used for treatment include oral estriol (Dogs: initial dose, 1 mg daily. If response, reduce to 0.5 mgdaily or on alternate days. If no response to initial treatment,2 mg once daily (maximum 2 mg/animal daily), short acting natural oestrogen, and oral diethylstilbestrol at doses of up to 1.0 mg/ day,3-5days, followed by weekly treatment. Phenylpropanolamine: an alpha adrenergic compound commonly used to treat urinary incontinence in spayed bitches, effective in cases of retrograde ejaculation in infertile male dogs. (Dogs: 1 mg/kg 3 times daily given with food; Cats: 1.01.5 mg/kg twice daily).The onset of action may take several days. Adverse effects may include restlessness, aggressiveness, irritability and hypertension.The dose of phenylpropanolamine should be reduced if used concurrently with oestrogen therapy. Surgery may be necessary if medical treatment alone proves unsuccessful.
108
Excessive urinary retention that may lead to incontinence is caused by detrusor muscle paralysis or excessive urethral sphincter contraction. Parasympathomimetics, such as bethanechol (Dose: .Horses: 50100 micrograms/kg 23 times dailyPO; Dogs: 525 mg 3 times daily ,PO: Cats: 1.255.0 mg 3 times daily), reproduce the effects of parasympathetic nerve stimulation; they possess the muscarinic rather than the nicotinic effects of acetylcholine and improve voiding by increasing the tone and contractions of the detrusor muscle. Treatment should be initiated at the lowest dose and increased after 48 hours if no improvement. Phenoxybenzamine (Dose.Dogs: 0.250.5 mg/kg 23 times daily,PO; Cats: 0.5 mg/kg twice daily.,PO) and prazosin (Dogs: (< 15 kg bodyweight) 1 mg/dog 23 times daily;(> 15 kg body-weight) 2 mg/dog 23 times dailyCats: 0.251.0 mg/cat 23 times daily) act by blocking alphaadrenoreceptors of the smooth muscle of the bladder neck and proximal urethra allowing relaxation of the urethral sphincter. Oral diazepam may assist by causing centrally mediated relaxation of the urethral skeletal muscle and reduction of urethral resistance; the recommended dose for dogs is 200 micrograms/kg (0.2 mg/kg) 3 times daily and for cats is 1.25 to 5 mg/cat 3 times daily, although the duration of action is short lived. An alternative drug is dantrolene sodium ( Dogs, cats: 2 mg/kg,PO, twice daily), which acts peripherally and is used for dogs and cats. Many of the above drugs take some time to have a clinically observable effect and treatment should be continued for up to 3 to 4 weeks before deciding that the condition is unresponsive to a particular drug. DRUGS FOR UROLITHIASIS Urate uroliths are more soluble in alkaline urine. Dietary control to reduce protein intake and urine alkalinisers are used as preventive treatment. Allopurinol (Dogs: urate calculi, 10 mg/kg,PO, 3 times daily for 4 weeks then 10 mg/kg once daily) reduces the formation of uric acid from purines by inhibiting xanthine oxidase. Penicillamine (Dose. Dogs: cystine calculi, 15 mg/kg,PO, twice daily preferably on an empty stomach. form a more soluble sulfide compound that is more readily excreted. It is used as an adjunct to dietary management and urinary alkalinisation in the management of cystinuria. Best given on an empty stomach because food interferes with its absorption. Thiazide diuretics may be used to reduce the recurrence of calcium-containing uroliths (for example, calcium oxalate
108
calculi) in dogs.Dietary management and potassium citrate have also been used in the control of calcium oxalate urolithiasis.
*****
A NOTE ON EXPLORING THERAPEUTIC UTiLITY OF LIVESTOCK WASTES

JAGANNATHA RAO.B
Nearly all basic necessities of life were woven around the cow, with contributions in all aspects of life, including farming and manure, food and nourishment, transport, fuel burning of dried cow dung cakes and medicinal usage of cow dung and cow urine. The advantage of application of livestock waste as organic manure to soils is the oldest and widely accepted practice, which seldom requires any information or education for end users. Livestock manure application increases the nitrate, ammonium, extractable phosphorus, extractable potassium and sulphate sulphur contents of the soil up to 1 feet depth. Soil texture, fertility and crop yields are improved-more prominently when applied consecutively for 3 years . It acts like broth for multiplication of soil microorganisms. Cow and buffalo dung is a good alternative feed resources for fish ponds. It is prepared by mixing the cow dung (on fresh basis) with 1.5% super phosphate thoroughly and kept under shade or covered with coconut leaves to prevent evaporation of moisture in the dung. Increasing scarcity of firewood has forced many villagers to burn dungcakes in cooking their food. Eco-Fae-Brick produces high quality and low price bricks by utilizing the abundant cow dung in Jogjakarta, India.
108
Cow dung is used to line the wall of rustic houses as it proves to be a superior and cheap insulator as well as line the wall of rustic houses as it proves to be a superior and cheap insulator. Medicinal value of cow dung and urine is traditionally popular for centuries. Cow dung has an excellent mosquito repellent property and is used to produce repellents. Only zebu cattle urine is used in all the medicinal preparations through ages. Cow urine acts as activity enhancer and availability facilitator for bioactive molecules including anti-infective and anti-cancer agents. Apart from its use for biogas, fuel, energy, the most interesting although traditionally used is utilizing these for the preparation of much spoken Panchagavya and its beneficial effect on all creatures around us. PANCHAGAVYA: Ancient wisdom is a treasure house of knowledge systems to safeguard the health and well- being of humankind, animals and plants. Vrikshayurveda is one such knowledge system, advocating agriculture with the use of natural inputs. It promotes a system which synchronizes all agricultural operations with natural forces emanating out of the Panchabhootas, viz. Earth, Water, Air, Fire and Space. When human beings, animals and plants were in perfect harmony, everything was wholesome and no remedial, correctional and improvement measures were required, as there is no ailment. Consequent to the domination and exploitation of flora and fauna by humans, and deviation from a natural life-style, problems cropped up due to forced imbalances in natural elements, and well-being. Agriculture was no exception. Thus, Health Care for soil, plant, microand macro-organisms as well as humans has deteriorated over time; chemical agriculture has worsened the scenario and health hazards have increased exponentially. Panchagavya for Farmers: This ignited a chain of experiments conducted over three years, to standardize the present form of Panchagavya, the single organic input which can act as a growthpromoter and immunity booster. The product has revolutionized and revitalized organic agriculture and its poised to sweep the whole world in days to come. Improving the Panchagavya recipe has been done with addition of other ingradients, in order to accelerate fermentation process ( sugar, jaggery, bananas, tender coconut watetr etc); eliminating bad odour (toddy); Method of preparation : . By using the quantity of ingredients
108
specified in the following table, one can obtain approximately 20 litres of Panchagavya. INGREDIENTS : Fresh cow dung : 5 Kg + Cows urine: 3 Litres + Cows Milk :2 Litres + Cows Curd: 2 Litres+ Cows ghee: 1/2 Kg+ Sugarcane juice: 3 Litres + Tender Coconut water: 3 Litres + Banana (ripe) : 12 No+ grape juice : 2 Litres Metal containers should not be used for preparing Panchagavya; but wide mouthed mud pot, concrete tank or plastic cans are used. First put the fresh cow dung and cows ghee into the container and mix it thoroughly twice daily for 3 days. On the fourth day add the rest of the ingredients and stir it twice daily for 15 days. The Panchagavya stock solution will be ready after the 18th day,which should be kept in the shade and covered with a wire mesh or plastic mosquito net to prevent houseflies from laying eggs and the formation of maggots (worms) in the solution. If sugarcane juice is not available, add 500 grams of jaggery dissolved in 3 litres of water. Add 100 grams of yeast powder and 100 grams of jaggery to 2 litres of warm water. After 30 minutes, add this solution to replace toddy in Panchagavya. Another method is, you take 2 litres of tender coconut water and keep it in a closed plastic container for 10 days. After fermentation it becomes toddy. This solution can be prepared before hand and used to replace toddy. When stirred twice daily, the Panchagavya solution can be kept for 6 months without any deterioration in its quality. Whenever the solution becomes thick due to evaporation of water over a long period, suitable quantity of water can be added to keep it in a liquid state. Physico-Chemical and biological Properties of Panchagavya:Panchagavya contains macro nutrients like N.P.K. 13 essential micro nutrients necessary for the plants, many vitamins, essential amino acids, growth promoting factors like IAA, G.A and beneficial microorganisms like azatobacter, phospho bacteria and pseudomonas in abundant numbers. It also contains some useful fungi and actinomycetes. The beneficial micro organisms present in the Panchagavya Micro organisms per gram of Panchagavya.
Nitrogen fixing AZOSPIRILLUM Nitrogen fixing AZATOFACTOR Phosphorus solublysing PHOSPO BACTERIA Immunity enhancing PSEUDOMONAS 10 X10 10x9 10 x7 10x6
Panchagavya contains all the essential macro and micro nutrients ( calcium, sodium, phosphorous, magnesium. Manganese, iron, zinc, copper, sulphur) required for the plants
108
Panchagavya for Animal Health: After successful studies on plants using Panchagavya, trials were started on animals and humans. So far, the results are highly encouraging and very successful. Many formers have started using Panchagavya and they gratefully inform other farmers of its effectiveness. Mode of Action :Basically, Panchagavya is a living elixir of many microorganisms, bacteria, fungi, proteins, carbohydrates, fats, amino acids, vitamins, enzymes, known and unknown growth promoting factors, micronutrients, trace elements, antioxidants and immunity enhancing factors.When taken orally by animals and human beings, the living microorganisms in the Panchagavya stimulate the immune system and produce a lot of antibodies against the ingested microorganisms. It acts like a vaccine. This response of the body increases the immunity of animals and humans and thus helps prevent illness and cure diseases.It slows down the aging process and restores youthfulness. The other factors present in Panchagavya improve appetite, digestion, and assimilation and elimination of toxins in the body. Constipation is totally cured. Thus, the animals and humans become hale and healthy with shining hair and skin. The weight gains are impressive. One has to see it and experience it to believe how effective it can be. Pigs: Panchagavya was mixed with drinking water or feed at the rate of 10 ml to 50 ml per pig depending upon the age and weight. The pigs became healthy and disease free. They gained weight at a faster rate. The feed-to-weight conversion ratio increased tremendously. This helped the piggery owners to reduce the feed cost and to get very good returns due to increased weight. Goats and Sheep: The goats and sheep became healthy and gained more weight in a short period after having administrated 10 ml to 20 ml Panchagavya per animal per day depending upon the age. Cows: Studies have shown that, the cows fed with panchagavya mixed it in the feeding trough with animal feed and water at the rate of 100 ml per cow per day, have became healthier with increased milk yield, fat content and SNF. The rate of conception increased. Reduced the incidence of retained placenta, mastitis and foot and mouth disease The skin of the cow is shiny with more hair. Instead of spraying urea on paddy straw (hay) before staking, a few farmers sprayed the 3 percent solution of Panchagavya, layer after
108
layer during the staking, and allowed it to ferment. The cows prefer such hay compared to unsprayed hay stock. Poultry: When mixed with the feed or drinking water at the rate of 1 ml per bird per day, the birds became disease-free and healthy. They laid bigger eggs for longer periods. In broiler chickens the weight gain was impressive, and the feed-to-weight conversion ratio improved. Fish: Panchagavya was applied daily with fresh cow dung in fishponds. It increased the growth of algae, weeds and small worms in the pond, thus increasing the food availability to fish. The only precaution is that fresh water must be added to the ponds at frequent intervals. Otherwise, the growth of algae, weeds and other organisms will compete with the fish for available soluble oxygen in the water. Alternatively, mechanical agitators can also be used to increase the oxygen content in the water. In ten months time each fish grows to a weight of 2 to 3 kegs. With reduced death rate of small fingerlings and increased weight or marketable fish, the fisheries became more profitable. GOMARI SANGEEVI (Herbal Antibiotic): . It is a decoction of fresh neem bark and leaves of the jackfruit tree. It is prepared by adding 300 grams of fresh neem bark ( after discarding the dried outer layer) and 200 grams of green leaves of jackfruit tree to 5 litres of water and boil it in a mud pot to reduce it to 2.5 litres of concentrated decoction. After filtering it, the red coloured decoction can be used as oral medication for cattle. Dosage(crude)Cattle500mlonetimedose.Calves-250ml; goat-100ml; Features: Controls and prevents foot and mouth disease in cattle; Prevents and cures all kinds of fever in animals.; Acts as a de-worming agent; Restores the fertility status. GOSANJEEVI (Herbal Cattle Immunity booster) : . It contains leaves of Azadiracta indica, Albizzia amara, Tinospora cardifolia, Andrographis paniculata and roots of Withania somnifera. After shade drying, powder the above ingredients by pounding in a stonemortar. Each ingredient should be powdered separately. Then mix them in the following proportion to make 1 kg of powder for usage. Azadiracta indica leaf powder 300 grams Albizzia amara leaf powder 300 grams Withania somnifera root powder 300 grams Tinospora cardifolia leaf powder 50 grams
108
Andrographis paniculata leaf powder 50 grams Dosage: 50 gm once a day mixed with the cattle feed and drinking water of the cattle. Special Features: Boosts the immunity to all kinds of diseases in cattle.; De-worms, cleanses intestine, and enhances digestion and assimilation.; Upgrades quality of milk with increased milk yield, fat content and SNF and nutrients. ; Regulates the ovulation cycle and increases conception rate.; Prevents retained placenta; Prevents mastitis, fevers and foot and mouth disease. Some of the herbal acaricides that are proven to be effective for topical application of domestic animals are given below 1. Neem leaves and urine: Neem leaves ..130kgs, Water .50 lts, Cow urine .20 lts Soak the neem leaves in water and cow urine close the container, opening once a week to stir vigorously. Dilution ratio : 1:4 2. Tabacco leaves and Cow Urine : Tabacco leaves ..4 kgs, Water 5 lts, Cow urine 10 lts. 3 days old, fermented. Boil the tobacco leaves in water for 30 minutesAdd 40 lts. Of fresh water and 10 lts. Cow urine Dilution ratio : 1:5 The following preparation is used as effective disinfectant for animal houses Preparation of Pesticide from cow dung and urine: Take 5 kg. of cow dung + 5 litres of cow urine + 5 litres of water. Mix all the three ingrediants and put it in an earthen pot and tie the face. Keep it for 4 days, every day stir the solution twice in a day and keep the pot insight compost pit. After 4 days mix 200gm. of lime and spray 1:9 proportion Panchagavya for Human Health: 50 ml of filtered Panchagavya mixed with 200 ml of water, tender coconut water or fruit juice taken orally in empty stomach in the morning. Has shown to be effective supportive therapyfor:AIDS/HIV,psoriasis,neurologicaldisorders, Diabetes mellitus, PulmonaryTuberculosis, arthritis etc. There are two forms of Cow Urine 1) One is called Go-Ark (Distilled Cow Urine) Cow urine is boiled and the vapor is collected (process is called distillation) to make cow urine distillate for oral intake.
108
2) Then the other form of it is Ghanavati: Mostly this is used to reduce the cholesterol in the blood and to decrease the excess weight. It can be easily given to children in cough and other diseases. Signifance Of Go-Ark: In Ayurveda (Medical Science of scriptures) it is said that the main cause of disease is the imbalance of three elements Air (Vata), Bile (Pitta), Mucous (kapha). Cow urine balances these three elements, Samya dosharogata meaning when three elements are balanced there are no diseases. Properties Of Cow Urine: Cow urine is antifungal, antibacterial, antibiotic, antiallergic, antimicrobial, etc. Cow urine also works in a wonderful way to recuperate dead cells, especially the cancerous cells. So it is used in the treatment of cancer also. People who are having pitta problem (imbalance of secretion of bile marked by heat body and having acidic problems), they can take cow urine in a less quantity mixed with eight times water and others can take in a higher quantity mixed with 2-4 times water. High Fever: Two to ten drops of Gomutra Ark every one and half an hour for high fever treatment line. And also massage of soles of the feet by luke warm ghee, you have to massage with a small round bottomed bowl (cup) (katori). Asthma: You add two pinches of turmeric powder in 10-15 ml of Go-Ark and add 40 ml of water and take 15 to 30 minutes before breakfast. It should be taken continuously for seven days. If the symptom persists then one should take twice in a week. Please avoid potato, chilled water and ice cream. Acidity: For acidity simple and sweet medicine is Rasagolla, a sweet prepared from the cows milk (only the thick portion by separating the water-part by adding citric acid or lemon to the boiling milk and filtering. Then it is squeezed and made into small balls and boiled in sugar water for some time). This is an effective medicine for acidity. Jaundice: Go-Ark with ayurvedic medicine called kutki is very beneficial. Take 3-4 pinches of kutki and 4 teaspoons of Go-Ark, mix it and take half an hour before breakfast in the morning and half an hour after dinner in the night for a total of 21 days. Then you can take thrice in a week. Diarrhea: banana added with curd and also flat rice. (All these items are for constipation. So it will stop diarrhea.) After that you can take 10-15 drops of Go-Ark with 40 ml water.Piles: For piles one glass of luke warm milk and add half lemon in it stir and take in the early morning.
108
CONCLUSIONS : Recognition of medicinal value for the dung and urine
of Indian cattle breeds may develop into a major income generating commodity even bypassing the returns on milk. The suggested way to recycle of livestock manure is energy generation and slurry produced there upon as manure. Irrespective of quantity and quality of inputs, farm animal waste has only diminished value and secondary importance to use as an alternative feed resource for livestock however, it may have comparatively better preference to feed fish in ponds. Utilization of slaughter house waste is an important aspect of modern meat plant management. Besides its economic importance, proper utilization of these wastes helps in reducing the environmental pollution substantially. *****
AN UPDATE ON NON STEROIDAL ANTIINFLAMMATORY AGENTS

SUNILCHANDRA.U
NonSteroidal Anti Inflammatory Drugs (NSAIDS) have the potential to relieve pain and inflammation without the immunosuppressive and metabolic side effects associated with corticosteroids.The analgesic, antipyretic and anti-inflammatory effects are devoid of sedation, hypotension, bradycardia and respiratory depression that makes them advantageous over opiods, though with lesser analgesic potency. The two broad groups of NSAIDs are carboxylic acid and enolic acid derivatives. Examples under enolic acids are phenylbutazone, oxyphenbutazone, dipyrone (analgin or metamizol), ramifenazone, amidopyrone, meloxicam, piroxicam, and tenoxicam. CarboxylicacidNSAIDaresalicylates(aspirin), diflunisal,ibuprofen,naproxen,carprofen, ketoprofen, diclofenac, fenclofenac, niflumicacid, sulindac, vedaprofen,fenprofen,flurbiprofen, nabumetone, azapropazone, tolmetintepoxalin, aceclofenac, tolfenamic mefenamic acid, meclofenamic acid, acetaminophen, flunixin, indomethacin, etodolac, eltenac etc., Pharmacological Effects: All NSAID, except for acetaminophen exhibit antipyretic, analgesic, and anti-inflammatory properties. In general, NSAID provide only symptomatic relief from pain and inflammation and do not significantly alter the course of pathologic
108
damage. As analgesics, they are generally less potent than opioids and are more effective against mild to moderate pain. Some parenteral formulations are highly alkaline and may cause tissue necrosis if injected perivascularly. Once absorbed, most NSAID are extensively (up to 99%) bound to plasma proteins, with only a small proportion of unbound drug available to be active in the tissues. Most NSAID are biotransformed in the liver to inactive metabolites that are excreted by the kidney via glomerular filtration and tubular secretion. Cats tend to be deficient in some glucuronyl transferases that are important for glucuronidation. As a result, drugs that are excreted as glucuronide conjugates in other species such as aspirin and paracetamol may have a prolonged half-life in cats, increasing the risk of toxicity due to drug accumulation. Indications: NSAIDs are primarily indicated for pain resulting from musculoskeletal injury either due to trauma (or surgery)and to reduce or relieve abdominal pain due to their analgesic, anti-inflammatory and antipyretic action.. They are also used as adjunctive therapy to antimicrobial treatment in acute respiratory diseases in cattle. Other use of NSAIDs is as antiendotoxic to reduce endotoxaemia( eg: flunixin, phenyl butazone) and antithrombotic (eg: aspirin) to prevent thrombosis. Side effects: The ability of NSAIDs to reduce the production of prostaglandins and thromboxane, and thus reduce inflammation, is also responsible for the potential toxicity of this drug class.Cellulitis, thrombophlebitis and tissue necrosis have been associated with intramuscular or perivascular injections of NSAIDs. All NSAIDs have the potential to cause gastric ulceration by inhibiting the production of PGE and PGI2. The only exception would appear to be paracetamol as it does not inhibit peripheral oxygenase. However, in the cat, the use of paracetamol is contraindicated as the products of its metabolism are extremely toxic. Agents such as H2 receptor antagonists (eg: ranitidine), proton pump inhibitors (eg: omeprazole) or cytoprotective drugs (eg: misoprostol, suclralfate) are administered to prevent/heal the gastric ulceration effect of NSAIDs. Renal toxicity: The potential for renal toxicity to occur in a volume depleted cat is a further potent reason why NSAIDs should not be
108
administered to any animal in shock post-traumatically animal that may be dehydrated.
nor to any
Haematological effects : Bleeding, thrombocytopenia, haemolytic anaemia and agranulocytosis. Prolongation of bleeding times can occur after administration of any of the NSAIDs. The reduced vasoconstriction and platelet aggregation is significant in patients with bleeding tendencies. Other adverse side effects of NSAIDs include hepatotoxicity, CNS (behavioural disturbances, seizure precipitaion) and skin (rashes, pruritus) manifestations. Meloxicam, ketoprofen, carprofen, flunixin, piroxicam and tepoxalin are effective and well- tolerated analgesics in cats when administered for short-term treatment (five days). Use of synthetic opioids such as buprenorphine, butorphanol or pethidine provide equally effective analgesia as NSAIDs without the risk of renal toxicity related to reduced renal perfusion. NSAID therapy to be discontinued if dog shows : decrease or increase in appetite or thirst, vomiting, diarrhea or black, tarry or bloody stools, lethargy, seizure, aggression or confusion, jaundice (yellowing of skin, gums or eyes), change in urinary habits and red, itchy skin Contraindications:NSAIDs are contraindicated in animals suffering from gastrointestinal ulceration or bleeding , blood dyscrasia. , cardiac, hepatic or renal impairment (insufficiency), dehydraion,, hypovolaemia or hypotension . Concurrent use of potentially nephrotoxic drugs (eg: aminoglycosides, diuretics, )should be avoided with these agents. NSAIDs administration is not advisable in in pregnanat animals and animals nearing the oestrus. Also, they have been found to delay the parturition, if used nearing term. Aged animals may pose additional risk for all the agents. Aspirin is used for the relief of moderate pain associated with musculoskeletal inflammation or osteoarthritis. In cats, aspirin may be used for its anti-platelet effects in thromboembolic disease, every 48 hr, to allow for prolonged metabolism.Vomiting and melena may be seen at higher doses. Overdose in any species can result in salicylate poisoning, characterized by severe acid-base abnormalities, hemorrhage, seizures, coma, and death
108
Acetaminophen has little ulcerogenic potential, with no effect on platelets or bleeding time; is more effective in inhibiting COX-3, in the brain rather than in the periphery. Dose-dependent adverse effects include depression, vomiting, and methemoglobinemia. Use in cats is contraindicated due to hemolytic anemia and centrilobular hepatic necrosis. Meloxicam is recommended to dogs, as a one-time loading dosage of 0.2 mg/kg, PO, followed by 0.1 mg/kg, PO, SID. Once a therapeutic effect is seen, the dosage can be titrated to the lowest possible dose. Once absorbed, meloxicam is highly protein bound (97%) and has a relatively long elimination half-life (12+ hr). GI safety appears to be greater for meloxicam . Vedaprofen is indicated for the treatment of pain and inflammation associated with musculoskeletal disorders in dogs and horses and for the treatment of pain associated with colic in horses (2 mg/kg, IV, as a single injection). Following administration PO, vedaprofen is rapidly absorbed. Biovailability is reduced if the drug is administered with food. The terminal half-life is 10-13 hr in dogs and 6-8 hr in horses. Etodolac has efficacy for the treatment of lameness associated with hip dysplasia. Although the risk of GI ulceration is low at therapeutic doses, hepatic, and renal adverse reactions have been reported after administration of etodolac, similar to other NSAID. Carprofen is approved for osteoarthritis and acute pain associated with soft-tissue and orthopedic surgery in dogs. Flunixin meglumine is used for the treatment of colic and for protection from septic/endotoxic shock due to any gastro-intestinal insult either postsurgical or medical such as in cases of peritonitis or diarrhoea. Also, used as an anti-inflammatory in the treatment of painful conditions of the eye including corneal ulcers, uveitis, conjunctivitis, and before and after eye surgery.Highly effective for treatment of visceral pain associated with colic, may have anti-endotoxic effects. Piroxicam: treatment of some cancers in dogs and cats, and to a lesser degree for pain due to osteoarthritis. It is used in many types of tumors, including nasal epithelial tumors, mammary tumors, colorectal tumors, oral squamous cell carcinoma, oral melanoma, prostatic
108
carcinoma,osteosarcoma. and some rectal neoplasms. Methotrexate should not be combined with piroxicam due to potential severe toxicity. Phenylbutazone is generally a safe and effective drug in the horse, in which it is commonly used for lameness, resulting from from soft tissue injury, muscle soreness, bone and joint problems, and laminitis. Phenylbutazone may be given intravenously or orally; pain relief and fever reduction usually starting within one to two hrs. In Dogs it is for the longer-term management of chronic pain particularly due to osteoarthritis . It can cross the placenta and is found in milk. It should be avoided or used with caution in pregnant or nursing animals. It may affect blood levels and duration of action of phenytoin, penicillin G, sulfonamides, sulfonylurea antidiabetic agents, barbiturates, promethazine, rifampin, chlorpheniramine, diphenhydramine Meclofenamate (meclofenamic acid) has similar pharmacologic activity as aspirin. In Horses, it is thought to be particularly useful in chronic problems of the hoof- navicular syndrome and laminitis. Nimesulide is used in dogs for relief of pain associated with musculoskeletal inflammation.Not indicated in puppies < 4 months age/ dogs<r 5kg; cats, and pregnant and lactating bitches. Ketoprofen prescribed for musculoskeletal pain from soft tissue injury, osteoarthritis or other bone and joint inflammation; efficacy comparable to that of opioids in the management of pain following orthopedic and soft-tissue surgery in dogs. Also used in managing colic for protection from bacterial toxins (endotoxemia). Aceclofenac has a faster, more potent analgesic, antipyretic and antiinflammatory activities, It is superior from other common NSAIDs as it has selectivity for COX-2, and is well tolerated, with better GI tolerability and improved cardiovascular safety . Tolfenamic acid: Caution with use in animals less than 6 weeks of age, or aged animals; avoid use in dehydrated, hypovolaemic, or hypotensive patients; safety in pregnancy has not been established Dose. Cattle: mastitis, 4 mg/kg,IV as a single dose; Bacterial respiratory disease:2 mg/kg, IV repeat once after 48 hours; Pigs: 2 mg/kg.IM, as a single dose; Dogs: chronic locomotor disease, 4 mg/kg once daily,PO. for 3 days given with food. Cats: febrile syndromes: 4 mg/kg,PO, once daily for 3 days given with food by subcutaneous injection, 4 mg/kg.
108
Many of the commercially available NSAIDs formulations are also available in combination with other suitable agents for their synergestic action in pain relieving. These include muscle relaxants like chlorzoxazone, carisoprodol, chlomezanone, methocarbamol, tizanidine and anti-inflammatory enzymes like serratiopeptidase. Adjuvant analgesic drugs: They are generally not considered to be primary first choice analgesics, but used in combination with other analgesic drugs in acute pain states to manage severe pain, so as to reduce the dose of the primary analgesic. Methocarbamol is a muscle relaxant, it may relieve muscle tension associated with arthritis in pets. Xylazine and Medetomidine hydrochloride are the injectable sedatives; very effective pain relievers . NMDA Receptor Antagonists like: ketamine,dextromethorphan, memantine, and amantadine. applied to the skin also as a specially compounded gel or paste. Gabapentin, used in dogs and cats for the treatment of chronic pain,of neuropathic origin , chronic arthritic pain and pain associated with malignancy. It is most effective when combined with other types of analgesic agents, for example NSAIDs, permitting the use of lower doses.. It should not be discontinued abruptly because withdrawal may precipitate seizures or rebound pain. The dosage should be decreased over the course of two to three weeks. It crosses the placenta and gets excreted in milk, needs careful monitoring during pregnancy or lacatation.
Gabapentin Amantadine Xylazine Medetomidine Dog 2.5-5 ,PO,bid 3,PO,sid 0.05-1, IV sid 0.001-0.005, IV,IM,tid Cat 5-10,PO,tid 3,PO,sid 0.05-1, IV sid 0.01-0.03, IV,IM tid
Local anaesthetics are peripherally acting analgesics. Long acting agent bupiavcaine is used along with lidocaine for long acting pain relief. A single dose of bupivacaine injected at a local site will provide local analgesia for 6-10 hrs. Dosage (mg/kg) and frequency of administration of commonly used NSAIDS
Dog NSAIDs Etodolac Carprofen Dipyrone (Analgin) Deracoxib Tepoxalin Meloxicam 10-15 PO sid 4.4 PO, IV, SC qid 25, IM, SC,bid 3-4, PO, sid 10 ,PO qid 0.1 SQ ONCE 0.1 PO qid Cat NR 1-3, SC,sid, 10-25, IM, SC ,sid NR 5, PO bid 0.3 SQ sid, , 0.1 SC then 0.05 PO qid x 5 days Cattle 4.4 PO, sid
108
Firocoxib Sodium salicyalte Ketoprofen Phenylbutazon e Aspirin Ibuprofen Naproxen Ketorolac Piroxicam Paracetamol Nimesulide Meclofenamic acid
5 , PO qid 10, IV,bid 2 IV, IM, SC q12-24h 10-15 PO q8-12h max 4 days 10-25 PO q8-12h 10,PO, eod 5,PO- primary dose, 2,PO- maintenance dose 0.3-0.5, IM,IV 0.3, PO,eod 10-15,PO,tid 5, IM, sid 2.2, PO, sid
NR 1-2 IV, IM, SC q1224h NR 10 q2-3 days 3,IV, IM, sid 10-20, PO, 2.5-5.0,sid 10, PO,q12h
then
0.25, IM 0.3, PO,eod NR NR 2.2, IV, sid, 20, IM
PO=oral, IV=intravenous, IM=intramuscular, SC=subcutaneous, IP=intraperitoneal, bid= twice a day, tid=three times a day, qid=four times daily, eod = every other day, NR= not recommended, q..h = for every .. hrs, sid= once daily CHRONDROPROTECTIVE COMPOUNDS Heparinoids: Polysulfated glycosaminoglycan and Pentosan polysulfate sodium, have been shown to improve clinical outcome in animals with osteoarthritis. These compounds are heparin-like in structure and high dosages may inhibit clotting mechanisms. Indicated in Non-infectious and non-immune arthritis. Contraindicated in advanced hepatic or renal impairment,uncontrolled bleeding, trauma, infection, neoplasia,concurrent treatment or within 24 hours of corticosteroids,NSAIDs . Dose.Pentosan polysulfate sodium ,Dogs:, 3 mg/kg, SC,repeat 3 times at 57-day intervals; Polysulphated glycosaminoglycan: Dose. Horses:, 500 mg,IM, at 4-day intervals; 250 mg,intraarticular Sodium hyaluronate: is the sodium salt of hyaluronic acid, which is a constituent of the high molecular weight cartilage matrix molecules, aggregated proteoglycans, and is also present in synovial fluid. Administered by intra-articular or IV route for joint diseases in the horse, Indications. Arthritis associated with synovitis; navicular disease Side-effects. Transient local reactions, Dose. Horses: by intra-articular injection, 2040 mg/joint,repeat if required;, 40 mg,IV. Chondroitin and glucosamine: Preparations containing these are administered orally and claimed to assist the repair of cartilage by providing the building blocks for new proteoglycan formation. A proportion of these ingested macromolecules may be absorbed intact, and some components penetrate the joint. Their beneficial effect on the course of disease in dogs with osteoarthritis is uncertain.
108
Dimethyl sulfoxide (dimethyl sulphoxide, DMSO): is a solvent that readily dissolves both water-soluble and lipid-soluble drugs and can be used to transport drugs through skin. It also possesses some antiinflammatory activity and causes dissolution of collagen. *****
GUIDELINES FOR HANDLING POISONING CASES

KALAKUMAR.M
OF VETEROLEGAL
Generally every veterinarian is encountered with two types of cases in poisoning of farm animals. Accidental and Malicious poisoning. The necropsy of the animals and the rapid diagnosis is helpful in the treatment of other affected animals in case of accidental poisoning. In case of malicious poisoning, which may turn up into medico legal case, the identification of poison is a must to establish the cause of death. In all poisonous cases, chemical analysis of the biological specimens is essential to know the cause of death or illness. Therefore, every veterinarian should know the salient points in collection and despatch of toxicological specimens to a laboratory. History of the case is of great importance in the diagnosis of poisoning. This includes the number of animals in the farm, number of affected, method of feeding, regularity of feeding, recent changes in the rations or attendants, whether pastures have been sprayed with pesticides or fertilizers, if rodenticides have been used and remnants of the bait removed and disposed properly, storage of poisonous substances etc. Inspection of the surroundings for empty pesticides or paint containers that are not really empty, presence of poisonous plants in the farm environment. Also, the possibility of industrial effluents coming in contact with grazing/watering sources should be given thought of. POST MORTEM: Necropsy by routine procedure is to be performed as soon as possible after the death of animal. Examine the animal externally and note incisions (for sui poisoning, snake bite etc.,) on the skin or mucous membranes. Examine the oral cavity for corrosive lesions (acids/alkali) or changes in colour of mucous membrane (nitrate, co, cyanide poisoning). As most of the toxins gain entry through gut,
108
examination of gut mucosa, the contents, their smell, colour and pH (acids, alkali, urea) is a valuable guide in diagnosing toxicoses. Poisoning by salts of heavy metals results in significant post mortem lesions but poisoning by alkaloids like strychnine produces very feeble lesions. The natural orifices, sub-cutaneous fat tissue, muscles, bones and teeth (in fluorine poisoning), body cavities, and internal organs should be examined. The stomach should be punctured rather than cut open for organoleptic examination to note the character of smell. Puncture ensures greater accuracy and a longer time smell. Some of the poisons which emit characteristic smell are: bitter almond -hydrogen cyanide poisoning, garlic odour - phosphorus poisoning, rotten garlic or horse radish smell - selenium, tobacco odour nicotine, acetylene odour - zinc phosphide and ammoniacal odour- urea. Check the pH of the stomach contents by pH paper. Any variation in the normal pH of the sps. being examined indicates abnormality. (In urea poisoning-alkaline pH is observed in rumen liquor due to release of ammonia). The colour of stomach contents also indicates the cause of poisoning. Copper salts impart a greenish blue colour whereas picric and nitric acid impart yellow colour to the contents. The contents of the stomach vary from traces to flakes of paints or lead objects, grains or baits, seeds etc., like wise small and large intestine should be examined. Blood should be examined for its colour and clotting characters. Cyanide poisoning imparts cherry red colour, arsenic imparts rose red colour and nitrate poisoning turns blood brown in colour. In abrus and cyanide poisoning-blood remains fluid after death.Examination of other visceral organs should be done in relation to their size, colour etc. eg: - spleen size is decreased and colour is changed to dark brown or black in copper poisoning and spleen size is increased in T-2 mycotoxicoses.Lymph nodes are swollen, haemorrhagic, oedematous and dark upon exposure to radiation. Bone marrow becomes pale and gelatinous with yellowish tint.The description of morphological changes should be noted clearly and absence of changes should be notified. The most important lesions found should be underlined. In case of small animals (poultry, small dogs, lab animals) the cadavers are sent as it is, in case of large animals the stomach contents are collected from the vicinity of patho anatomic changes in the gastric
108
mucosa. If there are no changes a representative sample is collected, but in medium sized animals the stomach tied at oesophageal and duodenal end, intestine tied at both ends and bladder with tied ends is sent separately. Collection of samples: A successful toxicological investigation requires appropriate specimens, history and clinical signs, necropsy lesions and circumstantial evidences. All the specimens are to be taken in separate containers (polythene jars/covers), securely tied, properly labelled with particulars of date, case No., organs collected, species, name of preservative used etc. A sample of the preservative used, brief history of the case along with treatment given particulars should be sent. It is always preferable to send the specimens through a special messenger. In medico legal cases, the specimens should be sealed in the presence of a witness. The quantity for the kind of sample to be sent is as follows.Wholeblood:10-20ml;Serum:10-20ml;Milk:50100ml;Urine:50-100 ml;Water: 200 ml; Faeces : 50 g ; Feed : 0.5 - 1kg. Mode of preservation : 1. Ice for about 72 hrs. 2. Alcohol (95% ethyl alcohol) 1 ml/g of tissue is the ideal preservative for toxicological specimens. Formaline should never be used as it hardens the tissue without giving scope for scraping and interferes in the analysis. Blood and serum should be refrigerated and never frozen. A sample of the preservative used should be sent. It is always better to have a duplicate sample stored properly in a refrigerator for future reference Sample for analysis should include a suspected source material; often gut contents, so that ingestion of suspected material can be proved. Secondly, a sample of tissue (depending on tissue affinity of the suspected poison) must be included, to prove that absorption of the poison has occurred. It is always advisable to include a sample of liver to confirm absorption of orally ingested poison. In survival cases the following materials may be sent for analysis:Stomach wash, ruminal contents, vomitus, blood, urine, saliva, dung, water and feed, suspected forage/ poisonous plant/s is the ideal samples for laboratory analysis. Note: Always send a sample of preservative if used in separate container with proper label Toxicological specimens for laboratory examination
Sl.No. 1. Suspected poison HCN/Cyanide Specimen Remarks required Forage / ingesta, Rush samples frozen in whole blood,Liver air tight bottle to laboratory
108
2.
Organochlorine pesticides
3. 4. 5.
Organophosphat es &Carbamates Znic phosphide Nitrate/nitrite
6. 7.
Oxalates Ammonia/Urea
8.
9.
Heavy metals(Lead, Mercury) Mycotoxins
GIT/ Stomach contents in 1% mercuric chloride is ideal Cerebrum, fat, liver, Use only glass kidney, ingesta containers, Avoid aluminum foil for wrapping specimens Feed, ingesta, liver, urine Liver, kidney, gastric contents Forage, ingesta, body Ingesta in chloroform fluids, Serum . Ocular or formalin filled air fluid water samples tight container Fresh forage, kidneys Fix in formalin Whole blood or Frozen / 1-2 drops of serum, urine Rumen sat. solution of contents mercuric chloride Kidney, whole blood, Heparinized, do not use liver and urine EDTA Forages, feed sample, airtight containers or liver kidney, brain plastic bags. Cloth bags for dry feeds
*****
THERAPEUTIC MANAGEMENT OF CRITICAL PATIENTS IN CLINICS

VIVEK.R.KASARALIKAR
Critically ill patient is special challenge to the clinician as the underlying problem is not evident for about 24 to 48 hours after initial presentation. Expeditious therapy in right time can be life saving. Most common clinical conditions in ambulatory patients are trauma with internal/ external hemorrhage, poisoning and post surgical complication. In fact, specialized care of emergent patient begins with initial phone call from the owner and instructions to be given regarding first aid and transport procedures. Level of consciousness, breathing pattern and external hemorrhage should be enquired on priority. The important first aid measures are:
108
Immobility and transport on firm flat surface Mouth to nose resuscitation in critical patient which is unconscious and not breathing (Ten to twelve times per minute) Pulsating arterial bleeding is controlled by digital pressure and pressure bandage Penetrating foreign objects should be left in place till specialized help is available Head elevated by 200 in altered mental status after head or spinal injury Evaluation and initial treatment: Three important assessment criterion in emergency patients are A, B and C by evaluating certain parameters . A : Airway: Airway patency should be evaluated on priority. Noisy breathing without need of stethoscope suggests Large airway problem e.g. trachea and bronchus, whereas, inspiratory dyspnoea implies extra-thoracic airway compromise. Loud expiratory sounds reflect towards pathology of intra-thoracic airway including bronchioles and lung parenchyma. B :Breathing: Sequence of respiratory compromise is increased in respiratory rate initially, followed by change in respiratory pattern. Laboured open mouth breathing with development of cyanosis suggests significant compromised pulmonary function. In both the above conditions, immediate Oxygen administration is the priority. Intra-nasal catheter is the best choice for compromised breathing patients, whereas slash tracheotomy with endotracheal intubation is preferred in unconscious and apneic patients (Nasal Oxygen flow rate should be kept at 50 100 ml/kg/min). C: Circulation: Hemodynamic and cellular changes that occur as a result of abnormality in circulation is referred as shock or peripheral circulatory failure.; is clinically classified in to four main categories.
Hypovolemic: occurs due to atleast 15-25 % t deficit in circulatory blood volume Cardiogenic shock: occurs due to failure of heart to pump requisite quantity of blood in to circulation Distributive shock: due to impaired distribution of circulatory blood volume as a result of peripheral vasodialatation Septic shock: This is endotoxin mediated shock
108
Therapeutic management of critically ill patient:

1. Cardio-pulmonary
Resuscitation (CPR):Hallmarks of Cardiopulmonary arrest are a) stage of apnea with cyanosis of visible mucous membranes b) absence of palpable pulse c) absence of heart sounds and d) dilatation of pupils Guidelines for Cardio-pulmonary resuscitation
a) Positioning
of animal:Lateral recumbency on small animal examination table is optimal position in small sized dogs (< 7 kgs), whereas dorsal recumbency is preferred for large sized dogs. ventilation should be performed in patients in apneic stage.Compression rate should be 60 to 120 per minute and the compression ventilation ratio should be 15:2. It means for every 15 compressions 2 cycles of ventilation should be performed.
b) Resuscitation:Chest compression coupled with mouth to nose
2. Management of shock: Assessment of shock is governed by
these parameters Pale to cyanotic mucous membranes Tachycardia with weak pulse Significant fall in Systolic blood pressure (Below 60 mm of Hg) Central Venous Pressure (CVP) less than 5 mm of H2O Elevated level of Blood lactate (> 80 mg/dl) Significant increase in Capillary Refill Time (CRT) Therapeutic management: Emphasis should be given to
Fluid therapy:The main aim of fluid therapy is to restore circulation
and improve the tissue perfusion. Choice between crystalloid and colloidal solutions should be determined. Crystalloid supplements fluid along with electrolytes, whereas colloidal solutions expand the plasma volume.Commonly used colloidal solutions are: Dextran 70, Hexastarch,Gelatin polymers, Frozen plasma, Packed cell component. Commonly used crystalloids are: Normal Saline, Lactated Ringers solution, Dextrose Normal Saline, 7.5 % Normal saline and Hypertonic dextrose solution Corticosteroids:Stabilization of cell membrane, blocking of arachidonic acid metabolism and gluconeogenesis are few important roles of corticosteroids in the treatment of shock
108
Cyclo-oxygenase inhibitors:These decrease the prostaglandin synthesis and other vaso-active amines.Eg; Flunixin Meglumin( 0.25 mg/kg); Ketoprofen(0.5- 2.2 mg/kg) Antibiotic therapy in septic shock: Broad spectrum antibiotic therapy has additional advantage in endotoxin related shock. Antibacterials with synergistic action are also preferred in septic shock. III to IV generation ceophalosporin like cefoperazone, ceftrioxone and cefixim are frequently used in small animal practice. Control of hemorrhage and blood transfusion: Antifibrinolytic drugs are preferred to counteract extensive hemorrhage. PAMBA (Para amino methyl benzoic acid), EACA (Epsilon amino caproic acid) and Botropase have fast styptic activity Alpha Adrenergic agonist: These drugs help in improving cardiac output and thereby improve tissue perfusion. Dopamine used @ 5 10 g/kg/min as constant infusion has positive ionotropic effect and increase the systolic pressure.
*****
108
AN UPDATE ON MANAGEMENT OF OBSCURE DISEASES OF KARNATAKA

SHRIDHAR N. B.
The obscure diseases do not have a scientific description and documentation in veterinary literature. Hence, a systematic study was done in the present investigation. The disease conditions causing morbidity and mortality in cattle and buffaloes of Western Ghat and other areas of Karnataka were investigated and documented and an attempt was made to find the appropriate therapy. LIGHTNING DISEASE/ NEUROSIS The clinical signs were salivation, generalized clonic and tonic seizures, nystagmus, hyperaesthesia, ataxia, paddling movements during recumbency and stereotyped gnawing behavior in terms of ingestion of animate (its own skin) or inanimate object. These clinical signs simulated rabies. Earlier, these clinical signs were attributed to rabies, trypanosomiasis and hypomagnesaemia. From the clinical ailing cases, the blood smears were negative for the presence of trypanosoma parasites. Necropsy revealed congestion of the brain, heart, lungs and liver. Histologically, the brain revealed vacuolar degeneration and infiltration of leucocytes. This condition was subsequently confirmed as plant Ficus tsjahela toxicity and the same condition was mimicked by feeding the leaves (50 g/kg) to calves. In clinical ailing animals, there was normocalcemia, normophosphataemia, normomagnesemia but a transient hyperglycemia after the manifestation of seizures. The clinically ailing cattle were successfully treated with a twice a day three day regimen of diazepam (0.4 mg/kg) intravenously plus orally. After this diazepam therapy, the clinical signs are subsided. PERINEAL OEDEMA This condition was seen among (Local nondescript 26, Malnad Gidda 60, Gir 10, Sahiwal 8 or Zebu X Holstein Frisian, HF 36 or jersey 22 cross breed) cattle and buffaloes (54). Initially, there occurred a triangular black or brown patch on the perineum. Over a period of a week, an evident oedema was noticed in the perineal region (vagina or scrotum, rectum and thigh region. Such ailing cattle or buffaloes had normothermia, anorexia, adipsia, oliguria, impaction, hard pelleted dung, tenesmus and a terminal downer status accompanied by hypothermia (up to 95oF) followed by death. At necropsy, the renal
108
pelvis had jelly-like appearance, abomasal congestion and ulcer, empty small intestines with scanty faeces in the large intestines. In all these clinical toxicity conditions, no bacteria were isolated and there washypercreatininemia and azotemia, but normoglycemia, normocalcemia and normophosphataemia. Similar clinical signs and necropsy changes were noticed in animals accidentally fed Mimosa invisa, Mimosa pudica, Embelia tsjerianum-cottam, Anagallis arvensis or Cassia spectabilis to cattle and buffaloes. This condition was also experimentally induced by feeding the said plants to calves. The biochemical and necropsy changes reflected the toxic plant nephropathy as a pathological cause for the clinical condition of perineal oedema. Few animals in early stage of the disease responded to the therapy with sodium thiosulphate ( 25 mg/kg, 20% solution) and fluid therapy. DYSPNOEA SYNDROME In (young and adult) cattle, there was fever (103 to 104oF), anorexia, hypodipsia, dry cough, dyspnoea and occasional brisket oedema. This status persisted for a week to fortnight followed by debility and death. A transient recovery was noticed after a therapy with H1-antihistaminics, corticosteroids and antibacterials. At necropsy, the lungs showed congestion, petechiae and oedema. Histologically, there was leucocytic infiltration in the alveolar spaces. A microbial cause especially Pasteurella, E.coli.or Mycoplasma or Infectious Bovine Rhino trecheaitis (IBR) was suspected initially. No bacteria were isolated or identified from the animal materials. The therapy in these cases was not encouraging. BLINDNESS IN NEONATAL CALVES Zebu X HF or jersey cross-bred calves and buffalo calves usually were born blind. Some calves showed mild tremors, excitation or coma and foul body smell. None of the calves responded to vitamin A therapy. No bacteria were isolated from the various samples of affected calves. The cerebrospinal fluid collected did not reveal any abnormality. Within a month, the calves died. At necropsy, there was congestion in cerebral cortex, liver and spleen. The possible toxic cause may be a plant or its constituents like nitrate. MYCOTOXICOSIS
108
In Northern Karnataka, the farmers feed the fungal contaminated sorghum fodder of the previous years to their cattle and buffaloes. The buffaloes and cattle ingesting such stale sorghum fodder showed clinical signs of paraplegia, salivation, staggering gait and dyspnoea. The fungi were identified as Rhizoctonia, Macrophomina phaseolina, Aspergillus niger and Penicillium species from this stale sorghum fodder. The dominant fungi was Rhizoctonia which was reported to cause toxicity in animals. There was an increase in blood serum AST and ALT values in ailing cattle and buffaloes indicating liver damage. After treatment with atropine (2 g/kg i.m twice a day for 5 days), these clinically ailing cases recovered. The response to atropine therapy suggested the possible contribution of the cholinomimetic mycotoxin (Slaframine) produced by the dominant Rhizoctonia. After stopping the culprit feed, the affected cattle responded to the therapy of potassium acetate (5-10 mg /kg, 5% solution) along with B-complex vitamins. ABORTION Repeated abortions were noticed within two to eight months of gestation in 180 cross-bred cows. The serological tests for brucellosis and /or infectious bovine rhinotracheitis were negative. The feed and fodder samples from such areas were negative for aflatoxin and no fungi was isolated from either the animal or plant feed materials. From the aborted material, no bacteria could be isolated. The impression smears from these materials were also negative for any bacteria or protozoa like Trichomonas foetus. As some of the feed materials (plants and commercial branded feeds) had high nitrate content, the abortion could have been due to possible nitrate toxicity. TAIL AND EAR GANGRENE This condition was observed in buffaloes. The tip of the tail dried and subsequently the gangrenous tail dropped off. In some buffaloes, concomitantly, there was drying and loss of the tip of ears. From the feed and fodder samples, there was no evident Claviceps purpurea (ergot) sclerotia. Hence, this condition was not due to ergotism. The exact cause could not be established. However the condition was successfully treated using a solid sulfur source formulation mixture containing sodium sulphate 30 g, zinc sulphate 2 g, copper sulphate 2 g, ferrous sulphate 50 g and 1 kg of magnesium sulphate was prepared to serve as a source of sulfur. All the animals were given a 20
108
g mixture (in liquid jaggery or mixed in feed) twice daily for a fortnight. The deciduous lesions healed faster after the application of ointment prepared by mixing sulphur and zinc oxide powders equal parts in petroleum jelly(1:10). VOMITING / EMESIS SYNDROME Cattle and buffaloes showed a vomiting syndrome characterized by projectile emesis. In few buffaloes it was due to Rhizoctonia infested sorghum fodder ingestion. No success was obtained in spite of therapy with metoclopramide and other antiemetic drugs. THEILITIS IN BUFFALOES Buffaloes were affected in their first or second lactation had an initial acute theilitis characterized by painful and swollen (one or two) teats. The milking became difficult and the milk from the affected quarter was apparently normal. Such milk samples had no bacteria upon culture and sensitivity test. After 4 to 5 days, one to two circumscribed blackening of skin (1 cm) occurred around the base of the teat and body of the teat. The base of the teat that had circumscribed gangrene withered off naturally leaving a crater in a fortnight. This condition was not spreading in a buffalo to other quarters or to other animals in the herd. The milkers even after touching and handling the affected teat were unable to spread this condition to others in the herd. All these suggest the non-infectious nature of this condition. The therapy with a 4 to 6 teat spray of 100 g (metered inhaler for 4 to 5 days) with an intranasal preparation of salbutamol (Asthalin Inhaler, Cipla) metered inhaler cured 20 of 25 ailing cases. There are 2- adrenergic receptors in the teat. Hence, the success of the present 2- adrenergic agonist therapy was perhaps by relaxing the teat tissue. Few cases were also successfully treated with a topical paste of the plant preparation containing bark of Croton oblongifolius and tuber of Curcuma longa. Few animals responded to the therapy of strontium bromide (Ekjebrol, 10 ml ampoule, 10% solution, Juggat Pharma,) 50 ml given daily for 4 days along with antihistaminics and anti-inflammatory agents. Ground leaves paste of Scleropyrum wallichianum and Breyania patens applied moderately cured thelitis in early stages. POSTERIOR PARAPLEGIA
108
This condition occurred in local and cross-bred cattle and buffaloes let out for grazing in forest or plantation areas. Stall fed animals were less affected. Although plant toxicity was suspected, we are still unable to pinpoint to a particular plant. The condition was clinically characterized by hind limb paresis and tail flaccidity, moderate to severe frothy salivation (not drooling), dysphagia, hyporexia, staggering gait, normo or hypothermia, dyspnoea, impacted rumen and occasional diarrhoea There was no change in blood cell or chemistry parameters. Below one year age group cattle were not affected. This condition is suspected as tick paralysis, since few animals with heavy tick infestation responded to ivermectin therapy. However this has to be proved experimentally. The animals given 10% potassium acetate 100 ml intravenously plus 10 g /100kg orally twice a day for 5 days were recovered. STANDING COW SYNDROME In this condition, the animal stood continuously for more than 20 days. This occurred in HF x Jr CB cows, Malnad Gidda animals and buffaloes. They were unable to lie down and not responded to therapy with muscle relaxants and anti-inflammatory agents. There were no change in serum biochemistry and haematology or gross or microscopic changes in vital organs like brain, liver, spleen and kidney. The exact etiology is yet to be explored. SALIVARY SYNDROME Profuse foamy salivation, fever, hyporexia was noticed in 80 Malnad Gidda animals in a particular portion of Sagar, Hosanagar and Tirthahalli Taluks of Shimoga District. Ticks were noticed in the ailing animals. There was no response to therapy to treatment with antibiotics, anti parasitic drugs, atropine, and antitrypanosomal drugs, calcium, sodium thiosulphate, potassium acetate infusions. Fluid therapy has improved the condition. The disease could not be reproduced even after blood transfusion from ailing animal to normal animal. This was not transmissible. Tick paralysis was one of the suspected conditions. HAEMOGLOBINURIA This transitory and recurrent haemoglobinuria was noticed in 28 cross-bred and 8 local cattle but not in buffaloes. This condition occurred not only in animals let out for grazing but also in stall- fed animals. The clinical signs were normothermia, transient
108
haemoglobinuria and recovery without treatment. Affected cattle showed pot belly appearance and rough hair coat If the condition goes unnoticed and untreated the animals died due to anaemia. Blood smear examination revealed no haemoprotozoa. Bacteriological examination revealed no pathogenic bacteria. There was hypohaemoglobinemia, normophosphataemia, normocalcaemia and normomagnesaemia It was non transmissible. The animals received 0.5 g ferrous sulphate for a fortnight were recovered. Some cows have responded to phosphorus therapy in the form of a 0.02M solution phosphate buffer 100 ml slow i/v twice a day for 4 days or 1% sodium salt of 4-dimethylamino-2methylphynyl-phosphinic acid 10 ml/animal/day for 5 days (TonophosphanR, Intervet). Some cases were due to hypophosphataemia and responded to the same therapy mentioned as above. Yet exact cause has to be established.
*****
MYCOTOXINS AND ZOOTOXINS OF VETERINARY IMPORTANCE : REMEDIES

VIJAY KUMAR.M
Mycotoxins are the toxic metabolites released by moulds under certain conditions conducive for their growth. Acute or chronic toxicoses can result from exposure to feed or bedding contaminated with toxins that may be produced during growth of various saprophytic or phytopathogenic fungi or molds on cereals, hay, straw, pastures, or any other fodder. The principles that characterize mycotoxic diseases: the cause may not be immediately identified; they are not transmissible from one animal to another; treatment with drugs or antibiotics has little effect on the course of the disease; outbreaks are usually seasonal because particular climatic sequences may favor fungal growth and toxin production and study indicates specific association with a particular feed.
108
There are various types of mycotoxins and are classified as follows. Based on the causative organism: Aflatoxins - Aspergillus flavus, A. parasiticus.;Rubratoxins - Penicillium rubrum, P.purpurogenum.; T-2 toxins - Fusarium sp. F.gramaenareum and F. roseum.; Ergotoxins Claviceps purpurea and C. paspali.Among these most common are aflatoxins. Aspergillus moulds grow rapidly when the moisture is <15%and the temperature is 24-25C.They commonly affect GNC, CSC, coconut cake, sunflower cake, wheat, sorghum, millets, soybean, peas and almonds. Susceptibility:Ducks, rabbits, dogs, pigs, calves, chicken, cows, quail and sheep are susceptible in the order of preference. Broilers are more susceptible than layers. Calves are more susceptible than adult dairy cattle. Maximum allowable conc. in dairy cattle is 20 ppb (0.02 ppm)Depending on fluorescence aflatoxins are classified into B1, B2, and G1, G2. B1 is most toxic and need to be converted into its active metabolites.Toxicity is through ingestion of aflatoxin-contaminated feed. Aflatoxins are not accumulated to any appreciable extent by animal tissues with the exception of milk. Signs:Acute - sudden death or anorexia, depression, dyspnoea, coughing, nasal discharge, anaemia, epistaxis, bloody faeces, possible convulsions and death. Subacute - jaundice, hypoprothrombinemia, haematomas and haemorrhagic enteritis. Chronic - decreased feed efficiency, decreased productivity and weight gain, rough hair coat, anaemia, enlarged abdomen, mild jaundice, depression and anorexia. Abortions may occur. Postmortem Lesions: Wide spread heamorhages,Icterus,Gastroenteritis,Hepatic necrosis,Massive centrilobular necrosis,fibrosis of bile duct,Enlarged liver,Hydrothorax, Ascites,Oedema of Gall bladder wall,Pericellular cirrhosis Diagnosis: based on History,Clinical signs,PM findings,Detection of Aflatoxin M1 in milk & urine,liver, kidney,Serum liver enzymes SGOT,SGPT,ALP elevated,Reduced prothrombin activity,Hyperbilerubinemia,Tlc,HPLC,RIA,ELISA
108
Differential diagnosis: Warfarin (haemorrhages), coal tar (mottling of liver) Copper poisoning (haemoglobinuria, hemolysis); Pyrrozolidine alkaloids (present in plants), CCl4, bluegreen algae, crotalaria are hepatotoxic. Treatment: 1. Avoidance of contaminated feed. 2. Hydrated sodium calcium alumino silicate (HSCAS) adsorb aflatoxins @5kg /ton 3. Stanozolol (2 mg / kg) I/M decreases hepatic necrosis 4. Oxytetracycline (10mg / kg) I/M decreases hepatic necrosis.( Never administer oxytetracycline and stanzolol combination, they are mutually antagonistic) 5. Activated charcoal 6.7 mg / Kg I/R as 30% W/V slurry in M/15, PH7 PBS(Along with charcoal,stanzolol/oxytetracycline(any one) ) 6. GSH Precursors Cysteine,methionine @2.2mg/kgi/p 7. Multi vitamins Like E,K & Selenium 8. Feeding easily digestible and low fat diet containing adequate protein Sample collection : Samples can be taken at various stages:growing crops or during transport or storage. Whenever possible, samples should be taken after particulate size has been reduced (Ex: by shelling or grinding) and soon after blending has occurred (as in harvesting, loading, or grinding).Most effective if small samples are taken at periodic, predetermined intervals from a moving stream of grain or feed. These individual stream samples should be combined and mixed thoroughly, after which a subsample of 10 lb (4.5 kg) should be taken.. A suggested method of probe sampling is to sample at 5 locations, each 1 ft (30 cm) from the periphery of a bin, plus once in the center. This should be done for each 6 ft (2 m) of bin depth. Thus, taller bins would require more samples, and the total weight should be >10kg. Dry samples are preferable for transport and storage. Samples should be dried at 176-194F (80-90C) for > 3 hr to reduce moisture to 1213%. If mold studies are to be done, drying at 140F (60C) for 6-12 hr should preserve fungal activity.Containers should be appropriate for the nature of the sample. For dried samples, paper or cloth bags are recommended. Plastic bags should be avoided unless grain is dried thoroughly. Plastic bags are useful for high-moisture samples only if refrigeration, freezing, or chemicals are used to retard mold growth during transport and storage. Once a sample has been cooled or frozen, warming may induce condensation and allow mold growth. ZOOTOXINS
108
Out of 236 species of snakes in India, only 50 are venomous, However, the common poisonous snakes of India that man and animal come into contact, are : Cobra, Krait, Russels viper and Sea scaled viper, Apart from these, the other venomous snakes found in India includes Sea snakes, Pit viper and King cobra.. In animals, many a time incidence of snakes bite is near leg region and nostrils. Sensitivity: Horse>Man>Sheep>Cattle>Goat>Dog>Pig>Cat Venom composition: The venom compositions vary significantly among various class of poisonous snakes. Therefore, the course of toxicity as well as well as cause of death will be different, and obviously therapeutic approach will also vary. On most occasions, the identification of snake is not available or doubtful. The nature of toxicity of poisonous snakes are: Elapidae: Cobra , King Cobra, Krait- Neurotioxic; Viparidae: Russel viper- Haemotoxic; Crotalidae: Pit Viper- Neutrotoxic Haemotoxic. All the bites from venomous snakes do not lead to death due to dry bites which means that no venom was injected. But, some snake venoms (krait) do not have immediate effect even in a bad bite, it is wise to give veterinary/medical care. COBRA:. identified by their defence display by spreading their long bones to their famous hood. ; are most active at dust, having along the wedges of agricultural fields in search of rats/mice. For this reason they live mostly in cultivated area.. The cobra venom is rich in enzymes, cardiotoxic, neurotoxic factors. The cobra venom is rich in enzyme acetylcholinesterase. Therefore, rapid depletion of acetylcholine (ACh) at neuromuscular junction occurs following envenomation. This leads to muscular paralysis (flacid paralysis). In addition to it, the alphaneurotoxin is a powerful cholinoceptor blocker (nicotinic receptors). These factors hinder the function of muscles involved in respiration and consequently death occurs due to respiratory paralysis. It is important to identify the big four dangerous snakes. At first sight cobra looks like a non-venomous rat snake, but, remember that the rat snake has a pointed head and larger eyes and it can run faster. The common krait has bluish-bluck body with white cross bands and the head is short and blunt. Kraits venom is 10 times as powerful as that of the cobra and of all the Asian snakes its venom is the most toxic (neurotoxic). Kraits are noctoural. They are active at night and rest during the day. They are found throughout India and live
KRAIT:
108
mostly in sandy soil in rat burrows. Their favarite hiding places are piles of wood (on bricks which provide many pray to shelter in. They are canibalistic- eat snakes, rats, lizards and birds. Famale lays eggs (1015) and stays with them until hatch. is a fat and bulky snake, but it can move with surprising speed when in danger. Its regular chain-like pattern and flat arrow shaped head make it easy to recognise. Its fangs are along and curved.. Venom is rich in proteolytic enzymes, hemolytic factors.
RUSSEL VIPER: PIT VIPERS: are forest snakes and feed on frogs and lizards. Commonly
found in coffee and tea plantations in India. Pit vipes have a small pits between nostrils and eyes. They are heat sensitive and can detect change in temperature when warm blooded animal comes near. Venom is not powerful and seldom results in death. First-Aid treatment: The first aim, in case of cobra/krait bite is to retard the absorption of venom from the site of bite. ;done by applying a torniquet, provided site of bite is suitable for that. Do not disturb/ or/excite the animal with little care incise the area (1/4) and bleed. It is always better to avoid KMnO4 solution for wound wash and instead use 5% soap wash in 30 min. after bite. It is not advisible to apply torniquet in case of vipers bite as this venom is rich in spreading factors (local tissue necrosis). Hospital treatment: The nature of hospital treatment practically depends on identity of the poisonous snake. Polyvalent antivenin is the drug of choce in the absence of identity. It is better to avoid administration of antihistaminic as they are found to increase toxic potential of certain vipers venom. Popularly, hospital treatment can be remembered as AAA: A = Antivenin.; A = Antibiotic (broad spectrum) andA = Antitetanus / Gas gnagrene antitoxins. The antivenin (monovalent/polyvalent) should be administered IV at the rate of 100 ml. (small animals) or 10-50ml. (large animals). Administer antivenom with 1:00 epinephrine (0.5-1 ml. s/c) to avoid shock. (Note: - Anitivenom should be stored at 40C. Do not administer if they are discoloured or after the date of expiry.) Apply 1-2ml. of antivenin over the wound (site of bite in case of viper bite. Monitor the cardio vascular activity constantly. Narcotic analeptic is recommended in case of cobra bite to counteract intense
108
pain. Epinephrine and corticosteroid to overcome hypotension and shock. Employ plasma volume expander (6% dextran-40) and calcium gluconate to reduce hemolysis. In case of viper bite, even if the patient survive, amputation may be performed to avoid spread of local tissued necrosis or gangrene formation. *****
A NOTE ON DRUGS MODIFYING ABNORMAL BEHAVIOUR IN PETS

U.SUNIL CHANDRA
Drugs modifying the abnormal behavior of animals are generally more effective if combined with behavior modification methods. The factors associated with animal behavioural disorders like etiology, predisposing factors, condition and the owners cooperation should be taken in to consideration before selecting a suitable pharmacological agent for behavioural abnormalities in small animals. Common behavioural problems noticed in companion animal species are aggression, house soiling, excessive vocalization, nocturnal restlessness, separation anxiety, fears, noise phobias, repetitive and compulsive disorders, cognitive dysfunction syndrome (neurodegenerative disorder). Considerations in drugs modifying abnormal behaviours: The majority of the drugs prescribed for behavioral problems in pets are unlicensed and not registered for veterinary use and will be used in an extra-label fashion., with few exceptions . Clients must be made aware of this and informed consent forms should be obtained before initiating the treatment. Many behaviour problems are not "cured", but can be managed or controlled. The client cooperation over administration of these drug is an important consideration as many of the drugs take a considerable time to produce desirable effects on the animal, requiring relatively long term administration (weeks to months). Drugs should always be considered as an adjunct to behaviour modification therapy, not as a replacement/ substitute. Client compliance is important as behaviour modifying drugs may take up to six to eight weeks to reach therapeutic blood concentrations. Drug therapy should always be gradually withdrawn. Behavioural modification techniques commonly
108
employed includes treatment of any concurrent disease, environmental manipulation, which can often be difficult to achieve in practice and surgery such as castration/ neutering (for aggression, urine spraying etc) . An overview of the classes of medications used as behavioural modifying drugs in behavioural abnormalities of dogs and cats are described in this article. Benzodiazepines (BZDs): The agents are oxazepam, clorazepate, lorazepam, temazepam, clonazepam, diazepam and alprazolam, the last two being most commonly indicated for treatment of anxiety related behaviour problems like urine spraying and short treatment for sound phobias (eg: fireworks, thunderstorms) because of their episodic nature and the rapid onset of action in dogs and cats. Cats may stagger for the first 3 - 4 days, which If it does not resolve, dose should be decreased or withdrawn as the potential for cumulative effects and toxicity due to the intermediate metabolite may occur.Oxazepam, is preferred in patients with liver disease. Responses to diazepam are highly individual, so that dose response must be titrated. Diazepam should be given prior to an anticipated fearful or phobic event. Adverse effects of ataxia, hyperexcitability and disinhibition. Alprazolam used in advance of an expected fearful or phobic event in the same way as diazepam. However, alprazolam may also be given after a phobic event in order to impair the dogs memory of it. It may be used to block the effects of unanticipated phobic events in order to prevent them from having an emotional impact on the animal in the future. The same caution as with that of diazepam apply with this drug. Tricyclic antidepressants (TCAs): They are indicated for anxiety related behavioural disorders in dogs and cats such as separation anxiety, obsessive-compulsive behaviors, stereotypies, aggression, and inappropriate elimination, urine spraying in cats, feline hyperaesthesia, compulsive disorders and behavioural problems secondary to idiopathic cystitis. Clomipramine and amitryptilline are the TCAs licensed for use in veterinary medicine., commonly used for separation anxiety, anxietyrelated aggression, urination due to submission or excitement, allergyrelated pruritus, urine marking and hypervocalization. The most common side effects are short term lethargy or sedation, mild and intermittent vomiting which is usually transient and increases or decreases in appetite. The antihistaminic effect of these agents may be a
108
useful adjunct in controlling pruritus due to atopy and food allergies. If urine retention or constipation occurs, stop administration until normal urination or defaecation is observed then reinstate at a lower dose. Contraindicated in animals with seizures, urinary retention or history of cardiac arrythmias and within two weeks of administration of a monoamine oxidase inhibitor. Selective Serotonin ReUptake Inhibitors (SSRIs): The most commonly used ones in small animals are fluoxetine, sertraline and fluvoxamine which have been used for treating psychogenic alopecia, allergy-related pruritus, anxiety related conditions, dominance-related aggression, fearful behaviors, obsessive-compulsive behaviors, and urine marking. Fluoxetine is approved drug in dogs, for inter-dog aggression in conjunction with behavioral training and neutering of the less dominant dog. Fluoxetine is also used for the treatment of obsessive-compulsive disorders in dogs. It reduces the clearance of diazepam, its active metabolite nordiazepam and alprazolam, so concurrent use should be avoided. Monoamine oxidase inhibitors(MAOIs): Selegiline is licensed preparation for the treatment of sound phobia problems. This reduces fearfulness, increases exploratory behaviour and has positive effects on cognition even in healthy animals. It takes 4-8 weeks to begin to become effective, and is a useful adjunct to behavioural therapy, especially in individuals that are frequently exposed to noise events, show signs of a generalisation or are inhibited in situations when they are fearful or anxious. For example, the drug might be used to increase the confidence of a dog that has become afraid of going outside after dark due to a number of fearful experiences. Azapirones: Buspirone is the only member, advocated for treatment of mild to moderate anxiety related problems and urine spraying in dogs and cats. Contraindicated in case of renal, hepatic impairment, epileptics, allergic reactions and caution is needed as treatment can lead to an increase in aggression as it may decrease the inhibitory effects of fear. It is ineffective in cases such as sound phobias or separation anxiety in dogs. Beta blockers: Porpranolol and pindolol are the common ones, indicated in treatment of situational anxieties in dogs and cats, used before the anticipated situation occurs. They are contraindicated in animals with cardiac disease, hypotension, and bronchospasm.
108
Hormonal preparations: cabergoline are the hormonal preparations used in treating behavioural practice. Progestins should only be given to neutered animals and used with caution. They should be avoided in diabetes mellitus, breeding animals and with concurrent corticosteroid use. The antiandrogen commonly used is delmadinone acetate. Cabergoline has antiprolactin effects and is recommended for the treatment of psedopregnancy in bitches and in spayed bitches with aggressive behaviour attributable to elelvated prolactin levels. Antihistamines: They are useful in the management of mild anxiety associated with travel, inappropriate night time activity and anxiety conditions in which pruritus plays a important role. They are contraindicated in animals with glaucoma,urinary retention and hyperthyroidism.Diphenhydramine and cyproheptadine are the H1receptor antagonists that are successful in some cases of spraying in cats. Alpha adrenoceptor stimulants: Phenylpropanolamine used in the treatment of sphincter mechanism incompetence in bitches and used to manage house soiling in these cases. Increased aggression is the possible side effect. Alpha adrenoceptor antagonists: Nicergoline is advocated for sleep disorders, diminished vigour and fatigue. It should not be administered within 24 hours of using alpha 2 agonists such as xylazine or medetomidine. Xanthine derivatives: Propentofylline is licensed for canine age related behavioural changes such as dullness, lethargy and cognitive decline,which respond better if combination therapy with selegiline is used. Neuroleptics (Antipsychotic agents): Low potency phenothiazine tranqillisers (acepromazine, chlorpromazine, and thioridazine hydrochloride) commonly used for sedation and restraint purpose, have side effects of sedation, anticholinergic effects, and -adrenergic blockade. High-potency agents (haloperidol, fluphenazine, trifluoperazine hydrochloride, prochlorperazine, thiothixene, risperidone) result in less sedation and fewer autonomic side effects but commonly result in extrapyramidal effects. Acepromazine is used as a short-term tranquilliser during phobic events related with fireworks and thunderstorms and travel associated behaviour problems. Oral dosing
108
produces unreliable effects, and onset of action may vary between 15 and 60. High doses may be required in order to sedate a dog during a phobic event. High doses may lead to hypovolaemia, hyperexcitability and extrapyramidal side effects in some animals. For these reasons it is not considered suitable for the management of canine noise phobias.
Dosage , route and frequency of administration of drugs used in behavioural abnormalities of dogs and cats( po=oral, IV=intravenous, SC=subcutaneous, bid= twice a day, tid=three times a day, sid= once daily)
BZDs: Diazepam Dog-0.55 -2..2 mg/kg po sid-bid; Cat- 0.2 - 0.4 mg/kg po sid-bid; Alprazolam- Dog- 0.01-0.1mg/kg,PO,bid, Cat -0.125 - 0.25 mg/cat po bid. 0.1mg/kg tid or as needed ; Oxazepam- Dog-0.2 1.0 mg/kg po sid-bid; Cat- 0.2 - 0.5 mg/kg po sid-bid; Clonazepam- dog-0.1 0.5 mg/kg po sid-bid, cat-0.016 mg/kg sid-qid; Clorazepate-dog-0.01-0.1 mg/kg po bid, cat-0.125-0.25 mg/kg po bid; TCAs: Amitriptyline -dog1-2mg/kg,po,bid, cat-0.5 - 1.0 mg/kg po sid; Clomipramine:dog--13mg/kg,pobid , cat- 0.25 - 0.5 mg/kg po sid; Nortriptyline : Dog- 0.5 - 1.0 mg/kg posid-bid , cat-0.5 - 1.0 mg/kg po, sid-bid; Doxepin: dog- 35mg/kg.po,bid,cat-0.5-2.0mg/kg/po,bid SSRIs: Fluoxetine: dog, cats- 0.5-1mg/kg,po,sid; Fluvoxamine : dog-12mg/kg,po,sid, cat-0.25 upto 1 - 2 mg/kg po bid; Sertraline: dog-12mg/kg,po,bid; Paroxetine:dog,cat-1mg/kg, po, sid; Azapirones: Buspirone: dog-1mg.kg, po,bid-tid, cat-0.5-1mg/kg, po, bid-tid (Total 5mg/cat); MAOIs: Selegiline:dog,cat- 0.5-1mg/kg, po,sid; Beta blockers: Propranolol dog- 0.5-3mg/kg,po,bid , cat- 0.2-1mg/kg,po,bid ; Pindolol dog-0.125-0.25mg/kg,po, bid; Antiepileptics: Phenobarbitone: dog-1-8mg/kg,po,bid, cat-1-2.5mg/kg,bid; Carbamazepine: dog- 4-8 mg/kg,po,bid; cat- Total 25mg, po,bid. Others:Dextroamphetamine:dog-0.2-1.3mg/kgpo,bid;Methylphendiate: dog-2-4 mg/kg,o,bid; Cabergoline:dog-5 mg/kg,po,sid;Phenylpropanolamine: dog-1.1-4.4 mg/kg,po,bid, cat1-1.5 mg/kg,po,bid; Nicergoline: dog- 250-500 g /kg,po,sid; cat- total dose1.25mg, po, bid; Propentofylline: dog-2.5-5 mg/kg,po, bid , cat-total dose-12.5mg, po, sid; Cyproheptadine dog-0.4 - 0.5 mg/kg po bid, 2 4mg/cat bid-tid; Diphenhydraminedog- 0.4 - 0.5 mg/kg po bid, 2 4mg/cat bid-tid; Medroxyprogesterone Acetate : Dog and cat - 10 mg/kg(female) 20 (male) SC max : 3 injections per year; Megestrol Acetate: Dog, cat-2.5 - 5 mg po sid; Acepromazine dog- 0.5-2.25mg/kg, po, tid, cat- 1.13-2.25mg/kg, po, tid *****
108
DIAGNOSTIC TESTS FOR DETECTION OF COMMON TOXICANTS

SNEHAL.M.BANSOD
Detection of Heavy metals: Place 10g of tissue (finely minced) in a beaker or test tube.Add 10 ml of 10% HCl.Introduce a copper wire into the test tube Boil for 10-15 min. (Do not inhale fumes) Remove the copper wire and place it on a filter paper Observe the colour of the copper wire. Inference: Black coloration - Arsenic or Bismuth; Shining silver deposit Mercury; Dull white deposit Silver; Dark colour with purple to blue; violet green - Antimony. Depending on the colour of copper wire the confirmatory test is conducted.If the deposit is black it can be confirmed whether it is due to arsenic or bismuth by placing the copper strip in 1-2 ml. of 10 % potassium cyanide. If the deposit is due to arsenic, it will dissolve, but if it is due to bismuth or antimony, it will persist.In mercury, colour of the deposit ranges grayish (50 mg) to shiny silver (100 mg). Detection of lead : Mince the liver/kidney piece or collect a small amount of scraping from stomach wall.Add a few drops of conc. nitric acid and heat gently till dry, (never over heat the sample as it turns black making reading difficult). Add a few drops of water and two drops of 10% pot. iodide solution.Development of yellow colour indicates presence of lead. Detection of Cyanide: a) in biological material: Take 50 g of finely ground tissue or stomach contents in a 100 ml flask and acidify thecontents with tartaric acid. Take a filter paper previously moistened with 10 % of guaiacol in alcohol and 0.1% of aqueous copper sulfate solution.Plug the mouth of flask and warm gently. Allow it to stand for 30 minutes. Observe the colour of paper. If cyanide is present, a blue colour develops. b) in the plant sample: Preparation of sodium picrate paper-Dissolve sodium bicarbonate 5 g and picric acid 0.5 g in 100 ml of distilled water. Cut filter paper into strips of 2. x 6. size. Dip the strips in the reagent and dry in cool place. Take the given sample in a test tube and add a few drops of water and chlorofom. Plug the test tube with cotton, hanging the dried picrate paper inside the test tube. The paper should not touch the fluid in the tube. Heat the tube gently till fumes evolve. Observe the colour of paper.If the colour of paper changes from yellow to brown it indicates that the plant sampleis positive for cyanide.(The leaves and stomach contents are to be frozen immediately after collection inpolythene bag as CN is likely to evaporate). Detection of fluorides: To a small quantity (1-3 ml) of urine or stomach contents add 3 ml of sodium hydroxide solution in a glass or porcelain dish.
108
Add a little quantity of powdered glass and mix thoroughly. Apply moderate heat till dry. Add 10 ml of concentrated sulfuric acid and cover the dish with a small plate from the under surface of which is suspended a drop of 5% sodium chloride solution. Place a small piece of ice on top of the plate to prevent evaporation of the drop. Heat gently for 3-5 min., carefully remove the drop and examine under low power of microscope. If the given specimen contains fluorides, silicon fluoride is formed which appears as small light pink hexagonal crystals along the rim of the drop, whereas the crystals of sodium chloride are large and square. Detection of Nitrite: a) Draw blood (10 ml) without anticoagulant from an affected animal and also from a known normal animal in 20 ml capacity test tubes.Place them in boiling water bath for 45 minutes. Cool them.Observe the colour of the blood and the surface.Blood sample containing nitrite is Salmon pink in colour, does not pull away fromthe side and the surface is level or concave. Normal blood sample is chocolate brown,pulls away from the side of tube and the surface is convex. b)In a plant sample: Dissolve 0.5 g of diphenylamine in 20 ml of distilled water and make up the volume to 100 ml with sulfuric acid. Store it in amber colored bottle. This is a full strength solution and can be made into half strength by diluting with equal parts of 80% sulfuric acid. To test a plant, place a drop of the reagent on the cut surface of plant. Observe the colour.A green to blue colour indicates the presence of nitrate.(A green to blue colour with a half strength solution indicates positive (++) for nitrate, which could be toxic to animal). Detection of Oxalates: a) 1ml of sample in a test tube, adding equal amount of 0.5% Congo red imparts a violet colour if oxalic acid is present. b) Solution of oxalic acid or oxalates decolorizes 1% Potassium dichromate acidified with sulfuric acid. c) 1ml of sample in a test tube, adding equal amount of 0.1% silver nitrate, produces a white precipitate of silver oxalate soluble in ammonium hydroxide as well as nitric acid. d) Take 1ml of sample in a test tube add equal amount of 25% calcium chloride, it gives a white precipitate of calcium oxalate, insoluble in acetic acid. Detection of zinc phosphide : Occurrence of poisoning depends on detection of gas phosphine which is rapidly lost on opening of carcass.Cut the samples received in to small pieces and weigh 10 gram of sample, grind it in a mortar & pestle with a small amount of distilled water. Take the grinded mixture in a screw capped test tube and add 2 ml of concentrated hydrochloric acid so as to acidify and to start reaction. Fill the Th of the tube with distilled water & put the filter paper soaked in 5% silver nitrate solution on the mouth of the tube and close the tube with the help of screw
108
cap. Keep the tubes in boiling water bath until the sample in the tube starts boiling (To absorb the fumes of the sample) . Cool the tube and observe the filter paper for interpretation. If the filter paper turns black, then it is suggestive for the presence of zinc phosphide, if there is no change in colour of filter paper then that sample does not contain zinc phosphide.
*****
CLINICAL MANAGEMENT OF COMMON TOXICITIES OF VETERINARY IMPORTANCE

VIJAYKUMAR.M
In veterinary field toxicities are often found as a result of ingestion of poisonous substances while grazing or through water. Suspicion of poisoning is also aroused when illness occurs in a number of previously healthy animals, all affected at a same time, sharing the same signs, necropsy findings, to the same degree of severity. Poisoning in most occasions is accidental in farm animals, but may occasionally be deliberate .
INSECTICIDES
Insecticides are the major source of poisonings in livestock.. Most of the insecticides are basically neurotoxic, hence they may share some of the clinical signs, Insecticides can be classified in to following categories: 1. Organochlorines: Eg: Aldrin, Endosulfan, Lindane, Dicofol etc 2. Oraganophosphates. Eg: Acephate, Malathion, Parathion, Methyl parathion, Dimethoate, Phosphamidon,, Chlorpyriphos, Chlorfenvinphos, Monocrotophos etc 3. Carbamates. Eg: Carbaryl, Metacil, Dimetan, Pyramat etc. 4. Pyrethroids (Synthetic): Deltamethrin, Cypermethrin,Permethrin, Allerthrin etc. 5. Miscellaneous: Chloronicotinic acid (nicotine), Arsenic compounds,Captan Organochlorines: By virtue of their high lipid solubility these agents can enter the neuronal membrane with ease and therefore interfere with normal functioning of the nerve membrane sodium channel. The clinical signs of toxicity can be broadly categorized in to:Behavioural signs - Anxiety, aggressiveness, abnormal posturing, maniac symptoms like jumping over inanimate objects, wall climbing etc. Neurological
108
signs Hypersensitive to external stimuli, spasm and twitching of freand hind quarter muscles, fascicualtions of facial and eye lid muscles and variations in body temperature (subnormal temperature to hyperthermia, up to 116F). Autonomic effects: Marked salivation (normally thick/ sticky saliva), Mydriasis, frequent urination, defecation and lacrimation. Organophosphates: Clinical essentially appears as a result of irreversible inhibition of AChE, causing accumulation of acetylcholine in the neuro-muscular junction leading to spastic paralyses. The cause of death is due to respiratory collapse. Muscaranic signs (miosis, watery, drooling saliva, urination, colic and /or defecation, lacrimation are the common signs followed by nicotinic effects (muscle fasciculations, tremors) and C.N.S effects( ataxia, convulsions and later depression of respiratory and circulatory centers). Hypotension, bradycardia and dyspnoea are observed in poisoned animals. Carbamates: The inhibition of AChE enzyme by carbamates is reversible, therefore, on most occasions animals recovers on own unless ingested large quantity of pesticide. Synthetic pyrethroids: Although these compound process low insect: mammalian toxicity ratio, treatment of poisoned animals may be a difficult task probably because of multiple mechanisms involved in toxicity and variations among pyrethroid class (type-I & type-II). Hypersalivation, lacrimation, mucoid nasal discharge, excitement, incoordination, extension of limbs are observed in deltamethrin toxicity in buffalo calves. Few pyrethroids also cause contact dermatitis.
RODENTICIDES
Anticoagulant rodenticides: These include warfarin (less used now a days) and second generation anticoagulant rodenticides viz: Bromadiolone , brodifucoum. The main source of poisoning is the ingestion of residues of the rodenticides or baits intended for killing rodents.. The poor coagulation mechanism cause massive internal haemorrhages over aperiod of time. Normally after period of about 2-5 days clinical signs appears and these include anorexia, pulmonary coughing (epitaxis, dyspnoea),hypothermia, haematuria, stiffness of hind quarters and sudden death. Internal haemorrhage, blood in the GIT(gastroenteritis), haemopericardium and menigeal/cerebral bleeding and haemorrhages in joints are the pathological lesions one can observe during necropsy. The affected animals should be shifted to
108
quiet and warm place and the line of treatment include Vitamin-K 1 in physiological saline (Vitamin-K3 not recommended) and cardio-vascular support. Zinc phosphide/ Aluminium phosphide: It is one of the cheapest and quite effective rodenticide. Monogastric species are more sensitive rather than ruminants. Clinical signs include anorexia, lethargy, abdominal pain, bloat (in ruminants), deep respiration, ataxia, prostration and dyspnoea, gasping, convulsions and death. Postmortum lesions include pulmonary congestion, edema, sub-pleural haemorrhages, congestion of liver and kidneys. Acetylene odour may be detected in stomach. No specific treatment is possible, however symptomatic and supportive care maybe given. Gastric lavage with 5% Sodium bicarbonate, Calcium boro-gluconate injection, anticonvulsants and measures to prevent shock can be undertaken as a life saving measure.
HERBICIDES AND FUNGICIDES
Dinitro-compounds: Dinitrophenol, DNP; dinitro-orthro cresol, DNOC); are some of the commonly used as herbicides. Accidental ingestion of foliage sprayed with these compounds may lead to toxicity in ruminants. These compounds induce methaemoglobinemia (intravascular haemolysis),hyperthermia, dark coloured blood and gastroenteritis. Rapid onset of rigor mortis, yellowish-green coloured tissues/urine may be recorded during post mortem examination. Zeneb & Thiram: Zeneb (Zinc-ethylene dithiocarbonate) and Thiram (Tetra-methyl thiuron sulfide) are the two most commonly used fungicides in agricultural practice. Although acute poisonings is less likely to observe in field, chronic toxicities may get unnoticed. Zeneb can induce thyroid hyperplasia, hypothyroidism, degenerative changes in myocardial, skeletal tissues and depletion of testicular germ cells. Thiram exposure may cause conjunctivitis, rhinitis, bronchitis, abortion (ewes) and teratogenic effects.
HYDROCYANIC ACID (HCN) /CYANIDE
The most prevalent form of HCN poisoning in livestock is caused by various cyanogeneetc plants capable of producing hydrocyanic acid. Such plants contain cyanogenetic glucocides (dhurrin in sorghum, amygdalin in bitter almond etc.) which hydrolyzed in to HCN in ruminants. Wilted, drought affected, injured (chopping, rinsing etc.) plants are more dangerous than fresh plants because of their
108
preformed HCN. Any plants possessing 20mg HCN per 100gm (wet wt.) may serve as potential source of HCN poisoning. Other source of cyanide poisonings are: industrial grade Na/K and calcium cyanide (also fertilizer) and effluents from vicinity of electroplating/metal coating industries workshop. Hyperoxygention of blood would lead to cherry red/ bright red colour of venous blood . Intoxicated animals shows salivation (frothy), bradypnoea, mydriasis, ataxia,tremors, epileptiform scizure, cardiac arrhythmia and clonic-tonic convulsions. Invariably loss of conscious, coma and death with several jerky and convulsive movements if poisoned animals are not attended with in a with in 1 hour after the appearance of clinical initial signs. Odour of the breath is ammonical/ bitter almond due to benzaldehyde production (often bloating, regurgitation is observed). Opening of rumen during post-mortem examination impart similar odour. Animals suspected for HCN poisoning must be differentiated from nitrite and other si milar agents before initiating antidote therapy . In addition to antidotes, per oral administration of Cobalt chloride(10 mg/kg)and glucose is also indicated. Treatment: Administer 1% sodium nitrite @ 15-25mg/kg,i.v followed by 25% sodium thiosulphate @ 1.25gm , slow i.v ; Na nitrite + Na thiosulfateCattle: 3gm + 15gm in 20ml water, s.c; Sheep/goats: 2gm+5gm in 15ml water,s.c. Cobalt chloride @10.2 mg/kg, per os; Approx. 4 lt. vinegar in 10-20lt. cold water; A large dose of vitamin B12 and anticonvulsants, if necessary. Give cobalt chloride 10mg/kg perorally. Fluid therapy with dextrose-saline is ideal
NITRATE/NITRITE
Drought is one of the root causes of nitrite toxicity in cattle/buffaloes. Nitrates are reduced to nitrite in ruminates. Otherwise, pigs are most sensitive species for nitrate toxicity. Contamination of drinking water with sewage, several plants species (Amarantus sps,Palak etc.), plants grown in highly acidic soil, water logging and rich nitrated fields / effluents zone, deep well water or pond water originated from leaching of top soil (after -nitrate fertilizer application) are some of the common source of nitrite poisonings. Water soaked/entry of moisture may also render paddy hays/ corn in to nitrite rich within 18-22 hours. Frequent application of fields with non-toxic weed killer 2,4-D and nitratic fertilizer favour accumulation of nitrtes in
108
plants. Any forage that contains over 1.5% nitrate (expressed as pot. nitrite) is considered relatively unsafe for livestock and should be fed with extreme caution. Nitrite ions induce meth-haemoglobenaemia as well as marked vasodilatation. Clinical signs include cyanosis, staggering gait, muscular tremors, rapid pulse, dyspnoea and dilated pupil. Opisthotonus, polyurea, chocolate brown colour of the blood and cyanotic mucous membranes are the characteristic features of nitrite toxicity. Untreated animals die with out a struggle. Reducing agents like Methylene blue or Ascorbic acid are the antidotes . Treatment: 1% Methylene blue @ 8.8mg/kg, i.v and repeat 30 min later and if necessary administer at 6-8hr. interval Broad spectrum antibiotics intra-ruminally; Administer 8-10L cold water and give osmotic purgatives Treat for hypotension/shock, (vasoconstrictors like 1:1000, 0.5 ml adrenaline, slow iv); Blood transfusion, if possible Mineral oil or mucilaginous substances and diluted vinegar (4-5 lt. in cold water, per os) must be administered to counter GI irritation and further reduction of nitrates in the rumen respectively. Cardiovascular support (vasoconstrictor); and stimulants to counter prostration.
POISONOUS PLANTS
Toxicities/ death due to ingestion of poisonous plants are also often being the etiology of poisoning in the farm animals. Commonly with plant poisonings there are perplexing epidemiological features. For example, animal already grazing in the dangerous field are often unaffected while recently introduced may be poisoned. Drought, starved, ailing from pica, hungry, ravenous animals, curiously excited animals (often do not eat), and young animals less discriminate plants with different texture (attraction). Poisonous plants often show geographical limitations in their distribution, particularly industrial enterprises may create poison hazard in local areas (Ipomea carnea, Amaranthus spinosus) and certain agricultural practices / soil type may also pose toxicities (eg. Nitrite, Selenium). Severe drought followed by rain/moisture/humid atmosphere favour accumulation nitrite in many plants. Similarly re-emergence of fresh leaves following harvesting also contains dangerous levels of HCN. Essentially the source of plant poisoning can be classified into: a. naturally occurring b. Commercial crops/byproducts and c. Conventional and non-conventional fodders. Immature sorghum, maize, flax (linseed); Manihot esculenta (tapioca) newly emerging bamboo shoots and rubber leaves are the common source of HCN poisonings. Accidental ingestion
108
of castor bean, rotten beat roots, adult nicotine leaves,Mimosa invisa (used to increase nitrogen fixation in soil) may become fatal.. Plants or foliage belonging to Brassicaceae sps.(Cruciferae) family i.e kale, rape,turnip, cabbage,reddish plants and mustard seeds or meal may elicit severe toxicities in animals when fed /ingested large quantity due to the presence of glucosinolates in such plants..Digestive disturbance(enteritis),goiter polioencephalomalacia (rape blindness), pulmonary emphysema are the sequelae. Bloat, photosensitization is also observed. Affected animals are to be treated symptomatically. Feeding of urea treated straws in excess/or fed to un-acclimatized animals may lead to urea poisoning, long term feeding of subabul may lead to hypothyrodism and feeding of fungus infested straws (sorghum, paddy or leguminous fodders) may pose threat of mycotoxicosis when fed relatively for a long period. Ficus tsjhela (Karnataka-Kerala boarder, Western Ghats); Acacia leucopholea (HCN), Amaranthus spinosus (nitrite); Jatropa curcus (purging nut); Crotalaria juncia (hepatotoxic pyrrolizidine alkaloids: monocrotaline);Flax(linseed, HCN); Ipomea carnea (LSD alkaloid like effects, also source of nitrite and cause photosensitization). Strychnous nux-vomica (coastal Karnataka); Abrus precatorius (Gulaganji); marking nut, Calitropis gigantica (yakka), croton oil and Yellow oleander are also some of the plant source of accidental poisonings and/or recorded in case of malicious poisoning in animals. Antidotes and supportive treatments for common poisonings in large animals
Poison/toxicity Heavy metals (Arsenic,antimony , mercury) Arsenic/Mercurial insecticides) Arsenic poisoning Antidote/ treatment British Lewisite(BAL) Dosage and method of treatment anti- BAL: 3mg/kg as 5% mixture of 10% benzyl benzoate in mineral oil. Give deep i.m injection every 4hr. on first two days, every 6hr. on third day and then b.i.d for next 10 days. In cattle and horse d-penicillamine sodium thiosulfate can also be used @ 8-10gram in the form of 10-20%solution (i.v) or 2030gram per-orally in 300ml water. Fluid therapy and other supportive treatment as required. Administer @ 30-40mg ,i..v + 60-80mg/kg; P.O, b.i.d or t.i.d for
108
Strychnine (Strychnous- nux vomica)
Lead
Warfarine Bromodiolone
Pyrethroids (Deltamethrin, Cypermethrin etc.) Carbamate insecticides Organophosphate s
Organochorines ( D.D.T;, B.H.C & endosulphan etc.,) Dinitro-herbicides (Dinitroorthocresol-DNOC & DinitrophenolDNP)
3-4 days Phenobarbital Phenobarbitone sodium sodium,30mg/kg,i.v Chloral hydrate Chloral hydrate @ 5g/45 kg, i.v Drench tannic acid and then purgative Rest the animal in cool, noise free & in dark room after a dose of purgative Calcium disodium Make 6.6% solution and EDTA administer @ 73 mg/kg,i.v (repeat or two treatment daily for 3 days if required). Combined thrapy with thiamine HCl @24mg/kg/day, s.c is more effective, Anticonvulsants, if required Vitamin- K1 Vitamin-K1: 300-500mg, S.C,every 4-6hr.Blood transfusion transfusion @ 20ml/kg or plasma @ 9ml/kg body wt; Sedatives/tranquilizer No specific antidote, Diazepam: 0.5-2 mg/kg, Diazepam HCl + i.vAtropine SO4 as required Atropine SO4 Activated charcoal (1-2kg), P.O Fluid therapy Atropine sulphate 0.25mg-0.5mg/kg,give intravenously and remaining by intra-muscular or subcutaneous route Atropine sulphate + Atropinization: 0.25mg2-PAM 0.5mg/kg,give i.v,remaining Or by i.m or s.c for every 3-6 hours. DAM(diacetyl Observe for papillary dilatation -monoxime) and recovery symptoms and continue treatment as required. 2-PAM: 20%solution @ 2550mg/kg,i.v or intra-muscualrly, Activated charcoal,P.O Fluid therapy and supportive care Pentobarbitone 30mg/kg,i.v and supportive care sodium Or 5g/45 kg ,i.v and supportive care Chloral hydrate In ruminants only: Treat for methaemoglobinemi a with methylene blue Or Ascorbic acid Methylene blue: 2-4%,810mg/kg,i.v every 8hr. Or Ascorbic acid: 5-10mg/kg,i.v; every8hr. for first 24-48hr.Note: Do not give antipyretics. Administer saline purgatives, DNS
108
Other Antidotes of clinical importance poisonings
used in various
Acepromazine maleate: (Acetyl-promazine): Indicated in seizures associated with amphetamine methamphetamine, 4-Methylimidazole, metaldehyde poisoning,usually preceding use ofbarbiturate or other anticonvulsant. Contraindicated in organophosphate or strychnine poisoning Dose: Dogs, Cats-0.03-0.05 mg/kg IV, IM;Swine-0.1-0.2 mg/kg IV, IM;Cattle, Horses- 0.02-0.1 mg/kg IV, IM;Sheep-0.03-0.05 IV; Goats 0.03-0.1 mg/kg Acetic acid (Dilute 4%-6%)/ : Indicated in Ammonia toxicosis; urea, carbon monoxide, hydrogen sulfide, and opiate, metallic salts; arsenic, selenium, tin, thallium, antimony Sheep, Goats-0.5-1 L/ animal/ PO Cattle, Sheep,Goats- 5-7 ml/kg of a dilute solution 1:4 or 1:5 with water or 20% DextrosePO Aminophylline/ Theophylline: Respiratory stimulants, used in benzodiazepine type poisonings: flurazepam, midazolam, forazepam. Dose: Horse- 4-15 mg/kg PO, IV; q8-12h Dogs- 4-10 mg/kg PO, IV; q812h Amyl Nitrite/ Isoamyl Nitrite/ Isopentyl Nitrite/: indicated in cyanide, hydrogensulfide, acrylonitrile,chloroform, iodine,nitrates and strychnine poisonings. Cattle,Horse -30-60 minute inhalation; Dogs- 1.55 minute inhalation Activated Charcoal: (10%): Carbon absorbent which absorbs toxic substancesand irritants, non-specific organics Not effectivefor minerals (elemental,acids, salts, alkalis), nor oils. Cattle, Sheep, Goats-1.0-3.0 g/kg PO; Horses-0.5-1.65 g/kg PO; Dogs,Cats -2-8 g/kg PO Atipamezole HCL: Indicated in medetomidine, xylazine,amitraz, midodrine, and phenylepherine overdose poisoning and Dogs- 50 mcg/kg IM q3-4h . Yohimbine HCl is alpha adrenergic antagonist with weak monamineoxidase (MAO) inhibition. Used in the treatment of drug overdose and poisoning of : Amitraz, Xylazine, Clonidine. Ascorbic acid(Vitamin C): indicated for drugs, plants and metal poisonings; copper,iron, selenium,chromium,cobalt,lead,arsenic,nitratenitrite,chlorates,aniline, hydrazine,hydroquinones, benzocaine, phenacetin, potassium permanganate, quinines, toluidine,sulfonamides, acetaminophen, ,Johnson Grass(Sorghum), Feed Grain plants that have been stressed with drought or herbicide and thereby accumulate nitrates. Cattle, Horses - 7.5-15 mg/kgIV,IM,SQ,PO;Dogs,Cat1025mg/kgIV,IM,,PO;Rabbits, Rodents100mg/kgIV,IM,SQ,PO;Swine,Sheep5-10mg/kgIV,IM,SQ,PO;Goats-2.5-5mg/kgIV,IM,SQ,PO.
108
Atropine Sulfate (dl-Hyoscyamine): Indicated in Poisonings: carbamate and organophosphatepesticides:Aldicarb,Fumarate,Bromophos,Carbaryl,Chl ofenvinphos,Chlorpyrifos,Diazinon,Dicrotophos,Dioxathion,Disulfaton,Fe nsulfothion,Fenthion,Malathion,Methidathion,Methiocarb,Methomyl, Parathion,Profenphos, Propoxur,Terbufos, Tetraethyl, pyrophosphate, Sarin, Soman, Tabun, Paraxon, Tacrine HCL,Baclofen, Bethanechol chloride, Bisprolol, Chloroform,Nicotine,Mushroom,CarbolicAcid, Phenol,Benzene,physostigmine,Nitrobenzene, Cyanides,Opium, Morphine, as well as to treat poisoning associated bradycardia,hypotension. Dose: Cattle, Horse,Dog, Cat, Swine,Sheep, Goats, Birds,Reptiles, Rabbits, Rodent -0.1-2.0 mg/kg administer dose IV ;with the remainder SQ or IM Calcium gluconate/ Calcium borogluconate: (Calcium chloride; Calcium lactate) : Indicated in hypocalcemia and cardiac dysrhythmias associated with hyperkalemia: Lead, Fluoride, Carbon tetrachloride, Ethylene glycol, Oxalic acid, Chlorinated hydrocarbons, Hydrogen fluoride, Hydrofluric acid, Calcium channel blockers (Nifedipine,Diltiazem),Phosphine, Hypermagnesemia, Oxalates. Dose: Ca gluconate: Cattle, Horses, Sheep,Goats, Swine -150-250 mg/lg IVslowly, PO; Dogs, Cats 25-150 mg/kg IV slowly PO; Birds 50-100 mg/kg IV slowly ,PO Ca chloride: Cattle,Horses25-125 mg/kg IV slowly PO; Sheep,Goats20-30 mg/kg IV slow,PO; Swine- 20-60 mg/kg IV ,Dogs, Cats 5-50 mg/kg IV slow; Ca lactate: cattle, Horses, Goat, Sheep- 40250 mg/kg PO ; Swine-40-500 mg/kg PO PRN; Dogs, Cats-30-150 mg/kg PO Diazepam/ Methyl Diazepam: Anticonvulsant and Anxiolytic, indicated in the treatment of seizures that may be caused bydirect toxic effects or secondary to hypoxia or other metabolic or electrolyte disturbance; Isoniazid, Lithium, Salicylates, Theophylline,Caffine, Theobromine, Amphetamines, Nicotine, Atropine, Aminopyridine,Lead,Metaldehyde,Cyanides,Fluoroacetate,Mycotoxins,O rganochlorines,Organophosphates,Carbamates,TricyclicAntidepressants ,Strychnine, Cocaine, Opioids, Mefenamic Acid, Methylxanthines, Phenylethylamines, Ergot Alkaloids . Dose: Cattle, Sheep,Goats -0.5-2.0 mg/kg IV, IM; Horses -0.5-50.0 mg/kg IV, IM ; Swine- 0.5-10.0 mg/kg IV, IM; Dogs- 0.5-5.0 mg/kg IV, IM; Cats-0.5-2.5mg/kg IV, IM; Rabbits- 0.510.0 mg/kg IV, IM; Birds -0.5-2.0 mg/kg IV, IM Egg white: Natural clear colloidal protein (albumin) mass;denatures, coagulates, and is heat sensitive, has good demulcentproperties. Indicated in thetreatment of mercury,copper, tin, silver,hydrogen peroxide,phenol, picric acid,formaldehyde, ether,alcohol, household cleaners and detergents, corrosive chemical poisonings. Dose: Dogs,
108
Cats, Calves, Foals, Lambs,Kids, Pigs11-2 egg whites/5-10 kg PO; Usually administered with milk Epinephrine: Positive inotrope,cardiovascular stimulantand bronchodilator. Usedin the treatment of insect bite-induced anaphylaxis,insect bite poisoning, drug-induced anaphylaxis, drug poisoning; beta-blocker poisoning, chloroquine,vaccines, ants, Bees or honey bees. Dose: Cattle,Horses, Sheep, Goats, Swine, Dogs, Cats 0.010.02 mg/kg (0.45-0.9 ml 1:1,000/kg) IM,SQ; 0.01-0.02 mg/kg (1:10,000) IV. Gelatin : Heterogeneous mixture of water-soluble proteins derived from natural collagen; absorbent (absorbs 5-10 times its weight), demulcent, stabilizer, thickener, texureizer, and hemostatic sponge. Used in the treatment of household chemical poisoning; aqueous cleaners, bases and alkalis.Dose: Dogs,Cats, Foals, Lambs,Kids, Pigs. (2 tablsp/5-10 kg)3-6 g/kg PO Sodium Bicarbonate/ Baking Soda : Short-acting, potent antacid. Systemic alkalinizer , used to correct metabolic acidosis and to alkalinize urine in poisonings and drug overdose: AmitriptylinePerphenazine, Amitryptyline, Doxepin, Ethylene Glycol, Formaldehyde, Glycol Ethers,Imipramine, Metformin, Methanol, Nortriptyline, Potassium Chloride, Propylene Glycol, Quinidine, Strychnine, Trimipramine Maleate, Ethanol, Salicylates, Chlorphenoxy Herbicides, Jimmyweed and Goldenrod (Isocoma), Sugar Beet (Beta) Dose should be equivalent to of calculated dose administered by slow intravenous infusion. Cattle-70-180 mg/kg PO ; Horses-40-120 mg/kg PO; Sheep, Goats-20-100 mg/kg PO ; Dogs-20-80 mg/kg PO ; Cats-20150 mg/kg PO. Phytonadione/Phylloquinone/Phytomenadione (Vitamin K1): promotes liver biosynthesis and regeneration of clotting factors . Will not reverse the anticoagulant effects of heparin. Used in the treatment of hypoprothrombinemia caused by drug overdose, chemical, rodenticide and plant poisonings: Coumarin, Indandione, Quinidine, Quinine, Salicylates, Sulfonamides, Brodifacoum, Bromadiolone, Chlorphacinone, Hydroxycoumarin, Indanedione, Pindone, Dicumarol, Warfarin, sweet Clover Dose: Cattle, Horses, Sheep, Goats, Swine, Birds- 0.5-2.5 mg/kg SQ, IMdaily; Dogs, Cats -2-5 mg/kg PO, SQ, IM daily in divided dose Dimercaprol: Chelator of metal ions which form soluble sulfhydral group-ion complexes that areeliminated in the urine; used for the treatment of gold, cobalt, antimony,Contraindicated in Cadmium poisoning,arsenic (except arsine), copper, mercury,bismuth, hromium,nickle, tungsten, zinc,and methyl bromide poisoning. and
108
much less effective in lead, selenium and thallium poisoning Dose: Cattle, Horses, Sheep,Goats, Swine, Dogs,Cats- 1-2 mg/kg IM qid;Contraindicated in Cadmium poisoning. Neostigmine: competitive inhibitor of acetylcholinesterase. Used in the treatment of non-depolarizing neuromuscular blocking agents. treatment of curare, atropine, ivermectin, avermectins,tubocurarine, gallamine, atracurium, pancuronium , botulism (Cl. Botulinum), and as a secondary agent in the treatment of Coral and Cobra (Naja) snake bite and Tetrodotoxin poisoning.Dose: Dogs- 0.001-0.05 mg/kg SQ, IM; Cats-0.01-0.04 mg/kg IM; Cattle, Horses- 0.02-0.4 mg/kg SQ, IV; Swine0.03-0.06 mg/kg IM; Sheep, Goats-0.01-0.03 mg/kg SQ;Corticosteroids may decrease effects.
*****
108

Systemic Veterinary Pharmacology and Clinical Toxicology

Caricato da

Informazioni sul documento

Descrizione originale:

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Systemic Veterinary Pharmacology and Clinical Toxicology

Caricato da

Copyright:

Formati disponibili

PHYSIOLOGY OF DOMESTIC ANIMALS:

NUTRACUETICALS AS THERAPEUTICS IN LIVESTOCK HEALTH

permute salmonella shedding

milk Alpha-lactalbumin Beta-lactalbumin Lactoferrin

immunomodulator Immune system defense

1. Superoxide dismutase (SOD): It is an enzyme required for

c. They alter bacterial metabolism system

d. They stimulate immune

Beneficial effect of probiotics and prebiotics:

PROTOCOLS OF DRUGS FOR VETERINARY PATIENTS UNDERGOING SURGERY

1. Strictly it should be given before 30 minutes and not later than 60

Isotonic/hypert onic Isotonic/hypert onic Isotonic/hypert onic Isotonic/hypert onic isotonic

ANAESTHETIC PROTOCOL PROBLEM

TRANQUILIZERS, INTRAVENOUS ANAESTHETICS AND DISSOCIATIVES IN VETERINARY PRACTICE

THERAPEUTIC MANAGEMENT OF PRODUCTION DISEASES OF RUMINANTS

Ruminants, dairy animals in particular undergo a remarkable

ON: DRUGS ACTING ON HAEMATOPOIETIC SYSTEM

DRUGS ACTING ON EYE AND EAR

THERAPEUTIC MANAGEMENT OF DERMATOLOGICAL DISORDERS

PARASITIC SKIN DISEASES

Usage Mild shampoo with antimicrobial acitivity excellent

Antibacterial, Antifungal, Antiviral acid/ Antimicrobial Antifungal Keratolytic

Selenium sulfide Diphenhydrami ne Hydrocortisone L-rhamnose Aloe vera

Keratolytic, Keratoplastic, Degreasing Antipruritic

Occlusive agents that decrease transepidermal water loss

EXPLORING THE RUMEN AND ITS MICROBES FOR THERAPEUTIC BENEFITS

AN UPDATE ON HORMONES OF THERAPEUTIC UTILITY IN ANIMAL REPRODUCTION

DRUGS ACTING ON DIGESTIVE SYSTEM

poloxalene/kg;Dimethicone Oral suspension, 1 %, 2%. Dose. Cattle: 100 ml, sheep: 25 ml

DOSAGES OF DRUGS ACTING ON DIGESTIVE SYSTEM OF ANIMALS.

ANTIEMETICS Acepromazine Chlorpromazine Prochlorperazin e Propantheline Dimenhydrinat e

Isopropamide Diphenhydramine Cyclizine Meclizine

0.2-0.4 mg/kg, IM, 0.1-0.2 mg/kg, PO,

Dolasetron ; 0.22 mg/kg, IV,

0.6 mg/kg, IV,

0.01-0.02 mg/kg/hr, IV infusion

Horses: 4 mg/kg, PO,

*****THERAPEUTIC PROTOCOLS IN HEPATIC AND RENAL IMPAIRMENTS

1. Extension of the dosing interval. dose.

2. Reduction of the maintenance

Ureic gastropathy Antiemetic/Gas troprokinetic Uremic gastropathy

AN UPDATE ON : DRUGS ACTING ON RESPIRATORY SYSTEM

AN UPDATE ON : DRUGS ACTING ON GENITOURINARY SYSTEM

A NOTE ON EXPLORING THERAPEUTIC UTiLITY OF LIVESTOCK WASTES

CONCLUSIONS : Recognition of medicinal value for the dung and urine

AN UPDATE ON NON STEROIDAL ANTIINFLAMMATORY AGENTS

administered to any animal in shock post-traumatically animal that may be dehydrated.

0.25, IM 0.3, PO,eod NR NR 2.2, IV, sid, 20, IM

GUIDELINES FOR HANDLING POISONING CASES

Organophosphat es &Carbamates Znic phosphide Nitrate/nitrite

Heavy metals(Lead, Mercury) Mycotoxins

THERAPEUTIC MANAGEMENT OF CRITICAL PATIENTS IN CLINICS

Therapeutic management of critically ill patient:

b) Resuscitation:Chest compression coupled with mouth to nose

2. Management of shock: Assessment of shock is governed by

AN UPDATE ON MANAGEMENT OF OBSCURE DISEASES OF KARNATAKA

MYCOTOXINS AND ZOOTOXINS OF VETERINARY IMPORTANCE : REMEDIES

A NOTE ON DRUGS MODIFYING ABNORMAL BEHAVIOUR IN PETS

DIAGNOSTIC TESTS FOR DETECTION OF COMMON TOXICANTS

CLINICAL MANAGEMENT OF COMMON TOXICITIES OF VETERINARY IMPORTANCE

Strychnine (Strychnous- nux vomica)

Pyrethroids (Deltamethrin, Cypermethrin etc.) Carbamate insecticides Organophosphate s