Toxicology

Toxicology is the study of the adverse effects of chemicals (including drugs) on living systems and the means to prevent or ameliorate such effects. In addition to therapeutic agents, toxicologists examine many environmental agents and chemical compounds that are synthesized by humans or that originate in nature. The toxic effects of these agents may range from disturbances in growth patterns, discomfort, disease or death of individual organisms or on whole ecosystems. There are many subspecialties of toxicology including: clinical toxicology, regulatory toxicology (both of these found in the pharmaceutical and toxicology industry), forensic toxicology, occupational toxicology, and risk assessment. The current need for toxicologists is outlined in a recent online Science publication.

Introduction of pollution
Pollution is the introduction by man into the environment of substances or energy liable to cause hazards to human health, harm to the living resources and ecological systems, damage to structures or amenity or interference with legitimate uses of the environment. Pollution had always been misused for contamination which can be defined as the presence of elevated concentrations of a substance in the air, water, soil or any other such thing not necessarily resulting in a deleterious effect. Water pollution, therefore, is the direct or indirect human introduction of substances into the water environment such as to harm living resources, affect human health by various cytotoxic and infilterative disorders and impair water environment quality. Any definition of pollution should take the following important points into account: Pollution is not merely the addition of a substance to the water environment, but its addition at rate faster than the environment can accommodate it. There are natural levels of chemicals such as arsenic and mercury in the environment but only if these levels exceed critical values can they be considered pollutants. Pollutants are not only chemicals. Forms of energy like heat, sound, and &- particles, The impact of pollution on the environment: Pollution x affluence x technological development (Meadows et. a.l. 1992). The combined effect of population, affluence and technology are the factors responsible for pollution and other types of environmental degradation. Pollution arose as a result of technological development. The first major oil pollution incident in UK was in 1967. 120,000 tonnes of crude oil was washed upon many cornish beaches. The effect was that sea birds could not fly because oil coated their feathers. The result was hampering of insulatory properties, death and hypothermia. Sea weed couldn't photosynthesise. Gills of fish were covered, no feeding and no respiration. This also caused termination of most of the fish.Over 60,000 chemicals are in common use while up to 500 new ones are introduced to the commercial market annually. Similarly, the production and use of energy, production and use of industrial

chemicals and increased agricultural practices have had a deleterious effects on water affecting man's health generally and specifically.

Types Of Pollution
Pollution can be classified based on transport media as air, water and soil. Air Pollution This can be defined as any gaseous or particular matter in the air that is not normal constituent of the air or is not normally present in such a high concentration. Air pollution is one of the most difficult to control because it poses international and national threat. The pollution in air can be caused by burning fossil fuels e.g. oil, natural gas and coal as well as those released everyday by vehicle exhaust such as Carbon monoxide, oxides of nitrogen and hydrocarbons such as ethane and methane (CO, NO2, NO3, C2H4, C2H6, respectively). Water Pollution Water pollution becomes most obvious when it involves poisoning of drinking water or causes the death of a large number of fish or other aquatic population. This could be caused by sewage. Disposal of sewage wastes into a large volume of water could reduce the biological oxygen demand to such a great level that the entire oxygen may be removed. This would cause the death of all aerobic species fish. Some toxic chemicals released into the rivers and seas such as Pb, Cu, Zn, Hg, CN will cause the death of fish, algae and lesions in human beings even at very low concentrations. These are related to occupational hazards and constitute elements of environmental pollution especially with respect to pollution by heavy metals. Such incidents had been reported in the past. For example, the Minimata and Niigata epidemics in Japan in 1950s and 1960s respectively. The Minimata epidemic was a case of mercury poisoning caused by consumption of fish from the Minimata Bay of Japan which was heavily contaminated by mercury compounds discharged by a nearby plastic industry. This epidemic occurred during 1953 60 and was the 1 st serious outbreak of Hg poisoning. It was characterized by severe damage to the nervous system leading to ataxia, paraesthesia (abnormal pricking sensations), loss of vision and hearing and ultimately death. The primary pollutant was inorganic Hg, but an organic derivative, methyl mercury was found in the fish. This was converted by methylation through the microorganism in the water, fish gut, mud or all. Organomercury compounds being lipid soluble have very high affinity for cellular lipids and therefore accumulate in lipids of nervous tissues (Okoye 1992). This was a typical case of metabolic activation giving rise to a toxic metabolite.

Poison & principal of treatment of poisioning

Introduction Cases of poisoning may be treated in many places, e.g. at the scene of the accident, during transport, in a hospital. The type of care that can be given will depend on whoever makes the initial contact with the patient and in what circumstances. Certain members of the community, such as firemen, policemen, and teachers, may frequently be the first to be faced with poisoning cases. In rural areas, nurses and primary health care workers, and even agronomists and veterinarians, may have to deal with poisoned persons. They all need at least some basic training in first aid as well as in decontamination and measures for their own protection. An IPCS handbook on this first level of response to poisoning is in preparation. Most cases of poisoning, however, will be treated through a country's normal health service facilities, usually at a general hospital, far from a poison information centre and without access to a specialized clinical toxicology unit. According to patients' needs, treatment may be given by different services within the hospital, including the following: * Emergency services. In practice, emergency services receive a relatively high number of poisoning cases, as they function on a round-the-clock basis and are provided with trained personnel and basic equipment for decontamination and life-support measures. * Intensive care units. Intensive care units are usually well provided with highly specialized personnel and equipment for resuscitation, life-support measures, and care of critical poisoning cases. * General medical units. Basic medical care of non-critical poisoning cases can be provided within general medical units in which staff have received some training in, or information on, clinical toxicology and which are in close contact with poison information centres. * Specialized services. Specialized services offer the advantage of well trained medical staff and appropriate equipment for the management of poisoning cases in which specific organs or physiological functions are affected; they include nephrology, gastroenterology, neurology, cardiology, and haematology services.

* Paediatric departments. Poisoned children are frequently treated in paediatric department. To be able to treat poisoned patients, general hospitals need equipment for: *gastrointestinal, cutaneous, and ocular decontamination (e.g. equipment for gastric lavage) *immediate, and often longer-term, life-support measures (e.g. endotracheal intubation, assisted and controlled ventilation, parenteral fluid therapy, pharmacological treatment, cardiac pacing, defibrillation) *continuous cardiac and circulatory monitoring (through ECGs, blood pressure measurements, etc.) and monitoring of other vital functions *X-ray examinations *initial and repeated general biomedical laboratory analyses (e.g. acid-base balance, blood gases, electrolytes, blood glucose, liver and kidney function, and coagulation) *initial and repeated specific toxicological analyses of body fluids such as blood, urine, and stomach contents (the choice of analyses will vary according to local patterns of poisoning) *haemodialysis, peritoneal dialysis, haemoperfusion Signs and Symptoms of Alcohol Poisoning The following are signs to look out for in an individual who is suspected of ingesting large amounts of alcohol: 1. Slurred speech: When people drink alcohol and become intoxicated, they tend to become very loud and loquacious. As they drink increasingly larger amounts, they become quieter; and at the stage of alcohol poisoning, they find it difficult to talk. 2. Inability to walk: As the nerve centers in the brain are depressed by high concentrations of alcohol, the motor nerves which control the muscles do not function properly. 3. Vomiting: Alcohol in large amounts irritates the stomach and causes vomiting. 4. Confusion, stupor and unconsciousness: This is due to the fact that alcohol depresses nerve centers in the brain. 5. Slow breathing (about 8 breaths per minute or less) and irregular breathing: This is caused by the depressing effect that alcohol has on the respiratory centers in the brain.

6. Seizures: Excessive alcohol intake causes dehydration and the blood sugar level to fall (hypoglycemia) which leads to seizures. 7. Hypothermia: Hypothermia means low body temperature. The body temperature of the drinker is unusually low in alcohol poisoning. 8. Blue-tinged or pale skin color

Treatment of Alcohol Poisoning

In alcohol poisoning, it is best to get the sufferer to a hospital as soon as possible so that he or she gets professional help. The treatment given is supportive as the only way alcohol poisoning stops is when the alcohol is cleared from the body. 1. Monitor the patient carefully: If an individual is suspected of suffering from alcohol poisoning, he or she should not be left alone at any given time. As the person is usually vomiting, make sure that he or she does not choke on their own vomit. 2. Prevent breathing or choking problems: It is best to lay the person on his or her side (especially the left side) to prevent any vomit from being aspirated into the lungs or from choking the person. 3. Stomach pumping: This is done to remove any alcohol which has not yet been absorbed from the stomach. 4. Administration of fluids to prevent dehydration and hypoglycemia: Dehydration and hypoglycemia cause seizures which can lead to brain damage. If the person is still conscious, try to give water when he or she is not vomiting. Fluids are usually given intravenously (which is the best way) as sufferers of alcohol poisoning are usually unconscious. These fluids include sugar solutions which improve blood sugar level and prevent hypoglycemia. 5. Administration of Oxygen: Oxygen is given to combat the effect of slow and irregular breathing caused by alcohol poisoning. 6. Dialysis: Kidney dialysis is done to hasten the clearance of alcohol from the bloodstream Barbiturate poisoning Barbiturates are a type of depressant drug that cause relaxation and sleepiness. A barbituate overdose occurs when someone accidentally or intentionally takes more than the normal or recommended amount of this medication. This is life threatening

Causes Barbiturate abuse is a major addiction problem for many people. Most people who take these medications for seizure disorders or pain syndromes do not abuse them,. However, those who become addicts usually start by abusing medication prescribed for them or other family member Symptoms Symptoms of barbiturate intoxication and overdose include:

Altered level of consciousness Difficulty in thinking Drowsiness or coma Faulty judgment Incoordination Shallow breathing Slowness of speech Sluggishness Slurred speech Staggering Excessive and long-term use of barbiturates, such as phenobarbital, may produce the following chronic symptoms:

Changes in alertness Decreased functioning Irritability Memory loss Exams and Tests The health care provider will measure and monitor the patient's vital signs, including temperature, pulse, breathing rate, and blood pressure. Blood and urine tests will be done to screen for drugs. Treatment Most overdoses of this type of medication involve a mixtures of drugs, usually alcohol and barbiturates, or barbiturates and opiates (heroin or Oxycontin). Some users use a combination of all four drugs. Those who take such combinations tend to be:

A new user who does not know that such combinations can lead to coma or death Experienced users who intentionally use them to become consciousness. The second group is among the most difficult to treat. The patient may receive a medicine called naloxone (Narcan) , if an opiate was part of the mix. This medicine will often rapidly restore consciousness and breathing.

There is no direct antidote for this type of overdose. Breathing support, such as a breathing machine, may be needed until all the drug is removed from the body. Digitalis Toxicity . Digitalis is a medication prescribed to certain heart patients. Digitalis toxicity is a complication of digitalis therapy, or it may be occur when someone takes more than a large amount of the drug at one time. (This is called an acute ingestion.)
The most common prescription form of this medication is called digoxin. Digitoxin is another form of digitalis.
Causes
Digitalis toxicity can be caused by high levels of digitalis in the body, or a decreased tolerance to the drug. Patients with decreased tolerance may have "normal" digitalis levels in their blood. Digitalis toxicity can occur from a single exposure or chronic overmedication, or it may occur in patients with normal blood levels of digitalis if other risks are present. People with heart failure who take digoxin are commonly given medications called diuretics, which remove excess fluid from the body. Many diuretics can cause potassium loss. Low levels of potassium in the body increase the risk of digitalis toxicity. Digitalis toxicity may also result in persons who take the drug and who have low levels of magnesium in the body. Risks include taking digitalis medications such as digoxin or digitoxin along with medications that interact with digitalis such as quinidine, verapamil, amiodarone, and others. Reduced kidney function will cause digitalis to build up in the body rather than be removed normally through urine. Therefore, any disorders that disrupt kidney functioning (including dehydration) make digitalis toxicity more likely.

Symptoms
o o o o o
Confusion Irregular pulse Loss of appetite Nausea, vomiting, diarrhea Palpitations Visual changes (unusual) Blind spots in vision Blurred vision Changes in color perception Halos or rings of light around objects Seeing lights or bright spots Additional symptoms that may be associated with digitalis toxicity include:

Decreased consciousness Decreased urine output

Difficulty breathing when lying down Excessive nighttime urination Overall swelling

Exams and Tests

The heart rate may be rapid or slow and may be irregular. An ECG is done to check for irregular heart beats. Blood tests will be done to check:

BUN and creatinine (which help reveal kidney function) Digoxin and digitoxin levels Potassium level Magnesium level See also:

Blood chemistry Digoxin - test Digitoxin - test

Treatment
In an emergency, assist breathing as needed (see CPR) and get professional medical help. Arrhythmias are treated according to which arrhythmia develops. If toxicity is due to a recent, acute single exposure, treatment may involve:

Activated charcoal Tube through the mouth into the stomach to wash out the stomach (gastric lavage) Digitoxin blood levels may be lowered with repeated doses of charcoal, given after gastric lavage. Methods to cause vomiting are usually not performed because vomiting can worsen slow heart rhythms. In severe cases, medications called digoxin-specific antibodies may be prescribed. Hemodialysis may be required to reduce the levels of digitalis in the body

Methyl Salicylate poisoning

Methyl salicylate is a wintergreen-scented chemical found in many over-thecounter products, including muscle ache creams. Methyl salicylate overdose occurs when someone accidentally or intentionally takes more than the normal or recommended amount of a product containing this substance.
Where Found

Deep-heating creams (Ben Gay, Icy Hot) used to relieve sore muscles and joints

Oil of wintergreen Solutions for vaporizers Note: This list may not include all products that contain methyl salicylate.
Back to TopSymptoms

o o o o o o o o o o o o o o o o o o o o o o

Bladder and kidneys Kidney failure Eyes, ears, nose, and throat Eye irritation Loss of vision Ringing in the ears Throat swelling Heart and blood Collapse Lungs and airways Difficulty breathing No breathing Rapid breathing Nervous system Agitation Coma Confusion Convulsions Deafness Dizziness Drowsiness Hallucinations Headache Fever Seizures Stomach and intestines Nausea Vomiting, possibly bloody

treatment
The National Poison Control Center (1-800-222-1222) can be called from anywhere in the United States. This national hotline number will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week. Take the container with you to the hospital, if possible

Strychnine

Strychnine is an odorless, white, bitter crystalline powder that can be inhaled, taken orally, or mixed and given intravenously. It is a strong poison that needs only a small amount to produce severe health affects, including death (1).

Signs and Symptoms: Following the ingestion of strychnine, symptoms of poisoning usually happen within 15-60 minutes. People exposed to low or moderate doses by any route could have (1): -Agitation -Ability to be easily startled -Apprehension/ Fear -Restlessness -Painful muscle spasms -Fever -Kidney/Liver injury Treatment: Strychnine poisoning can be treated with barbiturate sedatives and muscle relaxants by avoiding unnecessary sensory stimulation, if caught in time (2).

With the proper treatments the poison can be eliminated and withdrawn from the body in a few days due to strychnine's relatively short half-life of about ten days (2). There have been treatments done in strychnine poisoned horses where xylazine was beneficial. Pentobarbital and diazepam were also used in treating the sick horses. Mineral oil and charcoal also proved to be beneficial in decreasing the amount of strychnine in the ailmentary tract of the horses (6). "The minimum lethal dose is about 50 to 100 mg for adults after the ingestion"( 7). Narcotic poisoning Symptoms Narcotics users can develop tolerance, as well as psychological and physical dependence to opioids when they take them over an extended period of time. Tolerance refers to a decreased response to a drug, with increasing doses required to achieve comparable effects. Psychological dependence refers to compulsive drug use in which a person uses the drug for personal satisfaction, often in spite of knowing the health risks. Physical dependence occurs when a person stops using the narcotic but experiences a withdrawal syndrome (or set of symptoms).

Signs and symptoms of narc analgesia (feeling no pain), sedation, euphoria, respiratory depression (shallow breathing), small pupils, bloodshot eyes, nausea, vomiting, itching skin, flushed skin, constipation, slurred speech, confusion, poor judgment, and needle marks on the skin .

Signs and symptoms of narcotic withdrawal: The withdrawal syndrome from narcotics generally includes signs and symptoms opposite of the drug's intended medical effects. The severity of the withdrawal syndrome increases as the drug dose increases. The longer the duration of the physical dependence to the narcotic increases, the more severe the withdrawal syndrome. Symptoms of heroin withdrawal generally appear 12-14 hours after the last dose. Symptoms of methadone withdrawal appear 24-36 hours after the last dose. Heroin withdrawal peaks within 36-72 hours and may last seven to 14 days. Methadone withdrawal peaks at three to five days and may last three to four weeks. Although uncomfortable, acute narcotic withdrawal for adults is not considered life-threatening unless the person has a medical condition that compromises their health (for example, if someone has severe heart disease). Some of the signs and symptoms of narcotic withdrawal are listed below: Anxiety Irritability Craving for the drug Increased respiratory rate (rapid breathing) Yawning

Runny nose Salivation Gooseflesh Nasal stuffiness Muscle aches Nausea or vomiting Abdominal cramping Diarrhea Sweating Confusion Enlarged pupils

Tremors Lack of appetite Complications of narcotic abuse: Many complications can result from narcotic abuse, the most common being infectious conditions. Infections of the skin and deeper layers Abscesses in skin, lungs, and brain Infection of the heart valves Pneumonia Fluid in the lungs Liver dysfunction Intestinal slowdown Seizures Coma and other neurological complications

Infectious arthritis Loss of menstrual cycle Overdose and death Premature and growth-retarded infants Neonatal withdrawal: Up to 70% of babies delivered from pregnant women who use narcotics experience neonatal withdrawal, a potentially fatal condition.

Paracetamol toxicity is caused by excessive use oroverdose of the analgesic drug paracetamol (called acetaminophen in North America). Mainly causing liver injury, paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States and the United Kingdom it is the most common cause ofacute [1][2] liver failure. Many individuals with paracetamol toxicity may have no symptoms at all in the first 24 hours following overdose. Others may initially have nonspecific complaints such as vague abdominal pain and nausea. With progressive disease, signs of liver failure may develop; these includelow blood sugar, low blood pH, easy bleeding, andhepatic encephalopathy. Some will spontaneously resolve, although untreated cases may result in death. Damage to the liver, or hepatotoxicity, results not from paracetamol itself, but from one of itsmetabolites, N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI depletes the liver's natural antioxidantglutathione and directly damages cells in the liver, leading to liver failure. Risk factors for toxicity include excessive chronic alcohol intake, fasting or anorexia nervosa, and the use of certain drugs such as isoniazid.

Treatment is aimed at removing the paracetamol from the body and replacing glutathione. Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose; the antidote acetylcysteine acts as a precursor for glutathione, helping the body regenerate enough to prevent damage to the liver. A liver transplant is often required if damage to the liver becomes severe. Patients treated early have a good prognosis, whereas patients that develop major liver abnormalities typically have a poor outcome. Efforts to prevent paracetamol overdose include limiting individual sales of the drug and combining paracetamol with methionine, which is converted into glutathione in the liver.

Signs and symptoms

The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within [11] hours of overdose, and consists of nausea, vomiting, pallor, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of [12][13] poisoning. The second phase occurs between 24 and 72 hours following overdose and consists of signs of increasing liver damage. In general, damage occurs in hepatocytes as they metabolize the paracetamol. The individual may experience right-upper-quadrant pain. The increasing liver damage also alters biochemical markers of liver function; International normalized ratio (INR) and the [14] hepatictransaminases alanine transaminase and aspartate transaminase rise to abnormal levels. Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome ormultiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is [15] produced more in the kidneys than in the liver. The third phase follows at 3 to 5 days, and is marked by complications of massive hepatic necrosisleading to fulminant hepatic failure with complications of coagulation defects, hypoglycemia, kidney failure, hepatic encephalopathy, cerebral edema, sepsis, [11] multiple organ failure, and death. If the third phase is survived, the hepatic necrosis runs its course, [16] and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received.

Treatment
Gastric decontamination
In adults, the initial treatment for paracetamol overdose is gastrointestinal decontamination. Paracetamol absorption from the gastrointestinal tract is complete within two hours under normal circumstances, so decontamination is most helpful if performed within this timeframe. Gastric lavage, better known as stomach pumping, may be considered if the amount ingested is potentially life-threatening and the [42] procedure can be performed within 60 minutes of ingestion. Activated charcoalis the most common gastrointestinal decontamination procedure as it adsorbs paracetamol, reducing its gastrointestinal [43] [44] absorption. Administering activated charcoal also poses less risk of aspirationthan gastric lavage. It appears that the most benefit from activated charcoal is gained if it is given within 30 minutes to two [45][46] hours of ingestion. Administering activated charcoal later than 2 hours can be considered in patients that may have delayed gastric emptying due to co-ingested drugs or following ingestion of sustained- or

delayed-release paracetamol preparations. Activated charcoal should also be administered if co-ingested [31] drugs warrant decontamination. There was reluctance to give activated charcoal in paracetamol [47] overdose, because of the concern that it may also absorb the oral antidote acetylcysteine. Studies have shown that 39% less acetylcysteine is absorbed into the body when they are administered [48] together. There are conflicting recommendations regarding whether to change the dosing of oral acetylcysteine after the administration of activated charcoal, and even whether the dosing of [48][49] acetylcysteine needs to be altered at all. Intravenous acetylcystine has no interaction with activated charcoal. Inducing vomiting with syrup of ipecac has no role in paracetamol overdose because the vomiting it [3] induces delays the effective administration of activated charcoal and oral acetylcysteine. Liver injury is extremely rare after acute accidental ingestion in children under 6 years of age. Children with accidental exposures do not require gastrointestinal decontamination with either gastric lavage, activated charcoal, or syrup of ipecac.

Benzodiazepine Poisoning and Treatment Benzodiazepines taken alone rarely cause severe complications or fatality in overdose, and deaths after hospital admission are rare.However, combinations of benzodiazepines with these drugs, alcohol, barbiturates, opiates or tricyclic antidepressants is particularly dangerous, and may lead to coma and death. In the case of alcohol and barbiturates not only do they have an additive effect, they also increase the binding affinity of benzodiazepines to the benzodiazepine binding site which results in a very significant potentiation of the CNS and respiratory depressant effects. Benzodiazepines are commonly used in self-poisoning by drug overdose.The various benzodiazepines differ in their toxicity since they produce varying levels of sedation in overdose, with oxazepam being least toxic and least sedative and alprazolam, flunitrazepam and temazepam the most toxic and most sedative in overdose. Temazepam is more frequently involved in drug-related deaths causing more deaths per million than other benzodiazepines. However, in countries

where alprazolam is commonly prescribed, alprazolam is even more dangerous in overdose than temazepam, causing more fatalities, higher rates of admission to ICU and higher rates of mechanical ventilation. Zopiclone, a benzodiazepine receptor agonist has similar overdose potential as benzodiazepines. Signs and symptoms: Benzodiazepine overdose may present with intoxication, somnolence, impaired balance, impaired motor function, anterograde amnesia, ataxia, and slurred speech. In cases of severe overdose this may progress to profound coma, respiratory depression, hypothermia, hypotension, and pulmonary aspiration, with the possibility of death. Severe consequences are rare following overdose of benzodiazepines alone but the severity of overdose is increased significantly if benzodiazepines are taken in overdose in combination with other medications. Significant toxicity may result following recreation drug misuse in conjunction with other CNS depressants such as opiates or ethanol. elderly and those with chronic illnesses are much more vulnerable to lethal overdose with benzodiazepines. Fatal overdoses can occur at relatively low doses in these individuals. Benzodiazepine overdose related coma may be characterised by an alpha pattern with the central somatosensory conduction time (CCT) after median nerve stimulation being prolonged and the N20 to be dispersed. Brain-stem auditory evoked potentials demonstrate delayed interpeak latencies (IPLs) I-III, IIIV and I-V. Toxic overdoses therefore of benzodiazepines cause prolonged CCT and IPLs.

Treatment: Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose.Gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose. It is only recommended if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage is not recommended. Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their wide distribution and lipid solubility.
Organophosphate poisoning results from exposure toorganophosphates (OPs), which cause the inhibition ofacetylcholinesterase (AChE), leading to the accumulation of acetylcholine (ACh) in the body. Organophosphate poisoning most commonly results from exposure to insecticides or nerve agents. OPs are one of the most common causes of poisoning worldwide, and are frequently intentionally used in [1][2] suicides in agrarian areas. There are around 1 million OP poisonings per year with several hundred thousand resulting in fatalities annually. Organophosphates inhibit AChE, causing OP poisoning by phosphorylating the serine hydroxyl residue on AChE, which inactivates AChE. AChE is critical for nerve function, so the irreversible blockage of this enzyme, which causes acetylcholine accumulation, results in muscle overstimulation. This causes disturbances across the cholinergic synapses and can only be reactivated very slowly, if at all. Paraoxonase (PON1) is a key enzyme involved in OP pesticides and has been found to be critical in determining an organisms sensitivity to OP exposure

Symptoms
The health effects associated with organophosphate poisoning are a result of excess acetylcholine (ACh) present at different nerves and receptors in the body because acetyocholinesterase is blocked. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are tachycardia, hypertension, and hypoglycemia. Overstimulation ofnicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When

there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can [6][7] occur. The effects of organophosphate poisoning are recalled using the mnemonic SLUDGEM (Salivation,Lacrimation, Urination, Defecation, Gastrointestinal motility, Emesis, [8] miosis) An additional mnemonic is MUDDLES: miosis, urination, diarrhea, diaphoresis, lacrimation, [9] excitation, and salivation. The onset and severity of symptoms, whether acute or chronic, depends upon the specific chemical, the route of exposure, the dose, and the individuals ability to degrade the compound, which the PON1 enzyme level will affect.

Treatment and Prevention

Current antidotes for OP poisoning consist of a pretreatment with carbamates to protect AChE from inhibition by OP compounds and post-exposure treatments with anti-cholinergic drugs. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such [14][15] as trimedoximeor obidoxime), though the use of "-oximes" has been found to be of no benefit, or [16][17] possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks [18] the action of acetylcholine peripherally. These antidotes are effective at preventing lethality from OP poisoning, but current treatment lack the ability to prevent post-exposure incapacitation, performance [19] deficits, or permanent brain damage. Enzyme bioscavengers are being developed as a pretreatment to sequester highly toxic OPs before they can reach their physiological targets and prevent the toxic effects from occurring. Significant advances with cholinesterases (ChEs), specifically human serum BChE (HuBChE) have been made. HuBChe can offer a broad range of protection for nerve agents including soman, sarin, tabun, and VX. HuBChE also possess a very long retention time in the human circulation system and because it is from a human source it will not produce any antagonistic immunological responses. HuBChE is currently being [19] assessed for inclusion into the protective regimen against OP nerve agent poisoning. Currently there is potential for PON1 to be used to treat sarin exposure, but recombinant PON1 variants would need to first be generated to increase its catalytic efficiency. One other agent that is being researched is the Class III anti-arrhythmic agents. Hyperkalemia of the tissue is one of the symptoms associated with OP poisoning. While the cellular processes leading to cardiac toxicity are not well understood, the potassium current channels are believed to be involved. Class II anti-arrhythmic agents block the potassium membrane currents in cardiac cells, which makes [20] them a candidate for become a therapeutic of OP poisoning. Five days of an organic food diet has been shown to dramatically reduce the organophosphorus pesticides in the urine of children

Chelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxicationthose involving lead, arsenic or mercury the standard of care in the United States dictates the use of dimercaptosuccinic acid(DMSA).[citation needed] Other chelating agents, such as 2,3-dimercapto-1-propanesulfonic acid(DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine. No approved medical research has found any benefits to chelation therapy for other diseases or ailments

Deferoxamine (also known asdesferrioxamine B, desferoxamine B,DFO-B, DFOA, DFB or desferal) is a bacterial siderophore produced by theactinobacteria Streptomyces pilosus. It has medical applications as a chelating agentused to remove excess iron from the body.[1]The mesylate salt of DFO-B is commercially available.

Mechanism
Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron, the agent reduces the damage done to various organs and tissues, such as the liver. A recent study also shows that it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma). Deferoxamine may modulate expression[2] and release of inflammatory mediators by specific cell types.[3]

Uses
Deferoxamine is used to treat acute iron poisoning, especially in small children. This agent is also frequently used to treathemochromatosis, a disease of iron accumulation that can be either genetic or acquired. Acquired hemochromatosis is common in patients with certain types of chronic anemia (e.g. thalassemia andmyelodysplastic syndrome) who require manyblood transfusions, which can greatly increase the amount of iron in the body. Administration for chronic conditions is generally accomplished by subcutaneous injection (SQ infusion) over a period of 812 hours each day. Administration of deferoxamine after acute intoxication may color the urine a pinkish red, a phenomenon termed "vin rose urine". As an alternative to injections, in 2009 Iranian researchers developed the world's first pill version of deferoxamine; [4]when used, the pills reportedly avoid the pain commonly experienced after receiving injections of the drug.

Apart from iron toxicity, deferoxamine can be used to treat aluminium toxicity (an excess of aluminium in the body) in select patients although it is not FDA approved for this use. A study published in January 2008 suggests that deferoxamine can be used to speed fracture healing.

Dimercaprol (INN) or British anti-Lewisite (abbreviatedBAL), is a compound developed by British biochemists atOxford University during World War II.[1][2] It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent.[3] Today, it is used medically in treatment of arsenic, mercury, goldand lead, and other toxic metal poisoning.[4] In addition, it has in the past been used for the treatment of Wilson's disease, a genetic disorder in which the body tends to retain copper

Biochemical function
Arsenic and some other heavy metals act by chemically reacting with adjacent thiol residues on metabolic enzymes, creating a chelate complex that inhibits the affected enzyme's activity.[6] Dimercaprol competes with the thiol groups for binding the metal ion, which is then excreted in the urine.[citation needed] Dimercaprol is itself toxic, with a narrow therapeutic range and a tendency to concentrate arsenic in some organs. Other drawbacks include the need to administer it by painful intramuscular injection.[7] Serious side effects include nephrotoxicity and hypertension. Dimercaprol has been found to form stable chelates in vivo with many other toxic metals including inorganicmercury, antimony, bismuth, cadmium, chromium,cobalt, gold, and nickel. However, it is not necessarily the treatment of choice for toxicity to these metals. Dimercaprol has been used as an adjunct in the treatment of the acute encephalopathy of lead toxicity. It is a potentially toxic drug, and its use may be accompanied by multiple side effects. Although treatment with dimercaprol will increase the excretion of cadmium, there is a concomitant increase in renal cadmium concentration, so that its use in case of cadmium toxicity is to be avoided. It does, however, remove inorganic mercury from the kidneys; but is not useful in the treatment of alkylmercury or phenyl mercury toxicity. Dimercaprol also enhances the toxicity of selenium andtellurium, so it is not to be used to remove these elements from the body
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA (for other names, see Table), is a polyamino carboxylic acid and a colourless, water-soluble solid. Itsconjugate base is namedethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ("six-toothed") ligand and chelating agent, i.e. its ability to "sequester" metal ions such as

Ca2+ and Fe3+. After being bound by EDTA, metal ions remain in solution but exhibit diminished reactivity. EDTA is produced as several salts, notably disodium EDTA and calcium disodium EDTA.

EDTA is used to bind metal ions in the practice of chelation therapy, e.g., for treating mercury andlead poisoning.[11] It is used in a similar manner to remove excess iron from the body. This therapy is used to treat the complication of repeated blood transfusions, as would be applied to treatthalassaemia. Alternative medical practitioners believe EDTA acts as a powerful antioxidant to prevent free radicals from injuring blood vessel walls, therefore reducing atherosclerosis.[12] The U.S. FDAapproved the use of EDTA for lead poisoning[13] on July 16, 1953, under the brand name of Versenate[14], which was licensed to the pharmaceutical company Riker. It has not approved it for the treatment of atherosclerosis.[15] Dentists and endodontists use EDTA solutions to remove inorganic debris (smear layer) and lubricate the canals in endodontics. This procedure helps prepare root canals for obturation. Furthermore, EDTA solutions with the addition of a surfactant loosen up calcifications inside a root canal and allow instrumentation (canals shaping) and facilitate apical advancement of a file in a tight/calcified root canal towards the apex. It serves as a preservative (usually to enhance the action of another preservative such as benzalkonium chloride or thiomersal) in ocular preparations and eyedrops.[16] In evaluating kidney function, the complex [Cr(edta)]- is administered intravenously and its filtration into the urine is monitored. This method is useful for evaluating glomerular filtration rate.[17] EDTA is used extensively in the analysis of blood. It is an anticoagulant for blood samples forCBC/FBEs. Laboratory studies also suggest that EDTA chelation may prevent collection of platelets on the lining of the vessel [such as arteries] (which can otherwise lead to formation of blood clots, which itself is associated with atheromatous plaque formation or rupture, and thereby ultimately disrupts blood flow). These ideas have so far been proven ineffective;[18] however, a major clinical study of the effects of EDTA on coronary arteries is currently (2008) proceeding.[19] EDTA played a role in the O.J. Simpson trial when the defense alleged that one of the blood samples collected from Simpson's estate was found to contain traces of the compound.[20]

EDTA is a slime dispersant, and has been found to be highly effective in reducing bacteMethods of detection and analysis
The most sensitive method of detecting and measuring EDTA in biological samples is selected-reaction-monitoring capillary-electrophoresis mass-spectrometry (abbreviation SRM-CE/MS), which has a detection limit of 7.3 ng/mL in human plasma and a quantitation limit of 15 ng/mL. This method works with sample volumes as small as ~7-8 nLrial growth during implantation of intraocular lenses.