Pharmacology

INTRODUCTION
Pharmacology is a medical science that forms a backbone of the medical profession as drugs form
the corner stone of therapy in human diseases. Therefore, it is of utmost importance to describe the
pharmacological basis of therapeutics in order to maximize the benefits and
minimize the risks of drugs to recipients. This lecture note on pharmacology is primarily a note
for undergraduate health science students such as MBBS, public health, nursing, midwifery and
laboratory technology students. However, other health professionals whose career involves
drug therapy or related aspects should also find much of the material relevant.
The goal is to empower the practitioner through an understanding of the fundamental scientific
principles of pharmacology. The effects of prototypical drugs on physiological and
patho-physiological processes are clearly explained to promote understanding. Other related
drugs are touched briefly. The selection of the drugs is based on the national drugs list for
Somalia, Somaliland & WHO on the accumulated experience of teaching pharmacology to many
health profession students.
The chapters open with a list of objectives to guide the reader, and most end with questions and
case studies which challenge the reader’s understanding of the concepts covered with in the
chapter. Most sections have an introduction that provides an overview of the material to be
covered.
Readers are encouraged to refer the references mentioned for further information and we hope
that this material will be a valuable companion in our pursuit of a fundamental understanding in
a most fascinating area of clinical knowledge of pharmacology.
Abdirahman M. Osman (D.pharm, MPH, PG Research )

And Dr. Aidorous ali : BSC, Pharmacology, MBBS, Diploma
of laboratory Diploma education
September 2018
1
CHAPTER ONE: BASIC PHARMACOLOGY
Introduction
Pharmacology is defined the study of substances that interect with living systems through chemical
processes especially by binding to regulatory molecules and activating or inhibiting normal body
processes.
Medical pharmacology is often defined as the science of substances used to prevent, diagnose and
treat disease.
Greek words of Pharmacology can be abbreviated pharmakon which means drug or poison and
Logos which means study of.
History of Pharmacology
Prehistoric people undoubtedly recognized the beneficial or toxic effects of many plant and animal
materials. Early written records from China and from Egypt list remedies of many types, including
a few still recognized as useful drugs today. Most, however, were worthless or actually harmful. In
the 1500 years or so preceding the present, there were sporadic attempts to introduce rational
methods into medicine, but none was successful owing to the dominance of systems of thought
that purported to explain all of biology and disease without the need for experimentation and
observation. These schools promulgated bizarre notions such as the idea that disease was caused
by excesses of bile or blood in the body, that wounds could be healed by applying a salve to the
weapon that caused the wound, and so on.
Around the end of the 17th century, reliance on observation and experimentation began to replace
theorizing in medicine, following the example of the physical sciences. As the value of these
methods in the study of disease became clear, physicians in Great Britain and on the Continent
began to apply them to the effects of traditional drugs used in their own practices. Thus, materia
medica—the science of drug preparation and the medical use of drugs—began to develop as the
precursor to pharmacology. However, any real understanding of the mechanisms of action of drugs
was prevented by the absence of methods for purifying active agents from the crude materials that
2
were available and—even more—by the lack of methods for testing hypotheses about the nature of
drug actions.
In the late 18th and early 19th centuries, François Magendie, and later his student Claude Bernard,
began to develop the methods of experimental animal physiology and pharmacology. Advances
in chemistry and the further development of physiology in the 18th, 19th, and early 20th centuries
laid the foundation needed for understanding how drugs work at the organ and tissue levels.
Paradoxically, real advances in basic pharmacology during this time were accompanied by an
outburst of unscientific promotion by manufacturers and marketers of worthless "patent
medicines." Not until the concepts of rational therapeutics, especially that of the controlled
clinical trial, were reintroduced into medicine—only about 50 years ago—did it become possible
to accurately evaluate therapeutic claims.
Around the same time, a major expansion of research efforts in all areas of biology began. As new
concepts and new techniques were introduced, information accumulated about drug action and the
biologic substrate of that action, the drug receptor. During the last half-century, many
fundamentally new drug groups and new members of old groups were introduced. The last three
decades have seen an even more rapid growth of information and understanding of the molecular
basis for drug action. The molecular mechanisms of action of many drugs have now been
identified, and numerous receptors have been isolated, structurally characterized, and cloned. In
fact, the use of receptor identification methods (described in Chapter 2) has led to the discovery of
many orphan receptors—receptors for which no ligand has been discovered and whose function
can only be surmised. Studies of the local molecular environment of receptors have shown that
receptors and effectors do not function in isolation; they are strongly influenced by companion
regulatory proteins. Decoding of the genomes of many species—from bacteria to humans—has led
to the recognition of unsuspected relationships between receptor families and the ways that
receptor proteins have evolved.
3
Definations
1. Clinical Pharmacology: It evaluate the pharmacological action of drug preferred route

of administration and safe dosage range in human by clinical trails.
2. Drugs: Drugs are chemicals that alter functions of living organisms. Drugs are generally
given for the diagnosis, prevention, control or cure of disease.
3. Pharmacy: It is the science of identification, selection, preservation, standardisation,
compounding and dispensing of medical substances.
4. Pharmacodynamics: The study of the biological and therapeutic effects of drugs (i.e,
“what the drug does to the body”).
5. Pharmacokinetics: Study of the absorption, distribution metabolism and excretion
(ADME) of drugs (“i.e what the body does to the drug”).
6. Pharmacotherapeutics: It deals with the proper selection and use of drugs for the
prevention and treatment of disease.
7. Toxicology: It’s the science of poisons. Many drugs in larger doses may act as poisons.
Poisons are substances that cause harmful, dangerous or fatal symptoms in living
substances.
8. Chemotherapy: It’s the effect of drugs upon microorganisms, parasites and neoplastic
cells living and multiplying in living organisms.
9. Pharmacopoeia: An official code containing a selected list of the established drugs and
medical preparations with descriptions of their physical properties and tests for their
identity, purity and potency e.g. Indian Pharmacopoeia (I.P), British Pharmacopoeia
(B.P).
What is a Drug?
In WHO drug is defined, any substance or product that is used to explore a physiological systems
or pathological states for the benefit of the recipient.
Word of drug derived from French word, drogue meaning dry herb which is used for diagnosis,
prevention and cure of a disease.
Dose, it is the quantity of the drug.

4
Dosage, it is the schedule of the dose, frequency and duration of administration of drugs
Drug dosage
Dose is the appropriate amount of a drug needed to produce a certain degree of response in
a patient.
Dose can be classified into:
1. Standard dose e.g contraceptives , chloroquine
2. Regulated dose e.g anticoagulants, diuretics
3. Target level dose e.g digoxin, lithium
4. Titrated dose e.g anticancer drugs & levodopa
Sources of Drugs
Drugs are obtained from different sources. They are natural and synthetic.
1. plants: atropine from atropa belladona, digoxin from digitalis purpura, morphine from
papavarum somniferum, quinine from cinchona bark.
2. Animals: insulin, heparin and gonadotropin
3. Minerals: magnesiun sulphate, iron, lithium.
4. Microorganisms: penicillins from penicillium chrysogenum, cephalosporins.
5. Human sources: growth hormone, insulin, chorionic gonadotropins from pregnancy ladys
urine.
5
Rights of Pharmacology
Right drug
Right dose
Right time
Right route
Right patient.
Essential Drug Concept
W.H.O has defined (essential drugs) as those drugs which satisfy priority health needs of
the population.
They are selected with due regard to public health relevance evidence on efficacy, safety
and comparative cost effectiveness.
Should be available at all times and adequate amounts.
Development and evaluation of new drugs:

The ultimate aim of pharmacological studies in animals is to find out a therapeutic agent suitable
for clinical evaluation in man. No doubt, animal studies provide analogies and serve as useful
models. The administration of biologically active agent to human beings is associated with an
element of risk, which cannot be predicted by even the most careful and exhaustive animal
experiments.
Scientists all over the world are in a continuous effort to develop new drugs although drug
development is an extremely technical and enormously expensive operation. Among the
contributors to new drug development, pharmacologists are more concerned in evaluating “new
chemical entities” (NCE). Synthesis and evaluation of thousands of NCEs are usually necessary
for new drugs to be introduced in the market. Research and development of new drugs have
been done under strict government regulations which have greatly increased over the past
couple of decades.
6
Drug development comprises of two steps.
a) Preclinical development and
b) Clinical development
A) Preclinical development: Synthesis of new chemical entities is done as per research policy
decision which is based on:
(i) Random synthesis
(ii) Structure activity relationship (SAR)
(iii) Biochemical and pharmacological insight and
(iv) Chance finding.
The aim of the preclinical development phase for a potential new medicine is to explore the
drug’s efficacy and safety before it is administrated to patients. In this preclinical phase, varying
drug doses are tested on animals and/or in vitro systems.
If active compounds are found, then studies on animals are done which include
pharmacodynamics, pharmacokinetics, toxicology and special toxicological studies
(mutagenicity and carcinogenicity) have to be done. In this study single dose is used for acute
toxicity and repeated doses for sub chronic and chronic toxicity studies. Most of the preclinical
tests have to be conducted in accordance with the standards prescribed.
B) Clinical development: About one in 1000 NCEs reach this stage. The steps to be studied in
this stage include:
a) Pharmaceutical study
b) Pharmacological study
c) Clinical trial.
a) Pharmaceutical study covers stability of formulation and compatibility of the NCEs with other
tablet or infusion ingredients.
b) Pharmacological study includes further chronic toxicological study in animal, initially animal
metabolic and pharmacokinetic study. When studies in animals predict that a NCE may be
useful medicine i.e. effective and safe in relation to its benefits, then the time has come to
put it to the test in man i.e. clinical trial.
c) Studies on human or Clinical Trial:
Clinical trial is a means by which the efficacy of drug is tested on human being. It may also give
7
some idea about the risk involved. It is divided into 4 phases. With each phase, the safety and
efficacy of the compound are tested progressively.
Phase - I: This is the first exposure of the new drug on man which is usually conducted in
healthy volunteers and which is designed to test the tolerable dose, duration of action. This
phase is usually carried out in only one centre on 20 to 50 subjects.
Phase - II: This phase comprises small scale trials on patients used to determine dose level and
establish that the treatment offers some benefit. It usually involves 100-500 patients and is
usually conducted in several centres.
Phase - III: Full scale evaluation of treatment comparing it with standard treatment is done in
this phase. It involves randomised control trials on 250 to 2000 patients and is done in multiple
centres. Information from all studies are received by the “Committee of safety of medicines”
(CSM). If the drug is satisfied by the CSM, the product license is issued then the drug is marketed.
Phase - IV: It is also called as phase of post marketing surveillance. Reports about efficacy and
toxicity are received from the medical practitioners and reviewed by the committee of review of
medicines. Renewal or cancellation of the product license depends on the comment of the
review committee.
Pregnancy categories
Pregnancy categories can be divided into:
1. A
2. B
3. C
4. D
5. X
Drug Classification
Drugs are classified by:
1. Chemistry, e.g electrolytes

8
2. Mechanism, e.g beta-blockers and benzodiazepines.
3. Disease, e.g anti-hypertensive and anti-emetics
Classification of drugs by legal purposes
Drugs are grouped for legal purposes as follows:
1. Official drugs: drugs which are included in the pharmacopeias of that particular country are
termed official drugs.
2. Dangerous drugs: this include drugs of addiction. E.g opium and cannabis.
3. Prescription drugs (POM): drugs which are given only by the prescription of the doctor.
4. Over the counter (OTC): drugs which are available by public with out prescription.
Pharmacopoeia
Book containing directions for the identification of samples and the preparation of
compound medicines, and published by the authority of a government or a medical or
pharmaceutical society
A reference work for pharmaceutical drug specifications.
9
Pharmacopoeia
1. IP: Indian pharmacopoeia
2. BP: British Pharmacopoeia
3. USP: United states Pharmacopoeia
4. P.P: Pakistan Pharmacopoeia
5. C.P: Chinaca Pharmacopoeia
Drug Nomenclature
A drug generally has three categories of names:
1. Chemical name
2. Non-proprietary name
3. Proprietary name
10
Chemical name
It describes the substance chemically,. E.g 1-isopropylamino-3-1-naphthyloxy propan 2-ol.
This is cumbersome and not suitable for use in prescribing.
Non-proprietary name
It is the name accepted by a competent scientific body/authority, e.g united states adopted
name (USAN) by the council of USAN council.
Similarly, there is the British approved name (BAN) of a drug. The non proprietary names
of newer drugs are kept uniform by an agreement to use the recommended international
non proprietary name (rINN) in all member countries of W.H.O.
Proprietary (Brand) name
It is the name assigned by the manufacturers and is his property or trade mark.
One drug may have multiple proprietary names.
Example: altol, atcardil, atecor, aten, betacard, lonol, tenormin, tenalol for atenalol from
different manufactures.
Brand names are designed to be catchy, short, easy, to remember.
Adverse Drug Reactions
1. Side-effects. e.g Atropine: dry mouth
2. Toxic effects: mostly seen with higher doses. E.g Morphine, respiratory depression.
3. Drug tolerance: single dose of streptomycin producing vestibular dysfunction.
4. Idiosyncratic reactions: e.g barbiturates produce CNS stimulation.
5. Allergic reactions: immunologically based adverse reactions to drugs are called allergic
reactions which are not related to pharmacological actions of drugs.
11
Factors modifying the action of drugs
1. Body weight, Clarks rule: dose: body weight in kg times average adult dose divide by 70.
Example
A patient whose body weight is 65kg has been taken paracetamol. If the average adult dose
of paractemol is 500mg. Calculate the dose of this patient.
Result: 464.3 mg
Body surface area (BSA): The individual dose = BSA (m2) / 1.7 times average adult dose.
The BSA (m2)= BW(kg) 0.425 times Height (cm) 0.725 times 0.007184
Result: 677.1 mg
2. Age, Youngest rule: age in years times adult dose divide by age in years plus 12.
Example
A patient whose his age is 11 years has been taken Aspirin 365mg. Calculate the dose of
this patient.
Result: 174.56mg
Dillings Formula: child dose= Age times adult dose divide by 20.
Result: 200.175mg
3. Sex
4. A species and race
5. Diet and environment
6. Route of administration. E.g Magnesium sulphate
7. Genetic factor. E.g G6PD patients causes hemodialysis.
12
8. Diseases. E.g liver diseases
9. Renal dysfunction. E.g kidneys, streptomycin, Amphotericin B, phenytoin.
10. Tolerance: can be grouped into natural and acquired.
Pregnancy considerations
Increased maternal heart rate, cardiac output and blood volume.
Drugs may cross placenta
Drugs may cross into a breast milk
Teratogens
Pediatric considerations
Decrease oral absorption
Thinner skin
Decrease plasma protein concentration
Increase extracellular fluid in neonate
Altered metabolic rates
Decrease elimination
Decrease metabolism
Geriatric considerations
Decrease oral absorption
Decrease plasma protein concentration
Decrease muscle mass
Increase fat body

13
Decrease liver/ renal function
Multiple drugs
Multiple diseases
Pharmaceutical Abbreviations
Drug Dosage
1. CC: Cubic Centimeter
2. G: Gram
3. Gr: Grain
4. Gtt: Drop
5. Lb: Pound
6. Ml: Milliliter
7. Qs: Quantity Sufficient
8. ss: One half
9. tbsp: Tablespoon
10. tsp: Teaspoon
11. ID: intradermal
12. IM: intramuscular
13. IV: intravenous
14. OD: right eye
15. OS: left eye
16. OU: both eyes

14
17. PO: by mouth
18. SC: subcutaneous
19. SL: sublingual
20. AA: of each
21. Ac: before meals
22. Ad lib: as desired
23. bid: Twice a day
24. h: hour
25. hs: hour of sleep
26. noct: night
27. pc: after meals
28. prn: when needed
29. qd: every day
30. qh: every hour
31. qid: four times a day
32. qod: every other day
33. sos: if necessary
34. stat: immediately
35. tid: three times a day
15
Routes of Drug Administration
Drugs may be administered by various routes:
1. Enteral
2. Parentral
3. Rectal
4. Topical
Enteral routes
Enteral means through gastrointestinal tract.
1. Oral route
It is the most common route of administration. GIT has a large surface area and different
PH at different parts helps absorption of drugs. At the same time some drugs can be
destroyed by the enzymes secreted in gastrointestinal tract.
Advantages
Convenient: patients can swallow them selves
Economical: oral compounds are cheaper.
Non-invasive : no technique is required, no syringes and needles.
Disadvantages
Slow onset of action
Bitter drugs may cause irritation like nausea and vomiting.
Some drugs are not absorbed. E.g streptomycin
Some are destroyed. E.g insulin
16
Cannot be given to unconcious and uncooperative patients
Some drugs may undergo extensive first pass metabolism.
Various oral preparations
Powders
Tablets
Capsules
Mixtures
Syrups
Linctus: syrup with soothing agent.
Emulsion
Factors that affects oral route
Food interferes with absorption of some drugs.
Milk, calcium can affect
Drugs should be swallowed with lot of water and sitting position.
Parenteral Routes
Parenteral routes include:
1. Injections
2. Transdermal
3. Inhalation
4. Transmucosal
17
Injections
1. intradermal: in intradermal injection the drug is injected into the layers of skin. E.g BCG
vaccine.
2. Sub-cutaneous: when the drug is injected below the skin, it is absorbed slowly.
3. Intramuscular: is an injection in to the skeletal muscles.
4. Intravenous: the drug is injected directly into the vein.
Advantages & disadvantages IV
Advantages
1. In emergency
2. Unconscious patients
3. When the drug is not suitable for IM or subcutaneous injections.
4. When large volumes are required. E.g NS, 5% Dextrose
Disadvantages
1. Rupture of vein
2. Transmission of diseases through blood transfusion
3. Should be given only to trained person
Inhalational Administration
Some drugs may be given by inhalation through nose to produce either local action on the
respiratory tract or systemic action. They are absorbed through lungs. E.g beclomethasone,
salbutamol.
18
Transdermal Administration
Highly lipid soluble drugs can be absorbed effectively from the skin. The drug is applied
the skin in the form of a patch having the drug container which releases the drug at a
constant rate.
Advantages
1. Prolonged and slow action
2. Can be removed when it is not required.
Disadvantages
1. Absorption can be variable
2. Slow action
3. Sometimes there will be skin reaction
Transmucosal Administration
Sublingual route: A number of drugs can be absorbed from the thinner portion of oral
mucosal. The drug is kept in the form of tablet or powder under the tongue.
Advantages
1. It is rapidly absorbed it bypasses liver and first pass metabolism.
2. Easy procedure
3. Quick action
Disadvantages
1. All drugs cannot be given by this route
2. Sometimes it may cause irritation of mucosa

19
Rectal administration
Rectum can serve as useful site for drug administration especially in unconscious patients
and if nausea and vomiting are severe.
Highly lipid soluble drugs are readily absorbed by rectal route.
Topical
It is employed for local action of drugs; the various preparations for topical use are
ointment, creams, lotions and paints, eye drops, ear drops, and nasal drops.
CHAPTER TWO: PHARMACOKINETICS & PHARMACODYNAMICS
2.0 Pharmacokinetics
Pharmacokinetic is the study of what actually happens to a drug from the time it is put into
the body until the time all of it and it is metabolites have left the body.
Pharmacokinetic is what body do to the drug.
Pharmacokinetic is the study of absorption, distribution, metabolism and excretion

(ADME).
Absorption
• Drug absorption is the processes of incorporating a drug into the body and its various
tissues, organs and other biological sites.
• If two medications have the same bioavailability, they are said to be bio-equivalent.
• Bioavailability is the amount of a drug in a particular dosage form that is absorbed into the
circulation.
20
• There are various factors that affecting the rate of drug absorption, these include
administration route of a drug, food, and fluids, administered with a drug, the dosage
formulation, the status of the absorptive surface, and the acidity of the stomach.
Distribution
Once a drug enters the blood stream (circulation), it is distributed throughout the body.
A drug can be freely distributed to extravascular tissue only if it is not bound to a protein. If
a drug is bound in to a protein, it is generally too large to pass into tissues.
The transport of a drug that in the body by the blood stream to its site of action is referred
to us distribution.
There are three primary proteins that carry that bind to and carry drugs throughout the body
and they are:
Albumin (most important)
Alpha 1 acid glycoprotein
Corticosteroid binding globulin
Distribution can be classified into two compartments:
Rapid distribution like heart, liver, kidney and brain.
Slow distribution like muscle, skin and fat
A theoretical volume, called volume of distribution, is sometimes used to describe the

various areas where drugs may be distributed.
Typically a drug that is highly water soluble will have a small volume of distribution and
high blood concentrations.
Fat soluble drugs have a large volume of distribution and low blood concentrations.
21
Metabolism
Metabolism is also referred to as biotransformation because it involves the biologic

transformation of a drug into an inactive metabolite, a more soluble compound or a more
potent metabolite.
Biotransformation is the next step after absorption and distribution.
The organ most responsible for the biotransformation or metabolism of drugs is the liver.
Other tissues and organs that aid in the metabolism of drugs are the kidney, lungs, plasma,
and intestinal mucosa.
Biotransformation means chemical alteration of the drug in the body.
The biotransformation capabilities of the liver can vary considerably from patient to
patient.
Hepatic biotransformation involves the use of an enormous variety of microsomal

enzymes.
Biotransformation reactions can be classified into:
1. non-synthetic or phase I reactions: like oxidation, reduction, hydrolysis, cyclization, and

decyclization.
2. Synthetic reactions: like glucuronide conjugation, acetylation, methylation, sulfate

conjugation, Glycine conjugation, glutathione conjugation.
Excretion
The elimination of drugs from the body is referred to as excretion.
The primary organ that is responsible for excretion is kidney.
Two other organs that also play an important role in the excretion of drugs are the liver and
the bowel.
22
The actual act of excretion is accomplished through glomerular filtration, resorption, and
tubular
Excretion is the passage out of systemically absorbed drug.
The excretion of drugs by the intestines is another common route of elimination. This is
also referred to as biliary excretion. Drugs that are eliminated by this route are taken up by
the liver, released into the bile, and eliminaccomplished through glomerular filtration,
resorption, and tubularated in the feces.
It is the time it takes for one half of the original amount of a drug in the body to be
removed and is a measure of the rate at which drugs are removed from the body.
E.g tetracycline 500mg, it is first half life is 250mg.
Half life of some representative drugs
Aspirin 4 hours
Penicillin G 30 minutes
Doxycycline 20 hours
Digoxin 40 hours
Digitoxin 7 days
Phenobarbitone 90 hours
Onset, Peak, Duration
a therapeutic The terms onset, peak, and duration are used to describe drug effects.
A drug onset of action is the time it takes for the drug to elicit a therapeutic response.
The time it takes for a drug to reach it is maximum therapeutic response is its peak effect.
23
The duration of action of a drug is the time that drug concentration is sufficient to elicit
response.
Pharmacodynamic
The study of the mechanism of drug actions in living tissues is called pharmacodynamics.
Pharmacodynamics is what drug does to the body.
Pharmacodynamics can be classified into:
Therapeutic utility
Mechanism of action
Receptor interactions
Principles of drug action
The principles of drug actions are as the following:
1. Stimulation
2. Depression
3. Irritation
4. Replacement
5. Cytotoxic actions
Stimulation
It refers to selective enhancement of the level of activity of speacilized cells. e.g adrenaline
stimulates heart, pilocarpine stimulates salivary glands. However excessive stimulation is
often followed by depression of that function, e.g picrotoxin a central nervous system
stimulant produces convulsions followed by coma and respiratory depression.
24
Depression
It means selective diminution of activity of specialized cells. E.g barbitutares depress CNS,
quinidine depresses heart. Certain drugs stimulate one type of cells but depress the other.
E,g acetylcholine stimulates intestinal smooth muscle but depress sinoatrial node in heart,
thus most drugs cannot be simply classed as stimulants or depressants.
Irritation
This connotes a nonselective often noxious effect and is particularly applied to less
speacilized cells. Mild irritation may stimulate associated function. E.g bitters increase
salivary and gastric secretion, counterirritants increase blood flow to the site, but strong
irritation results in inflammation, necrosis, and morphological damage.
Replacement
This refers to the use of natural metabolites, hormones or the Air congeners in deficiency
states. E.g levodopa in parkinsonian, iron in anemia, insulin in diabettes.
Assignment
Describe the therapeutic index concept including formula and ways of calculation.
Combined effects of drugs
When two or more drugs are given simultaneously or in quick succession, they may be
either indifferent to each other or exhibit synergism or antagonism.
The interaction may take place at pharmacokinetic level or at pharmacodynamic level.
Synergism
When the action of one drug is facilitated or increased by other, they are said to be
synergistic. In synergistic pair both the drugs can have action in the same direction or given
alone one may be inactive but still enhance the action of the other when given together.
Synergism can be:
25
1. Additive
2. Supraadditive
Additive
The effect of the two drugs is in the same direction and simply adds up. E.g effect of drugs
A+B= effect of drug A + effect of drug B.
Examples are the following:
Aspirin + paracetamol = analgesic/antipyretic
Nitrous oxide + halothane = general anesthesia
Amlodipine + atenalol = antihypertensive
Glibenclamide + Metformin = hypoglycemic
Ephedrine + Theophylline = bronchodilator
Supraadditive
The effect of combination is greater than the individual effects of the components.
Effect of drug A + B is greater than effect of drug A + effect of drug B.
Examples are the following:
1. Acetylcholine plus physostigmine
2. Levodopa plus carbidopa plus benserazide
3. Adrenaline plus cocaine plus desipramine
4. Sulfamethaxazole plus trimethoprim
5. Enalapril plus hydrochlorothiazide
26
Antagonism
When one drug decreases or abolishes the action of another, they are said to be
antagonistic.
Effect of drug A + B is less than effect of drug A + effect of drug B.
Antagonism can be classified into:
1. Physical antagonism e.g charcoal adsorbs alkaloids
2. Chemical antagonism e.g heparin intercts penicillin
3. Physiological antagonism e.g glucagon & insulin
4. Receptor antagonism e.g agonist & antagonist drugs
Pharmacotherapeutics
Pharmacotherapy is a dynamic process that should be occurring continuously throughout a

patient’s therapy.
The use of a medicaation to treat a pathologic condition is called Pharmacotherapeutics.
Acute Therapy
Acute therapy involves intensive drug therapy and is typically implemented in the critically
ill patient. It is generally needed to sustain life. Examples are the administration of
vasopressors to maintain blood pressure and cardiac output after open heart surgery or the
use of volume expanders in a patient who is in shock.
Maintenance Therapy
Maintenance therapy typically does not eradicate the problems the patient may have but
doesn’t prevent progression of the disease. It is used for the treatment of chronic illnesses
such as hypertension.
27
The drug therapy maintains the patient’s blood pressure within certain limits, which
prevents certain end organ damage.
Supplemental Therapy
Supplemental or replacement therapy supplies the body with a substance needed to

maintain normal function.
This substance may be needed either because it cannot be made or because it is deficient in
quantity.
Examples are the administration of insulin to diabetic patients or iron to patients with iron
deficiency anemia.
Palliative Therapy
The goal of palliative therapy is to make the patient as comfortable as possible. It is typically used
in the end stages of an illness when all possible therapy has failed.
The use of high dose narcotic analgesics to relieve pain in the final stages of cancer is an example;
the use of oxygen in end stage of pulmonary disease is another.
Supportive Therapy
Supportive therapy maintains the integrity of the body functions while the patient is
recovering. Providing fluids and electrolytes to prevent dehydration in a patient with the flu
who is vomiting and has a diarrhea is an example.
Giving fluids, volume expanders or blood products to a patient who has lost blood during
surgery is an example.
Prophylactic Therapy
Prophylactic therapy is drug therapy provided on the basis of prior practical experience. It
is based on scientific knowledge often acquired during years of observation of a disease
and it is causes.
28
CHAPTER THREE: AUTONOMIC NERVOUS SYSTEM
Parasympathomimetic Drugs
Acetylcholine is released from the parasympathetic nerve endings through out the body and
also at motor nerve endings in voluntary or skeletal muscles.
It causes contraction of the skeletal muscle.
It is actions are short lived as it is destroyed by acetylcholinestrase enzyme within fraction
of a second.
There are some drugs which mimic the actions of acetylcholine and have prolonged effect.
Drugs
Bethanechol
Pilocarpine
Acetylcholine
Methacholine
Carbachol
Arecoline
Actions of Drugs
Actions of the drugs are classified into two:
1. Muscarinic
2. Nicotinic
Muscarinic Actions
Heart
Blood vessels
Smooth muscle
Glands
Eye
Nicotinic Actions
Autonomic ganglia
Skeletal muscles
29
M.O.A
These drugs mimic the actions of Ach.
It causes contraction of the bladder causing passage of urine.
Therapeutic Uses
The most important use of carbachol and bethanechol is urinary retention following
surgical operation .
Pilocarpine: is mainly used as eye drops causing constriction of the pupil and may useful in
glaucoma.
Side-effects
Colicky pain
Diarrhea
Fall in B.P
Bethanechol
Has been used in postoperative/postpartum nonobstructive urinary retention, neurogenic
bladder, congenital megacolon and gastrointestinal reflex.
S/E: Belching, colic, involuntary urination/defecation, flushing, sweating, fall in Bp,
bronchospasm.
Pilocarpine
It is obtained from the leaves of pilocarpus microphyllus and other species. It has
prominent muscarinic actions and also stimulates ganglia, mainly through ganglionic
muscarinic receptors.
Pilocarpine causes marked sweating, salivation, and increase other secretions as well. The
cardiovascular effects are complex.
Small doses generally cause fall in BP (muscarinic) but higher doses elicit rise in Bp and
tachycardia which is probably due to ganglionic stimulation.
Applied to the eye, it penetrates cornea, and promptly causes miosis, ciliary muscle
contraction and fall in intraocular tension lasting 4-8 hours.
Pilocarpine is used only in the eye as 0.5%-4% drops. It is a third line drug in open angle
glaucoma. An initial stinging sensation in the eye and painful spasm of accommodation are
frequent side effects.
30
It is available PILOCAR 1%, 2%, 4% eye drops, CARPINE 0.5% eye drops, PILODROPS
2% eye drops.
Anticholinestrase Drugs
These drugs prevent the breakdown of acetylcholine by blocking the action of
cholinesterase enzyme. The action of acetyl choline thus is intensified at the two important
sites.
Many anticholinestrase compounds are used as insecticides are misused by certain people
for suicidal purpose. They are called organophosphorus compounds.
Classification of Drugs
Anticholinesterases are classified into two main parts:
1. Reversible
2. Irreversible
Reversible drugs
1. Physostigmine
2. Neostigmine
3. Pyridostigmine
4. Edrophonium
5. Rivastigmine
6. Donepezil
7. Galantamine
8. Tacrine
Irreversible drugs
1. Dyflos
2. Echothiophate
3. Parathion
4. Malathion
5. Diazinon
6. Carbaryl
31
Therapeutic uses
As Miotic
Mysthenia Gravis
Paralytic ileus to increase the intestinal motility.
Atony of bladder
Cobra bite
Belladona poisoning
Other drug over dose
Alzheimers disease
Adverse effects
Intestinal colic and diarrhea
Excessive salivation and sweating
Pupils are constricted
Bradycardia and fall of B.P
Respiratory rate is slow
Treatment
Termination of further exposure
Fresh air
Wash the skin and mucous membrane with soap and water
Gastric lavage according to need
Maintain patient airway
Maintain BP, hydration
Control of convulsion by Diazepam
Atropine antidot 0.6mg/ml to 2mg/ml inj.
Parasympatholytic Drugs
These drugs inhibit the action of acetylcholine on parasympathetic nerve endings or they
block the cholinergic receptors in the concerned organs.
They are generally referred to as ganglion blockers and neuromuscular blockers.
32
1. Natural alkaloids
Atropine
Hyoscine
2. Semi-synthetic derivatives
Ipratropium bromide
Tiotropium
Hyoscine butyl bromide
3. Synthetic compounds
Cyclopentolate
Tropicamide
Actions of Drugs
Cardiovascular system
Central nervous system
Eye
Smooth muscles
Glands
Body temperature
Local anaesthetic
Atropine
Atropine: is an alkaloid obtained from the plant atropa belladona and is used since very
long time. It can be given orally, subcutaneously, intramuscularly, and or intravenously.
It has all opposite effects of acetylcholine.
Atropine is rapidly absorped from the G.I.T
It has 3-4 hours of halflife
Atropine sulphate is available 0.6mg – 2mg i.m/i.v and 1-2% eye drop, 5% eye ointment.
33
Clidinium
It is available in 2.5 mg oral for once a day.
It is combined benzodiazepines drugs
It is used for the treatment of dyspepsia, gastritis, peptic ulcer, irritable bowel syndrome
and colic.
Therapeutic uses
Relief of abdominal colic and biliary colic
Dilate the pupil (mydriasis), donot give with a glaucoma patient.
Preoperative medication (reduce salivary and bronchial secretions)
Very useful in Organo phosphorus compounds poisoning (0.6mg-2mg IV every half hour
till patient recovers or pupils start dilating).
Preanaesthetic Medication
They are useful in motion sickness to suppress the vomiting and nausea.
Parkinson disease
Asthmatic bronchitis
Gastritis, Peptic ulcer
Bradycardia
The sympathomimetic Drugs

These group of drugs mimic the effects produced by activation of sympathetic nervous
system. These drugs are classified based on the chemical structure into:
1. Catecholamines e.g adrenaline, nor-adrenaline
2. Non-catecholamines e.g phenylephrine, methoxamine, oxymetazoline, xylometazoline.
(alpha 1)
Epinephrine
Epinephrine: it is the one of the substance produced by sympathetic nerve stimulation. It is

also prepared synthetically for it is chemical and experimental use.
34
Therapeutic uses
Anaphylactic reactions: adrenaline is given as 0.5ml intramuscularly of the 1:1000 solution.
Cardiac arrest: it can be given IV as bolus injection of 0.5 ml or intracardiac injection.
Acute bronchial asthma: 0.5ml subcutaneously. Note: ask the patient any heart disease
before.
Epistaxis: lamp of adrenaline can be broken and put into a cotton swab to pack into the
nose to stop bleeding. It is very useful as it produces vasoconstriction and stops bleeding.
Dopamine
Dopamine is also an endogenous substance mainly in the CNS, but when given parenterally
it doesn't cross the blood brain barrier.
It is the drug of choice for Cardiogenic shock but should be given after IV fluids dose in
5% dextrose to give 400g of dopamine per ml.
Inject very slowly intravenously.
Salbutamol
Salbutamol is the most widely used agonist used in bronchial asthma.
It can be given by oral, IV, and inhalation.
It is used for acute bronchial asthma 200 microgram by inhalation is given to relieve
bronchospasm & in chronic bronchial asthma 2mg-8mg orally BID, TID.
It is given as uterine relaxant to prevent premature labor.
Sympatholytic or adrenergic blocking agents
These drugs block alpha and beta adrenergic receptors.
They are classified:
1. Alpha adrenergic blockers
2. Beta adrenergic blockers
Alpha adrenergic drugs
Prazocin
Doxazocin
Terazocin
Phentolamine
Phenoxy benzamine
35
Ergotamine
Beta adrenergic blockers
Sotalol
Timalol
Propranalol
Atenalol
Metaprolol
Acebutalol
Reduce intraocular pressure
Side-effects
Bronchospasm
Cold extremities
Hallucinations
Fatigue
Lethargy
36
CHAPTER FOUR: CARDIOVASCULAR DRUG AGENTS
Cardiac glycosides
Cardiac glycosides are drugs that increase the rate at which the heart beats is known as
positive inotropic effects.
• Cardiac glycosides used to solve the problems of congestive heart failure (CHF).
• In patients with congestive heart failure occurs when the ejection fraction compared with
the total amount of blood in the ventricle is decreased. Cardiac glycosides are one of the
oldest and most effective groups of drugs.
• They were originally obtained from either digitalis purpurea or digitalis lanata plants both
commonly referred to as foxglove.
• The cardiac glycosides have been the mainstay of therapy for CHF for more than 200 years
and they continue to be one of the most frequently used positive inotropic agents.
Drugs
1. Digoxin: is the most prescribed drug in this group, it has less side effects.
2. Digitoxin: not frequently used because of it is side effects.
Mechanism of action
The primary beneficial effect of digitalis is thought to be an increase in myocardial
contractility. By doing this cellular sodium concentration and calcium concentration
increases.
Digoxin
Digoxin is the most commonly prescribed digitalis glycoside. It is highly effective agent in
the treatment of CHF.
May also used clinically to improve myocardial contractility and thus reverse Cardiogenic
shock.
Digoxin is contraindicated in patients who have shown in:
1. Hypersensitivity
2. Tachycardia
Digoxin is available in: 50microgram elixir, 50,100, 200 microgram liquid filled capsule, 125, 250,
500 microgram tablet and 100, 200 microgram per mal injection. Adult dosage is 1-1.5mg/day,
0.125-0.5 mg. Premature dosage is 0.015-0.025mg/kg.
37
Side-effects
Anorexia
Nausea
Vomiting
Confusion
Colored vision
Headache
Fatigue
Toxicity and management overdose

1. Discontinue the drug.
2. Determine digoxin and electrolyte level.
3. Administer potassium supplements for hypokalemia.
4. Start ECG monitoring.
5. Administer digibind for severe overdose.
Anti-dysrhythmic Agents
• A dysrhythmia is any deviation from the normal rhythm of the heart, thus the more
accurate term for an irregular heart rhythm is dysrhythmia.
• There are many conditions in which dysrhythmia can develop:
1. Myocardial infraction
2. Cardiac surgery as a result of coronary disease.
There are numerous drug available to treat dysrhytmias and these are classified based on
where and how they affect cardiac cells.
The most commonly used system is the Vaughan Williams classification.
Class one
Class 1A: Disopyramide, Procainamide and Quinidine
Class 1B: Lidocaine, Phenytoin, Tocainide and Mexiletine
Class 1C: Propafenone, Flecainide and Entainide
38
Class Two: Propranaolol, Esmolol and sotalol
Class three: Amiodarone and Bretylium
Class four: Adenosine, Verpamil and Diltiazem
Side-Effects
Hypersensitivity
Nausea
Vomiting
Diarrhoe
Dizziness
Headache
Blurred vision
Toxicity management of overdose

• The main toxic affects of the anti-dysrhythmics involve:
1. Heart
2. Circulation
3. CNS
• Speacific antidotes are not available and the management of an overdose involves
maintaining adequate circulation and respiration.
Quinidine
Quinidine has both direct action on the electrical activity of the heart and indirect (ant
cholinergic) effect.
It is ant cholinergic results in inhibition of the parasympathetic nervous system.
Significant adverse effects of the agent include
1. Cardiac asystole
2. Arterial embolism
3. Ventricular ectopic beats
Contraindicated
1. Hypersensitivity
2. AV block
3. Abnormal rhyths
Quinidine is available in 324mg quinidine gluconate tablets, 275 mg quinidine
polygalacturonate tablets, 300mg quinidine sulfate tablets.
Parentrally quinidine gluconate comes as an 80mg/ml injection.
Adult dosage is 324 – 648 mg q8h-q12h, IM 600mg followed by 400mg q2h.
Procainamide
It is similar to that of Quinidine but it differs from Quinidine in that it is indirect effect
(anticholinergic is weaker).
Procainamide is useful in the management of atrial and ventricular tachydysrhymias.
It is a pregnancy category C drug.
Available 250, 375, 500mg capsules, 500, 750, 1000mg film coated tablets and 100,
500mg/ml injection
39
Disopyramide
Disopyramide is used primarily for the treatment of ventricular dysrhymias.
It can produce significant side-effects including:
1. Anticholinergic effects
2. Cardiovascular depression
For these reasons it is use is limited, especially in patients with poor left ventricular
function.
Significance adverse reactions from it are hypotension and widening of the QRS interval on
ECG.
It is available orally in 100- 150mg capsules
Adult dosage is 150mg q6h.
Lidocaine (1B)
It is one of the most effective drugs for the treatment of ventricular dysrhytmias.
It can only administer intravenously because it has extensive first pass effect, that is when
taken orally, the liver metabolizes most of it.
It is accomplished by blockade of sodium channels.
Lidocaine is the drug of choice for treating the acute ventricular dysrhymias.
Available 100mg/ml IM injection, 10, 20, 40, 100, 200mg/ml IV injection.
Propafenone( 1C)
Propafenone reduces sodium current in purkinje fibers and to lesser extent in myocardial
fibers.
Propafenone has a mild beta-blocking effects.
It is also believed to have calcium channel blocking effects, which contributes to
propafenone mild negative inotropic effects.
It should be used with causion in patients with congestive heart failure, because of it is
beta-blocking agents and it is mild inotropic effects.
The most frequently reported adverse reaction is dizziness.
Patients may also complain
1. Metallic taste
2. Constipation
3. Headache
4. Nausea
Propafenone is contraindicated:
1. Bradycardia
2. Hypersensitivity
40
3. Bronchial asthma
4. Hypotension
Available orally as 150, 300mg, and the adult dosage is 150mg q8h.
Quinidine Case Study

ID/CC: A 56 year old male comes to the cardiology unit for evaluation of ringing in his
ears (Tinnitus), dizziness, GI distress (nausea, vomiting, diarrhea), and headaches.
HPI: He also complains of blurred vision and impaired hearing. The patient had a
myocardial infarction one year ago and has been receiving oral Quinidine antiarrhythmic
therapy.
Labs: CBC: normal, widening QRS.

Treatment: Monitor ECG and vital signs, discontinue the drug, change to different
antiarrhythmic drug. Treat cardio toxic effects with sodium lactate.
Discussion: Quinidine, Procainamide, and Disopyramide are class 1A antiarrhythmic that
acts by blocking sodium channels, increasing the effective refractory period. They are used
for both atrial and ventricular arrhythmias. All these agents have low therapeutic toxic
ratios and may produce severe adverse reactions. Cinchonism is commonly produced by
drugs that are cinchona derivatives, such as Quinidine and quinine. The effects may occur
with only one dose.
Atenalol (Tenormin) class II

It is a cardio-selective beta blocker that means it blocks the beta one adrenergic receptor.
Atenalol also activates beta two in the lungs and could therefore exacerbate a pre-existing
case of asthma or COPD.
It is also useful in the treatment of hypertension and angina pectoris.
It is available orally 25, 50, 100mg tablets, 0.5mg/ml IV injection.
Propranolol (class II)

Propranolol is one of the first beta blockers introduced into clinical practice and this
occurred in 1967.
It was then primarily used in the treatment of dysrhymias.
Propranolol is a non-speacific blocker that blocks both beta one and beta two adrenergic
receptor in the heart and the lungs.
Propranolol is the oldest of this class of drugs, there are now many indications of It is use:
1. Hypertension
41
2. Angina pectoris
3. Dysarrythemia
Available as 10, 20, 40, 60, 80, 90 mg tablets, 60, 80, 120, 160 mg capsules, 20, 40,
mg/5ml oral solution, 1mg/ml injection.
Amiodarone
Amiodarone markedly prolongs the APD (action potential duration) and ERP (effective
refractory period).
Amiodarone also known to block both the alpha and beta adrenergic receptors.
Amiodarone is a very lipophilic, there fore it may cause un wanted effects.
Amiodarone can cause
1. Hypothyrodism
2. Hyperthyrodism
Amoidarone is contraindicated in patients
1. Hypersensitivity
2. Severe bradycardia
3. Second or third degree of heart block.
Amiodarone is available 200mg orally tablets.
Amiodarone is a pregnancy category C agent.
Diltiazem
Diltiazem is primarily indicated for the temporary control of a rapid ventricular response in
a patient with atrial fibrillation.
It is available both orally and parenterally, 30, 90, 120 mg tablets and 5mg/ml injection.
Verpamil
Verpamil inhibits calcium ion influx across the slow calcium channels in cardiac
conduction tissue.
Usually decreases the heart beat at least 20 percent.
Verpamil is also used to treat:
1. Angina pectoris
2. Hypertension
It is available 40, 80, 120mg tablets, and 2.5 mg/ml injection parenterally.
It is a pregnancy category C.
42
Introduction of Angina Pectoris
Angina pectoris is a pain syndrome due to induction of an adverse oxygen supply/ demand
situation in a portion of the myocardium.
Two principal forms are recognized:
1. Classical angina (stable): is the most common one and attacks are predictably provoked
by exercise, eating. The underlying pathology is severe arteriosclerotic affliction of larger
coronary arteries.
2. variant/prinzmetals/unstable angina: is an uncommon form and attacks occur at rest or
during sleep and are unpredictable. They are due to recurrent localized (occasionally
diffuse) coronary vasospasm which may be superimposed on arteriosclerotic coronary
artery disease.
Anti-anginal Drugs
The main classes of drugs used to treat angina pectoris are:
1. Nitrates
2. Beta-blockers
3. Calcium channel blockers
4. Potassium channel blockers e.g Nicorandil.
5. Others. E.g Dipyradimole, Trimetazidane, Ranolazine and oxyphedrine.
There are three main therapeutic objectives of anti-anginal drug therapy:
1. It must minimize the frequency of attacks and decrease the duration of the anginal pain.
2. Improve the patients functional capacity with as few side-effects
3. Prevent the worst outcome, myocardial infarction.
Nitrates/Nitrites
Organic nitrates were introduced into medicine in the 19th century, de-nitrition in the
smooth muscle cell releases nitric oxide which is the main physiological vasodilator.
Nitrates, in particular nitroglycerin have long been the mainstay of both the prophylaxis
and treatment of angina.
This class of anti-anginal agents was first discovered by sir Thomas lauder brunton in
England who noted that amyl nitrate was just effective as venesection in the management
of angina.
Few years later, a chemically related substance glyceryl trinitrate (nitroglycerin) was
successfully isolated.
They are available in a wide variety of preparations including:
1. Sublingual, Bucal, Chewable tablets, Oral tablets, Capsules, Ointments, Patches, Inhalable
sprays, Intravenous solutions
Nitrates can be classified into:
1. Rapid acting agents
Amyl nitrate
Nitroglycerin
2. Long acting agents
Erythrityl tetra nitrate
43
Isosorbide dinitrate
Isosorbide mononitrate
Mechanism of Action
The nitrates dilate all blood vessels, but they primarily affect the blood vessels of the
venous circulation.
This venodilation is the result of relaxation of the smooth muscle that surrounds veins.
Nitrates also have a potent dilating effect on the coronary arteries.
Activation of nitric oxide, stimulates guanosine mono-phosphate, and this results
relaxation then vasodilation.
Nitroglycerin
Nitroglycerin has traditionally been the most important drug used in the symptomatic
treatment of ischemic heart conditions such as angina.
it has classified pregnancy category C agent.
Nitroglycerin is administered many other routes to pass first pass effect.
Available sublingual 0.3, 0.4, 0.6 mg tablets, 0.4mg/metred dose aerosol, 5mg/ml IV,
2.6mg, 6.5mg tablets, 2.5, 6.5, 9, 13mg capsules, 2% ointment and 0.1, 0.2, 0.3, 0.4 mg
patches.
Adult dosage is 2.5-6.5mg q8h-q12h, sublingual 0.15-0.6mg Prn, transdermal, apply one
patch q24h.
Isosorbide Dinitrate
Isosorbide is an organic nitrate and therefore a powerful explosive.
When Isosorbide dinitrate is metabolized in the liver, it is broken down into two active
metabolites.
It is used for the acute relief of angina pectoris and for prophylaxis.
It is a pregnancy category C drug agent.
Available orally 40mg capsules, 5, 10, 20, 30, 40mg tablets and 2.5, 5, 10mg sublingual
tablets.
Adult dose is sublingual 2.5-10mg Prn and 5-30mg q8h-q12h.
Nadolol
Nadolol is a non-selective beta-blocker indicated for the prophylactic treatment of angina
and hypertension.
It is the most hydrophilic of all beta blockers which may be a beneficial characteristic in
elderly patients because as we age we lose muscle mass and gain fat.
Water soluble drugs such as nadolol will have more consistent and reliable effect.
It is a pregnancy category C agent.
It is only available orally as 20, 40, 80, 120, 160mg tablets.
Adult dosage is 80-240mg/day as a single dose.
Nifedipine
Nifedipine is a calcium channel blocker drug.
It is given by sublingually.
Available 10, 20mg capsules, 30, 60, 90mg tablets.
Adult dosage is 10mg Tid.
44
Anti-hypertensive Agents
The anti-hypertensive drugs are classified based on their mechanism of action
1. Adrenergic agents
2. Vasodilators
3. Diuretics
4. ACEI
5. Angiotensin II receptor Blockers
6. Calcium channel blockers
7. Beta-blockers
Adrenergic Agents
1. Centrally acting drugs
Clonidine, Guanabenz, Guanfacine and Methyldopa .
2. Peripherally acting drugs: Guanadrel, Guanethidine and Reserpine
Mechanism of action
The centrally acting adrenergic agents decrease blood pressure by stimulating the alpha 2
receptors.
The peripherally acting adrenergic agents decrease blood pressure by blocking alpha 1
adrenergic receptors.
Side-effets
Dry mouth
Drowsiness
Sedation
Constipation
Headache
Sleep disorders
Nausea
Rash
Clonidine
Clonidine is primarily used for it is ability to decrease blood pressure.
It is also useful in the management of Opiod withdrawal.
It has better safety profile than the other centrally acting adrenergics and has the advantage
of being available in several dosage forms.
Contraindicated in a patients who have shown hypersensitivity.
Available 0.1, 0.2, 0.3 mg as patch, 0.1, 0.2, 0.3mg tablets orally.
Adult dosage is 0.2-0.8mg/day divided dose.
Reserpine
Reserpine is derived from rauwolfia alkaloids.
Reserpine promote sodium and water resorption and their anti-hypertensive effects my
diminish.
Reserpine, always it is combined with diuretics.
Reserpine classified pregnancy category D.
Contraindicated in patients who have:
1. Mental illness
2. Peptic ulcer
45
3. Hypersensitivity
Available in 0.1, 0.25mg tablets.
Adult dose is 0.1 - 0.25mg/day divided or single dose.
Prazosin
It is the oldest of the alpha 1 blockers.
It reduces both peripheral vascular resistance and blood pressure by dilating both arterial
and venous blood vessels.
It is shown beneficial in the treatment of hypertension.
It is classified in pregnancy category C.
Available 1, 2, 5 mg capsules.
Angiotensin converting enzyme inhibitors (ACEI)
ACEI represent a large group of anti-hypertensive agents.
There are currently more than seven agents available for clinical use.
ACEI are beneficial in the treatment of CHF, because they prevent sodium and water
resorption by inhibiting aldosterone secretion.
Side-Effects
Dizziness
Mood changes
Headache
Dry cough
The most pronounced symptom of overdose of ACEI is hypotension.
Treatment is symptomatic and supportive:
1. Administering IV fluids
2. Hemodialysis is effective for the removal of Captopril and lisinopril.
Captopril
Captopril was the first ACEI to became available in this group.
It is given to a hospitalized patients because of it is short half life.
Available 12.5, 25, 50, 100mg tablets.
Adult dosage is 25-150mg 2-3 times aday.
Enalapril
Enalapril is the only currently available ACEI that is available in both oral and parentral
preparations.
Parentral formulation offers the hemo-dynamic benefit of inhibiting ACE activity in an
acutely ill patient who cannot tolerate oral medications.
Enalapril differs from Captopril in that it is a prodrug and relies on a functioning liver to be
converted to it is active form.
Although it is half life is slightly longer that of captopril, it may in some instances still have
to be given twice daily.
Available 2.5, 5, 10, 20mg tablets and 1.25mg/ml injection.
VASODILATORS
Hydralazine Hcl
It is contraindicated in patients with known hypersensitivity.
46
Adult dosage is 10mg Qid 2-4 days followed by 25mg Qid for balance of week.
Minoxidil
Available topical 2% minoxidil solution used to treat hair loss.
Adult dosage is 10-40mg per day or divided dose.
It is contraindicated into a hypotensive patients.
Sodium Nitroprusside
It is contraindicated with a known hypersensitivity patients.
This drug use is limited to the management of the hypertensive emergencies.
Peadtric dosage is 0.3-10mg/kg
Diuretics
Diuretics are drugs, which increase renal excretion of salt and water: are principally used to
remove excessive extracellular fluid from the body.
In order to understand the action of diuretics it is important to have some knowledge of the
basic processes that take place in the nephron (unit structure of kidney.
Approximately 180 liters of fluid is filtered from the glomerulus into the nephron per day.
The normal urine out put is 1-5 liters per day. The remaining is reabsorbed in different
areas of nephron.
There are three mechanisms involved in urine formation:
a) Glomerular filtration
b) Tubular reabsorption
c) Tubular secretion. These processes normally maintain the fluid volume, electrolyte
concentration and PH of the body fluids.
Classification of Diuretics
• Most of the diuretics used therapeutically act by interfering with sodium reabsorption by
the tubules. The major groups are:
I. Thiazides and related diuretics: e.g. Hydrochlorothiazide , chlorthalidone,
bendrofluazide.
II. Loop diuretics.
a. furosemide,
b. ethacrynic acid .
III. Potassium sparing diuretics.
a. triamterene,
b. amiloride,
c. spironolactone.
IV. Carbonic anhydrase inhibitors.
a. acetazolamide
V. Osmotic diuretics.
a. Mannitol
b. glycerol
Loop Diuretics
• Loop diuretics like furosemide inhibit Na+- K – 2Cl symporter in the ascending limb.
47
• Adverse effects: Hypokalemia, nausea, anorexia, vomiting epigastric distress, fatigue
weakness muscle cramps, drowsiness, Dizziness, hearing impairment and deafness are
usually reversible.
• Therapeutic uses: acute pulmonary edema, edema of cardiac, hepatic and renal disease.
Hypertension, cerebral edema, in drug overdose it can be used to produce forced diuresis to
facilitate more rapid elimination of drug.
Potassium Sparing Diuretics
Potassium sparing diuretics mechanism of action: Potassium sparing diuretics

(spironolactone, triamterene, amiloride) are mild diuretics causing diuresis by increasing
the excretion of sodium, calcium and bicarbonate but decrease the excretion of potassium.
Adverse effects: G.I. disturbances, dry mouth, rashes confusion, orthostatic hypotension,
hyperkalaemia, Hyponatraemia .
Therapeutic uses: used with conjunction with thiazides or loop diuretics in edema due to,
cardiac failure nephrotic syndrome and hepatic disease.
Carbonic anhydrase Inhibitors
IV. Carbonic anhydrase inhibitors: these drugs like acetazolamide inhibit the enzyme
carbonic anhydrase in renal tubular cells and lead to increased excretion of bicarbonate,
sodium and potassium ions in urine. In eye it results in decrease information of aqueous
humor. Therefore these are used in treatment of acute angle glaucoma. Main adverse
effects of these agents are drowsiness, hypokalemia, metabolic acidosis and epigastric
distress.
Osmotic Diuretics
Osmotic diuretics: these drugs like mannitol and glycerine (glycerol) are freely filtered at
the glomerulus and are relatively inert pharmacologically and undergo limited reabsorption
by renal tubule. These are administered to increase significantly the osmolality of plasma
and tubular fluid. Some times they produce nausea, vomiting, electrolyte imbalances. They
are used in cerebral edema and management of poisoning.
Anti-lipemic Agents
Anti-lipemic agents are drugs used to lower the rate of cholesterol and triglycerides.
Anti-lipemic drugs can be classified based on their mechanism of actions.
48
Classification
1. Statins
e.g, lovastatin, simvastatin, pravastatin, atorvastatin and rosuvastatin.
2. Bile acid sequestrants (Resins)
e.g, cholestyramine, colestipol.
3. Activate lipoprotein lipase (fibric acid derivatives)
e.g, clofibrate, gemfibrozil, bezafibrate and fenofibrate.
4. Inhibit Triglyceride Synthesis. E.g nicotine.
Bile acid sequestrants
Bile acid sequestrants also called bile acid binding resins and ion exchange resins.
Cholestyramine and colestipol are prime examples of these group.
Both these agents have been used widely for more than 20 years and have been evaluated
extensively in well controlled clinical trials.
Generally these drugs lower plasma concentration of LDL cholesterol.
Mechanism of action
The bile acid resins bind bile and this prevents the resorption of the bile acids from the
small intestine.
Decrease LDL 15-30% and Triglyceride is not affected (effects).
Side-effects
Constipation
Heart burn
Nausea
Belching
Bloating
Note: It is important to initiate the therapy with low doses and instruct patients to take the
drugs with meals to reduce the side-effects.
Because of bile acid sequestrates are not absorbed, an overdose could cause obstruction of
the GIT, therefore treatment of an overdose involves restoring gut motility.
Drug-Drug interactions
All drugs should be taken at least 1 hour before or 4-6 hours after the administration of the
ion exchange resins.
High dose of bile acid sequestrant will decrease the absorption of fat soluble vitamins. E.g
vit A, D, E, K.
49
Cholestyramine
It is a prescription only drug.

It may interfere distribution of the proper amounts of fat soluble vitamins to the fetus or
pregnant women taking these agents.
It is only available 4-9 gram packets of powder to be taken as an oral suspension.
Lovastatin
Lovastatin was the first agent in this drug class to be approved for use and this occurred in
1987.
It is indicated primarily for the treatment of type 2A, and 2B hyperlipidemias.
Effective in lowering the LDL cholesterol level and to some degree the triglyceride levels.
Recommended daily dose is 20-80mg/day PO.
It is a pregnancy category X agent.
Effect on lipids: Decrease LDL 20-55% and Triglyceride 10-35%.
Gemfibrozil
Gemfibrozil is a fibric acid derivative that lowers VLDL level.
It is highly effective for lowering the plasma triglyceride levels.
It is indicated for the treatment of type 4 and 5 hyperlipidemias and in some cases of the
type 2B form.
Available as 600mg orally tablet
It is a pregnancy category B agent.
Effects of lipids: Decrease LDL 5-20% and Triglyceride 20-50%.
Nicotinic Acid
Nicotinic acid is also known niacin, very unique lipid lowering agent.
Nicotinic acid is a vitamin B3 drug.
It is an effective and inexpensive medication.
Niacin is often given in combination with other anti-lipemic drugs to enhance the lipid
lowering effects.
It is a pregnancy category A agent.
Niacin is contraindicated in:
1. Hypersensitivity
50
2. Peptic ulcer
3. Hepatic diseases
4. Hemorrhage
5. Lactating women
6. Severe hypotension.
Available as an over the counter drug.
Available 25, 50, 100, 250, 500, 750mg tablets.
It is commonly given in 2-4 divided doses of 1.5-6g per day.
Effect on lipids: Decrease LDL 15-20% and Triglyceride 20-50%.
Anti-Coagulant drugs
Introduction
Coagulants are substances which promote coagulation, and are indicated in hemorrhagic
states.
Fresh whole blood or plasma provide all the factors needed for coagulation and are the best
therapy for deficiency of any clotting factor; also they act immediately.
Drug profiles
1. Vitamin K. E.g, vit k1 (phytonadione), vit k3 (menadione, acetomenaphtone). Vit k can be
water soluble or fat soluble.
1929 dam produced bleeding disorder in chicken by feeding deficient diet. This was later
found to be due to decreased concentration of prothrombin in blood.
In 1939, alfalfa grass isolated- vit k1, while sardine (sea fish) is isolated-vitk2, and
synthetic compounds have been produced by vit k3.
Uses
1. Dietary deficiencies.
2. Prolonged antimicrobial therapy.
3. Obstructive jaundice
4. Liver disease (viral hepatitis)
5. Newborn
6. Overdose of anticoagulant
51
7. Prolonged high dose of Salicylates
Anti-coagulants
Drugs that prevent the formation of a clot by inhibiting certain clotting factors are called
anti-coagulants.
These agents are only given prophylactically because they have no direct effect on a blood
clot.
There uses vary from preventing clot formation to preventing the extension of preformed
clot or a thrombus.
Once a clot forms on the wall of a blood vessel, it may dislodge and travel through the
blood stream.
If it goes to the brain, it causes stroke.
If it goes to the lungs, it causes pulmonary emboli.
If it goes to the veins in the lungs, it causes deep vein thrombosis.
Anti-coagulants can prevent all of these from occurring, if used the correct manner.
There are both orally and parenterally administered anti-coagulants.
1. Heparin
2. Warfarin
3. Phenindione
4. Hydroxy coumarin
Uses
1. Deep vein thrombosis
2. Myocardial infarction
3. Unstable angina
4. Rheumatic heart disease. E.g Warfarin is effective in this case.
5. Cerebrovascular disease.
6. Vascular surgery.
52
Side-effects
Nausea
Vomiting
Bleeding
Abdominal cramp
Hypoaldosteronism
Toxicity management
Symptoms that may be attributed to toxicity or an overdose of anti-coagulants are:
1. Hematuria
2. Melena (black tarry feces)
3. Mucous membrane bleeding
4. Gum bleeding
Anti-platelet
These are drugs which interfere with platelet function and are useful in the prophylaxis of
thromboembolic disorders.
The clinically important antiplatelet drugs are:
1. Aspirin
2. Dipyridamole
3. Ticlopidine
4. Clopidogrel
5. Abciximab
Aspirin
It inhibits the enzyme COX 1 & TX-synthase- inactivating them irreversibly.
Aspirin induced prolongation of bleeding time lasts for 5-7 days.
Maximal inhibition of platelet function occurs at 160mg aspirin per day.
It is available 75mg, 80mg, 300mg, 360mg, and 600mg.
53
CHAPTER FIVE: NSAIDS
Introduction
Non-steroidal anti-inflammatory drugs have:
1. Analgesic
2. Anti-pyretic
3. Anti-inflammatory
Non-selective COX inhibitors
1. Salicylates, e.g Aspirin.
2. Propionic acid derivatives, e.g ibuprofen, naproxen, ketoprofen.
3. Aryl-acetic acid derivatives, e.g diclofenac and aceclofenac.
4. Pyrrolo-pyrrole derivative, e.g ketorolac.
5. Indole derivatives, e.g Indomethacin
Selective COX-2 inhibitors
1. Celecoxib
2. Etoricoxib
3. Parecoxib
Analgesic-antipyretic with poor anti-inflammatory action
1. Paraaminophenol derivatives, e.g paracetamol (acetominophen)
Pyrazolone derivatives, e.g metamizol (dipyrone) and propiphenazone.
Benzoxazocine derivatives, e.g nefopam.

54
Mechanism of action
NSAIDS blocked prostaglandin generation.
Therapeutic Uses
1. Analgesia
2. Anti-pyretic
3. Anti-inflammatory
4. Anti-thrombotic
5. Closure of ductus arteriosus in newborn.
Side-effects
Shared toxicities due to prostaglandin synthesis inhibition:
1. Gastric mucosal damage
2. Bleeding, inhibition of platelet function.
3. Limitation of renal blood flow, sodium and water retention.
4. Delay, prolongation of labour
5. Asthma and anaphylactoid reactions in susceptible individuals.
Aspirin
Aspirin is acetylsalicylic acid and it is rapidly converted in the body to salicylic acid which
is responsible for most of the actions. It is one of the most oldest analgesic anti-
inflammatory drugs and is a still widely used.
Aspirin is available 1oomg, 300mg, 325mg and 650mg tabs. Ecosprin 75, 150, 325 mg
tabs. Loprin 75, 162.5 mg
55
Adverse Effects
Nausea, Vomiting, Epigastric pain, Peptic ulceration, Hypersensitivity, Rash
Ibuprofen
Ibuprofen was the first member of this class to be introduced in 1969 as a better tolerated
alternative to aspirin. Inhibit prostaglandin synthesis. It is used for analgesic, anti-
inflammatory and anti-pyretic. Inhibition of platelet aggregation is short lasting with
ibuprofen
Therapeutic uses
Analgesia, Antipyretic, Anti-inflammatory, Rheumatoid arthritis, Osteoarthritis,

Musculoskeletal disorders, Soft tissue injuries, Fractures, Suppress swelling
Adverse Effects
Gastric discomfort , Nausea, Vomiting, Headache, Dizziness, Blurring vision, Depression

Rash, Precipitate aspirin induced asthma
Diclofenac sodium
It is well absorbed drug, It inhibits prostaglandin synthesis. Metabolized and excreted both
in urine and bile. The plasma half life is 2 hours. Available as 50mg TDS, then 75mg BD
oral.
Therapeutic Uses
Rheumatoid, Osteoarthritis, Toothache, Dysmenorrhoea, Analgesia, Antipyretic , Anti-

inflammatory
Side-Effects
Epigastric pain, Nausea, Headache, Dizziness, Rashes, Gastric ulceration , Bleeding
56
Indomethacin
It is a potent anti-inflammatory drug with prompt anti-pyretic action. Indomethacin relieves

only inflammatory or tissue injury related pain. It is a highly potent inhibitor of
prostglandin synthesis. Indomethacin is well absorbed orally and rectal absorption is low.
Therapeutic uses
Potent anti-inflammatory, Analgesia, Closure of ductus arteriosus BID, 0.1-0.2mg/kg.
Side-Effects
Gastric irritation, Nausea, Anorexia, Gastric bleeding, Diarrhea, Frontal headache, Mental
confusion, Hallucination, Dizziness, Depression.
Metamizol (Dipyrone)
Metamizol is a derivative of amidopyrine is a potent and promptly acting analgesic and

antipyretic, but having poor anti-inflammatory effect.
It can be given: Orally, IM, IV
Metamizol has:
1. Pain during injection, Gastric irritation
Few cases of agranulocytosis were reported and metamizol is banned in USA and Europe.
Available 0.5-1.5mg oral/IM/IV
57
CHAPTER SIX: DIGESTIVE DRUG AGENTS
Antacids
• Antacids have been used for centuries in the treatment of patients with acid related
disorders.
• They were the principle of anti-ulcer treatment until the availability of histamine 2 blockers
in the late of 1970s.
• The ancient Greece used crushed coral (calcium carbonate)in the first century to treat
patients of dyspepsia
• These are basic substances which neutralize gastric acid and raise PH of gastric contents.
• Antacids donot decrease acid production, rather agents that raise the antral PH to greater
than 4.
However antacids are extensively used, especially on OTC market.
In addition many antacids contain simethicone which reduces gas and bloating.
Basically there are three forms of antacids:
1. Aluminum antacid
2. Calcium antacid
3. Magnesium antacid
4. Sodium bicarbonate inj
The OTC antacid formulations are available:
1. Capsules
2. Tablets
3. Parenteral
58
4. Powders
5. Chewable tablets
6. Suspension
Classification of Antacids
1. systemic: sodium bicarbonate and sodium citrate
2. Naonsystemic: mg hydroxide, magnesium trisilicate, aluminum hydroxide gel, and calcium

carbonate
Mechanism of action
Antacids originally believed to work by neutralization of gastric acidity.
They donot nothing for prevent over production of acid.
They do this by stimulating:
1. Mucus
2. Prostaglandin
3. Bicarbonate secretion
Drug Effects
The primarily drug effect of antacids is the reduction of the symptoms associated with
various acid related disorders such as peptic ulcer disease and hyperacidity.
The ability of antacids to reduce the pain associated with acid related disorders is thought
to be result, inhibition of protein digesting ability of
Side-Effects
Mg results diarrhea
Increase sodium load

59
Al & Ca can result constipation.
Rebound hyperacidity
Sodium bicarbonate
It is water soluble but the duration of action is short.
It is potent neutralizer, Ph may rise above 7.
It is absorbed systematically, large doses will induce alkalosis
Produces carbon dioxide in stomach, distention, discomfort, belching, risk of ulcer

perforatioan.
Increases sodium load, may worsen edema and CHF.
Aluminum
The amount of antacid necessary to neutralize hydrochloric acid depends on the:
1. Patient
2. Condition been treated
3. Buffering capacity of the preparation used.
Adult dosage is 5-10ml 3-4 times a day, Hs.
Calcium
Calcium carbonate neutralization will produce gas and possible belching, for this reason it
may be combined with an anti-flatulent type of drug such as simethicone.
Calcium containing products have a long duration of acid action, which can
cause hyperacidity rebound.
Calcium carbonate is available 1-2 tabs Prn.
60
Magnesium
Mg containing antacids commonly cause a laxative effect and frequent administration of

these antacids alone often cannot be tolerated.
Administration of Mg containing antacids is dangerous in patients with renal failure,

because of failing of kidney cannot excrete extra Mg and accumulation may occur.
Histamine-2 Blockers
Histamine -2 blockers reduce Hcl but donot abolish stimulated acid secretion.
They have become the most popular drugs for the treatment of many acid related disorders.
These can be attributed by their:
1. Efficacy
2. Safety profile
3. Patient acceptance
Drugs
4. Cimetidine
5. Famotidine
6. Nizatidine
7. Ranitidine
Mechanism of action
They have ability of blocking parietal cells.
They reduce the amount of Hcl in the parietal cells.
61
Side-Effects
Confusion
Lethargy
Headache
Abdominal cramp
Cimetidine
In 1977 Cimetidine was the first agent in this class to be released in the market.
Cimetidine comes available 200, 300, 400, 800mg tablets, 300mg/ml,

200mg/ml, 150mg/ml parentral injection.
Proton pump inhibitors (PPI)
PPI is introduced for the treatment of acid related disorders.
The enzyme H+/K+ ATPase is the final common step in acid Secretory processes.
PPI drugs are:
1. Omeprazole 20mg
2. Lanzomeprazole 30mg
3. Esomeprazole 40mg
4. Pantoprazole 20, 10mg
5. Rapiprazole 20mg
Mechanism of action
PPI irreversible binds to H+/K+ATPase. The binding of this enzyme prevents the
movement of hydrogen ions out of the parietal cell into the stomach, there by blocking all
gastric acid secretion.
62
PPI makes the patient achlorhydric.
Side-effects
Headache
Dizziness
Vomiting
Nausea
Rash
Fatigue
Omeprazole
Omeprazole is a prod rug.
Omeprazole is degraded at low PH and must be given in granules.
Omeprazole inhibits cytochrome P450 system, decreasing metabolism of

Warfarin, diazepam, Carbamazepine, and phenytoin and enhancing the effect of
these drugs.
Omeprazole is currently approved only for the acute treatment of severe gastrointestinal
reflux disease un responsive to:
1. Antacids
2. Antiflatulents
3. H2-blockers
Adult dosage is 20mg/day for 4-8 weeks.
Ulcer protective agents
Sucralfate: it is compound of aluminum and sucrose which coats the base of the ulcer
63
protecting it from pepsin and acid allowing it to heal.
64
Dosage is 1gm 1 hour before each meal
Bismuth Compound
It protects the ulcer by causing coagulation at the base of the ulcer. It has also anti H.
pylori action.
It should not be combined with antacids.
The tongue and the stool may appear black after taking dosage 120gm 1 hour before
meals and at the bed time.
Prostaglandins
Prostaglandins exert some protective effect on the gastric mucosa and this is why
NSAIDs which inhibits prostaglandin synthesis can cause peptic ulceration.
One of the prostaglandin preparation misoprostol reduces the risk of gastric ulcers in
patients who are taking NSAIDS, especially in elderly patients having history of ulcers.
Treatment of H. pylori
For helicobacter pylori associated ulcers, there are two therapeutic goals:
1. Heal the ulcer
2. Eradication of the organism
The best treatment regimen is for a 10-14 days of Triple Drug regimen.
The regimen consists of:
1. PPI, E.g omeprazole 20mg BD
2. Clarithromycin 500mg BD
3. Metronidazole 400mg BD
Treatment of NSAIDS associated ulcers
For treatment of aspirin or other NSAIDS induced ulcers the best treatment is to give a
proton pump inhibitor, which provides prompt healing of the ulcer.
PPI are also useful in bleeding ulcers as they raise the gastric PH. It is observed that intra
gastric PH above 6 may enhance coagulation and platelet aggregation.
65
Anti-diarrheals Agents
Diarrhea is defined as the abnormal frequent passage of loose stools.

Diarrhea is the abnormal passage of stools with increased frequency, fluidity and weight.
Diarrhea is divided into:
1. Acute diarrhea
2. Chronic diarrhea
Causes of Diarrhea
Acute Diarrhea
1. Bacterial
2. Drug induced
3. Viral
4. Nutritional
5. Protozoal
Chronic Diarrhea
1. Tumors
2. Diabetes mellitus
3. Hyperthyroidism
4. Addison's disease
5. Irritable bowl syndrome
Anti-diarrhoe Agents
Electrolytes
Bulk agents
Absorbents
66
Anti-inflammatory
Opioids
Intestinal flora modifiers
Bismthus subsalicyte
Bismuth subsalicte is a pregnancy category C agent.

It should be used with caution in children and teenagers who have or are recovering
from chicken pox or flu because of attendance risk of Reyes syndrome.
Bismuth subsalicyte have two harmless side-effects:
1. Darkening of the stool
2. Darkening of the tongue
It is available in a OTC drug.
Available 262 mg chewable tablet and 262 mg/15ml suspension.
Attapulgite
Attapulgite has replaced the use of kaolin-pectin in this preparation.

Kaolin is a naturally hydrated aluminum compound that is now rarely used as an anti-
diarrheal agents.
How ever pectin which is extracted from the apples or citrus fruit and is used in many
combination products.
The original kaopectate contained 980mg/5ml of kaolin and 21.7 mg/5ml of pectin.
Attapulgite is an OTC agent.
Available 300mg chewable tablet and 600mg/15ml solution.
67
Diphenoxylate & Atropine (Lomotil)
Lomotil is a synthetic opiate agonist that is structurally related to meperidine.

It has little or no analgesic activity.
It is classified in a pregnancy category C agent.
Available as 2.5mg/5ml + 0.025mg/5ml atropine solution, and 2.5mg + 0.025mg,
diphenoxylate and atropine respectively.
Loperamide
Loperamide is a synthetic anti-diarrheal that similar to diphenoxylate.

Decreases the number of stools and water content.
It is the only opiate anti-diarrheal agent that is available as an OTC medication.
Loperamide is a pregnancy category B agent.
Available 1mg tab, 1mg/5ml oral.
It is an OTC medication.
Available 1g powder, 1g tablet, and 1g capsules.
Laxatives
Laxatives are used for the treatment of constipation, which is defined as a condition of
abnormally infrequent and difficult passage of feces through the lower GIT.
Constipation is not a disease but it is a symptom of disease.
Causes of Constipation
Pregnancy
Hypothyroidism
Hypokalemia
Parkinsons disease
Iron supplements
Anti-cholinergics
Poor fluid intake
Lack of exercise
68
Anxiety
Stress
AL-antacids
Bulk-forming agents
1. Methylcellulose
2. Psyllium
3. Polycarbophil
Stool Softeners- Emollient
1. Docusate salts
2. Mineral oil
3. Glycerin
Hyperosmotic
1. Lactulose
2. Sorbitol
Saline
1. Mg sulphate
2. Mg phosphate
3. Mg citrate
Hyperosmotic
1. Lactulose
2. Sorbitol
Saline
1. Mg sulphate
2. Mg phosphate
3. Mg citrate
Chloride channel activator
1. Lubiprostone: stimulate the chloride channel 2 in the intestine by increasing the secretion.
69
Opiod receptor antagonist
1. Methylnaltrexone
2. Alvimopan
5HT4 receptor antagonist
1. Tegaserod
2. Cisapride
3. Prucalopride
Side-Effects
Decreased absorption of vitamins
Nutrient malabsorption
Gastric irritation
Skin rash
Mg toxicity
Methylcellulose
Methylcellulose is a synthetic bulk forming laxative that attracts water into intestine,
absorbs excess water into stool and stimulating intestines.
Contraindicated in patients who have shown
1. Hypersensitivity
2. Hepatitis
3. It is a pregnancy category C agent.
4. It is an OTC medication.
5. Available 105mg, 364mg powder and 500mg tablets.
6. Adult dosage is 1 tabs, 1-3 times per day.
Mineral Oil
Mineral oil is the only lubricant laxative in the emollient category.
Prevent water from escaping the stool and lubricating the intestines.
It is a mixture of liquid hydrocarbons derived from petroleum.
It is classified in a pregnancy category C agent.
70
Mineral oil agents are available as enemas or as suspensions, 1.4, 2.75, 4.75mg/5ml.
Adult dosage is 15-45ml as a single daily dose.
Peadtric dose is 5-15ml per day.
Lactulose
• It is a disaccharide sugar containing one molecule of galactose and one molecule of

fructose.
• It is a synthetic derivative of the natural sugar lactose, which is not digested in the stomach
or absorbed in the small intestine.
• Lactulose is classified pregnancy category C agent.
• Available 3.33g/5ml oral or rectal solution.
Glycerin
Glycerin promotes bowel movements by increasing osmotic pressure.
It is very mild laxative, commonly used in children.
It is classified pregnancy category C agent.
Availabale 4ml per applicator rectal solution.
Magnesium salts
It is classified pregnancy category B agents.
Magnesium salts are:
1. Mg saline
2. Mg citrate
3. Milk magnesia
71
4. Epsom salts
Cautiously given to all patients with renal insufficiency because they can be absorbed
systematically causing hypermagnesimia.
Available as magnesium hydroxide 77.5mg/ml suspension and milk of magnesia 300-
500mg tablets.
Anti-emetic Agents: Classification of Drugs
Anti-cholinergics
1. Scopolamine
2. Hyocine
3. Hyoscyamine
Antihistamines
1. Meclizine
Neuroleptic agents
1. Metoclopramide
2. Domperidone
Serotonin blockers
Tetrahydrocannabinoid (THC)
1. Dronabinol
Mechanism of Action
These drugs blocks:
1. Acetylcholine
2. Histamine
3. Dopamine
4. Serotonin
5. Stimulation of THC.
Scopolamine
• Scopolamine is the primary anti-cholinergic drug used as an anti-emetic.
• It has potent effects on the vestibular nuclei, which are located in the inner ear and
represent the area of the brain that controls balance.
72
• Works by blocking ACH, correcting and imbalance between the two neurotransmitters
ACH and nor-epinephrine.
• This makes the scopolamine one of the most commonly used drugs for the treatment and
prevention of motion sickness.
• It is classified pregnancy category C agent.
• Available as 0.3, 0.4, 1 mg/ml parentral.
• Scopolamine hydrobromide salt that is used for ophthalmic purposes.
Meclizine (Bonamine)
Most commonly treated disorders are:
1. Dizziness
2. Vertigo
3. Nausea
4. Vomiting
Contraindicated by:
1. Hypersensitivity
2. Shock
3. Lactation
Available as 12.5, 25, 50mg tablets and 15,25, 50mg capsules.
Metoclopramide
Metoclopramide is the oldest and most commonly used drug in the anti-emetic drugs.
It is available by prescription.
Classified pregnancy category B agent.
Available as 5mg, 10mg/5ml oral solution, 5, 10mg tablets and 5mg/ml injection.
Contraindicated by:
1. Breast cancer
2. Seizure
3. Hypersensitivity
4. GI obstruction
73
CHAPTER SEVEN: RESPIRATORY DRUG AGENTS
H1 antagonists include
1. Diphenhydramine
2. Chlorpheniramine
3. Terfenadine
4. Astemizole
Therapeutic Uses
They are greatest value in the treatment of nasal allergies.
They are used for palliative therapy of common colds
They are used to prevent nausea and vomiting, for motion sickness
They reduce nasal, salivary and lacrimal gland secretion.
Proved to be safe and effective as sleep aid.
Mechanism of actions
Work by inhibiting the action of histamine through out the body.
Prevent stimulation of chemo trigger receptor zone (CTZ).
Side Effects
Dry mouth
Drowsiness
Constipation
Impotence
Sedation
74
Nervousness
Restlessness
Difficulty in urinating
Astemizole
Has the longest half-life (20-60 hrs)
Dosed once a day
Has very poor ant cholinergic activity.
Indicated for the treatment of seasonal variation especially in allergy rhinitis.
Cautiously given with a patient who have liver problem.
Contraindicated patients with hypersensitivity.
It is classified pregnancy category C.
Available in 10mg.
Recommended 10mg/day, given as a single dose.
Loratidine (claritin)
It is a non-sedating antihistamine drug.
Used to relieve symptoms of seasonal allergies, hay fever.
Contraindicated in patient shown hypersensitivity.
Available in 10mg tablet.
Recommended once a day

75
Terfenadine (seldane)
Terfenadine was the first non-sedating anti histamine to come available.
Has short half life
Used to relieve the symptoms of seosonal allergic rhinitis.
Available only for oral preparation.
Terfenadine it self comes 60mg tablet, the combination product contains 60mg of
Terfenadine and 120mg of pseudoephedrine.
Usual recommended dosage is 60mg twice daily, BID.
Diphenhydramine (Benadryl)
Diphenhydramine is older and traditional anti-histamine.
Has potent of ant cholinergic effect.
Contraindicated for
1. Hypersensitivity
2. Nursing mother
3. Neonates
• Available oral, parentral, and topical preparations. 25mg-50mg cap oral 12.5mg/5ml syrup
10mg/ml- 50mg/ml injection, 1%-2% cream topically.
76
Chlorpheniramine(priton)
Available as 4mg, 8mg, and 12mg tablets.
Available as POM or OTC
Recommended oral dosage is 4mg ever 4 hrs or 6 hrs, given with a full glass water.
Cyproheptidine
Available as 2mg/5ml syrup and 4mg tablets.
It is recommended 4mg in TID, QID.
It is a pregnancy category B.
Dimenhydrinate
It is a POM drug, available 50mg tablets.
Recommended oral adult dosage is 50mg-100mg every 4 to 6 hours.
Recommended in children for 25mg-50mg ever 6 or 8 hour.
Taken half an hour before the travel.
It is rated in pregnancy category B.
Promethazine (phenergan)
It is a prescription drug available as 25 and 50mg/ml injection, as a 6.25 and 25mg/ml

syrup.
The recommended adult dosage is 12.5mg and 25mg TID.
It is rated pregnancy category C.
77
Clemastine (tavist)
It is a prescription drug available as 0.67mg/5ml syrup and 1.34mg, 2.68 mg tablets.
The recommended oral adult dosage is 1.34mg and 2.68mg TID.
It is rated in pregnancy category B agent.
Anti-tissuves
1. Pharyngeal demulcents
a. Lozenges
b. Cough drops
c. Glycerine
d. Linctuses containing syrup
2. Expectorants
a. Sodium or potassium citrate
b. Potassium iodide
c. Guiphenesin
d. Ammonium chloride
3. Antitussives
a. Codeine
b. Pholcodeine
c. Noscapine
d. Dextrometrophan
e. Chlophedianol
78
f. Chlorpheniramine
g. Diphenhydramine
h. Promethazine
4. Adjuvant antitussives
a. Salbutamol
b. Terbutalin
This causes a signal to be sent to the cough center in the medulla of the brain, which in turn
stimulates the cough.
Cough can be classified into:
1. Productive cough
2. Non-productive cough
There are two main categories of these agents:
1. Narcotic agents
2. Non-narcotic agents
Narcotic Agents
Narcotic agents have anti-tissuve effects.
They are effective in suppressing the cough reflex.
They are POM drugs.
Their use lead dependence
1. Codeine
2. Hydrocodeine
79
Non-narcotic
Non-narcotic antitissuve drugs are less effective than the narcotic ones.
They are available either alone or combination with other agents, they are POM drugs.
1. Dextromethorphan
2. Benzonatate
Mechanism of Actions
The narcotic anti-tissuves codeine and Hydrocodeine suppress the cough reflex through a
direct action on this cough center.
Non-narcotic drugs suppress the cough reflex by anesthetizing (numbing) and thus keeping
the cough reflex from being stimulated in the medulla.
Therapeutic Uses
Anti-tissuves are primarily used to stop the cough reflex, when the cough is non-
reproductive and harmful
Side-Effects
Dizziness
Headache
Drowsiness
Dry mouth
Nausea
Vomiting
Constipation
80
Dextromethorphan
Dextromethorphan is a non narcotic anti tissuve drug.
It is widely used because of safety, non-addicting and does not cause respiratory
depression.
Adult dose is 10-30mg q4h-q8h
It is contraindicated, hypersensitivity, headache and asthma.
Benzonatate (Tessalon)
It is a non narcotic anti-tissuve drug.
Anesthetizing or numbs the cough receptor.
Available only in a POM.
It is a pregnancy category C
Adult dose is 100mg TID.
Codeine
It is a very popular narcotic anti-tissuve drug.
It is a potentially addictive.
Depress respirations and the CNS activity.
Adult dose is 10-20mg q4h-q6h.
It is contraindicated:
1. Hypersensitivity
81
2. Respiratory depression
3. Seizure disorders
Somaliland Anti-tissuves
Flucor day
1. Paracetamol 250mg
2. Pseudoephedrine 30mg
3. Dextromethorphan
Kuf-Go
1. Aminophylline
2. Diphenhydramine
3. Ammonium chloride
Bronchophane
1. Guaiphenesin 50mg
2. Ephedrine HCL 7.5mg
3. Diphenhydramine HCL 5mg
4. Dextromethorphan 4.58mg
Tussilar
1. Chlorpeniramine maleate 0.080 g
2. Dextromethorphan 0.125g
3. Ephedrine HCL 0.150g
4. Guaiphenesin 1g
82
Bronchodilators
Beta-agonists
Beta-agonists are large group of drugs that are commonly used during the acute phase of an
asthmatic attack.
They are agonists or stimulators of the sympathetic nervous system.
There are three types of beta-agonist bronchodilators:
1. Non-selective adrenergic drugs, which stimulate the alpha, beta one (cardiac), and beta two
(respiratory) receptors.
E.G, epinephrine
2. Non- selective beta adrenergic drugs, which stimulate both beta one and beta two receptors. E.g
isoproterenol
3. Selective beta two drugs, which only stimulate the beta two receptors.
Albuterol (Salbutamol)
Mechanism of Action
Bronchodilators begins at the speacific receptors.
stimulating receptors, dilate the airways.
Albuterol (Salbutamol)
It is a commonly used drug in acute asthma attacks.
Used for prevention of acute attacks
It is a prescription drug
Available 2-4mg tablet, 2mg/5ml syrup, 0.083% solution and 0.5 % concentration solution.
83
Pediatric dose is 0.1mg/kg TID or 2mg Tid or Qid.
Adult dose is 2 inhalational q4h-q6h.
Available in the forms of:
1. Aerosol
2. Solution
3. Powder
Metaproterenol
Metaproterenol is a synthetic sympathomimetic bronchodilator that stimulates both beta

one and beta two receptors.
It is available as a POM drug
Contraindicated:
1. Hypersensitivity
2. Narrow angle glaucoma
Orally it came's as a 10mg/5ml solution, 10mg-25mg tablets.

Inhalation 0.65mg per spray
Peadtric dosage is 10mg Tid, Qid.
Adult dosage20mg Tid, Qid.
Epinephrine
Epinephrine, ephedrine, ethylnorepinephrine are all beta-agonist bronchodilators, that work

by stimulating both beta and alpha receptors.
Epinephrine is available with or with out prescription.
Subcutaneous 10 microgram/kg/dose
84
Aerosol 0.2mg per inhalational Prn.
Xanthine Derivatives
Xanthenes are natural alkaloids that consists of:
1. Caffeine (stimulant)
2. Theobromine (diuretic)
3. Theophylline
Xanthenes are used for prevention and treatment of asthmatic patients.
Xanthenes are used as a bronchodilator.
Theophylline
Theophylline is the most commonly used drug for all xanthine derivatives as well as all
bronchodilators.
It is used for chronic respiratory disorders and relief of mild to moderate acute asthma.
It is classified in a pregnancy category C.
Contraindicated in patients with hypersensitivity.
Theophylline is available oral, rectal, parenteral, and topical.
Pediatric, usual dose is 2.5 mg/kg in q6h
Adult dose is 160mg q6h
Dosage forms
1. Capsules 100mg- 200mg
2. Tablets 100,125, 200, 250, and 300mg.
3. Injection 25,2500, 5000mg/ml
85
4. Suppository 250mg and 500mg.
Mechanism of Action
They all cause bronchodilation by increasing the levels of the energy producing substance.
Increase levels of CAMP produce competitively inhibit phosphodiestrase enzyme.
Corticosteroids
Corticosteroids are used for in the treatment of chronic asthma for their anti-inflammatory
effects which lead to decreased airway obstruction.
Corticosteroids are used also for prophylactic in acute attacks.
The corticosteroids do this by preventing the release of substances that produce

inflammation of lungs.
Corticosteroids administered inhalation has an advantage over orally administered

corticosteroids in that their action is limited to the topical site of action.
Drugs of corticosteroids are:
1. Beclomethasone
2. Dexamethasone
3. Triamcinolone acetonide
4. Flunisolide
Contraindicated
Pregnant women
Lactating women
Children below 2 years
Side-Effects
86
Pharyngeal irritation
Coughing
Dry mouth
Oral fungal infections
Beclomethasone
Administered by oral and inhalation.
Used for the treatment of bronchial asthma.
Beclomethasone oral solution or rectal suspension has also been used in the management of
inflammatory diseases of the gastrointestinal tract (GIT).
The primary sites of Beclomethasone are bronchi and bronchioles.
It is rated in a pregnancy category C.
Cromolyn
Cromolyn is a mast cell stabilizer indicated for the prevention of bronchospasm and
bronchial asthmatic attacks.
It is classified pregnancy category B agent.
Available for both oral and ophthalmic administration as well as nasal and oral inhalation.
It is a prescription drug, POM.
Available in nasal solution 5.2 mg per metred spray.
Ophthalmic solution 4 %
Capsule 100mg
Adult dose is 5-20mg several times in a day, nasal solution 5.2mg 3-6 times a day.
87
Nedocromil
Nedocromil is indicated for the prevention of bronchospasms and bronchial asthma attacks.
Only available as an aerosolized inhaler.
It is used for mild to moderate bronchial asthma.
It is available only in POM.
Adult dose is 14mg per day.
88

Pharmacology

Caricato da

Informazioni sul documento

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

Pharmacology

Caricato da

Copyright:

Formati disponibili

INTRODUCTION

Abdirahman M. Osman (D.pharm, MPH, PG Research )

1. Clinical Pharmacology: It evaluate the pharmacological action of drug preferred route

Dose, it is the quantity of the drug.

Dose can be classified into:

1. Standard dose e.g contraceptives , chloroquine

2. Regulated dose e.g anticoagulants, diuretics

3. Target level dose e.g digoxin, lithium

4. Titrated dose e.g anticancer drugs & levodopa

2. Animals: insulin, heparin and gonadotropin

3. Minerals: magnesiun sulphate, iron, lithium.

4. Microorganisms: penicillins from penicillium chrysogenum, cephalosporins.

Essential Drug Concept

Should be available at all times and adequate amounts.

Development and evaluation of new drugs:

Pregnancy categories can be divided into:

Drugs are classified by:

1. Chemistry, e.g electrolytes

3. Disease, e.g anti-hypertensive and anti-emetics

Classification of drugs by legal purposes

Drugs are grouped for legal purposes as follows:

A reference work for pharmaceutical drug specifications.

1. IP: Indian pharmacopoeia

2. BP: British Pharmacopoeia

3. USP: United states Pharmacopoeia

4. P.P: Pakistan Pharmacopoeia

5. C.P: Chinaca Pharmacopoeia

A drug generally has three categories of names:

It describes the substance chemically,. E.g 1-isopropylamino-3-1-naphthyloxy propan 2-ol.

This is cumbersome and not suitable for use in prescribing.

Proprietary (Brand) name

One drug may have multiple proprietary names.

Brand names are designed to be catchy, short, easy, to remember.

Adverse Drug Reactions

1. Side-effects. e.g Atropine: dry mouth

3. Drug tolerance: single dose of streptomycin producing vestibular dysfunction.

4. Idiosyncratic reactions: e.g barbiturates produce CNS stimulation.

4. A species and race

5. Diet and environment

6. Route of administration. E.g Magnesium sulphate

7. Genetic factor. E.g G6PD patients causes hemodialysis.

9. Renal dysfunction. E.g kidneys, streptomycin, Amphotericin B, phenytoin.

10. Tolerance: can be grouped into natural and acquired.

Increased maternal heart rate, cardiac output and blood volume.

Drugs may cross placenta

Drugs may cross into a breast milk

Decrease oral absorption

Decrease plasma protein concentration

Increase extracellular fluid in neonate

Altered metabolic rates

Decrease oral absorption

Decrease plasma protein concentration

Decrease muscle mass

Increase fat body

1. CC: Cubic Centimeter

7. Qs: Quantity Sufficient

8. ss: One half

10. tsp: Teaspoon

11. ID: intradermal

12. IM: intramuscular

13. IV: intravenous

14. OD: right eye

15. OS: left eye