General Pharmacology

3rd year
1.1 Pharmacology- An Introduction
The word pharmacology is derived from two Greek words, pharmacon meaning a drug, and logos
meaning an opinion or reason. It can be defined as
“The science which deals with the history, source, physical properties, chemical properties, compounding,
biochemical effects, physiological effects, mechanism of action, absorption, distribution,
biotransformation, excretion, therapeutic and other uses of drugs, is called pharmacology.”
“The study of a substance that interacts with the living system through chemical processes especially by
binding to regulatory molecules and activates or inhibits normal body processes”
“The science of substances used to prevent, diagnose and treat disease.”
Drug:
The word drug comes from Drogue meaning a dry herb. A drug can be defined as:
“A substance, material or product used for the purpose of diagnosis, prevention and relief of symptoms or
cure of disease.”
WHO defines drug as:
“A substance, material or product used or intended to be used to modify or explore the physiological
processes or pathological states for the benefit of the recipient.”
General Features of a Drug:
• Variability in molecular size
• Variability in shape
• Variability in chemical nature
• Variability in lipid/water partition coefficient
• Variability in degree of ionization
• Physical Properties
• Variability in molecular size

Smaller sized molecules are easily absorbed than larger molecules. Normally the molecular weight is
between 100-1000 but may be higher or lower. Streptokinase is an example of large molecular weight
drug while lithium or nitric oxides are of small molecular weight.
• Variability in shape
Drugs may be globular or linear in structure. Their shape is modified according to the receptor on which
they act.
• Variability in chemical nature

Tertiary compounds are lipid soluble while the quaternary compounds are water soluble. Tertiary
compounds can cross the membranes easily as compared to the quaternary compounds. This is because of
the fact that the quaternary compounds are ionized.
• Variability in lipid/water partition coefficient

Lipid soluble drugs (having higher lipid water partition coefficient) are more retained in the body while
water soluble drugs are easily excreted out.
• Variability in degree of ionization

Polar or ionized forms of drugs are lipid insoluble. Non polar drugs are water insoluble or lipid soluble.
Ionized forms of drugs can pass through the specific places i.e. through channels like Na+ and K+
channels.
• Physical Properties

Drugs may be solids, liquids or gases. Examples include halothane and nitrous oxide, both of which are
gases.
Solubility of gases is greater than that of liquids, while solubility of liquids is greater than that of solids.
Rational Drug Therapy
Administration of the right drug indicated for the disease in right dose through an appropriate route for
the right duration.
Rational drug therapy applies to the doctor.
Drug Abuse
Drug when used for non medical purposes is known as drug abuse. It is the wrong use of a drug other
than for the disease e.g. addiction of certain drugs, like morphine, nicotine.
Misuse of Drug:
Drug that is not required by the patient i.e. drug therapy that is not justified. If violate the quantity or
duration of the required drug, it is known as misuse.
History of Drug Development
Drug Development in Ancient Civilizations:
Egyptian- Medical Papyrus 1600 B.C
Ebers Papyrus 1550 B.C
China- Shen Nung
India- Ayurvedic medicine
Ancient Greek Culture- Hippocrates 460-377 B.C
Galen 130-201 A.D
Roman- Theophrastus 372-287 B.C
Dioscorides 57 A.D
Persians
Drug Development during the Middle Ages
Paracelsus (1493) is known as grandfather of science of pharmacology. According to him:
• Most body reactions are chemical in nature
• One must never use a combination of drugs.
• Every drug is a poison; it is the dose that matters.

Development in chemistry
Development in botany
• Opium poppy
• Cinchona bark- for malaria
• Digitoxin from Digitalis purpura- for edema due to cardiac failure
• Castor oil- for constipation
• Atropa belladonna- source of atropine and thiosine
• Hyoscyamus Niger- source of thiosine

Morphine was isolated as a pure compound in 1805.

Claude Bernard in 1856 found Curare
Fleming in 1928 found Benzyl penicillin which became the first antibiotic.
Modern Drug Development
• Salicylic acid- anti-inflammatory, synthesized from phenol in 1800 by Kolbe and Lautemann.
• Acetyl salicylic acid (aspirin) was synthesized from salicylic acid in 1899 by Dreser.
• Prontosil, therapeutically inactive dye is transformed in the body to an antibacterial sulfonamide, was
developed by Domagk in 1935.
• Acetazolamide and thiazide are diuretics
• Sulfonyl ureas are anti diabetic.
• H1 antihistamines were developed by Bovet in 1944
• Beta adrenoreceptors were discovered by James Black in 1960
• H2 antagonists (Cimetidine for peptic ulcer) were developed in 1970,
• Immunoglobulins and gene therapy

1.2 Branches and Divisions of Pharmacology

Pharmacology is the science of drugs. It is the study of chemical substances that interact with the living
things by chemical processes, especially by binding to regulatory molecules, i.e. receptors.
In 1847, Rudolph established the first institute of pharmacology.
Drug:
The word drug comes from a French word ‘Drogue’ meaning a dry herb. It can be defined as:
“Substance or material that is used or intended to be used to modify or explore physiological processes or
pathological states, for the benefit of the recipient.”
Branches of Pharmacology:
Following are the important branches of Pharmacology:
• Pharmacokinetics
• Pharmacodynamics
• Therapeutics
• Chemotherapy
• Toxicology
• Clinical Pharmacology
• Pharmacy
• Pharmacognesy
• Pharmacogenetics
• Pharmacogenomics
• Pharmacoepidemiology
• Comparative Pharmacology
• Animal Pharmacology
• Pharmacoeconomics
• Posology

1. Pharmacokinetics:
The word Pharmacokinetics is derived from two words, Pharmacon meaning drug and kinetics meaning
putting in motion. It can be defined as:
“The branch of pharmacology that deals with the absorption, distribution, metabolism and excretion of
drugs and their relationship with the onset, duration and intensity of the drug effect.”
What the body does to the drug is pharmacokinetics. For example, the absorption, distribution,
metabolism and excretion of Paracetamol is included in Pharmacokinetics.
2. Pharmacodynamics:
Pharmacodynamics is the branch of Pharmacology that deals with the mechanism of action of drug and
the relation between the drug concentration and its effect.
It is the study of physical and chemical effects of drugs on body, parasites and microorganisms.
What the drug does to the body is pharmacodynamics. For example, adrenaline acts on adrenal receptors,
stimulates adenyl cyclase system producing effects such as cardiac stimulation and hyperglycemia is
studied in Pharmacodynamics.
3. Therapeutics:
The branch of pharmacology that deals with the art and science of treatment of disease. It is the
application of pharmacological information together with the knowledge of disease, for the prevention
and cure of the disease.
4. Chemotherapy:
Chemotherapy refers to the treatment of diseases by chemicals that kill the cells, especially those of
microorganisms and neoplastic cells. It is classified into two divisions:
• Antibiotics

Includes the choice of drugs most potent against the organism or least toxic. Examples include
Erythromycin given for gram positive organisms and Aminoglycans for gram negative organisms.
• Antineoplastics

Examples include:
Methotrexate, which is an anticancer drug. It inhibits the dihydrofolate reductase and interferes with the
DNA synthesis and repair.
Vinca alkaloids, which bind tubulin of microtubules, and arrest mitosis in metaphase.
5. Toxicology:
Toxicology is the branch of pharmacology which includes the study of adverse effects of drugs on the
body. It deals with the symptoms, mechanisms, treatment and detection of poisoning caused by different
chemical substances.
The main criterion is the dose. Essential medicines are poisons in high doses and some poisons are
essential medicines in low doses.
6. Clinical Pharmacology:
Clinical pharmacology is the scientific study of drugs in man. It includes pharmacokinetic and
pharmacodynamic investigations in healthy or diseased individuals. It also includes the comparison with
placebos, drugs in the market and surveillance programmes.
The main objectives are:
• Maximize the effect of drug
• Minimize the adverse effects
• Promote safety of prescription

Aims include:
• Generate optimum data for use of drug.
• Promote usage of evidence based medicine.

7. Pharmacy:
Pharmacy is the branch of Pharmacology and is the art and science of compounding by dispensing drugs,
preparing suitable dosage form for administration to man and animals. The health profession blends
health science with chemical science and effective use of drugs.
8. Pharmacognosy:
Pharmacognosy is the identification of drugs by just seeing or smelling them. It is a crude method no
longer used. Basically it deals with the drugs in crude or unprepared form and study of properties of drugs
from natural sources or identification of new drugs obtained from natural sources.
9. Pharmacoeconomics:
Pharmacoeconomics deals with the cost of drugs. In this discipline the cost of one drug is compared with
another for same use. The cheap drugs are preferred.
10. Pharmacogenetics:
Branch of pharmacology dealing with the genetic variations that cause difference in drug response among
individuals or population.
Example includes succinyl choline which is a skeletal muscle relaxant used in general anesthesia. It is
metabolized by pseudocholine esterase and has short duration of action. The presence of enzyme is
determined by the gene and lack of this is recessively inherited. This may lead to respiratory paralysis,
apnea and death. Halothane in some patients may lead to malignant hyperpyrexia. G6PD deficiency may
lead to hemolysis on administration of antimalarial drugs.
11. Pharamcogenomics:
Pharmacogenomics is the broader application of genomic technologies to new drug discovery and further
characterization of older drugs.
Recombinant DNA technology involves the artificial joining of DNA of one specie to another. E. coli is
mostly used. In this way we can get huge amounts of drug in purified form which is less antigenic.
Examples include GH, interferon and vaccines.
12. Pharmacoepidemiology:
Pharmacoepidemiology deals with the effects of drugs on a large population. The effects may be good or
harmful. It is conducted in three ways:
• Observational cohort studies
• Case control studies
• Phase trials

a. Cohort studies:
Patients receiving drugs are collected and followed up to determine the outcomes. It is prospective
(forward looking) research, however, is time consuming and lengthy.
b. Case Control Studies:
These are retrospective studies. They reverse the direction of scientific logic from forward looking to
backward looking.
c. Phase Trials:
These include different phases:
• Human pharmacology (20 to 50 subjects), pharmacokinetics and pharmacodynamics of the drug are
observed in either healthy volunteers or diseased subjects. These studies are carried out by experienced
staff and in such premises where facilities are available.
• Therapeutic exploration (50 to 300 subjects), drugs are compared with placebos
• Therapeutic confirmation (250 to 1000 subjects), safety, efficacy of drugs is compared with the drugs
already present
• Therapeutic use (2000 to 10000 subjects), the opinion of physicians prescribing the drugs is collected
regarding dosage and efficacy. Surveillance programmes are lengthy when conducted outside hospitals.

13. Comparative Pharmacology:

Branch of pharmacology dealing with the comparison of one drug to another belonging to the same or
another group.
14. Posology:
Posology deals with the dosage of drugs. Example includes paracetamol given as one tablet of 500mg
thrice a day.
15. Animal Pharmacology:
Animal pharmacology deals with the different properties of drugs in animals. A vast variety of animals
are utilized including rabbits, mice guinea pigs, etc. Drugs are given to the animals and all parameters
(their behavior, activities, vital signs, etc.) are recorded. Any change is noted down. If found to be useful
in animals, then the drug is tested on humans.
1.3 Scientific Sources of Drug Information
The scientific sources of drug information include:
• Textbooks
• Medial publications
• Pharmacopoeia
• Monographs (writings on one topic, single document)
• Professional seminars (USP conventional and European council meetings)
• Databases, CDs

Miscellaneous Sources:
• Mail brochures
• Library catalogues
• Advertisements
• Displays
• Pharmaceutical representatives
Pharmacopoeia:
Pharmacopoeia is an official book published legally in a country for the manufacturing of drugs. A
pharmacopoeia describes:
• Standard of drugs
• Physical properties
• Tests for identity/purity/potency/efficacy

Common pharmacopoeias include:

• USP (Unites States pharmacopoeia)
• BP (British pharmacopoeia)
• European pharmacopoeia
• International pharmacopoeia
• Martin Dale extra pharmacopoeia

Compendium:
Compendium is the comprehensive collection of knowledge in a field.
Essential Drugs:
Drugs which satisfy health care needs of a large population and are available readily all the time in that
particular area, are known as essential drugs.
WHO has provided a model list of essential drugs which includes 300 items and is updated every two
years.
Formularies:
Formularies are the lists of licensed medicines containing information about formulas for manufacturing
as well as information regarding compounding and testing of drugs.
1.4 Routes of Drug Administration
The path taken by the drug to get into the body is known as the route of drug administration. A drug may
be in ionized or unionized form.
Classification:
• Enteral
• Parenteral
• Inhalation
• Topical
• Enteral Route:

Enteral route is through the alimentary canal. It might be:

• Oral
• Sublingual
• Per rectum
• Oral Route:

Oral route is the most common route of drug administration. It is mostly used for the neutral drugs. It may
be in the form of tablets, capsules, syrup, emulsions or powders.
Advantages:
• It is convenient
• It is the cheapest available route
• It is easy to use
• It is safe and acceptable.

Disadvantages:
• Less amount of drug reaches the target tissue.
• Some of the drug is destroyed by gastric juices e.g. adrenaline, insulin, oxytocin
• Absorption has to take place which is slow, so is not preferred during emergency.
• It might cause gastric irritation
• It might be objectionable in taste.
• It might cause discoloration of teeth e.g. iron causes staining, tetracyclines below 14 cause brown
discoloration so are not advisable during pregnancy.

First Pass Effect:

First pass effect is the term used for hepatic metabolism of drug when absorbed and delivered through
portal blood. Greater the first pass effect, less amounts of the drug reach the systemic circulation.
• Sublingual Route:

Sublingual route involves tablets placed under the tongue or between cheeks or Gingiva. The drug should
be lipid soluble and small.
Advantages:
• Rapid absorption takes place.
• Drug is dissolved easily
• Drug enters the blood directly
• Less first pass effect.
• Spitting out of the drug removes its effect

Disadvantages:
• This method is inconvenient.
• Irritation of the mucous membrane might occur
• Person may swallow the drug
• Might be unpleasant in taste.

Examples of drugs given by this route include nitroglycerin, isoprenaline and oxytocin Nifedipine used
for the treatment of hypertension in emergency is given by sublingual route.
• Rectal Route:

Drugs in solid forms such as suppositories or in liquid forms such as enema are given by this route. This
route is mostly used in old patients. Drugs may have local or systemic actions after absorption.
Advantages:
• This route is preferred in unconscious or uncooperative patients.
• This route avoids nausea or vomiting
• Drug cannot be destroyed by enzymes.
• This route is preferred if drug is irritant.

Disadvantages:
This route is generally not acceptable by the patients.
Locally acting drugs include glycerin and Bisacodyl suppository
Systemic acting drugs include Indomethacin (anti inflammatory) and aminophyllin (bronchodilator)
Retention enema is diagnostic and is used for finding the pathology of lower intestines.
Drugs given by rectal route have 50% first pass metabolism.
• Parenteral Route:

Parenteral route includes:

Injections:
• Intra muscular
• Intra venous
• Intra-arterial
• Intra-cardiac
• Intra-thecal
• Intraosseous- into bone marrow
• Intrapleural
• Intraperitoneal
• Intra-articular
• Intradermal (Intracutaneous)
• Subcutaneous route (Hypodermic)

Hypospray or jet injections

Advantages:
• Parenteral route is rapid.
• It is useful for uncooperative patients
• It is useful for unconscious patients
• Inactivation by GIT enzymes is avoided
• First pass effect is avoided
• Bioavailability is 100%

Disadvantages:
• Skill is required
• It is painful
• This method is expensive
• It is less safe.

Classification:
• Site of Release:

Site of release may be intradermal, intraperitoneal, intrapleural, intracardiac, intra-arterial, intrathecal

(into meninges of spinal cord), intra-articular (into joint cavity).
• Subcutaneous:

Subcutaneous route might be used for the arm, forearm, thigh and subscapular space.
The volume used is 2ml. Insoluble suspensions like insulin and solids might be applied by this route.
Advantages:
• Absorption is slow and constant
• It is hygienic

Disadvantages:
• It might lead to abscess formation
• Absorption is limited by blood flow

Examples of drugs given by subcutaneous route include insulin, adrenaline and norplant.
• Intramuscular route:

Intramuscular route might be applied to the buttock, thigh and deltoid. The volume used is 3 ml.
Advantages:
• Absorption is rapid than subcutaneous route.
• Oily preparations can be used.
• Irritative substances might be given
• Slow releasing drugs can be given by this route.

Disadvantages
Using this route might cause nerve or vein damage.
• Intravenous injections:

Intravenous injections might be applied to the cubital, basilic and cephalic veins.
Advantages:
• Immediate action takes place
• This route is preferred in emergency situations
• This route is preferred for unconscious patients.
• Titration of dose is possible.
• Large volume of fluids might be injected by this route
• Diluted irritant might be injected
• Absorption is not required
• No first pass effect takes place.
• Blood plasma or fluids might be injected.

Disadvantages:
• There is no retreat
• This method is more risky
• Sepsis-Infection might occur
• Phlebitis(Inflammation of the blood vessel) might occur
• Infiltration of surrounding tissues might result.
• This method is not suitable for oily preparations
• This method is not suitable for insoluble preparations
• Intraarterial route:

This method is used for chemotherapy in cases of malignant tumors and in angiography.
• Intradermal route:

This route is mostly used for diagnostic purposes and is involved in:
Schick test for Diphtheria
Dick test for Scarlet fever
Vaccines include DBT, BCG and polio
Sensitivity is to penicillin
• Intracardiac route

Injection can be applied to the left ventricle in case of cardiac arrest.

• Intrathecal route:

Intrathecal route involves the subarachnoid space. Injection may be applied for the lumbar puncture, for
spinal anesthesia and for diagnostic purposes. This technique requires special precautions.
• Intra-articular route:

Intra-articular route involves injection into the joint cavity. Corticosteroids may be injected by this route
in acute arthritis.
• Intraperitoneal route:

Intraperitoneal route may be used for peritoneal dialysis.

• Intrapleural route:

Penicillin may be injected in cases of lung empyma by intrapleural route.

• Injection into bone marrow

This route may be used for diagnostic or therapeutic purposes.

Hypospray/Jet Injection:
This method is needleless and is subcutaneous done by applying pressure over the skin. The drug solution
is retained under pressure in a container called ‘gun’. It is held with nozzle against the skin. Pressure on
the nozzle allows a fine jet of solution to emerge with great force. The solution can penetrate the skin and
subcutaneous tissue to a variable depth as determined by the pressure. Mass inoculation is possible but the
method is expensive, definite skills are required and cuts might result.
• Inhalation:

Inhalation may be the route of choice to avoid the systemic effects. In this way drugs can pass directly to
the lungs. Drugs used involve volatile drugs and gases. Examples include aerosols like salbutamol; steam
inhalations include tincture and Benzoin
Advantages:
• Rapid absorption takes place.
• Rapid onset of action takes place.
• This route has minimum side effects.
• No first pass effect takes place.
• This method is easy.
• Fewer doses are required.

Disadvantages:
• Special apparatus is required.
• Irritation of the respiratory tract may take place.
• Cooperation of the patient is required.
• Airway must be patent.
• Topical route:

Drugs may be applied to the external surfaces, the skin and the mucous membranes. Topical route
includes:
• Enepidermic route

When the drug is applied to the outer skin, it is called enepidermic route of drug administration. Examples
include poultices, plasters, creams and ointments.
• Epidermic route (Innunition):

When the drug is rubbed into the skin, it is known as epidermic route. Examples include different oils.
• Insufflations:
When drug in finely powdered form is blown into the body cavities or spaces with special nebulizer, the
method is known as insufflations.
• Instillation

Liquids may be poured into the body by a dropper into the conjunctival sac, ear, nose and wounds. Solids
may also be administered.
• Irrigation or Douching

This method is used for washing a cavity e.g. urinary bladder, uterus, vagina and urethra. It is also used
for application of antiseptic drugs.
• Painting/Swabbing

Drugs are simply applied in the form of lotion on cutaneous or mucosal surfaces of buccal, nasal cavity
and other internal organs.
Time of Action using Different Routes of Administration
Drugs take different time durations Delay time for Action
after injection using different routes
to perform their actions. Some of the
approximate time intervals are given
below: Route of Drug
Administration
Intravenous route 30-60 seconds
Intraosseous route 30-60 seconds
Endotracheal inhalation 2-3 minutes
Sublingual route 3-5 minutes
Intramuscular route 10-20 minutes
Rectal route 5-30 minutes
Ingestion 30-90 minutes