Pharmacology Introduction

Introduction
What is pharmacology?

Pharmacology is the science that deals with drugs (in Latin, pharmac- means
drug, -logy means science). Pharmacology can be subdivided into two main branches:

1- Pharmacokinetics, which concerns "what the body does to the drug". This
includes drug absorption, distribution, metabolism and excretion.

2- Pharmacodynamics, which concerns "what the drug does to the body". This
includes the drug mechanism of action, biochemical and biological effects of
the drug on the living system, therapeutic uses and adverse effects.

What is a drug?

Drugs are chemical or biological substances used to change biological systems

by interacting with them for the purpose of diagnostic, preventive, suppressive or
curative outcomes.

Drug sources:

Drugs can be obtained as one of the following:

1- Natural products:

These are obtained from animal, plant or microbial sources. These include:

i) Alkaloids like morphine (from opium poppy plant), atropine (from

belladonna leaves) and colchicines (from autumn crocus).

ii) Peptides from animal or human sources, like somatostatin and

glucagon.

iii) Steroids from human or animal sources like testosterone, estradiol

and hydrocortisone.

iv) Hormones like insulin (from animal sources and recombinant DNA
technology) and thyroid hormones (from animal sources).

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Pharmacology Introduction

v) Glycosides like digitalis (plant source) and streptomycin (from

microbial source).

vi) Vitamins from various plants and animals.

vii) Polysaccharides from human or animal sources that can be used

directly (heparin) or after depolymeraization (enoxaparin) or
structural modification (sucralfate).

viii) Antibiotics produced by micro-organisms like penicillin, tetracycline

and doxorubicin.

2- Synthetic products:

These include:

i) Products similar to natural products but with structural modifications like

hydroxymorphone (similar to morphine) and ampicillin (like penicillin).

ii) Peptidomimetics that contain similar functional group spacing to natural

compounds but with different structure, e.g. losartan (resembles angiotensin
II).

iii) Completely new structures obtained by chemical synthesis and subjected to

screening tests, e.g. barbiturates, sulfonamides, thiazides and
benzodiazepines.

Drug classification:

Drugs may be classifies according to different criteria:

1- According to therapeutic uses:

Drugs may be classified as anti-diabetics, anti-hypertensives, anti-convulsants,

diuretics, ..etc.

2- According to drug actions on biological systems, including:

i) Site of action, e.g. CNS acting drugs, GIT acting drugs, ..etc.

ii) Physiological effect, e.g. vasodilator.

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Pharmacology Introduction

iii) Type of molecular interaction, e.g. receptor blocker, receptor agonist,

enzyme inhibitor, channel blocker, ..etc.

3- According to chemical structure:

Drugs may be alkaloids, steroids, glycosides, barbiturates, aminosugars,

polypeptides, polysaccharides, ..etc.

Drug nomenclature:

Drugs may be named according to one of the following systems:

1- Chemical name of the drug according to organic chemistry rules.

2- Generic name (non-proprietary name), which is the official name of the drug
used in pharmacological literature, pharmacopoeias and pharmacology books.

3- Trade name (proprietary name), which is denoted by the manufacturer or

pharmaceutical company.
NHCOCH3
OCOCH3

COOH
OH

1 2

For example, structure (1) has the following names:

 Chemical name: Acetylsalicylic acid, ortho-acetoxybenzoic acid.

 Generic name: Aspirin.

 Trade name: [Rivo]R, [Entrophen] R, [Aspirin] R.

Structure (2) has the following names:

 Chemical `name: N-acetyl-para-aminophenol.

 Generic name: Acetaminophen, paracetamol.

 Trade name: [Abimol]R, [Tylenol] R, [Paramol] R.

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Pharmacology Introduction

Pharmacokinetics
For an administered drug to exert a pharmacological effect at the site of action,
it must pass the following barriers (Figure i):

1- The drug must pass several membranes until it reaches systemic circulation
(absorption). These membrane barriers depend on the route of administration
(absorption from inhalation routes or parenteral routes is faster than that of oral
routes) and the intended site of action (drugs acting on CNS must pass the
blood brain barrier).

2- The drug has to be concentrated in the extracellular fluids at the site of action
in an amount sufficient to perform a pharmacological effect and escape
excessive distribution at sites of loss (plasma protein binding, fat storage,
other tisuues).

3- Active drugs should avoid excessive metabolism to inactive forms before

reaching site of action. Alteranatively, pro-drugs should be metabolized to
active forms before reaching site of action. Drug metabolism occurs in the
liver (microsomal and non-microsomal) or in other tissues (extrahepatic
metabolism).

4- After performing drug effect, the drug should be eliminated by metabolism

(metabolic clearance) or excretion by the kidney (renal clearance by
glomerular filtration or tubular secretion) or by other routes like bile secretion.
Excretion of drugs may be prolonged by renal tubular reabsorption (kidney) or
enterohepatic circulation (hepatobiliary system).

2- Drug route of administration:

Different routes of drug administration differ in drug bioavailability (rate and

extent of drug absorption). This may dramatically modify drug effects, drug onset
and duration of action. These include routes for local action and routes for systemic
action (including enteral, inhalation and parenteral routes).

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Pharmacology Introduction

A) Transdermal and topical administration:

Transdermal (percutaneous) drug absorption is the placement of a drug

formulation (lotion, ointment, cream, paste or patch) on the skin surface for systemic
absorption (Figure ii). Small lipid-soluble drugs (e.g. nitroglycerin, nicotine,
scopolamine, clonidine, fentanyl, testosterone and 17-β-estradiol) are absorbed
readily from the skin.

Packing

Drug reservoir

Semipermeable
membrane

Adhesive

Protective strip
Figure (ii): Transdermal adhesive strip

Alternatively, drugs may be applied topically for local effects (to avoid
systemic toxicity or to localize drug effect). Examples are antimicrobials
(antibacterials and antifungals) and local anaesthetics. Local anaesthetics may be
applied together with a vasoconstrictor like adrenaline to localize the anaesthetic (to
increase action) and prevent systemic absorption (to decrease drug toxicity).

Other topical routes of administration include:

 Eye, ear and nose drops.

 Urethral or vaginal solutions.

 Mouthwashes and gargles.

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Pharmacology Introduction

B) Enteral administration:

This is represented by drug administration through the alimentary canal (from

mouth to anus), including:

1- Peroral (oral) administration:

The drug is administered orally, swallowed and undergoes absorption from the
GIT through the mesenteric circulation. By means of tributaries of the portal vein
(Figure iii), all the absorbed drug from the GIT first percolates through the liver; a
process called hepatic first-pass effect. Such pathway significantly affects drug
metabolism.

Oral medications may be liquids (aqueous solutions, spirits, tinctures, aromatic

waters, suspensions, emulsions), tablets (immediate-release, modified-release, enteric
coated, chewable, lozenges) or capsules (hard or soft gelatin capsules).

Drug molecules are absorbed throughout the GIT but most absorption takes
place at the duodenal region due to the greater surface area (more villi and microvilli
that are responsible for absorption).

Oral drug administration may allow prolonged drug effect in drugs undergoing
enterohepatic circulation in which a portion of the absorbed drug is secreted by bile
into the gut and then reabsorbed.

Although the oral route is the most convenient, most economic and safest route
of drug administration, many limitations of this route are present, including the
following:

 Irritant drugs that cause excessive vomiting, e.g. tartaremetic.

 Acid-labile drugs such as peptide hormones (insulin).

 Drugs that are extensively inactivated in the liver through first-pass effect.

 Insoluble and non-absorbable drugs, e.g. hexamethonium, except when

required for local effect in the GIT (e.g. streptomycin).

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Pharmacology Introduction

 Complexation with some food components retards the absorption (e.g.

tetracycline and calcium).

 Unconscious patients (unable to swallow).

 Convulsions (loss of control on epiglottis may lead to respiratory tract

aspiration).

 Emergency cases (due to slow action).

Liver
Stomach

Portal vein
Mesentry
tributaries

Figure (iii): Portal circulation

2- Buccal and sublingual administration:

A tablet or lozenge is placed in the mouth in contact with the buccal mucosa.
This allows for absorption of small, lipid-soluble molecules through the epithelial
lining of the mouth. Alternatively, a tablet can be placed under the tongue
(sublingual) and the drug is absorbed from the sublingual veins.

Buccal and sublingual drug administration allow for systemic absorption of the
drugs without passing into the liver (no first-pass effect).

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Pharmacology Introduction

3- Rectal administration:

Drugs are administered in the form of liquids (enemas) or suppositories.

Absorption takes place through the mucosal surface and rectal veins. The lower two-
thirds of the rectum allow for direct systemic absorption bypassing hepatic first-pass
effect.

C) Respiratory tract administration:

This includes:

1- Intra-nasal administration:

The drug is administered to the nasal mucosa in the form of drops or spray for
the purpose of local (e.g. decongestants) or systemic effects.

2- Pulmonary inhalation:

The drug is administered by various devices like metered dose inhalers (MDI),
spacers, nebulizers or dry powder aerosols. Drug absorption from the bronchial tree is
very rapid and avoids hepatic first-pass effect.

D) Parenteral administration:

This includes:

1- Intra-venous injection:

The drug is injected directly into venous blood, pooled to the heart during
diastole through superior and inferior vena cavae and then distributed to the whole
body by cardiac systole.

This route has many advantages:

 Rapid action, so it is most suitable in emergency cases.

 This type of administration also ensures 100% bioavailability.

 Large volumes of drugs, nutrients electrolyte solutions can be given.

 Irritant, hypertonic, acidic or alkaline solutions can be given by this route

slowly as the preparation is diluted in a large volume of blood.
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Pharmacology Introduction

However, this route has many disadvantages:

 Allergic reactions are more common.

 Rapid administration may cause toxic effects even at normal dose levels.

 Overdoses can not be withdrawn nor absorption be retarded.

2- Intra-arterial injection:

The drug is injected into an artery to attain high drug concentration in a tissue
or an organ before being diluted in the general circulation.

3- Intra-muscular injection:

The drug is injected in the form of solution or suspension deep in skeletal

muscles. Drug absorption rate is dependent on lipid solubility of the drug, vehicle
composition and vascularity of the injected region.

4- Subcutaneous injection:

The drug is injected under the skin. The rate of drug absorption is slower than
intramuscular route as subcutaneous regions are less vascular than muscular tissue.
Some drugs in which slow absorption is necessary are given subcutaneously, e.g.
insulin and adrenaline.

5- Inta-articular injection:

This route is important when direct injection of a drug inside a joint is

required, e.g. corticosteroids in arthritis.

6- Intra-dermal (intra-cutaneous) injection:

The drug is injected in the dermis to minimize systemic absorption and

toxicity, e.g. allergic skin tests.

7- Intra-thecal injection:

The drug is injected into the spinal fluid. The specific gravity of the drug
determines the region of its effect.

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Pharmacology Introduction

Pharmacodynamics
Pharmacodynamics is a branch of pharmacology concerned with the study of
biochemical and physiological effects of drugs and the mechanisms by which they
produce such effects.

Drug actions result from the dynamic interactions between drug molecules and
cellular components resulting in perturbation of the normal physiology. Any cellular
macromolecule may act as a drug receptor. This receptor may be a cell surface
receptor or an intracellular receptor (ion channel, enzyme, protein, microsome or
nuclear material).

Certain drug receptors normally act as physiological receptors for endogenous

components, e.g. adrenergic receptors for adrenaline and noradrenaline. Drugs whose
responses mimic the response elicited by the endogenous component are termed
agonists. An agonist therefore is a drug having both affinity and intrinsic activity at
the receptor. For example, bethanechol is a cholinergic receptor agonist as its action
on the cholinergic receptor resembles that of the endogenous component
acetylcholine.

Drugs that have affinity but lack intrinsic activity at the receptor site are
termed antagonists as they block the action of the endogenous component without
having an action themselves.

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Pharmacology Introduction

Enhancement of drug action:

 Additive effect occurs when two different drugs with the same
pharmacological effect are given together yielding an effect equal in magnitude
to the sum of the individual drug effects, e.g. trimethoprim and
sulfamethoxazole (1 + 1 = 2).

 Synergistic effect occurs when the two drugs with the same effect are
combined together to yield an effect greater in magnitude than the sum of the
individual effects, e.g. penicillin and gentamicin against pseudomonal
infections (1 + 1 = 3).

 Potentiation occurs when a drug lacking an effect alone is combined to a drug

with a pharmacologic effect resulting in increased effect of the latter, e.g.
combination of carbidopa with levodopa (1 + 0 = 2).

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