INTRODUCTION to Pharmacology

What is pharmacology?

• It is the study of the actions, mechanisms, uses, and adverse effects of drugs

• A Drug is any natural or synthetic substance that alter the physiologic state of a living organism

Drugs are divided into:

• Medicinal drugs:These are used in the prevention, treatment and

diagnosis of disease

• Non-medicinal drugs or social drugs:These are used for purposes other than treatment

e.g. illegal mood- altering substances such as cannabis, heroin and cocaine

Drugs name and classification

Factors that are used to classify drugs:1. Pharmacotherapeutic action2. Pharmacologic action3. Molecular action4. Chemical nature

Definitions

• Pharmacodynamics:• It is what the drug do to the body i.e. drug

actions on the receptor, tissue, organ or system.• Pharmacokinetics:• It is what the body to the drug i.e. absorption,

distribution, metabolism and elimination

Pharmacodynamics

Targets of drugs

• Receptors • Enzymes• Ion channels• Carrier molecules• Physical or Chemical

Drug receptors

• Highly specific, highly sensitive binding site• Found on the surface of the cell membrane,

enzyme molecules on nuclear membranes.

• Receptor Specificity– There are a number of specific ligands and a number

of associate receptors

• Affinity• The extent to which the ligand is capable of binding

and remains bound to a receptor• High affinity: The ligand bind well and remains bound

for long enough to activate the receptor• Low Affinity: The ligand binds less well and may not

remain bound long enough to activate the receptor

The receptor intrinsic activity

• The extent to which the ligand activates the receptor

• High intrinsic activity: the ligand produces a large effect on the post synaptic cell

• Low intrinsic activity: the ligand produces a small or inconsistent effect on the post synaptic cell

Classes of Ligands

• Agonists–High affinity–High intrinsic activity

• Antagonist–High affinity– Low intrinsic activity

Agonists • An agonist is a drug that binds to a receptor and

activates it to give a response• There are 2 types of agonists:1. Full agonist: is a drug when bound to a receptor

produces 100% of the maximum possible biologic response

2. Partial agonist: a drug that produce less than 100% of the maximum possible biologic response no matter how high their concentration

Antagonist • An antagonist is a drug that bind to a receptor and

produce no response. • Type of drug antagonism: 1. Receptor antagonists a) Competitive: the antagonists competes with the

agonist at the same receptor site of an agonist and binds to it reversibly. By increasing the concentration of drug agonist the antagonism is abolished. E.g. antihistamine competes with histamine at its receptor site

b) Non competitive: the antagonist binds irreversibly to a different site on the enzyme e.g. than the agonist, noncompetitive agonists can not overcome by increasing the concentration of the drug agonist. E.g. succinylcholine is irreversible neuromuscular blocker.

R+

R

AGONIST

ANTAGONIST

Activated state

Resting state

RESPONSE

-ve-ve

Continue …2. Physiological antagonism: e.g. glucagon and

insulin. Histamine and epinephrine 3. Chemical antagonist: is the type of a drug that

acts by binding chemically to the compounds and inactivates it. E.g. chelating agents, charcoal (poisoning with iron)

4. Pharmacokinetic antagonist: by increasing the metabolism and excretion of a drug, e.g. enzyme induction to speed metabolism

Dose- response curve

• The response to increasing doses of an agonist or antagonist are plotted graphically.

• It can measure the following:• Efficacy: is the maximum effect (Emax) which can

be obtained from a large dose of the drug.• Potency: is the amount (dose) of drug or

concentration in the plasma that can produce a similar effect by a dose of another drug

• EC50 (Effective concentration): is the concentration that produce 50% of the maximum effect.

• ED50 (Effective dose): is the dose that produces the response of 50% of subjects

• LD50 (Lethal dose): is the dose that cause death in 50% of subjects

• Non competitive antagonist will bind irreversibly with the receptor leading to decrease in number of receptors available for binding with the agonist

• This will cause the maximum effect of the agonist to be less than when it is used alone or with competitive antagonist

Therapeutic index

• Is the ratio between the average maximum tolerated dose LD50 and the average minimal effective dose ED50

TI= LD50/ ED50

• It indicates the margin of safety in use of a drug

• The higher the TI the safer the drug