• Biochemical & physiological effects of a drug and its mechanism of action (MOA)

• Effects of the drug on the body via the interaction of the drug molecules with molecules of the body

• Receptors are the central focus of investigation of drug effects and their mechanism of action

Drug Receptors

• Receptors are responsible for selectivity of drug action: the molecular size, shape & electrical charge of a drug determines whether it will bind to a specific receptor

• The receptors affinity for binding to a drug determines the concentration of the drug required to form a significant number of drug-receptor complexes

• The total number of receptors often limits the maximal effect a drug may produce

• Binding of the drug to the receptor may result in one of two effects:

1) Agonist effect: binding of drug to the receptor alters the functioning of the receptor

2) Antagonist effect: binding to the receptor does not affect receptor function but simply prevents subsequent binding of agonist molecules

Receptors

• Most receptors are proteins

• Include: i) Regulatory proteins (mediate action of endogenous chemical signals such as hormones & neurotransmitters

ii) Enzymes (may be inhibited or activated by drug binding)

iii) Transport proteins (eg Na⁺, K⁺—ATPase)

iv) Structural proteins (eg tubulin)

Antagonist

• Receptor antagonists bind to a receptor but do not activate it

• The effects result from preventing agonists (other drugs or endogenous molecules) from binding to & activating the receptor

• Two types of antagonist: 1) Competitive antagonist

2) Irreversible antagonist

1) Competitive antagonist

- Increasing concentrations of a competitive antagonist progressively inhibit agonist response

- Sufficiently high concentrations of agonist can surmount the effects of a given concentration of antagonist

2) Irreversible antagonist

- Bind to the receptor in a irreversible (or nearly irreversible fashion)

- Due to very high affinity for receptor thereby precluding binding of receptor to agonist

Relationship between Drug Concentration & Response

• Response to low doses of a drug usually increases in direct proportion to dose, however, as doses increase, the incremental response diminishes until it eventually has no further effect

• EC50% is the concentration of the drug that produces 50% of maximal effect

• ED50 (effective dose or median dose) is the least concentration of a drug that is effective in 50% of the subjects

Relationship between Drug Dose & Clinical Response

a)Potency

• Refers to the dose or concentration of a drug to produce a given effect

• Drugs A & B are more potent than C & D

• Drug A is more potent than B at the lower part of the response range [25% of max response]; at 90% of max response, drug B is more potent than A

b) Maximal Efficacy

• Drugs B, C & D have equal maximum efficacy, while all have greater maximal efficacy than does drug B

c) Shape of Dose-Response Curves

• The extremely steep dose-response curve of D may have important clinical implications if the upper portions of the curve produce undesirable effects