Intro to Drug Action

Key definitions

• Pharmacology: the study of the manner in which the function of living tissues and organs is modified by chemical substances

• Pharmacology: what a drug does to the body

• Pharmacokinetics: what the body does to a drug

• Drug: any single synthetic or natural substance of known structure used in the treatment, prevention or diagnosis of disease

• Medicine: chemical preparation containing one or more drugs; therapeutic effect

• Selectivity: the ability of a drug to distinguish between different molecular targets within the body

Agonists and antagonists

• Agonist: drug that binds to a receptor to produce a cellular response
• Temporarily activate receptors by producing a conformational change
• Possess affinity and efficacy

• Affinity: strength of association between ligand and receptor (binding)

• Efficacy: ability of an agonist to evoke a cellular response (activation)

• Antagonist: drug that reduces, or blocks, the actions of an agonist by binding to the same receptor – do not activate them
• Possess affinity but lack efficacy

Potency and efficacy

• Potency: amount of drug required to produce a desired effect

• Efficacy: maximum response achievable from drug

EC50

• Concentration of agonist that elicits half maximal effect

• Easy to see using semi-logarithmic plot of concentration vs. effect - sigmoidal relationship

Competitive and non-competitive antagonism

Competitive antagonism

• Binding of agonist and antagonist occur at same (orthosteric) site - competitive

• Cause parallel right shift of agonist concentration response curve with no depression in maximal response

Non-competitive antagonism

• Agonist binds to normal site and antagonist binds to separate (allosteric) site - not competitive

• Both may occupy sites simultaneously, but activation cannot occur when antagonist is bound

• Depress the slope and maximum response curve, but do not cause a rightwards shift