Pharmacology, Part 1: Introduction to Pharmacology and Pharmacodynamics

Schematic representation of receptor concept. Ligands specific for receptor may produce response across cell membrane, may produce partial response, or may block response.

Steady-state dose–response curve. Plateau (arrow) represents dose for which maximal effect is achieved and above which additional dose does not change effect. There is also a drug dose below which no noticeable effect will be observed. Slope of line indicates how small (steep) or large (flat) a change in dose is required to observe increased effects.

(Left) Dose–response curve representing concepts of potency and efficacy. High potency (drug A) is represented by shift to left from drug B: strong effect with low dose. Submaximal effect (drug C) despite increasing dose demonstrates lower efficacy than for drug A. (Right) Dose–response curve can also be used to represent same drug but with different outcomes (B on right). Curve A represents targeted therapeutic effect, and 50% effective dose (ED₅₀) is dose that produces effect in 50% of population. Curve C represents same drug but more dire effects, and 50% lethal dose (LD₅₀) is dose that produces death in 50% of population. Difference between curves A and C is therapeutic window (TW) or margin of safety and can be represented as therapeutic index by expressing ratio LD₅₀/ED₅₀. Curve B provides example of drug that would have narrow therapeutic window or lower therapeutic index.

After repeated doses of drug, patient may develop tolerance (A on left), which means patient needs higher doses to generate same effect (move from curve A to B) or has lower effects from same dose (curve A to C). Individual may develop tolerance to targeted effect of drug without developing tolerance to side effects, which changes therapeutic index. After repeated doses of drug, patient may also develop sensitization (B on right), which means patient generates greater effects from same dose (move from curve A to B) or has same effects from lower dose (curve A to C). Individual may develop sensitization to one effect of drug without developing sensitization to other effects.

Agonist activity at receptor may be altered by antagonist, potentiated by allosteric activation of other receptors, or inhibited by allosteric inhibition at other receptors.