Most pharmacologic agents produce their physiologic effects by binding to a drug-specific receptor, which brings about a change in cellular function. The majority of pharmacologic receptors are cell membrane–bound proteins, although some receptors are located in the cytoplasm or the nucleoplasm of the cell.
- Desensitization and Downregulation of Receptors. Receptors are dynamic cellular components that adapt to their environment. Prolonged exposure of a receptor to its agonist leads to desensitization; subsequent doses of the agonist produce lower maximal effects.
- Agonists, Partial Agonists, and Antagonists. Drugs that bind to receptors and produce an effect are called agonists. Partial agonists are drugs that are not capable of producing the maximal effect even at very high concentrations. Compounds that bind to receptors without producing any changes in cellular function are referred to as antagonists. Competitive antagonists bind reversibly to receptors, and their blocking effect can be overcome by high concentrations of an agonist (competition). Noncompetitive antagonists bind irreversibly to receptors.
- Dose–response relationships determine the relationship between increasing doses of a drug and the ensuing changes in pharmacologic effects (Fig. 7-3: Schematic curve of the effect of a drug plotted against dose).
- Concentration–Response Relationships (Fig. 7-4: The changes in plasma drug concentration and pharmacologic effect during and after an IV infusion). The magnitude of the pharmacologic effect is a function of the amount of drug present at the site of action, so increasing the dose increases the peak effect. Larger doses have a more rapid onset of action because pharmacologically active concentrations at the site of action occur sooner. Increasing the dose also increases the duration of action because pharmacologically effective concentrations are maintained for a longer time.