Pharmacodynamics: The Mechanism of Drug Action
Most drugs act by binding to and altering the function of regulatory macromolecules, usually neurotransmitter receptors, hormone receptors, or enzymes. Binding may be a reversible association mediated by electrostatic and/or van der Waals forces, or it may involve formation of a covalent intermediate. If the drug–receptor interaction stimulates the receptor’s natural function, the drug is termed an agonist. Stimulation of an opposing effect characterizes an antagonist. Corresponding effectors of enzymes are termed activators and inhibitors. This terminology is crucial to understanding Chapter 16.
The relationship between the initial drug–receptor interaction and the drug’s clinical dose-response curve may be simple or complex. In some cases, the drug’s clinical effect closely reflects the degree of receptor occupancy on a moment-to-moment basis. Such is usually the case for drugs that affect neural transmission or for drugs that are enzyme inhibitors. In contrast, some drug effects lag hours behind receptor occupancy or persist long after the drug is gone. Such is the case with many drugs acting on hormone receptors, because their effects are often mediated through a series of biochemical events.
In addition to differences in timing of receptor occupancy and drug effects, the degree of receptor occupancy can differ considerably from the corresponding drug effect. For example, because the amount of carbonic anhydrase present in the ciliary processes is 100 times that required to support aqueous secretion, more than 99% of the enzyme must be inhibited before secretion is reduced. On the other hand, some maximal hormone responses occur at concentrations well below those required for receptor saturation, indicating the presence of “unbound receptors.”
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.