Pharmacodynamics Introduction

Pharmacodynamics is the study of biological responses to drug action. To be useful, a drug must act selectively on a particular target. The four main protein drug targets are receptors (most common), enzymes, transporters or carrier molecules, and ion channels.

Affinity describes how tightly a drug binds to its receptor, measured by the dissociation constant KD — the drug concentration at which 50% of receptors are occupied. Higher KD means lower affinity (more drug required to occupy receptors).

Potency is the amount of drug required to produce a particular effect, defined by EC50 on a concentration-response curve (the concentration producing 50% of maximal response). A more potent agonist has a lower EC50.

Efficacy is the ability of a drug to produce a response, defined as Emax. Positive efficacy = agonist; negative efficacy = inverse agonist; no efficacy = antagonist (binds without activating). Agonists have both affinity and efficacy. Full agonists elicit maximal tissue response. Partial agonists bind with affinity but fail to produce maximal response even at 100% receptor occupancy — they are less efficacious than full agonists. Antagonists block agonist binding without activating the receptor.

Allosteric modulators bind to a site distinct from the endogenous ligand site, altering the interaction of the endogenous ligand with its target. They can enhance or diminish receptor activity. Reversible antagonism is non-covalent and surmountable — increasing agonist concentration can overcome the block (parallel rightward shift on the concentration-response curve). Irreversible antagonism is covalent and non-surmountable — it depresses Emax and reduces available receptors.

The relationship between drug concentration and response is described using a concentration-response curve, typically sigmoidal on a log scale. Comparing drugs on such curves allows clinicians to assess relative potency (EC50 position on x-axis) and relative efficacy (Emax on y-axis).