Chapter 5: Pharmacodynamics Learning Objectives 1. Define pharmacodynamics and its relationship to the action of drugs on the body. ● Pharmacodynamics is the study of how drugs interact with the body to produce their effects. It looks at how drugs work at the molecular, cellular, and physiological levels to impact the body. Chapter 5 Readings In Chapter 5, the basic features of the dose-response relationship are discussed, including maximal efficacy and relative potency. Dose-response curves reveal three phases: phase 1 where low doses have no measurable response, phase 2 where an increase in dose corresponds to an increase in response, and phase 3 where further increase in dose does not elicit a greater response. Pharmacodynamics is defined as the study of the biochemical and physiologic effects of drugs on the body and how they are produced. Bullet points Intrinsic activity ● ● ● Intrinsic activity refers to the ability of a drug to activate a receptor upon binding Drugs with high intrinsic activity cause intense receptor activation and have high maximal efficacy Drugs with low intrinsic activity cause slight activation and have low maximal efficacy Simple occupancy theory ● ● ● The intensity of the response to a drug is proportional to the number of receptors occupied A maximal response occurs when all available receptors have been occupied This theory does not explain drug potency or differences in maximal efficacy Agonists, antagonists, and partial agonists ● ● ● Agonists activate receptors and mimic the actions of endogenous regulatory molecules Antagonists block the actions of endogenous regulatory molecules Partial agonists mimic the actions of endogenous regulatory molecules but produce intermediate responses Modified occupancy theory ● ● ● Explains observations that cannot be accounted for with the simple occupancy theory Considers the ability of a drug to activate receptors in addition to receptor occupancy Drugs with different intrinsic activities can occupy the same number of receptors but produce different responses Agonists ● ● ● ● ● An agonist is a noncompetitive (insurmountable) antagonist An agonist has both affinity and high intrinsic activity It binds irreversibly to receptors, allowing the agonist to bind to receptors and activate receptor function Therapeutic agents can function as agonists and produce effects Examples include dobutamine, which mimics the action of NE at heart receptors, and insulin, which mimics the actions of endogenous insulin Noncompetitive antagonists ● ● ● ● ● Noncompetitive antagonists bind irreversibly to receptors Inhibition by noncompetitive antagonists cannot be overcome They reduce the total number of receptors available for activation by an agonist Their effects are rarely used therapeutically Effects of noncompetitive antagonists may subside as receptors are replaced Competitive antagonists ● ● ● Competitive antagonists bind reversibly to receptors They produce a receptor blockade by competing with agonists for receptor binding If an agonist and a competitive antagonist have equal affinity, the receptor will be occupied by the agent in the highest concentration