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INTRODUCTION

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Pharmacodynamics deals with the effects of drugs on biologic systems, whereas pharmacokinetics (Chapter 3) deals with actions of the biologic system on the drug. The principles of pharmacodynamics apply to all biologic systems, from isolated receptors in the test tube to patients with specific diseases.

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RECEPTORS

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Receptors are the specific molecules in a biologic system with which drugs interact to produce changes in the function of the system. Receptors must be selective in their ligand-binding characteristics (so as to respond to the proper chemical signal and not to meaningless ones). Receptors must also be modifiable when they bind a drug molecule (so as to bring about the functional change). Many receptors have been identified, purified, chemically characterized, and cloned. Most are proteins; a few are other macromolecules such as DNA. Some authorities consider enzymes as a separate category; for the purposes of this book, enzymes that are affected by drugs are considered receptors. The receptor site(also known as the recognition site) for a drug is the specific binding region of the receptor macromolecule and has a relatively high and selective affinity for the drug molecule. The interaction of a drug with its receptor is the fundamental event that initiates the action of the drug, and many drugs are classified on the basis of their primary receptor affinity.

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EFFECTORS

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Effectors are molecules that translate the drug-receptor interaction into a change in cellular activity. The best examples of effectors are enzymes such as adenylyl cyclase. Some receptors are also effectors in that a single molecule may incorporate both the drug-binding site and the effector mechanism. For example, a tyrosine kinase effector enzyme is part of the insulin receptor molecule, and a sodium-potassium channel is the effector part of the nicotinic acetylcholine receptor.

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GRADED DOSE-RESPONSE RELATIONSHIPS

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When the response of a particular receptor-effector system is measured against increasing concentrations of a drug, the graph of the response versus the drug concentration or dose is called a graded dose-response curve (Figure 2–1A). Plotting the same data on a logarithmic concentration axis usually results in a sigmoid curve, which simplifies the mathematical manipulation of the dose- response data (Figure 2–1B). The efficacy (Emax) and potency (EC50 or ED50) parameters are derived from these data. The smaller the EC50 (or ED50), the greater the potency of the drug.

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FIGURE 2–1

Graded dose-response and dose-binding graphs. (In isolated tissue preparations, concentration is usually used as the measure of dose.) A. Relation between drug dose or concentration (abscissa) and drug effect (ordinate). When the dose axis is linear, a hyperbolic curve is commonly obtained. B. Same data, logarithmic dose axis. The dose or concentration at which effect is half-maximal is denoted EC50, whereas the maximal ...

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