Pharmacodynamics The Mechanisms of Drug Action

PD is the study of drug action on the biologic and physiologic processes of both cells and biologic systems. The targets of drug interaction are usually specific macromolecules that induce a physiologic or biochemical change; DNA, RNA, or other macromolecules involved in cell division (e.g., microtubules); an enzyme found either intracellularly or in the plasma; an ion channel protein or structural protein.4 Many newer drugs bind to receptors that normally bind an endogenous regulatory ligand (e.g., growth factors, neurotransmitters, hormones) and drug binding to this receptor alters its function and/or its downstream signaling responses. Agonists are drugs that mimic the endogenous ligand for the receptor (e.g., opioids, granulocyte colony stimulating factor (G-CSF), recombinant human erythropoietin (rhEPO). Antagonists are drugs that block the effects of the endogenous ligand (e.g., trastuzumab (Herceptin) monoclonal antibody against HER-2/neu; flutamide, an androgen receptor antagonist). Partial agonists are agents that possess both agonist/antagonist activities (e.g., tamoxifen-mixed estrogen receptor agonist/antagonist). Enzyme inhibitors bind directly to endogenous enzyme and inhibit their function (e.g., methotrexate, dihydrofolate reductase inhibitors; epidermal growth factor receptor (EGFR)-associated tyrosine kinase I inhibitors, i.e., Tarceva; topoisom-erase I inhibitors, i.e., camptothecins).

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