McKenna's Pharmacology, 2e

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P A R T 1  Introduction to nursing pharmacology

A. Agonist interaction with receptor site on cell

Drug A: An agonist that binds to receptor sites and produces an effect Drug B: Cannot bind to receptor sites on this cell and produces no effect

Molecule of Drug A bound to receptor site

Unoccupied receptor site for Drug A

B. Competitive antagonism

Molecule of Drug C bound to receptor site

Drug A: An agonist

Drug C: An antagonist of Drug A that binds to the same receptor sites as Drug A and prevents Drug A from binding

FIGURE 2.1  Receptor theory of drug action. A. Agonist interaction with receptor site on cell. Molecules of drug A react with specific receptor sites on cells of effector organs and change the cells’ activity. B. Competitive antagonism. Drug A and drug C have an affinity for the same receptor sites and compete for these sites; drug C has a greater affinity, occupies more of the sites and antagonises drug A. C. Non competitive antagonism. Drug D reacts with a receptor site that is different from the receptor site for drug A but still somehow prevents drug A from binding with its receptor sites. Drugs that act by inhibiting enzymes can be pictured as acting similarly to the receptor site antagonists illustrated in panels B and C. Enzyme inhibitors block the binding of molecules of normal substrate to active sites on the enzyme.

C. Non-competitive antagonism

Drug A: An agonist

Molecule of Drug D bound to receptor site different from receptor site for Drug A

Drug D: A competitive antagonist of Drug A that binds to different receptor sites from Drug A but still prevents Drug A from binding

to this phenomenon. A change in receptors or loss of receptors can develop when a drug is given repeatedly or continuously. Prolonged exposure to an agonist drug can often result in a gradual decrease in the number of receptors expressed on the cell’s surface or receptor downregulation. This has often been shown for β adren­ ergic receptors. The vanishing receptors are taken into the cells by endocytosis . Whereas prolonged use of an antagonist drug can result in r eceptor upregulation . Upregulation of receptor numbers is an increase in the number of receptors on the surface of target cells, making the cells more sensitive to a hormone or another agent. Selective toxicity Ideally, all chemotherapeutic agents would act only on receptors, structures or enzyme systems that are

essential for the life of a pathogen or neoplastic cell and would not affect healthy cells. The ability of a drug to attack only those systems found in foreign cells is known as selective toxicity . Penicillin, an antibiotic used to treat bacterial infections, has selective toxicity. It affects an enzyme system unique to bacteria, causing bacterial cell death without disrupting normal human cell functioning. Unfortunately, most other chemotherapeutic agents also destroy normal human cells, causing many of the adverse effects associated with antipathogen and anti­ neoplastic chemotherapy. Cells that reproduce or are replaced rapidly (e.g. bone marrow cells, gastrointestinal [GI] cells, hair follicles) are more easily affected by these agents. Consequently, the goal of many chemotherapeu­ tic regimens is to deliver a dose that will be toxic to the invading cells yet cause the lowest toxic effect to the host.