The fundamental principles that govern drug therapy are often overlooked by the busy clinician. This disregard frequently results in the use of particular drugs and regimens that may be less than ideal for the clinical situation being managed. By convention, these principles are categorized as pharmacokinetic and pharmacodynamic. Pharmacokinetic processes include drug absorption, distribution, biotransformation (metabolism), and elimination, essentially reflecting the influence of the body on the drug administered. Pharmacodynamics deals with the actual mechanisms of action and the effects a drug produces on the patient. This latter topic will be addressed in a future continuing education article.Abstract
Drug absorption. Following oral (PO) or topical administration, a drug requires lipid solubility in order to diffuse through the epithelium to reach the capillaries. When administered by intramuscular (IM) or subcutaneous (SC) injection, lipid solubility is not required to reach the capillaries. Once absorbed following PO administration, a drug must travel through the portal system to liver before reaching systemic circulation (venae cavae). See text for further explanation.
Drug distribution. Drug molecules (D) circulate in blood stream unbound and bound to plasma proteins. Only unbound drug is free to distribute into tissues. Systemically, distribution is a simple matter of diffusion through the loosely-joined endothelium of the capillaries. Distribution to the brain requires lipid solubility because the capillary endothelium is tightly bound and wrapped with astrocytes.
Parent drug and metabolites. Following administration, a parent drug may be converted to any number of metabolites. In this example, the parent drug is converted to 3 separate metabolites. Parent drugs and their metabolites can be active, inactive, toxic, or nontoxic. Furthermore, each has a separate pattern of elimination.
Drug half-life. This graph illustrates the changes in serum concentration of a drug following intravenous (IV) and oral (PO) administration. Following IV administration, the concentration is high within seconds and declines rapidly during the first 30 minutes. This decline is attributed primarily to distribution. Once this process is completed, serum concentration drops more gradually, reflecting elimination. Following PO administration, serum concentration increases as the drug is absorbed, until it peaks in 1 hour. This peak is never as high as that following IV administration because as the drug is absorbed, it is distributed and perhaps eliminated, while the remaining drug is continuing to be absorbed. Starting at 1 hour, however, concentration drops at the same rate regardless of the route by which it was administered. In each case the elimination half-life (T1/2β) is 2 hours. Following absorption and distribution of drugs, the process of elimination is identical, regardless of how a drug is administered.
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