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Pharmacology (Chapt. 6)

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jasmine's version from 2015-10-25 22:59

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Question Answer
3 Possible Outcomes When Two Drugs Interact 1) One drug may intensify the effects of the other; 2) One drug may reduce the effects of the other; and 3) The combination may produce a new response not seen with either drug alone
Potentiative Interactions One drug may intensify the effects of the other; The interactions may be beneficial or detrimental
Inhibitory Interactions One drug may reduce the effects of the other; The interactions may be beneficial or detrimental
4 Basic Mechanisms that Drug-Drug Interactions can Interact With 1) Direct chemical or physical interaction; 2) Pharmacokinetic interaction; 3) Pharmacodynamic interaction; and 4) Combined toxicity
Direct Chemical or Physical Interaction With these properties, drugs can undergo direct interaction with other drugs; This usually renders both drugs inactive; Frequently, yet not always; the interaction produces a precipitate and if happens, solution should be discarded; Significant interactions within the patient are much less likely than in a bottle
Never Combine two or more drugs in the same container unless it has been established that a direct interaction will not occur
Pharmacokinetic Interaction Drug-drug interactions can alter absorption, distribution, metabolism, and excretion, or elimination
2 Principle Mechanisms of Altered Distribution 1) competition for protein binding; and 2) Alteration of extracellular pH
Free Drug in Theory It can intensify effects, however since the newly freed drug usually undergoes rapid elimination, the increase in plasma levels of free drug is rarely sustained or significant
Alteration of Extracellular pH A drug with the ability to change this can alter the distribution of other drugs; For example, if a drug were to increase this, that drug would increase the ionization of acidic drugs in the extracellular fluid (i.e., plasma and interstitial fluid). And as a result, acidic drugs would be drawn from within cells (where the pH was below that of the extra cellular fluid) into the extracellular space. Hence, the alteration in pH would change drug distribution. This can be put to practical use in the management of poisoning by increasing the pH outside cells, thereby minimizing injury to cells
Drug-Drug Interactions that Increase Metabolism Process By inducing synthesis of hepatic drug-metabolizing enzymes
Drug-Drug Interactions that Decrease Metabolism Process By inhibiting synthesis of hepatic drug-metabolizing enzymes
Inducing Agents Drugs that stimulate the synthesis of CYP isozymes (closely related to enzymes with five responsible for the metabolism of most drugs
5 isozymes responsible for the metabolism of most drugs CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4
Inducing Agents taken with other medicine Dosage of the other drugs may need adjustment due to this may accelerate metabolism of the drugs; For example, if given an inducing agent with another drug, the other drug may need increased to maintain efficacy
Drugs that induce P-Glycoprotein can impact other drugs by way of reduced absorption, reduced fetal drug exposure, reduced brain drug exposure, and increased drug elimination
Drugs that induce P-Glycoprotein impact other drugs by Reduced Absorption By increasing drug export from cells of the intestinal epithelium into the intestinal lumen
Drugs that induce P-Glycoprotein impact other drugs by Reduced Fetal Drug Exposure By increasing drug export from placental cells into the maternal blood
Drugs that induce P-Glycoprotein impact other drugs by Reduced Brain Drug Exposure By increasing drug export from cells of brain capillaries into the blood
Drugs that induce P-Glycoprotein impact other drugs by Increased Drug Elimination By increasing drug export from liver into the bile and from renal tubular cells into the urine
Drugs the inhibit P-Glycoprotein impact other drugs by Opposite effects of induction
2 Basic types of pharmacodynamics interactions 1) Interactions in which the interacting drugs act at the same site; and 2) Interactions in which the interacting drugs act at separate sites; Both may be potentiative or inhibitory, and can be of great clinical significance
Inhibitory Interactions Interactions that occur at the same receptor; Occurs when an antagonist drug blocks access of an agonist drug to its receptor
Interactions resulting from actions at separate sites Even though two drugs have different mechanisms of action and act at separate sites, if both drugs influence the same physiologic process, then one drug can alter responses produced by the other; Interactions resulting from effects produced at different sites may be potentiative or inhibitory
Additional measures for reducing adverse interactions include Adjusting the dosage when an inducer of metabolism is added to or deleted from the regime; adjusting the timing of administration to minimize interference with absorption; monitoring for early signs of toxicity when combinations of toxic agents cannot be avoided; and being especially vigilant when the patient is taking a drug with a narrow therapeutic range
Reducing the rate of absorption Merely delays the onset of effects, so peak effects are not lowered; however, in contrast, reducing the extent of absorption reduces the intensity of peak responses
Food Reducing Drug Absorption Examples Calcium-containing foods such as milk products and calcium supplements can reduce drug absorption in tetracycline antibiotics. High-fiber foods such as wheat bran, rolled oats, and sunflower seeds can reduce drug absorption in digoxin [Lanoxin], used for cardiac disorders
Food Increasing Drug Absorption Example A high-calorie meal more than doubles the absorption of saquinavir [Invirase], as drug for HIV infection. If saquinavir is taken without food, absorption may be insufficient for antiviral activity
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