Clinical implications of the competitive inhibition of the debrisoquin-metabolizing isozyme by quinidine.
Approximately 10% of western populations are genetically deficient in the enzyme that metabolizes the antihypertensive drug debrisoquin. These "poor metabolizers" process many common medications in an aberrant fashion, resulting in a variety of untoward consequences including exaggerated drug effect, subtherapeutic drug concentrations, or complex drug interactions. A variety of medications, including neuroleptics, antidepressants, beta-blockers, and certain antiarrhythmics, are subject to the influence of this metabolic polymorphism. Quinidine administration changes persons to poor metabolizers of debrisoquin for the duration of therapy. Thus, the use of quinidine with any of the other drugs metabolized by this isozyme may be expected to result in a drug interaction in which a person's response will mimic that of a poor metabolizer. Because no test is commonly available to determine directly the debrisoquin metabolic phenotype, clinicians should be alert to unusual drug reactions in patients receiving quinidine concurrently with the other medications.
Caporaso
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Environmental Epidemiology Branch, National Cancer Institute NIH, Bethesda, Md 20892.
Shaw
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D019389:Cytochrome P-450 CYP2D6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency / Q000235:genetics; D004347:Drug Interactions; D006801:Humans; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010641:Phenotype; D011802:Quinidine / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000929:Antidepressive Agents, Tricyclic; D000959:Antihypertensive Agents; D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D011802:Quinidine