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Titolo:
Antiarrhythmic agents - Drug interactions of clinical significance
Autore:
Trujillo, TC; Nolan, PE;
Indirizzi:
Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, Boston, MA 02115USA Massachusetts Coll Pharm & Hlth Sci Boston MA USA 02115 ston, MA 02115USA Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA Univ Arizona Tucson AZ USA 85721 arm Practice & Sci, Tucson, AZ 85721 USA Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA Univ Arizona Tucson AZ USA niv Arizona, Sarver Heart Ctr, Tucson, AZ USA
Titolo Testata:
DRUG SAFETY
fascicolo: 6, volume: 23, anno: 2000,
pagine: 509 - 532
SICI:
0114-5916(200012)23:6<509:AA-DIO>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUSTAINED VENTRICULAR-TACHYCARDIA; CORONARY-ARTERY DISEASE; LOW-DOSE QUINIDINE; MEXILETINE-THEOPHYLLINE INTERACTION; ARRHYTHMIA SUPPRESSION TRIAL; CHRONIC ATRIAL-FIBRILLATION; HEALTHY VOLUNTEER SUBJECTS; COMBINATION THERAPY; AMIODARONE INTERACTION; PLASMA-CONCENTRATIONS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
231
Recensione:
Indirizzi per estratti:
Indirizzo: Trujillo, TC Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, 179Longwood Ave, Boston, MA 02115 USA Massachusetts Coll Pharm & Hlth Sci 179Longwood Ave Boston MA USA 02115
Citazione:
T.C. Trujillo e P.E. Nolan, "Antiarrhythmic agents - Drug interactions of clinical significance", DRUG SAFETY, 23(6), 2000, pp. 509-532

Abstract

The management of cardiac arrhythmias has grown more complex in recent years. Despite the recent focus on nonpharmacological therapy, most clinical arrhythmias are treated with existing antiarrhythmics. Because of the narrowtherapeutic index of antiarrhythmic agents, potential drug interactions with ether medications are of major clinical importance. As most antiarrhythmics are metabolised via the cytochrome P450 enzyme system, pharmacokinetic interactions constitute the majority of clinically significant interactions seen with these agents. Antiarrhythmics may be substrates, inducers or inhibitors of cytochrome P450 enzymes, and many of these metabolic interactions have been characterised. However, many potential interactions have not, and knowledge of how antiarrhythmic agents are metabolised by the cytochrome P450 enzyme system may allow clinicians to predict potential interactions. Drug interactions with Vaughn-Williams Class II (beta -blockers) and ClassIV (calcium antagonists) agents have previously been reviewed and are not discussed here. Class I agents, which primarily block fast sodium channels and slow conduction velocity, include quinidine, procainamide, disopyramide, lidocaine (lignocaine), mexiletine, flecainide and propafenone. All of these agents except procainamide are metabolised via the cytochrome P450 system and are involved in a number of drug-drug interactions, including over 20 different interactions with quinidine. Quinidine has been observed to inhibit the metabolism of digoxin, tricyclic antidepressants and codeine. Furthermore, cimetidine, azole antifungals and calcium antagonists can significantly inhibit the metabolism of quinidine. Procainamide is excreted via active tubular secretion, which may be inhibited by cimetidine and trimethoprim. Other Class I agents may affect the disposition of warfarin, theophylline and tricyclic antidepressants. Many of these interactions can significantly affect efficacy and/or toxicity. Of the Class III antiarrhythmics, amiodarone is involved in a significant number of interactions since it is a potent inhibitor of several cytochromeP450 enzymes. It can significantly impair the metabolism of digoxin, theophylline and warfarin. Dosages of digoxin and warfarin should empirically bedecreased by one-half when amiodarone therapy is added. In addition to pharmacokinetic interactions, many reports describe the useof antiarrhythmic drug combinations for the treatment of arrhythmias. By combining antiarrhythmic drugs and utilising additive electrophysiological/pharmacodynamic effects, antiarrhythmic efficacy may be improved and toxicity reduced. As medication regimens grow more complex with the aging population, knowledge of existing and potential drug-drug interactions becomes vital for clinicians to optimise drug therapy for every patient.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 09:41:19