Side effects and complications of amiodarone therapy

Raeder, Ernst A.; Podrid, Philip J.; Lown, Bernard

doi:10.1016/0002-8703(85)90238-8

Cited by 196 publications

(89 citation statements)

References 38 publications

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“…2) (11). The plasma concentration upon therapeutic administration of amiodarone is 0.1 -10 µM (20). Therefore, amiodarone may inhibit I NCX at therapeutic concentrations.…”

Section: Amiodaronementioning

confidence: 99%

Topics on the Na+/Ca2+ Exchanger: Pharmacological Characterization of Na+/Ca2+ Exchanger Inhibitors

2006

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Abstract. Using the whole-cell voltage clamp, we examined acute effects of various agents on Na + / Ca 2+ exchange current (I NCX ) in guinea-pig cardiac ventricular cells and transfected cells. Among the antiarrhythmic drugs, amiodarone, bepridil, dronedarone, cibenzoline, azimilide, and aprindine inhibited I NCX in a concentration-dependent manner. We also investigated the effects on NCX of 2,3-buanedione monoxim (BDM) and selective NCX inhibitors such as KB-R7943, SEA0400, and SN-6. The presence of trypsin in the pipette solution attenuated the inhibitory effects on NCX of amiodarone, bepridil, and BDM, suggesting that these drugs inhibit NCX from the cytosolic side. In contrast, the trypsin-insensitive NCX inhibitors were aprindine, azimilide, dronedarone, cibenzoline, KB-R7943, SEA0400, and SN-6. KB-R7943, SEA0400, and SN-6 suppressed the uni-directional outward I NCX more potently than the uni-directional inward I NCX . The mechanism of this mode-dependency is unknown, but is suggested to be related to intracellular Na + concentration.

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“…2) (11). The plasma concentration upon therapeutic administration of amiodarone is 0.1 -10 µM (20). Therefore, amiodarone may inhibit I NCX at therapeutic concentrations.…”

Section: Amiodaronementioning

confidence: 99%

Topics on the Na+/Ca2+ Exchanger: Pharmacological Characterization of Na+/Ca2+ Exchanger Inhibitors

2006

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“…Amiodarone is a complex drug with multiple electrophysiologic effects, unusual pharmacokinetics, and numerous potentially harmful drug interactions and adverse effects. 23,24 The prevalence of adverse effects has been reported to be as high as 15% in the first year of use and up to 50% during long-term use, even at low doses. 5,[22][23][24][25] Clinically significant extracardiac adverse effects, particularly with long-term use, include pulmonary and liver toxicity, hyper-and hypothyroidism, photosensitivity, neuropathy, blindness, and a blue discoloration of the skin.…”

Section: Guidelines Versus Clinical Practice: Why the Difference?mentioning

confidence: 99%

“…Amiodarone has clinically important drug interactions with digoxin, warfarin, simvastatin, procainamide, quinidine, and quinolone antibiotics, among many others. 23,24 Given the potential for extracardiac adverse effects and drug interactions, the amiodarone dosage should be kept at the lowest effective level, and regular and appropriate monitoring and follow-up of patients is essential. In patients taking digoxin and warfarin, for example, digoxin levels and prothrombin time should be monitored, keeping in mind that interactions with amiodarone do not peak until 7 weeks after initiating concomitant therapy.…”

Section: Guidelines Versus Clinical Practice: Why the Difference?mentioning

confidence: 99%

Antiarrhythmic drug therapy for atrial fibrillation: Are the guidelines guiding clinical practice?

Reiffel

Naccarelli

2006

Clin Cardiol

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Summary:The AFFIRM study showed no clear survival advantage for a rhythm versus rate control strategy in patients with atrial fibrillation (AF). However, rhythm control with antiarrhythmic drugs (AADs) is appropriate in a large number of patients with AF. The American College of Cardiology/ American Heart Association/European Society of Cardiology AF management guidelines include a safety-based algorithm for selection of AAD therapy. Class 1C agents are recommended as first-line therapy in patients without or with minimal structural heart disease. However, market research and clinical study data indicate a growing use of class III agents (mainly amiodarone) despite long-term safety and tolerability concerns, suggesting that clinical practice does not adhere to current guidelines.

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“…Prior reports [7][8][9][10][11][12] have shown a marked variation in the efficacy and tolerability of amiodarone for prevention of sudden cardiac death, and only few data over a long time frame are available. The long-term efficacy, toxicity, and tolerability of amiodarone and the long-term benefit of the ICD versus amiodarone in VT/VF survivors randomly assigned to therapy have not been reported previously.…”

Section: See P 107mentioning

confidence: 99%

Long-Term Comparison of the Implantable Cardioverter Defibrillator Versus Amiodarone

et al. 2004

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Background-The implantable cardioverter defibrillator (ICD) is superior to amiodarone for secondary prophylaxis of sudden cardiac death. However, the magnitude of this benefit over long-term follow-up is not known. Thus, our objective was to evaluate the long-term consequences of using amiodarone versus an ICD as first-line monotherapy in patients with a prior history of sustained ventricular tachycardia/ventricular fibrillation or cardiac arrest. Methods and Results-A total of 120 patients were enrolled at St Michael's Hospital in the Canadian Implantable Defibrillator Study (CIDS) and were randomly assigned to receive either amiodarone (nϭ60) or an ICD (nϭ60). The treatment strategy was not altered after the end of CIDS unless the initial assigned therapy was not effective or was associated with serious side effects. After a mean follow-up of 5.6Ϯ2.6 years, there were 28 deaths (47%) in the amiodarone group, compared with 16 deaths (27%) in the ICD group (Pϭ0.0213). Total mortality was 5.5% per year in the amiodarone group versus 2.8% per year in the ICD group (hazard ratio of amiodarone: ICD, 2.011; 95% confidence interval, 1.087 to 3.721; Pϭ0.0261). In the amiodarone group, 49 patients (82% of all patients) had side effects related to amiodarone, of which 30 patients (50% of all patients) required discontinuation or dose reduction; 19 patients crossed over to ICD because of amiodarone failure (nϭ7) or side effects (nϭ12). Conclusions-In

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Side effects and complications of amiodarone therapy

Cited by 196 publications

References 38 publications

Topics on the Na+/Ca2+ Exchanger: Pharmacological Characterization of Na+/Ca2+ Exchanger Inhibitors

Topics on the Na+/Ca2+ Exchanger: Pharmacological Characterization of Na+/Ca2+ Exchanger Inhibitors

Antiarrhythmic drug therapy for atrial fibrillation: Are the guidelines guiding clinical practice?

Long-Term Comparison of the Implantable Cardioverter Defibrillator Versus Amiodarone

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