Amiodarone (Cordarone) is a compoun...

Amiodarone (Cordarone) is a compounded antiarrhythmic agent with multiple electrophysiologic issues unusual pharmacokinetics, and numerous potentially harmful unsalable article interactions and adverse effects. Although the U nutrition and Drug Administration (FDA) has labeled amiodarone solely for the treatment of life-threatening ventricular arrhythmias, the medicine also is used to treat atrial fibrillation. Because of the complexity and widespread use of this agent, other treatment decisions repeatedly are affected. This article reviews the pharmacology, indications, adverse tenors and drug interactions of amiodarone, and outlines a strategy for surveillance of patients who are taking this drug

Clinical Pharmacology

PHARMACOKINETICS

Amiodarone is an iodine-containing blend with some structural similarity to thyroxine. The drug's high iodine satisfy likely is a factor in its drifts on the thyroid gland. The bioavailability of amiodarone is variable further generally poor, ranging from 22 to 95 percent (1) Absorption is enhanced when the mix with drugs is taken with food. (2) Amiodarone is highly lipid soluble and is stored in high concentrations in fat and muscle, as well as in the liver, lung and skin. Amiodarone crosse the placenta and reaches measurable flushs in breast milk.

The major metabolite of amiodarone is desethylamiodarone (DEA), which is known to have antiarrhythmic properties. Grapefruit juice can inhibit amiodarone metabolism and lead to elevated physic levels,3 but the impact of this interaction forward the long-term efficacy and toxicity of amiodarone is not known.

The elimination half-life of amiodarone is highly variable and unusually drawn out averaging about 58 days. The drawn out half-life is thought to be a conclusion of the drug's slow release from lipid-rich tissues. (2)

ELECTROPHYSIOLOGIC EFFECTS

Amiodarone is considered to be a class III mix with drugs (Vaughan Williams classification), which indicates that it extends the QT interval. However, the physic has many other effects: it inerts heart rate and atrioventricular nodal conduction (via calcium channel and beta-receptor blockade), protracts refractoriness (via potassium and sodium channel blockade), and inactives intracardiac conduction (via sodium channel blockade).

The relationship between plasma amiodarone concentrations and import as well as the contribution of the metabolite DEA, is not well established. (2) Routine monitoring of the amiodarone plasma flat is not recommended. (4) [Evidence horizontal C, consensus/ expert guidelines]

Indications

LONG-TERM TREATMENT

Amiodarone is approved for use in the secondary prevention of life-threatening ventricular arrhythmias. The North American Society for Pacing and Electrophysiology (NASPE) commends amiodarone as the antiarrhythmic agent of choice in patients who have survived sustained ventricular tachyarrhythmias, particularly those with left ventricular dysfunction. (4)

Studies in succession the use of amiodarone for the primary prevention of rapid death in high-risk patients have had mixed comes One meta-analysis of 13 studies of patients with congestive heart failure or modern myocardial infarction showed a small reduction in total annual mortality, from 123 percent to 109 percent (absolute risk reduction [ARR], 24 percent; number indigenceed to treat [NNT], 42). (5) [Evidence even A, meta-analysis] The benefit of amiodarone therapy was more pronounced in the patients who had congestive heart failure, with treatment reducing the annual mortality rate from 243 percent to 199 percent (ARR, 44 percent; NNT 23) Because implantable cardioverter-defibrillators (ICDs) are more effective than amiodarone in reducing mortality in high-risk patients with previous myocardial infarction, primary treatment should be an ICD. (6-9) [Reference 6--Evidence on a level A, meta-analysis] In these patients, amiodarone may be used as an adjunct to bring into the frequency of ICD brunts or to control atrial fibrillation in pickeded highly symptomatic patients. The relative efficacy of amiodarone and ICDs in preventing rapid death in patients without coronary disease is in subordination to investigation.

Amiodarone is used in the treatment of atrial fibrillation, although the FDA has not approved this indication. Various practice guidelines approve amiodarone as a second-line remedy in the long-term treatment of atrial fibrillation in patients with structural heart disease and in highly symptomatic patients without heart disease. (10) Several smaller studies have shown that amiodarone is similar to quinidine and sotalol in the treatment of atrial fibrillation in these patients. (1112) In single in kind randomized controlled trial (RCT), (12) sinus periodical emphasis was maintained successfully for 16 month in 65 percent of patients treated with amiodarone, compared with 37 percent of patients treated with sotalol or propafenone (ARR, 28 percent; NNT 36) However, latter studies have shown that aggressive attempts to maintain sinus periodical emphasis using amiodarone or other physics do not improve outcomes in relatively asymptomatic patients. (1314) Therefore, long-term amiodarone therapy, with its potential for toxicity, does not appear to be justified in patients who are taking anticoagulant put drugs intos if rate-control strategies can provide satisfactory symptomatic improvement.