Disease relevance of L 3428

• Amiodarone to prevent recurrence of atrial fibrillation [1].
• Images in clinical medicine. Amiodarone-induced pulmonary toxicity [2].
• During amiodarone therapy, ventricular tachycardia could be induced in 18 of 19 patients in whom it had been induced before therapy, but only six of these 19 had spontaneous recurrence during follow-up [3].
• More on amiodarone for ventricular tachyarrhythmias [4].
• We evaluated the effects of amiodarone in 45 patients with recurrent ventricular tachycardia or ventricular fibrillation [3].
• AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively [5].

Psychiatry related information on L 3428

• However, in the amiodarone group, there was a 35% risk reduction (95% CI 0-58, p = 0.05) in arrhythmic deaths [6].
• Many systemic drugs may produce ocular toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine, tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction agents and some herbal medications [7].
• These results suggest that iv amiodarone is effective in controlling refractory atrial and ventricular arrhythmias and may shorten the latency period [8].
• For patients with ventricular tachycardia, two-year survival was 91% in the conventional therapy group and 68% in the amiodarone group but incidence of sudden death was similar, probably reflecting increased non-sudden death due to advanced age and left ventricular dysfunction in the amiodarone-treated group [9].
• In the hot plate test (paw-lick), the amiodarone treated rats showed increased pain-thresholds throughout the treatment [10].

High impact information on L 3428

• Images in clinical medicine. Pigmentation related to amiodarone [11].
• Amiodarone in out-of-hospital cardiac arrest [12].
• After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001) [13].
• CONCLUSIONS: In patients with out-of-hospital cardiac arrest due to refractory ventricular arrhythmias, treatment with amiodarone resulted in a higher rate of survival to hospital admission [14].
• Patients who had cardiac arrest with ventricular fibrillation (or pulseless ventricular tachycardia) and who had not been resuscitated after receiving three or more precordial shocks were randomly assigned to receive 300 mg of intravenous amiodarone (246 patients) or placebo (258 patients) [14].

Chemical compound and disease context of L 3428

• AIT is primarily related to excess iodine-induced thyroid hormone synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), but mixed forms frequently exist [15].
• In group A, diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation [16].
• Xamoterol (a partial beta-agonist) was more effective than metoprolol as adjuvant therapy to amiodarone in the control of recurrent sustained ventricular arrhythmias and was not associated with any clinical deterioration of ventricular function [17].
• Adjuvant xamoterol or metoprolol in patients with malignant ventricular arrhythmia resistant to amiodarone [17].
• Managing chronic atrial fibrillation: a Markov decision analysis comparing warfarin, quinidine, and low-dose amiodarone [18].

Biological context of L 3428

• METHODS: In this double-blind, randomized study, 124 patients were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of seven days before elective cardiac surgery [19].
• Amiodarone was significantly more effective in suppressing ventricular arrhythmias and increased the left ventricular ejection fraction by 42 percent at two years [20].
• Although amiodarone was effective in suppressing ventricular arrhythmias and improving ventricular function, it did not reduce the incidence of sudden death or prolong survival among patients with heart failure, except for a trend toward reduced mortality among those with nonischemic cardiomyopathy [20].
• INTERPRETATION: Our findings do not support the systematic prophylactic use of amiodarone in all patients with depressed left-ventricular function after myocardial infarction [6].
• Exercise tolerance was significantly greater during treatment with xamoterol/amiodarone than during treatment with metoprolol/amiodarone or with amiodarone alone [17].

Anatomical context of L 3428

• The effects of amiodarone on the thyroid [15].
• Acute effects of amiodarone upon the canine sinus node and atrioventricular junctional region [21].
• Injections of amiodarone into the AV node artery during sinus rhythm regularly increased AV conduction time sometimes causing 2 degrees AV block at the highest concentration used [21].
• We report that the benzofuran amiodarone acts as a competitive antagonist to thyroid hormone action as defined by its dose-dependent ability to (a) bind to the thyroid hormone receptor and (b) inhibit T3-induced increases in growth hormone mRNA levels in a cultured rat pituitary cell line, GC cells [22].
• Like T3 itself, amiodarone also decreases transport of [125I]T3 across GC cell membranes [22].

Associations of L 3428 with other chemical compounds

• Treatment of AIH consists of L-T(4) replacement while continuing amiodarone therapy; alternatively, if feasible, amiodarone can be discontinued, especially in the absence of thyroid abnormalities, and the natural course toward euthyroidism can be accelerated by a short course of potassium perchlorate treatment [15].
• In terms of quality-adjusted life-years, amiodarone had the highest expected value (4.75 years), followed by warfarin (4.72 years), quinidine (4.68 years), and no treatment (4.55 years) [18].
• Linear regression analysis indicated a positive relation between plasma cholesterol and the cumulative dose of amiodarone (r = 0.25, P less than 0.05) [23].
• DESIGN: Consecutive entry trial, including cardiac patients who initiated amiodarone medication but excluding those with abnormal thyroid function (defined as peak thyroid-stimulating hormone [TSH] response to thyrotropin-releasing hormone [TRH] less than 2.8 or greater than 22.0 mU/L) either before or during amiodarone treatment [23].
• Thirty-one patients underwent an electrophysiology test on four occasions: at baseline; after 2-4 days of treatment with quinidine, mexiletine, or encainide; after 2 weeks of treatment with 1,200 mg/day amiodarone; and last, after 2-4 days of treatment with both amiodarone and the previously tested class I agent [24].
• The similarity to nutrient starvation responses seen in stationary phase cells, rapamycin treatment, and late stages of shift to diauxic conditions and nitrogen depletion suggests that amiodarone may interfere with nutrient sensing and regulatory networks [25].

Gene context of L 3428

• Of three mutants examined (vps45, vma3, and rcy1), all were found to have defective calcium homeostasis, supporting a correlation with amiodarone hypersensitivity [26].
• In addition, amiodarone may interact with other drugs (such as digoxin) via the inhibition of the P-glycoprotein membrane transporter system, a recently described pharmacokinetic mechanism of drug interactions.Bretylium is not metabolised; it is excreted unchanged in the urine [27].
• Induction of c-jun and TGF-beta 1 in Fischer 344 rats during amiodarone-induced pulmonary fibrosis [28].
• These studies indicate that CYP3A isozyme(s) mainly metabolize amiodarone to its N-deethylated derivative in human hepatic microsomal fractions [29].
• RESULTS: Amiodarone weakly inhibited CYP2C9, CYP2D6, and CYP3A4-mediated activities with Ki values of 45.1-271.6 microm [30].

Analytical, diagnostic and therapeutic context of L 3428

• Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation [14].
• Total hospitalization costs were significantly less for the amiodarone group than for the placebo group ($18,375+/-$13,863 vs. $26,491+/-$23,837, P=0.03) [19].
• INTERVENTION--Before cardioversion, patients received 600 mg of amiodarone daily during a 4-week loading period [31].
• Overall, 227 patients (45%) were discharged on conventional antiarrhythmic agents, 115 (23%) on amiodarone, 39 (8%) received an implantable defibrillator, and 120 (24%) received no specific antiarrhythmic therapy [32].
• Thyroidectomy for amiodarone-induced thyrotoxicosis [33].

References