Amiodarone syndrome

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Amiodarone (11), a benzofuran derivative, was initially developed as a coronary vasodilator in the early 1960 s [11,12]. Several years later, the efficacy of the compound as an antiarrhythmic agent began to be exploited. The first clinical trials with amiodarone were reported in 1974 [13]. Amiodarone was effective in controlling the tachyarrhythmias of eleven patients with Wolff-Parkinson-White syndrome. Since that time the compound has been studied extensively [14,15]. Recently, in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT), amiodarone was shown to reduce mortality during a mean 18 month period following myocardial infarction (13.8% deaths in placebo group vs. 2.1 % deaths in the treatment group) [16]. 

Oral- Amiodarone may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium scan, and pathological data consistent with pulmonary toxicity. The frequency varies from 2% to 17% fatalities occur in about 10% of cases. However, in patients with life-threatening arrhythmias, discontinuation of amiodarone therapy due to suspected drug-induced pulmonary toxicity should be undertaken with caution. 

Class II Ventricular tachycardia WPW syndrome Postoperative atrial fibrillation (i.v. amiodarone)... 

According to recent ACC/AHA/ESC Guidelines (see Zipes et al., 2006), in patients with sutained VT, direct-current cardioversion is appropriate and most effective, and also intravenous procainamide (or ajmaline in some European countries) is recommended as a reasonable choice for initial treatment for sustained monomorphic VT in patients with acute coronary syndrome. Intravenous amiodarone or lidocaine may be reasonable chose as alternative treatment. 

Amiodarone is effective in maintaining sinus rhythm in most patients with paroxysmal atrial hbrillation and in many patients with persistent atrial hbrillation. It is also effective in preventing recurrences of A-V nodal reentry and atrial tachyarrhythmias and in the prevention of reentrant rhythms and atrial hbrillation in patients with Wohf-Parkinson-White syndrome. Also, it is the most efficacious therapy for postoperative junctional ectopic tachycardia. 

Amiodarone is contraindicated in patients with sick sinus syndrome and may cause severe bradycardia and second-and third-degree atrioventricular block. Amiodarone crosses the placenta and will affect the fetus, as evidenced by bradycardia and thyroid abnormalities. The drug is secreted in breast milk. 

Contraindications Concurrent use of drugs that prolong the QT interval concurrent use of amiodarone, megestrol, prochlorperazine, or verapamil congenital or acquired prolonged QT syndrome paroxysmal atrial fibrillation severe renal impairment... 

Ventricular tachycardia, atrial fibrillation, and flutter (can convert recent-onset fibrillation or flutter to sinus rhythm). Amiodarone is used in the management of patients with supraventricular and ventricular arrhythmias, and arrhythmias associated with the WPW syndrome... 

Budesonide for collagenous colitis caused Cushing s syndrome in a patient with chronic renal insufficiency taking amiodarone for paroxysmal atrial fibrillation (477). 

The authors suggested that the development of Cushing s syndrome and its persistence at a low dosage of budesonide was caused by inhibition of the metabolism of budesonide by amiodarone. 

Ahle GB, Blum AL, Martinek J, Oneta CM, Dorta G. Cushing s syndrome in an 81-year-old patient treated with budesonide and amiodarone. Eur J Gastroenterol Hepatol 2000 12(9) 1041-2. 

Amiodarone-induced hyponatremia, due to the syndrome of inappropriate secretion of antidiuretic hormone, is rare (SEDA-21, 199 25). The mechanism is unknown. Unlike other adverse effects of amiodarone, it seems to occur rapidly and to resolve rapidly after withdrawal. 

Ikegami H, Shiga T, Tsushima T, Nirei T, Kasanuki H. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by amiodarone a report on two cases. J Cardiovasc Pharmacol Ther 2002 7(l) 25-8. 

Patel GP, Kasiar JB. Syndrome of inappropriate antidiuretic hormone-induced hyponatremia associated with amiodarone. Pharmacotherapy 2002 22(5) 649-51. 

Aslam MK, Gnaim C, Kutnick J, Kowal RC, McGuire DK. Syndrome of inappropriate antidiuretic hormone secretion induced by amiodarone therapy. Pacing Clin Electrophysiol 2004 27(6 Pt l) 831-2. 

Medications such as P-blockers, calcium channel blockers, digoxin, and amiodarone can be used to control cardiac conduction abnormalities (arrhythmias), and a pacemaker may be inserted to combat heart failure. The general supportive care measures used in acute stroke syndromes also should be followed. Death in patients with MELAS is usually the result of cardiac failure, pulmonary embolus, or renal failure. 

Amiodarone, for example (Fig. 1.12), was introduced as a coronary dilator for angina, but concern about comeal deposits, discoloration of skin exposed to sunlight and thyroid disorders led to the withdrawal of the drug in 1967. However, in 1974 amiodarone was found to be highly effective in the treatment of a rare type of arrhythmia known as the Wolff-Parkinson-White syndrome. Accordingly, amiodarone was reintroduced specifically for that purpose [22]. 

Arruodarone is used in chronic ventricular arrhythmias in atrial fibrillation it both slows the ventricular response and may restore sinus rhythm it may be used to maintain sinus rhythm after cardioversion for atrial fibrillation or flutter. Amiodarone should no longer be used for the management of reentrant supraventricular tachycardias associated with the Wolff-Parkinson-White syndrome as radiofrequency ablation is preferable. 

In 72 patients with paroxysmal atrial fibrillation randomized to either amiodarone 30 mg/kg or placebo, those who received amiodarone converted to sinus rhythm more often than those given placebo (22). The respective conversion rates were about 50 and 20% at 8 hours, and 87 and 35% after 24 hours. The time to conversion in patients who converted did not differ. One patient developed slow atrial fibrillation (35/minute) with a blood pressure of 75/ 55 mmHg. Three other patients who received amiodarone had diarrhea and one had nausea. In the control group two patients had headache, one had diarrhea, one had nausea, and two had episodes of sinus arrest associated with syncope during conversion to sinus rhythm the last of these was thought to have sick sinus syndrome. 

The commonest form of lung damage is an interstitial alveolitis, although pneumonitis and bronchiolitis obhter-ans have also been reported, as have sohtary localized fibrotic lesions, non-cardiac pulmonary edema, pleural effusions, acute respiratory failure, acute pleuritic chest pain, and adult respiratory distress syndrome (SEDA-17, 220) (SEDA-18, 201) (66-68). Amiodarone has also been reported to cause impairment of lung function, even in patients who do not develop pneumonitis (69), and preexisting impairment of lung function may constitute a contraindication to amiodarone. 

Adult respiratory distress syndrome occurred very rapidly in a 66-year-old man who took amiodarone 200 mg/day for a few weeks only (71). 

Amiodarone commonly causes phototoxicity reactions (186,187). The risk of phototoxicity increases with the duration of the exposure. Window glass and sun screens do not give protection, although zinc or titanium oxide formulations and narrow band UVB photo therapy can help (188-190). For most patients this adverse effect will be no more than a nuisance, and the benefit of therapy may be worthwhile. However, in a few cases treatment may have to be withdrawn. Histological examination of skin biopsies shows intracytoplasmic inclusions of phospholipids (191). There has been a single report of a severe case of photosensitivity in conjunction with a syndrome resembling porphyria cutanea tarda, resulting in bullous lesions (192). 

Lupus-hke syndrome has rarely been attributed to amiodarone. 

Ravina T, Gutierrez J. Amiodarone-induced AV block and ventricular standstill. A forme fruste of an idiopathic long QT syndrome. Int J Cardiol 2000 75(l) 105-8. 

Dickinson EJ, Wolman RL. Sicca syndrome associated with amiodarone therapy. BMJ (CUn Res Ed) 1986 293 510. 

Jones DB, Mullick EG, Hoofnagle JH, Baranski B. Reye s syndrome-like illness in a patient receiving amiodarone. Am J Gastroenterol 1988 83(9) 967-9. 

Rogers KC, Wolfe DA. Amiodarone-induced blue-gray syndrome. Ann Pharmacother 2000 34(9) 1075. 

Class III, which is used for certain tachycardia syndromes, includes amiodarone (whose mechanism of action is not clear), potassium-channel blockers and the atypical P-blocker sotalol. 

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