Amiodarone arrhythmia with

Figure 3.39 A 47-year-old man, who refers a history of paroxysmal arrhythmias, with a normal ECG. After 2 months of treatment with amiodarone, repolarisation, which was normal (A), showed a flattened and dome-like...

Hoffmann A, Follath F, Burckhardt D. Safe treatment of resistant ventricular arrhythmias with a combination of amiodarone and quinidine or mexiletine. Lancet (1983) i, 704-5. 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

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]. 

Amiodarone is a drug used for arrhythmias, which has very similar properties to flecainide. Both drugs may cause pneumonitis as a side-effect but risk is lower with flecainide. Signs of pneumonitis include progressive shortness of breath or cough. 

Amiodarone (16) has been the center of much interest because of its activity as a cardiac depressant useful in treating ventricular arrhythmia and many analogues have been prepared [4. I he originally patented procedure concludes simply by etherification of benzofuran-containing iodonated phenol 15 with 2-halodiethylaminoethane to give amiodarone (16) [5]. The synthesis t)f 15 is not detailed in the reference but the synthesis of benzbromarone contains closely analo-goii.s steps [6]. 

During or after treatment with IV amiodarone, patients may be transferred to oral amiodarone therapy. Use IV amiodarone for acute treatment until the patient s ventricular arrhythmias are stabilized. Most patients require this therapy for 48 to 96 hours, but IV amiodarone may be given safely for longer periods if needed. 

Parenteral Amiodarone shows considerable interindividual variation in response. Thus, although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose as needed is essential. The... 

Life-threatening arrhythmias Use amiodarone only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity. 

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. 

In patients with life-threatening arrhythmias, weigh the potential risk of hepatic injury against the potential benefit of therapy. Monitor carefully for evidence of progressive hepatic injury. Give consideration to reducing the rate of administration or withdrawing amiodarone IV in such cases. 

On the basis of two large randomized trials aimed at suppressing premature ventricular complexes after MI, so-called warning arrhythmias, it was discovered that many common antiarrhythmic medications actually increase the risk of mortality [20, 21]. Amiodarone also has been shown to have no definitive effect on mortality in patients after an MI, including in the recent SCD-HeFT trial [22-24]. In fact, of all antiarrhythmic medications, only beta blockers have been clearly shown to prevent SCD after MI [25], particularly among those with depressed LV function [11]. 

Cairns JA, Connolly SJ, Roberts R, et al. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations CAMIAT. Canadian Amiodarone myocardial infarction arrhythmia trial investigators. Lancet. Mar 8 1997 349(9053) 675-682. 

Amiodarone (Cordarone) is an iodine-containing benzo-furan derivative identified as a class III agent because it predominantly prolongs action potentials. Amiodarone also blocks sodium and calcium channels and is a noncompetitive p-receptor blocker. Amiodarone is effective for the treatment of most arrhythmias. Toxicity associated with amiodarone has led the U. S. Food and Drug Administration (FDA) to recommend that it be reserved for use in patients with life-threatening arrhythmias. 

Amiodarone may elicit life-threatening side effects in addition to presenting substantial management difh-culties associated with its use. The oral formulation of amiodarone is indicated only for the treatment of life-threatening recurrent ventricular arrhythmias (e.g., recurrent ventricular hbrillation and/or recurrent hemo-dynamicaUy unstable ventricular tachycardia) that have not responded to other potentially effective antiarrhythmic drugs or when alternative interventions could not be tolerated. Despite its efficacy as an antiarrhythmic agent, there is no evidence from clinical trials that the use of amiodarone favorably affects survival. 

Initiation of treatment with amiodarone should be done in the hospital setting and only by physicians familiar with the management of patients with life-threatening arrhythmias this is because of the life-threatening nature of the arrhythmias and the possibility of interactions with previous therapy and of exacerbation of the arrhythmia. 

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... 

Procainamide is effective against most atrial and ventricular arrhythmias. However, many clinicians attempt to avoid long-term therapy because of the requirement for frequent dosing and the common occurrence of lupus-related effects. Procainamide is the drug of second or third choice (after lidocaine or amiodarone) in most coronary care units for the treatment of sustained ventricular arrhythmias associated with acute myocardial infarction. 

An initial increase in cardiac arrhythmias (proarrhythmic effect) may occur when class III drugs are instituted. The most important proarrhythmia is known as torsades de pointes, which is a form of ventricular tachycardia that can be fatal.11,40 Specific class III agents are associated with various other side effects. Amiodarone, for example, is associated with pulmonary toxicity and liver damage. Other class III drugs may have a more favorable side-effect profile but may not be as effective as amiodarone in controlling arrhythmias. Side effects of class HI drugs there-... 

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. 

ATOMOXETINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/dalfopristin 3. ANTICANCER AND IMMUNOMODU-LATING DRUGS - arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafax-ine 5. ANTIEMETICS - dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemether with lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS-pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS - parenteral bronchodilators Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

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