Beta blockers Amiodarone

Phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin Iopanoic acid, ipodate, amiodarone, beta-blockers, corticosteroids, propylthiouracil, cholestyramine, colestipol, aluminium hydroxide, sucralfate, ferrous sulfate, some calcium preparations Interferon-c/, interleukin-2... 

AMIODARONE BETA-BLOCKERS Risk of bradycardia (occasionally severe), 1 BP and heart failure. Also, t plasma levels of metoprolol Additive negative inotropic and chronotropic effects. In addition, high-dose amiodarone is associated with t plasma levels of metoprolol due to inhibition of CYP2D6 For patients on beta-blockers, monitor BP closely when loading with amiodarone... 

Qf 2559 patients admitted to an intensive cardiac care unit over 3 years, 64 with major cardiac iatrogenic problems were reviewed (59). Qf those, 58 had dysrhythmias, mainly bradydysrhythmias, secondary to amiodarone, beta-blockers, calcium channel blockers, electrolyte imbalance, or a combination of those. Amiodarone was implicated in 19 cases, compared with 44 cases attributed to beta-blockers and 28 to calcium channel blockers. Qf the 56 patients with sinus bradycardia, 10 were taking a combination of amiodarone and a beta-blocker, six were taking amiodarone alone, and three were taking amiodarone plus a calcium channel blocker. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

Clinically important, potentially hazardous interactions with amiodarone, beta-blockers, caspofungin, cyclosporine, dairy products, danazol, erythromycin, etoricoxib, grapefruit juice, hemophilus B vaccine, HMG-CoA reductase inhibitors, ibuprofen, immunosuppressants, ketoconazole, lopinavir, lovastatin, mycophenolate, peanuts, potassium, potassium-sparing diuretics, rifabutin, rifampin, rifapentine, simvastatin, St John s wort, telithromycin, vaccines... 

Dronedarone is structurally related to amiodarone, which is known to inhibit the cytochrome P450 isoenzyme CYP2D6, by which metoprolol is metabolised (see Amiodarone + Beta blockers , p.246). This study also shows that dronedarone inhibits CYP2D6, effectively making extensive metabolisers into poor metabolisers. For more information on metaboliser status see Genetic factors , (p.4). 

Drugs that may affect procainamide include amiodarone, anticholinergics, antiarrhythmics, beta-blockers, ethanol, histamine H2antagonists, propranolol,... 

Drugs that may affect amiodarone include hydantoins, cholestyramine, fluoroquinolones, rifamycins, ritonavir, and cimetidine. Drugs that may be affected by amiodarone include anticoagulants, beta-blockers, calcium channel blockers, cyclosporine, dextromethorphan, digoxin, disopyramide, fentanyl, flecainide, hydantoins, lidocaine, methotrexate, procainamide, quinidine, and theophylline. Drug/Lab test interactions Amiodarone alters the results of thyroid function tests, causing an increase in serum T4 and serum reverse T3 levels and a decline in... 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

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]. 

A significant mortality benefit of ICD therapy was shown in the largest of the three studies, the AVID study. In this study, over 1,000 patients with ischemic cardiomyopathy and an EF < 40% who were resuscitated from VF or from symptomatic, sustained VT were randomized to antiarrhythmic medications (>90% amiodarone) or ICD implantation. The trial was stopped early because the ICD showed a significant survival benefit with an 11.3% absolute and 31.5% RR reduction for all-cause mortality over 3 years. Persistent benefit with the ICD was seen even after adjustment for age, beta blocker use, and baseline EF. 

Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators the OPTIC Study a randomized trial. JAMA 2006 295 165-71. 

VENLAFAXINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS-TCAs 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemetherwith lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS -sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

The combination of amiodarone with beta-adrenoceptor antagonists can be beneficial in the treatment of refractory ventricular tachycardia, especially when low doses of the beta-blockers are used. However, there have also been reports of adverse interactions in these circumstances, and various correspondents have commented on the possibility that beta-blockers may enhance the effects of amiodarone in reducing mortality in patients who have... 

In a systematic review, the beneficial interaction has been confirmed (249). Four groups of patients who had been studied in EMIAT and CAMIAT (SEDA-21, 198) were defined patients who had taken amiodarone plus beta-blockers, patients who had taken beta-blockers or amiodarone alone, and patients who had taken neither. The relative risks for all-cause mortality and all forms of cardiac death or resuscitated cardiac arrest were lower in the patients who had taken amiodarone plus beta-block-ers than in the other three groups. The results of this post hoc analysis should be regarded with caution, but in view of previous similar reports they are suggestive of a beneficial interaction of amiodarone with beta-blockers in patients who have had a previous myocardial infarction. The interaction was statistically significant for cardiac deaths and for dysrhythmic deaths or resuscitated cardiac arrest. In all other cases the relative risk was reduced, although not significantly. The risk was not affected by heart rate. This interaction has been reviewed (250). 

Boutitie F, Boissel JP, ConnoUy SJ, Camm AJ, Cairns JA, Juhan DG, Gent M, Janse MJ, Dorian P, Frangin G. Amiodarone interaction with beta-blockers analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators. Circulation 1999 99(17) 2268-75. 

Ogunyankin KO, Singh BN. Mortality reduction by anti-adrenergic modulation of arrhythmogenic substrate significance of combining beta blockers and amiodarone. Am J Cardiol 1999 84(9A) R76-82. 

Mibefradil inhibits CYP3A4 (2). Other drugs that are metabolized by this pathway accumulate as a result. Drugs that were commonly affected included amiodarone, astemizole, ciclosporin, cisapride, erythromycin, imi-pramine, lovastatin, propafenone, quinidine, simvastatin (9), tacrohmus (10), tamoxifen, terfenadine, thioridazine, and drugs that impair sinoatrial node function (for example beta-blockers) (6). 

B Because this patient has asthma and is wheezing, calcium channel blockers are the drug class of choice. Unlike beta-blockers and adenosine, they do not cause bronchospasm. Beta-blockers and adenosine should be used cautiously in patients with obstructive lung disease, and use should be avoided in patients with asthma. Digoxin is not contraindicated, but it is not the drug of choice due to its slow onset. Amiodarone is indicated for ventricular arrhythmias, but not PSVT. 

Concurrent use with beta-blockers, calcium blockers, amiodarone may lead to bradycardia. 

Answer E. Increased sympathetic activity is a major problem in hyperthyroidism and is best managed by use of beta blockers, which can offset cardiac stimulatory effects. Propranolol has an ancillary action in thyrotoxicosis in that it prevents conversion of T4 to T3 via its inhibition of 5 deiodinase. Amiodarone causes difficult-to-predict adverse effects on thyroid function and would not be appropriate in a patient with hyperthyroidism. Bretylium is an IV agent reserved for ventricular arrhythmias. Digoxin is not ideal because of its complex actions on the heart, which include both inhibition and stimulation. 

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