Atrial fibrillation (AF) is the most common arrhythmia in the world. Risk factor modification, anticoagulation, rhythm control, and rate control are the four pillars of its management. American College of Cardiology/American Heart Association (ACC/AHA) guidelines on management of AF were updated recently.

Treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. US guidelines were recently updated.

The treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. New US guidelines for the management of atrial fibrillation have recently been published.

Mirabegron (mir a beg’ ron; Myrbetriq [meer BEH trick] – Astellas), a beta-3 adrenergic agonist, has been approved by the FDA for the treatment of overactive bladder. It is the first beta-3 adrenergic agonist to be approved for any indication in the US. Mirabegron has been marketed in Japan since 2011. OnabotulinumtoxinA (Botox) was also recently approved by the FDA for treatment of overactive bladder and will be reviewed in a future issue.

The treatment of atrial fibrillation includes ventricular rate control, anticoagulation, conversion to normal sinus rhythm and maintenance of sinus rhythm. The choice of therapies that can achieve these goals is discussed in the text that follows. Some drugs are recommended here for indications that have not been approved by the FDA.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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Duloxetine (Cymbalta - Lilly) is the second drug to be approved by the FDA for treatment of fibromyalgia. Pregabalin (Lyrica), which is also approved for treatment of neuropathic pain and epilepsy, was the first. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that is already marketed for treatment of depression and diabetic neuropathy.

The drugs of choice for treatment of common cardiac arrhythmias are listed in Tables 1 and 2. Some drugs are recommended for indications that have not been approved by the FDA.

Duloxetine hydrochloride (Cymbalta - Lilly), a selective serotonin and norepinephrine reuptake inhibitor (SNRI) available for treatment of depression, has also been approved by the FDA for treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPN). Duloxetine is one of two drugs approved specifically for management of neuropathic pain due to diabetes; the other, pregabalin (Lyrica - Pfizer), will be marketed soon and will be reviewed in the next issue of The Medical Letter.

The FDA recently cleared the AmpliChip CYP450 Test (Roche), which analyzes blood-derived DNA to detect genetic variations in the activity of cytochrome P450 (CYP) enzymes CYP2D6 and CYP2C19 and determines the metabolizer status of the patient. The test is intended to help guide clinicians in prescribing individualized drug therapy. About 25% of all drugs, including many antidepressants and antipsychotics, are substrates of either CYP2D6 or CYP2C19. The test is being promoted initially to psychiatrists.

The drugs of choice for treatment of common cardiac arrhythmias are listed in the table that begins on the next page; some drugs are recommended for indications for which they have not been approved by the US FDA. The dosages and adverse effects of each drug are listed in the table that begins on page 80. Antiarrhythmic drugs may themselves cause arrhythmias, which can be fatal. Some of these drugs may increase rather than decrease mortality, especially in patients with structural heart disease.

Duloxetine hydrochloride (Cymbalta - Lilly), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), has been approved by the FDA for treatment of major depressive disorder in adults, and more recently for diabetic peripheral neuropathy as well. The Medical Letter will review its role in diabetic neuropathy in a future issue.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.

Carvedilol (Coreg - SmithKline Beecham and Boehringer-Mannheim), a betaadrenergic and alpha-adrenergic blocker approved by the FDA for treatment of hypertension in 1995, but not marketed at that time, has now been approved and marketed for treatment of mild or moderate (NYHA class II or III) heart failure stabilized on other drugs. It is being promoted as an add-on drug that reduces the morbidity and mortality of the disease.

Sotalol (hydrochloride (Betapace -Berlex; Sotacor -Bristol Laboratories of Canada), an antiarrhythmic drug that prolongs repolarization (Class III) and also has beta-adrenergic-blocking activity (Class II), was recently approved by the US Food and Drug Administration (FDA) for oral treatment of life-threatening ventricular arrhythmias.

Flecainide (Tambocor -3M Pharmaceuticals), first introduced in 1985 for treatment of ventricular arrhythmias, was recently approved by the US Food and Drug Administration for oral use to prevent supraventricular arrhythmias. The indications for using flecainide to treat ventricular arrhythmias were limited after a controlled trial found that post-myocardial infarction patients with asymptomatic ventricular arrhythmias who took the drug had twice as high a mortality rate as patients who took placebo (DS Echt et al, N Engl Med, 324:781, 1991).

Some commonly used systemic drugs that may cause pulmonary toxicity are listed in the table below. These adverse effects may sometimes be difficult to distinguish from the underlying disease (JAD Cooper, Jr et al, Am Rev Respir Dis, 133:321, 488, 1986). Pulmonary effects that are part of a generalized reaction or are indirect effects of drugs - on respiratory muscles, for example, or on the immune system - are not included here.

Propafenone (Rythmol - Knoll), a class IC antiarrhythmic drug used in Europe for treatment of various arrhythmias for more than 10 years, was recently marketed in the USA for oral treatment of life-threatening ventricular arrhythmias such as sustained ventricular tachycardia. This restrictive labeling reflects concerns arising from the interim report of the Cardiac Arrhythmia Suppression Trial, in which post-myocardial infarction patients with asymptomatic or mildly symptomatic ventricular arrhythmias treated with the class IC antiarrhythmic drugs encainide (Enkaid) or flecainide (Tambocor) had a higher mortality rate than patients taking placebo (CAST, N Engl J Med, 321:406, 1989).

Cerebral arterial spasm frequently causes ischemic neurological damage after subarachnoid hemorrhage from a ruptured intracranial aneurysm. Nimodipine (Nimotop - Miles), a 1,4-dihydropyridine calcium-entry blocker, was recently approved by the US Food and Drug Administration (FDA) for oral treatment of such patients; an intravenous preparation is available only for investigational use.