Alpha- and beta-blocking drugs are used in the treatment of hypertension, and when 1 drug can combine the receptor blockade, it should be expected to enhance therapeutic outcomes. Carvedilol, a nonselective beta-blocker with selective alpha-1 blocking actions, appears to offer better results than agents possessing only 1 variety of receptor-blocking activity. Carvedilol is available in 3.125-, 6.25-, 12.5-, and 25- mg tablet strengths from Apotex Inc, Caraco Pharmaceutical Laboratories, and Mylan Laboratories.
The beneficial actions for beta-blockers in congestive heart failure are based on theoretical action, suggesting a decrease of sympathetic outflow at the cardiac level or an alteration in renin release. The additional effect of alpha-1 blockade with carvedilol results in general peripheral arterial and venous dilation, with the effects on standing blood pressure being the most pronounced.
In general, beta-blockers are indicated for the treatment of hypertension, angina, and heart failure. Although carvedilol can be used as monotherapy, it is usually employed in conjunction with other drug management options (digoxin, thiazides, angiotensin- converting enzyme [ACE] inhibitors) to increase patient survival and reduce the frequency of hospitalization.
The nonselectivity of the beta-blocking effect of carvedilol means that bronchial asthma is a specific contraindication to its use, with deaths reported following even a single dose. It also is not recommended in the presence of hepatic impairment or among the elderly.
The additive hypoglycemic effects associated with beta-blockers generally require additional care among diabetic patients.
Dosing for hypertension starts at 6.25 mg twice daily, with an upper limit of 25 mg twice daily. For congestive heart failure, the dose is 3.125 mg twice daily, gradually titrating to response or to a maximum of 6.25 mg twice daily. Oral dosing is little affected by food. In polytherapy, however, carvedilol should be administered 2 hours prior to an ACE inhibitor to reduce orthostatic hypotension and other symptoms of general vasodilation. In addition, cessation of therapy should be done gradually to prevent rebound pressor effects.
Among patients hospitalized with congestive heart failure or left ventricular cardiac dysfunction, discharge use of drugs with beta-blocking effects has shown a significant reduction in mortality.
Extended-release verapamil (PM) is available in capsule form in 100-, 200-, and 300-mg strengths from Mylan Laboratories. Indications for verapamil include the management of Prinzmetal-variant, unstable, or chronic stable angina; hypertension; and to control ventricular rates at rest or with concurrent atrial fibrillation. It also is used to prevent the recurrence of paroxysmal supraventricular tachycardia.
The effect of calcium channel blockers such as verapamil on cardiac conduction can create serious adverse effects, and while the frequency is under 2% overall, they can range from asymptomatic firstdegree atrioventricular block to serious third-degree block. Other adverse effects from oral administration are seen in over 6% of users, requiring a reduction in dose. The severity of the side effects increases with concurrent use of betablockers or digoxin. In some cases, the negative inotropic effects associated with verapamil can actually cause congestive heart failure or pulmonary edema. The most common complaint from patients regarding verapamil is constipation.
To treat hypertension with the extended- release capsule version of verapamil (PM), the usual adult dose is 200 mg at bedtime, with upward titration to a maximum of 400 mg at bedtime. Blood pressure measurements should be carefully monitored.
The strong protein binding affinity for verapamil implies that other drugs (eg, aspirin, phenytoin, warfarin) could disrupt stabilized blood levels. Dosing with beta-blockers and digoxin requires careful monitoring to prevent toxicity and excessive hypotension.
Verapamil requires a reduced dose among the elderly and should be used cautiously with hepatic or renal impairment. Verapamil also may both prolong the effect of alcohol and increase blood concentrations by up to 17%. Although verapamil should be taken with food, grapefruit poses a potential interaction and should be avoided during this therapy.
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