Amlodipine Besylate and Benazepril Hydrochloride

The combination of a calcium channel blocker with an angiotensin-converting enzyme (ACE) inhibitor represents part of a trend in pharmacologic therapy: expecting that 2 agents will complement each other and represent an improvement in patient adherence to treatment.

Calcium channel blockers, such as amlodipine, appear to work well regardless of patients? ethnic origin, although African Americans respond to calcium channel blockers better than to ACE inhibitors or beta-blocking drugs.

Benazepril is an example of a prodrug, converted in the liver to its active form, known as benazeprilat. In general, ACE inhibitors such as benazepril cause vasodilation and then indirectly inhibit the actions of aldosterone. The effect of this inhibition allows for a shift in balance between angiotensin II and bradykinin, resulting in the reduction in vascular tone, an increase in sodium excretion, and ultimately diuresis.

ACE inhibitors also are demonstrating beneficial effects involving their localized actions on various endocrine systems, with the inflammatory processes, and on the development of atherosclerosis within arterial walls. Although an ACE inhibitor may not reverse existing plaque, it may still stabilize it, preventing its rupture and the ensuing complications.

Together, amlodipine and benazepril are indicated for the treatment of cases of hypertension where single-agent therapy has been proven ineffective. The once-daily generic capsule form of Novartis? Lotrel is marketed by Teva Pharmaceutical Industries Ltd.

Careful monitoring of blood pressure is important during treatment with this combination of an ACE inhibitor and calcium channel blocker, especially during initial titration or later upward adjustments in dose. Dosage adjustments should be made at monthly intervals. In addition, ACE inhibitors can cause renal impairment and a hepatic syndrome that initially appears as cholestatic jaundice. Patients taking this combination should be periodically monitored for elevations in renal or hepatic enzymes.

Alone, amlodipine (Norvasc, Pfizer Inc) has already been available as a single- entity generic drug for the treatment of hypertension, as has benazepril (Lotensin, Novartis). This particular combination is available in amlodipine strengths of 2.5, 5, and 10 mg with benazepril in either 10- or 20-mg strengths.

Nimodipine

With the potential for catastrophic consequences of a subarachnoid hemorrhage, quick therapeutic response is essential. The principal goal of drug treatment is to prevent delayed ischemic effects associated with cerebral vasospasms that can result from the hemorrhage. Nimodipine, a calcium channel blocker with preferential central nervous system activity, is used to reduce the incidence and severity of the ischemic events. Nimodipine is available as 30-mg capsules from Caraco Pharmaceutical Laboratories and Barr Pharmaceuticals Inc.

The administration of nimodipine following a diagnosis of subarachnoid hemorrhage should begin within 96 hours. Dosing has been determined by speculation and observation rather than through controlled clinical trials, given the nature of the condition. When treatment with nimodipine is started within 72 to 96 hours at doses of 20 mg to 90 mg (generally 60 mg) every 4 hours for 16 to 21 days, however, there is a reduction in frequency and severity of documented ischemic episodes. One British study did indicate that oral nimodipine can reduce ?poor outcomes? (a poor outcome being the euphemism for death or a vegetative state) by 40% and cerebral infarction by 34%. A Canadian study noted a nonstatistically significant increase in mortality despite the reduction in delayed ischemic neurologic outcomes. The use of nimodipine following acute ischemic stroke is being examined, with some evidence suggesting a reduction in mortality.

Nimodipine is also showing variable success in treatment of vascular migraine and cluster headache. Treatment in these conditions is usually 120 mg daily in divided doses and takes up to 4 months for benefits to emerge. Other studies are exploring the use of nimodipine in chronic focal epilepsy and ageassociated memory loss secondary to dementia or Alzheimer?s disease.