Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.
The combination of a calcium channelblocker with an angiotensin-convertingenzyme (ACE) inhibitor representspart of a trend in pharmacologictherapy: expecting that 2 agents willcomplement each other and representan improvement in patient adherenceto treatment.
Calcium channel blockers, such asamlodipine, appear to work well regardlessof patients? ethnic origin,although African Americans respond tocalcium channel blockers better thanto ACE inhibitors or beta-blockingdrugs.
Benazepril is an example of a prodrug,converted in the liver to its activeform, known as benazeprilat. In general,ACE inhibitors such as benazeprilcause vasodilation and then indirectlyinhibit the actions of aldosterone. Theeffect of this inhibition allows for a shiftin balance between angiotensin II andbradykinin, resulting in the reduction invascular tone, an increase in sodiumexcretion, and ultimately diuresis.
ACE inhibitors also are demonstratingbeneficial effects involving their localizedactions on various endocrine systems,with the inflammatory processes,and on the development of atherosclerosiswithin arterial walls. Although anACE inhibitor may not reverse existingplaque, it may still stabilize it, preventingits rupture and the ensuing complications.
Together, amlodipine and benazeprilare indicated for the treatment of casesof hypertension where single-agenttherapy has been proven ineffective.The once-daily generic capsule form ofNovartis? Lotrel is marketed by TevaPharmaceutical Industries Ltd.
Careful monitoring of blood pressureis important during treatment with thiscombination of an ACE inhibitor andcalcium channel blocker, especially duringinitial titration or later upwardadjustments in dose. Dosage adjustmentsshould be made at monthlyintervals. In addition, ACE inhibitors cancause renal impairment and a hepaticsyndrome that initially appears ascholestatic jaundice. Patients takingthis combination should be periodicallymonitored for elevations in renal orhepatic enzymes.
Alone, amlodipine (Norvasc, PfizerInc) has already been available as a single-entity generic drug for the treatmentof hypertension, as has benazepril(Lotensin, Novartis). This particular combinationis available in amlodipinestrengths of 2.5, 5, and 10 mg withbenazepril in either 10- or 20-mgstrengths.
With the potential for catastrophicconsequences of a subarachnoid hemorrhage,quick therapeutic response isessential. The principal goal of drugtreatment is to prevent delayedischemic effects associated with cerebralvasospasms that can result fromthe hemorrhage. Nimodipine, a calciumchannel blocker with preferentialcentral nervoussystemactivity, is usedto reduce theincidence andseverity of the ischemic events. Nimodipineis available as 30-mg capsulesfrom Caraco Pharmaceutical Laboratoriesand Barr Pharmaceuticals Inc.
The administration of nimodipine followinga diagnosis of subarachnoidhemorrhage should begin within 96hours. Dosing has been determined byspeculation and observation ratherthan through controlled clinical trials,given the nature of the condition. Whentreatment with nimodipine is startedwithin 72 to 96 hours at doses of 20 mgto 90 mg (generally 60 mg) every 4hours for 16 to 21 days, however, thereis a reduction in frequency and severityof documented ischemic episodes. OneBritish study did indicate that oralnimodipine can reduce ?poor outcomes?(a poor outcome being theeuphemism for death or a vegetativestate) by 40% and cerebral infarction by34%. A Canadian study noted a nonstatisticallysignificant increase in mortalitydespite the reduction in delayedischemic neurologic outcomes. The useof nimodipine following acute ischemicstroke is being examined, with someevidence suggesting a reduction inmortality.
Nimodipine is also showing variablesuccess in treatment of vascular migraineand cluster headache. Treatmentin these conditions is usually 120 mgdaily in divided doses and takes up to 4months for benefits to emerge. Otherstudies are exploring the use of nimodipinein chronic focal epilepsy and ageassociatedmemory loss secondary todementia or Alzheimer?s disease.