Dual calcium-channel blocker therapy in the treatment of hypertension.
OBJECTIVE
To review the in vitro receptor binding data of calcium-channel blockers (CCBs) and in vivo studies in humans regarding the use of dual calcium-channel blocker therapy, with a focus on the use of this therapy for hypertension.


METHODS
A MEDLINE search was conducted to identify literature pertaining to CCBs.


METHODS
In vitro studies and investigations that evaluated CCB receptor binding and the interactions between subclasses of CCBs were chosen. All studies in humans and clinical trials that evaluated the use of dual CCB therapy in the treatment of cardiovascular diseases were selected for review. Also, case reports describing the use of dual CCB therapy were included in this article.


METHODS
The methodology, results, and conclusions of the selected data were evaluated. Data regarding the in vitro receptor binding kinetics of CCBs, as well as interactions, were reported. Because there is limited information on dual CCB therapy for hypertension, clinical studies using this treatment for ischemic heart disease were also reviewed. They were summarized and compared on the basis of the degree of disease control (e.g., blood pressure, exercise tolerance), adverse effects, and other clinical endpoints of pharmacologic therapy.


RESULTS
In vitro studies have identified binding sites for the dihydropyridine (nifedipine), diphenylalkylamine (verapamil), and benzothiazepine (diltiazem) subclasses of CCBs, and indicate that they are allosterically related to each other within the voltage-sensitive calcium-channel receptor. Dihydropyridine binding affinity is decreased with concomitant verapamil binding, but is enhanced by concomitant diltiazem binding. Dual CCB therapy has been shown to be efficacious in patients with ischemic heart disease. Although this therapy is limited by dose-related adverse effects, it appears to have an important role in patients with ischemia that is refractory to conventional therapy, or for those whose therapeutic options are limited by contraindications. Theoretically, many patients with hypertension may benefit similarly from dual CCB therapy. Because data evaluating this treatment option are sparse, recommendations regarding safety, efficacy, and the role of dual CCB therapy for hypertension would be premature.


CONCLUSIONS
Controlled data evaluating dual CCB therapy for the treatment of hypertension are lacking. This treatment modality may be beneficial in the future, but requires further investigation to determine safety and efficacy.
Saseen
J J
JJ
Department of Pharmacy Practice, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Carter
B L
BL
D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D015220:Calcium Channels / Q000378:metabolism; D002986:Clinical Trials as Topic; D004110:Diltiazem / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D015736:Felodipine / Q000008:administration & dosage; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000188:drug therapy; D009543:Nifedipine / Q000008:administration & dosage; D011955:Receptors, Drug / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011955:Receptors, Drug; D004110:Diltiazem; D009543:Nifedipine; D015736:Felodipine