SUPPLEMENTATION OF IMMUNOSUPPRESSIVE REGIMENS WITH CALCIUM-CHANNEL BLOCKERS - RATIONALE AND CLINICAL EFFICACY

Calcium channel blockers (calcium antagonists) are a diverse group of drugs that are currently approved for the treatment of hypertension an d angina pectoris. They share a similar activity, despite their dissim ilar chemical structures: attenuation of the cellular influx of calciu m. Since the transmembrane flux of calcium is a common signalling syst em for cellular biochemical processes, calcium antagonists may influen ce numerous cellular functions. Many of these physiological processes are important in mediating responses to vasoconstrictor substances, su ch as may be involved in cyclosporin-mediated hypertension, nephrotoxi city and delayed graft function. Calcium antagonists are clinically us eful in cyclosporin-treated organ transplant recipients for the follow ing reasons: (a) they reduce the incidence of delayed graft function a nd may serve to allow cyclosporin induction therapy, thus avoiding the use of antibody induction therapy in the immediate perioperative peri od; (b) they reduce cyclosporin-induced intrarenal vasoconstriction an d may reduce the incidence of chronic cyclosporin-induced renal dysfun ction; (c) they are the preferred antihypertensive agents in cyclospor in-treated sodium-sensitive patients. It is possible, although less li kely, that calcium antagonists also: (a) exert additive immunosuppress ive effects with cyclosporin, and (b) attenuate atherosclerosis and/or chronic vascular rejection.