[Calcium inhibitors in the management of hypertensive patients on cyclosporine].
Cyclosporine (CsA) is an immunosuppressor widely used in all postoperative transplantation protocols. Nephrotoxicity and hypertension are the major secondary effects of cyclosporine. The CsA acts on two essential regulatory mechanisms of the blood pressure: the extracellular volume and the systemic vascular resistances. The incidence of hypertension in patients treated with CsA varies from 10% to 80% in the literature. In view of two main mechanismes implicated in CsA-induced hypertension the most logical therapeutic approach would be to use diuretics and calcium inhibitors. The major drawback of diuretic therapy is the risk of hyperuricaemia and attacks of gout, the predisposition to which is already increase by treatment with CsA. In addition, renal failure may rarely be observed. The calcium channel blockers are the drugs of choice in the treatment of CsA-induced hypertension. Not only are they effective in decreasing the blood pressure, but they also have a major advantage of having a nephroprotective effect against CsA. Cyclosporine is metabolised in the liver by cytochrome P450 3A4 dependant enzymes. Many pharmacological interferences have been described with this drug and other pharmacological agents. This type of interaction has been described with certain calcium inhibitors which inhibit hepatic and digestive degradation of cyclosporine and therefore increase its plasma concentrations. The choice of calcium inhibitors should be based on criteria of efficacy and tolerance and on the drug's pharmacokinetics. The interaction between cyclosporine and some calcium inhibitors exposes the patients to the risk of overdosage when treatments is instituted and of underdosage when the treatment is withdrawn.
Bagnis
C
C
Service de néphrologie, Groupe hospitalier Pitié-Salpêtrière, Paris.
Deray
G
G
D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D016572:Cyclosporine