Bagnis C, Deray G
Service de néphrologie, Groupe hospitalier Pitié-Salpêtrière, Paris.
Arch Mal Coeur Vaiss. 1998 Apr;91(4):411-4.
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exposes the patients to the risk of overdosage when treatments is instituted and of underdosage when the treatment is withdrawn.
环孢素（CsA）是一种广泛应用于所有术后移植方案的免疫抑制剂。肾毒性和高血压是环孢素的主要副作用。环孢素作用于血压的两个重要调节机制：细胞外液量和全身血管阻力。文献中环孢素治疗患者的高血压发生率在10%至80%之间。鉴于环孢素所致高血压涉及的两个主要机制，最合理的治疗方法是使用利尿剂和钙拮抗剂。利尿剂治疗的主要缺点是高尿酸血症和痛风发作的风险，而环孢素治疗已经增加了这种易感性。此外，很少会观察到肾衰竭。钙通道阻滞剂是治疗环孢素所致高血压的首选药物。它们不仅能有效降低血压，而且还有一个主要优点，即对环孢素有肾保护作用。环孢素在肝脏中由细胞色素P450 3A4依赖性酶代谢。已经描述了这种药物与其他药物之间的许多药物相互作用。已经描述了某些钙拮抗剂与环孢素之间的这种相互作用，这些钙拮抗剂会抑制环孢素的肝脏和消化道降解，从而增加其血浆浓度。钙拮抗剂的选择应基于疗效和耐受性标准以及药物的药代动力学。环孢素与某些钙拮抗剂之间的相互作用使患者在开始治疗时面临过量风险，而在停药时面临剂量不足风险。
