Berchtold P, Seitz M
Departement Innere Medizin; Inselspital, Bern.
Schweiz Med Wochenschr. 1996 Sep 21;126(38):1603-9.
The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
大多数免疫抑制剂的治疗效果是非特异性的，因此常常受到病毒、细菌或真菌性生物体感染风险增加以及恶性肿瘤发病率上升的限制。本简短综述涵盖了最常用的免疫抑制剂，如皮质类固醇、硫唑嘌呤、甲氨蝶呤、环磷酰胺和环孢素。长期使用皮质类固醇治疗最常见的风险是库欣样改变、糖耐量降低以及通常为良性的类固醇糖尿病。同样具有临床重要性的是骨质疏松症，因为必要时可通过体育锻炼、补充钙剂和维生素D治疗来预防。尽管尚无证据表明类固醇治疗期间消化性溃疡风险显著增加，但患者在接受皮质类固醇治疗时可能会出现胃肠道出血甚至穿孔，且不产生疼痛。盐皮质激素效应，如钠水潴留，仅在氢化可的松和泼尼松中可见，而对于地塞米松等合成类固醇，尽管其具有强大的抗炎活性，但不存在钠潴留。细胞毒性药物硫唑嘌呤、甲氨蝶呤和环磷酰胺最重要的副作用是骨髓抑制。由于中性粒细胞更新率高，患者最常出现中性粒细胞减少，而非血小板减少或贫血。中性粒细胞减少以及体液和细胞免疫机制受损，是免疫抑制治疗期间对细菌、病毒或寄生虫疾病易感性增加的原因。接受硫唑嘌呤（胆汁淤积性肝炎）和甲氨蝶呤（AST水平升高，很少出现肝纤维化或肝硬化）治疗的患者中曾有肝毒性报道。环磷酰胺在相当一部分患者中会导致出血性膀胱炎，以及尿路上皮肿瘤发病率增加。这两种副作用均可通过美司钠预防。环孢素最重要的副作用是急性和慢性肾毒性，通常与药物血浆水平显著升高有关。必须牢记，接受环孢素和酮康唑联合治疗的患者可能会发生严重肾毒性，因为后者可能会不适当地提高血浆环孢素水平。
