Günzler V
Division of Pharmaceutical Research, Hoechst AG, Frankfurt, Federal Republic of Germany.
Drug Saf. 1992 Mar-Apr;7(2):116-34. doi: 10.2165/00002018-199207020-00004.
The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects. The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy. This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity. The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients. This article reviews the most important chemical and pharmacokinetic properties of thalidomide. The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed. Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded. Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy. Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups. Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age. Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded. Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy. In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy.
镇静剂沙利度胺30年前因其致畸和神经毒性不良反应而退出市场。该化合物后来被发现对麻风结节性红斑(瘤型麻风的一种并发症)有极其显著的疗效。这种作用可能是由于对免疫系统的直接影响,因为沙利度胺没有抗菌活性。该化合物目前作为一种实验性药物用于治疗多种具有自身免疫特征的疾病,包括人类免疫缺陷病毒(HIV)患者中由非病毒和非真菌引起的复发性口疮。本文综述了沙利度胺最重要的化学和药代动力学特性。讨论了沙利度胺非镇静作用的可能机制及其在HIV患者中使用的安全性。由于沙利度胺免疫调节作用的机制尚不清楚,不能排除使用该化合物会加速HIV患者免疫状态恶化的可能性。临床证据表明,沙利度胺可能会使已有周围神经病变的患者病情加重。HIV患者对沙利度胺的过敏反应可能比其他患者群体更频繁。由于沙利度胺具有致畸活性,必须为育龄女性患者提供可靠的避孕措施。在对患有口腔溃疡的HIV患者开始使用沙利度胺治疗之前,应排除病变的真菌或病毒起源。沙利度胺不应用于已有HIV相关周围多发性神经病、多发性神经根病或脑病的患者。对于完全缓解的患者,停止沙利度胺治疗并在复发时重新使用比维持治疗更可取。