Masson C, Boulu P, Hénin D
Clinique Neurologique, Hôpital Beaujon, Clichy.
Rev Med Interne. 1992 May-Jun;13(3):225-32. doi: 10.1016/s0248-8663(05)81333-5.
During the last few years the list of drugs capable of inducing a iatrogenic neuropathy has been considerably lengthened. Drug toxicity to peripheral nerves may be discovered at the experimental stage, but it is usually recognized after the drug has been launched on the market, hence the importance of pharmacovigilance. The responsibility of a drug for the occurrence of neuropathy may be difficult to prove, particularly when the drug is used in the treatment of a disease which, by itself, may be responsible for a lesion of the peripheral nervous system. Iatrogenic neuropathies are usually axonal, but some drugs produce a primary disorder in the myelin-Schwann cell couple. Schwann cell diseases may be induced by drugs, such as perhexiline maleate, amiodarone or chloroquine, which inhibit lysosomal enzyme activity. In such cases inclusions representing fat-loaded lysosomes can be detected in various tissues, and particularly in Schwann cells. In certain patients, notably those treated with gold salts, an immune mechanism might be responsible for neuropathy. Most drug-induced neuropathies are due to a primary lesion of the neuron which is more often an axonopathy than a neuronopathy. It is usually a retrograde distal axonopathy the occurrence of which is attributed to a disorder of the fast retrograde axonal flow. In a few cases, the finding of a biochemical mechanism perturbing the axonal flow may help in preventing the occurrence of a iatrogenic neuropathy.
在过去几年中,能够诱发医源性神经病变的药物清单已大幅延长。药物对周围神经的毒性可能在实验阶段就被发现,但通常是在药物上市后才被认识到,因此药物警戒十分重要。一种药物导致神经病变的责任可能难以证明,尤其是当该药物用于治疗一种其本身可能导致周围神经系统病变的疾病时。医源性神经病变通常是轴索性的,但有些药物会在髓鞘 - 施万细胞对中引发原发性疾病。施万细胞疾病可能由抑制溶酶体酶活性的药物诱发,如马来酸哌克昔林、胺碘酮或氯喹。在这种情况下,可在各种组织中检测到代表富含脂肪的溶酶体的包涵体,尤其是在施万细胞中。在某些患者中,特别是那些接受金盐治疗的患者,免疫机制可能是神经病变的原因。大多数药物性神经病变是由于神经元的原发性病变引起的,这种病变更多的是轴索性病变而非神经元病变。通常是逆行性远端轴索性病变,其发生归因于快速逆行轴浆运输的紊乱。在少数情况下,发现一种干扰轴浆运输的生化机制可能有助于预防医源性神经病变的发生。