Cardiac drugs Amiodarone, a drug used for treating recalcitrant ventricular tachyarrhythmias, induces a motor-sensory neuropathy in about 5 percent of patients after several months of treatment. It may also cause a toxic myopathy. Perhexiline maleate for the treatment of angina pectoris may also cause a generalized, predominantly sensory polyneuropathy in a small proportion of patients. Hydralazine as a neurotoxic agent has already been mentioned. Affected persons show a striking neuronal lipidosis. Patients taking niacin to lower blood cholesterol levels may experience distal and truncal paresthesias, and a somewhat controversial neuropathy has also been identified.
The development of a sensorimotor neuropathy similar to that produced by INH may be associated with the chronic use of disulfiram in the treatment of alcoholism. Its neurotoxic effects have been attributed to the action of carbon disulfide, which is produced during the metabolism of the drug, and is known to cause polyneuropathy and sometimes an optic neuropathy in workers in the viscose rayon industry. Pathologic data, although scant, tend to discredit this notion, insofar as disulfiram evokes a wallerian type of axonal degeneration, whereas carbon disulfide neuropathy is characterized by swollen (giant) axons that are filled with neurofilaments (Bouldin et al).
Some patients who have taken phenytoin for decades may lose ankle and patellar reflexes and acquire mild distal symmetrical impairment of sensation, slowed conduction velocity in the peripheral nerves of the legs and rarely, weakness of the distal musculature. The mechanism and frequency of this complication are not clear. The cholesterol-lowering statin drugs have been tentatively implicated in a painful, paresthetic distal axonal polyneuropathy with retained reflexes (Gaist et al) but the evidence for this association is not strong; sometimes a period off the drug or a change to an alternative agent is all that can be tried but it should not preclude a search for alternative causes. More often the problem with statins is one of a toxic myopathy. Colchicine has long been known to cause a myopathy, but a few cases of predominantly axonal sensory neuropathy have also been reported (neuromyopathy).
Among various other agents that cause neuropathy are hydroxychloroquine and colchicine are known to cause a toxic neuropathy. The anesthetic agent trichloroethylene, as with the aforementioned stilbamidine, has a predilection for cranial nerves, particularly the fifth. The neurotoxicity is apparently caused by dichloroacetylene, formed as a product of trichloroethylene. The neuropathic potential of nitrous oxide has already been mentioned. Most of the group of tumor necrosis factor-alpha (TNF-α) inhibitors may cause a polyneuropathy, including small-fiber neuropathy, but this category of agents do not appear to have a direct toxic effect on nerves but instead alter immune function in some way that results in a process that simulates chronic inflammatory demyelinating polyneuropathy (see further on).
Residual effects of polyneuropathy were seen in patients with the toxic eosinophilia-myalgia syndrome; the problem was traced to the ingestion of adulterated l-tryptophan, which had been used in nonprescription drugs for insomnia. One patient under our care suffered permanent areflexic quadriplegia. There may be an eosinophilic infiltrate in nerves, but the neuropathy is probably the result of a direct toxic mechanism. A sensory neuropathy, resulting from excessive pyridoxine ingestion alluded to earlier, is still seen among individuals who take huge doses of vitamin supplements. Amitriptyline is capable of producing paresthesias, but the effect seems to be idiosyncratic and infrequent.