Polyneuropathies: When drugs damage nerves
The skin senses its surroundings. People with peripheral polyneuropathy often experience discomfort—or even no sensation at all. / © Adobe Stock/contadora1999
Hardly any other neurological condition is as diverse as polyneuropathy (PNP). Occasionally referred to as "peripheral polyneuropathy" or simply "peripheral neuropathy," it encompasses numerous etiologies, courses, and symptoms. A subgroup is drug-induced polyneuropathies, which can be caused by a wide variety of substance classes.
Polyneuropathies are generally characterized by the simultaneous damage of multiple nerves in different parts of the body, unlike mononeuropathy, in which only a single nerve is affected. Peripheral nerves lie outside the brain and spinal cord. A distinction is made between motor, sensory, and autonomic nerves (1–3).
Polyneuropathy can manifest itself very differently depending on which nerve fibers are affected. Typical symptoms include burning or stabbing pain, tingling, numbness, muscle weakness, and impaired temperature and pain perception. These symptoms make everyday activities difficult and increase the risk of falls. The symptoms are often particularly severe at night.
Since injuries or burns can go unnoticed due to impaired perception, the risk of infection increases, especially in areas of the body with poor circulation, such as the feet and lower legs. If the autonomic nervous system is affected, digestion, circulation, or bladder can also become disrupted.
The diverse and non-specific symptoms can be reminiscent of other diseases such as fibromyalgia or multiple sclerosis, so a careful differential diagnosis is important (1, 4).
Drug-induced polyneuropathies (DIPN) occur particularly frequently with certain chemotherapy drugs, but can also be triggered by some anti-infectives, cardiovascular medications, or immunosuppressants. When making a diagnosis, the physician will rule out other causes of nerve damage, such as diabetes, alcohol consumption, vitamin deficiencies, or immune disorders. It should be noted that various causes can overlap—especially in multimorbid patients.
The frequency of side effects varies with individual drugs. For example, some chemotherapeutic agents such as cisplatin, taxanes, or bortezomib are frequently associated with neuropathic side effects, while other drugs such as statins rarely cause neuropathic symptoms but are prescribed significantly more frequently (Table 1).
| Drug class | Examples |
|---|---|
| Anti-infectives | Quinolones, chloroquine, dapsone, ethambutol, isoniazid, linezolid, metronidazole, nitrofurantoin |
| antiviral therapy | Nucleoside analogues |
| Antirheumatics and immunosuppressants | Chloroquine, cyclosporine, tacrolimus, TNF-α inhibitors |
| targeted cancer therapies | BRAF/MEK inhibitors, immune checkpoint inhibitors |
| Chemotherapeutics | Bortezomib, platinum (oxaliplatin, cisplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine, vinblastine, vinorelbine) |
| cardiovascular medications | Amiodarone, propafenone, statins |
| other active ingredients | Lithium, phenytoin, overdose of pyridoxine (vitamin B6), thalidomide |
| Environmental toxins | Acrylamide, arsenic, lead, diethylene glycol, organophosphate compounds, mercury, carbon disulfide, thallium |
Table 1: Drugs with neuropathic potential (1, 2)
The risk of polyneuropathy increases in the presence of additional risk factors such as existing polyneuropathy, diabetes mellitus, or a genetic predisposition (3). Symptoms usually appear with a delay of weeks to months, as the side effect is dose-dependent and requires an accumulation of the neurotoxic drugs in the blood.
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