How can medications cause neuropathy?

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How can medications cause neuropathy?

Medications can cause neuropathy through a variety of mechanisms that lead to damage or dysfunction of the peripheral nerves. This condition, known as drug-induced peripheral neuropathy, can arise due to direct toxicity to the nerves, nutrient deficiencies caused by the drug, or interference with metabolic processes essential for nerve function.

Mechanisms by Which Medications Cause Neuropathy:

Direct Neurotoxicity: Some drugs can directly damage the nerve fibers (axons) or their protective coverings (myelin), leading to dysfunction in nerve signaling. This damage results in symptoms like pain, numbness, tingling, and muscle weakness. Drugs that commonly cause direct neurotoxicity include:
- Chemotherapy drugs: Certain cancer treatments, such as platinum-based agents (cisplatin, carboplatin), taxanes (paclitaxel), and vinca alkaloids (vincristine), are notorious for causing neuropathy. These drugs are toxic to rapidly dividing cells, including nerve cells, leading to peripheral neuropathy.
- Antiretroviral drugs: Used to treat HIV/AIDS, medications such as stavudine and didanosine can cause peripheral neuropathy by directly damaging nerve cells.
- Amiodarone: A medication used to control abnormal heart rhythms, which can induce neuropathy through long-term exposure.
Oxidative Stress: Certain drugs can increase oxidative stress within nerve cells, which leads to cellular damage and disrupts the normal function of the nerves. This oxidative damage can contribute to the development of neuropathy.
- Chemotherapy agents: Many chemotherapy drugs increase oxidative stress, which not only affects cancer cells but also damages peripheral nerves.
- Antibiotics: Some antibiotics, particularly fluoroquinolones (e.g., ciprofloxacin), can cause oxidative stress in nerve tissues, leading to sensory and motor neuropathy.
Nutritional Deficiencies: Some medications interfere with the absorption or metabolism of essential nutrients required for nerve health, particularly certain B vitamins. Nerve cells rely on a proper supply of these nutrients to maintain their function, and deficiencies can lead to nerve damage.
- Metformin: Used to manage diabetes, long-term use of metformin can cause vitamin B12 deficiency, which is essential for nerve function. A deficiency in B12 can lead to peripheral neuropathy.
- Isoniazid: A medication used to treat tuberculosis, isoniazid can cause a deficiency in pyridoxine (vitamin B6), leading to neuropathy if not supplemented appropriately.
- Alcohol: Though not a “medication” in the traditional sense, chronic alcohol use can cause significant nutrient deficiencies, especially of vitamins B1 (thiamine) and B12, which are crucial for nerve health.
Mitochondrial Dysfunction: Some drugs impair the function of mitochondria, the energy-producing structures within cells. Since peripheral nerves have high energy demands, disruptions in mitochondrial function can lead to nerve damage.
- Antiretroviral drugs: Some HIV medications can cause mitochondrial toxicity, leading to peripheral neuropathy.
- Chemotherapy agents: Certain chemotherapy drugs may affect mitochondrial function in peripheral nerves.
Impaired Nerve Repair Mechanisms: Certain medications can hinder the body’s ability to repair damaged nerves. This is particularly problematic for peripheral nerves, which are more susceptible to injury due to their length and exposure to external stressors.
- Colchicine: Used for gout treatment, colchicine can interfere with microtubule formation, which is critical for transporting nutrients and other molecules within nerve cells, leading to neuropathy.
- Phenytoin: An anticonvulsant used to manage seizures, long-term use of phenytoin can impair nerve repair, contributing to peripheral neuropathy in some individuals.
Immune-Mediated Neuropathy: Some medications can trigger an immune response that mistakenly attacks peripheral nerves, leading to neuropathy. This is often referred to as drug-induced autoimmune neuropathy.
- Immune checkpoint inhibitors: Used in cancer immunotherapy, drugs like nivolumab or pembrolizumab can cause autoimmune neuropathy by triggering an immune response against peripheral nerves.

Common Medications That Can Cause Neuropathy:

Chemotherapy Drugs:
- Platinum compounds: Cisplatin, carboplatin, and oxaliplatin.
- Taxanes: Paclitaxel, docetaxel.
- Vinca alkaloids: Vincristine, vinblastine.
Antibiotics:
- Fluoroquinolones: Ciprofloxacin, levofloxacin.
- Nitrofurantoin: Used to treat urinary tract infections, which can cause peripheral neuropathy, especially with long-term use.
Antiretroviral Drugs:
- Stavudine and didanosine (HIV medications) are known for their potential to cause nerve damage.
Anticonvulsants:
- Phenytoin: An older anticonvulsant that can cause neuropathy with chronic use.
Cardiovascular Drugs:
- Amiodarone: Used for arrhythmias, can cause neuropathy, particularly in patients on long-term treatment.
Statins:
- Though rare, some patients taking statins (used to lower cholesterol) may develop peripheral neuropathy.
Alcohol:
- Chronic alcohol consumption can cause alcoholic neuropathy, leading to nerve damage due to both direct toxicity and nutrient deficiencies (especially B vitamins).

Management of Drug-Induced Neuropathy:

Discontinuing the Medication: The first step in managing drug-induced neuropathy is often stopping or reducing the dosage of the offending drug if possible. In cases where this is not possible, close monitoring is required.
Symptom Management:
- Medications: Pain associated with neuropathy can be managed with drugs such as gabapentin, pregabalin, or duloxetine.
- Topical treatments: Capsaicin cream or lidocaine patches may help with localized nerve pain.
Nutritional Support: For medications that cause neuropathy through nutrient deficiencies, supplementation with vitamins (especially B12, B6, and folate) can be helpful.
Physical Therapy: To improve balance, strength, and mobility in patients with neuropathy.
Prevention: Regular monitoring of nerve function during treatment with high-risk medications can help detect neuropathy early. For example, doctors may periodically check vitamin levels in patients on medications like metformin or isoniazid.

In summary, medications can cause neuropathy through various mechanisms, including direct neurotoxicity, mitochondrial damage, nutrient deficiencies, and immune responses. Early detection and intervention are critical to preventing irreversible nerve damage.

Jodi Knapp