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“Awareness of the potential of medications to cause peripheral neuropathy is key to preventing significant nerve damage in treated patients.”

Peltier and Russell

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Objectives

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On completion of this chapter, the student/practitioner will be able to:

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  • Understand the common classes of medications that can induce neuropathy and the major pathophysiological mechanisms that are likely involved.

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Key Terms

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  • Apoptosis

  • Demyelination

  • Paresthesia

  • Peripheral neuropathy

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Introduction

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There are about 100 known causes of neuropathy.1 Medication-induced neuropathy accounts for about 4% of outpatient neurology cases.2 A representative list of drugs that can have neurotoxic effects is provided in Table 11-1.3 This chapter concentrates on chemotherapeutic agents (platinum drugs, taxanes, vinca alkaloids, thalidomide, bortezomib, suramin), leflunomide, statins, highly active antiretroviral therapy (HAART), antitumor necrosis factor alpha (anti-TNFα) drugs, and amiodarone.

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Mechanisms of Medication-Induced Neuropathy

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Neuropathy may be considered medication induced if it meets generally established criteria for associations, such as a temporal association (the onset of neuropathy coincides with the onset of medication use, stabilization or improvement of neuropathy when the drug is temporarily discontinued, and neuropathy resumes when medication is resumed), biological plausibility, absence of likely alternative explanations, and analogy (similar adverse effects occur with similar medications).56

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The underlying neuropathology typically involves three main processes that damage or destroy nerves: axonal degeneration, segmental demyelination, and neuronopathy.1 Medication-induced neuropathies often involve axonal degeneration, but any or all processes can occur concurrently.57 Symptoms can give insight into the type of nerve damage causing the neuropathy.58

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Spinal cord neurons are generally protected by the blood-brain barrier, whereas sensory, autonomic, and peripheral neurons are more vulnerable.3 The latter are supplied by capillaries with fenestrated walls, allowing relatively free exchange of small molecules with the circulatory system and extracellular fluid within ganglia.22 Medications can interfere with axonal transport (disrupting cell processes) or can damage the axon and the myelin sheath (Schwann cells). Anticancer agents that interfere with the increased mitochondrial activity that is typical of cancer cells likewise can interfere with mitochondrial activity of neurons and may lead to neuronopathy or death of the nerve cell.22 Ganglionopathy occurs when ganglia are damaged or die and results in sensory or autonomic symptoms.59

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Table Graphic Jump Location
Table 11-1Selected Drugs Associated With Medication-Induced Neuropathy

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