Drug induced peripheral neuropathy

- The most common pathological process in drug-induced neuropathies is axonal degeneration

- Peripheral neuropathies usually present sensory symptoms prior to progressing to motor disorders. And, most drugs associated with the condition cause either solely sensory neuropathies or mixed sensorimotor ones.

- Drug-induced peripheral neuropathies generally cause pain, burning, tingling, itching or other abnormal sensations. Muscular weakness may also occur , most commonly occur in the hands and feet.

Drugs groups include : Antimicrobials : Isoniazid , Ethambutol , Ethionamide , Nitrofurantoin , Metronidazole , Ciprofloxacin .. HIV Drugs : Amprenavir, didanosine, stavudine, zalcitabine and zidovudine Antineoplastic agents : - Vinca alkaloidssometimes used in chemotherapy, are particularly neurotoxic. Other cytotoxic drugs can cause peripheral neuropathies, but are less neurotoxic- oncolytic drugs : cisplatin, suramin, paclitaxel, chlorambucil, altretamine, carboplatin, cytarabine, docetaxel, dacarbazine, etoposide, ifosfamide with mesna, fludarabine, tamoxifen, teniposide, and thioguanine. Cardiovascular drugs- the coronary vasodilator perhexiline a prophylactic antianginal agent

that can cause segmental demyelination.- Other cardiovascular drugs :Hydrallazine , Amiodarone , Disopyramide ( demyelinating neuropathy ), Clofibrate

Hypnotics and psychotropics : Methaqualone is especially neurotoxic. AntirheumaticsGold (Aurolate) , Indomethacin , Chloroquine Anticonvulsants : Phenytoin is especially neurotoxic. Others : o Disulfiram is an alcohol deterrent often used by people in the early stages of recovery from alcoholism. The drug blocks normal alcohol metabolism, causing stomach upset and vomiting if alcohol is consumed. Peripheral neuropathy is a possible side effect of disulfiram. o Calcium carbimide (Temposil)o Dapsone (Aczone) : prolonged use used to treat skin disorders including leprosy, dermatitis herpetiformis and severe acne. It causes an almost exclusively motor neuropathy.

Alcoholic neuropathy

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The development of peripheral neuropathy, is a risk for persons who have consumed large quantities of alcoholic beverages over an extended period of time.

studies estimated that neuropathy is present in 25-66% of defined "chronic alcoholics."

The distribution and severity the disease depends on regional dietary habits, individual drinking habits, as well as an individual’s genetics.

alcoholic polyneuropathy has a high incidence in women , within the elderly population and in alcoholic patients whose parents had a history of alcoholism.

Certain genetic predisposition for some alcoholics in certain ethnic groups ( Southeast and East Asians ) which results in a failure to quickly metabolize acetaldehyde which increase the frequency of alcoholic polyneuropathy.

Alcoholic neuropathy is a primary axonal sensorimotor peripheral polyneuropathy characterized by wallerian degeneration of the axons and a reduction in the myelination of neural fibers

- Directly neurotoxic effect on spinal cord and neuronal organelles , acetaldehyde , a metabolite of ethanol, has a direct neurotoxic effect. Ethanol also impairs axonal transport and disturbs cytoskeletal properties.

- Indirect effect : nutritional deficiencies Alcoholics have disturbed social life , irregular lifestyle ,

imbalance diet Alcoholism may also result in loss of appetite, alcoholic

gastritis, vomiting, decrease food intake. Alcohol abuse damages the lining of the gastrointestinal

system and reduces absorption of nutrients that are taken lead to nutritional & vitamin deficiency

o most often thiamine deficiency disturb glycolysis prevent neurons from maintaining necessary (ATP) levels impaired nerve conduction

o Normal products of the liver, such as lipoic acid, may be deficient in alcoholics disrupt glycolysis and alter metabolism, transport, storage, and activation of essential nutrients

Symptoms : sensorimotor symptoms- An early warning sign : weight loss - Varies in severity : can be asymptomatic whereas the

most severe cases may result in profound physical disability

- Most of the cases : Gradual insidious and prolonged onset , rarely rapidly progressive onset

- symmetrical pattern, stocking-and-glove pattern of sensory disturbances , retrograde degeneration

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