Peripheral neuropathy drug-related

Hydralazine may cause a dose-related, reversible lupus-like syndrome, which is more common in slow acetylators. Lupus-like reactions can usually be avoided by using total daily doses of less than 200 mg. Other hydralazine side effects include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it may be useful in patients with severe chronic kidney disease and in kidney failure. 

Neurologic symptoms Motor weakness has been reported rarely. Most of these cases occurred in the setting of lactic acidosis. The evolution of motor weakness may mimic the clinical presentation of Guillain-Barre syndrome (including respiratory failure). Symptoms may continue or worsen following discontinuation of therapy. Stavudine therapy has been associated with peripheral neuropathy, which can be severe and is dose-related. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, a history of neuropathy, or concurrent neurotoxic drug therapy, including didanosine (see Adverse Reactions). 

Peripheral neuropathy - Patients developing moderate discomfort with signs or symptoms of peripheral neuropathy should stop zalcitabine. Zalcitabine-associated peripheral neuropathy may continue to worsen despite interruption of therapy. Reintroduce the drug at 50% dose (0.375 mg every 8 hours) only if all findings related to peripheral neuropathy have improved to mild symptoms. Permanently discontinue the drug when patients experience severe discomfort related to peripheral neuropathy or moderate discomfort progresses. If other moderate to severe clinical adverse reactions or lab abnormalities (eg, increased liver function tests) occur, interrupt zalcitabine (or both zalcitabine and the other potential causative... 

CNS toxicity occurs because isoniazid has structural similarities to pyridoxine (vitamin Be) and can inhibit its actions. This toxicity is dose-related and more common in slow acetylators. Manifestations include peripheral neuropathy, optic neuritis, ataxia, psychosis and seizures. The administration of pyridoxine to patients receiving INH does not interfere with the tuberculostatic action of INH but it prevents and can even reverse neuritis. Hematological effects include anaemia which is also responsive to pyridoxine. In some 20% of patients antinuclear antibodies can be detected but only in a minority of these patients drug-induced lupus erythematosus becomes manifest. 

The principal toxicity of linezolid is hematologic—reversible and generally mild. Thrombocytopenia is the most common manifestation (seen in approximately 3% of treatment courses), particularly when the drug is administered for longer than 2 weeks. Anemia and neutropenia may also occur, most commonly in patients with a predisposition to or underlying bone marrow suppression. Cases of optic and peripheral neuropathy and lactic acidosis have been reported with prolonged courses of linezolid. These side effects are thought to be related to linezolid-induced inhibition of mitochondrial protein synthesis. 

Considerable neuromuscular involvement also occurs in patients with AIDS.47 100 Peripheral neuropathies, myopathies, and various CNS manifestations (dementia, other psychological manifestations) can occur directly from HIV infection or secondarily, due to some other opportunistic infection.31 85 100 Likewise, peripheral neuropathies are a common side effect of certain anti-HIV drugs (didanosine, stavudine, zal-citabine), and myopathies are a side effect of zidovudine therapy.63 Patients with HIV disease often have painful symptoms such as joint pain, back pain, and pain related to neuropathies and myopathies.100 Hence, HIV disease can often be regarded as a degenerative neuromuscular disorder from the standpoint of a rehabilitation professional. Therapists can therefore help improve function and decrease pain in patients with HIV infection and AIDS.1 33... 

The most significant impact of these drugs on rehabilitation is related to their side effects, especially those of the immunosuppressants. These drugs are typically used in high doses to produce immunosuppressive effects, which are often achieved at the expense of serious and toxic side effects. Many immunosuppressants, especially the glucocorticoids, exert catabolic effects on bone, muscle, and other tissues. Other immunosuppressants, such as cyclosporine and tacrolimus, are neurotoxic and may cause peripheral neuropathies and CNS-related problems in balance and posture. 

Although many other alkaloids have been isolated from C. roseus only vinblastine and vincristine have been developed for clinical use. The antiproliferative activity of the two compounds is related to their specific interaction with tubulin, thus preventing assembly of tubulin into microtubules and arresting cell division (59). However, despite this apparent identical mechanism of action and their clear chemical similarities, vinblastine and vincristine display very different clinical effects. Vinblastine, for example, is used to treat Hodgkin s disease and metastatic testicular tumors, whereas vincristine is used mainly in combination with other anticancer drugs for the treatment of acute lymphocyticleukemia in children. Toxicity profiles are also different, in that vinblastine causes bone-marrow depression, whereas peripheral neuropathy often proves to be dose-limiting in vincristine therapy. 

Peripheral neuropathy occurs with statins, and perhaps with all cholesterol-lowering drugs, and may be related to reduced production of ubiquinone, as suggested in a review (5). Moreover, it appears that once a statin produces a neuropathy, rechallenge with any other statin is likely to cause a recurrence. This is reported to occur 1-3 weeks after rechallenge, whereas the resolution takes 4—6 weeks after withdrawal (5). 

Irreversible retinopathy and ototoxicity can result from high daily doses (>250 mg) of chloro-quine or hydroxychloroquine that lead to cumulative total doses of more than 1 g of base per kilogram body weight, such as those used for treatment of diseases other than malaria. Retinopathy can be avoided if the daily dose is 50 mg. Prolonged therapy with high doses of 4-aminoquinoline also can cause toxic myopathy, cardiopathy, and peripheral neuropathy these reactions improve if the drug is withdrawn promptly. Rarely, neuropsychiatric disturbances, including suicide, may be related to overdose. 

The most serious toxicities with didanosine are peripheral neuropathy and pancreatitis, both due to mitochondrial toxicity. It should be avoided in patients with a history of pancreatitis or neuropathy and should not be coadministered with other drugs that can cause neuropathy. Diarrhea is reported more frequently with didanosine than with other nucleoside analogs, perhaps related to the antacid in the oral preparations. The buffering agents also can impair the bioavailability of other coadministered drugs. 

South African patients, of whom 141 were coinfected with HTV, 23 taking antiretroviral drugs [32 . Details of serious adverse events were ascertainable in 331 patients and occurred in 27% of HIV-infected and 13% of HIV-uninfected individuals. The excess was attributable to increase incidences of peripheral neuropathy (8.3% versus 1.9%) and persistent vomiting (13% and 3.3%). The occurrence of serious adverse events was not related to antiretroviral drug use, although median CD4 cell counts were lower in those with adverse effects (130 versus 259 X 10 /1). 

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