Peripheral neuropathy stavudine causing

Zalcitabine therapy is associated with a dose-dependent peripheral neuropathy that can be treatment-limiting in 10-20% of patients but appears to be slowly reversible if treatment is stopped promptly. The potential for causing peripheral neuropathy constitutes a relative contraindication to use with other drugs that may cause neuropathy, including stavudine, didanosine, and isoniazid. Decreased renal clearance caused by amphotericin B, foscamet, and aminoglycosides may increase the risk of zalcitabine neuropathy. The other major reported toxicity is oral and esophageal... 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

In combination with other antiretroviral agents, stavudine has caused fatal lactic acidosis in some patients. It is also associated with motor weakness in which case it should be discontinued. Peripheral neuropathy is the most common toxicity associated with stavudine, which is more prevalent at high doses (4mg/kg per day). Neuropathy in these patients generally is associated with numbness, tingling or pain in feet or hands. Patients treated with the combination of stavudine and didanosine may also exhibit liver function abnormalities (hepatic steatosis) and pancreatitis. It may also be associated with the etiology of HIV lipodystrophy syndrome. 

VASODILATOR ANTIHYPERTENSIVES NNRTIs Risk of peripheral neuropathy when hydralazine is coadministered with didanosine, stavudine or zalcitabine Additive effect both drugs can cause peripheral neuropathy Warn patient to report early features of peripheral neuropathy if it occurs, the NNRTI should be stopped... 

Zalcitabine toxicides are similar to those of the other dideoxynucleotide analogs didanosine and stavudine. Severe peripheral neuropathy has been reported in up to 15% of patients. Pancreatitis occurs rarely with zalcitabine therapy, but coadministration of other drugs that cause pancreatitis should be avoided. One distinctive toxicity of zalcitabine is oral ulceration and stomatitis. An erythematous rash also is common but generally self-limited. The necessity of frequent administration, the risk of toxicides, and the inferior antiviral activity compared to more convenient agents limits the use of zalcitabine in the U.S. 

Stavudine (d4T) is a nucleoside reverse transcriptase inhibitor. While it has only minor hema-totoxic potential, the dmg is markedly neurotoxic, causing dose-limiting peripheral neuropathy. Resistance occurs via mutations in the pol gene, which encodes for several proteins including reverse transcriptase. The answer is (B). 

In vitro, stavudine had no significant effect on the intracellular activation ofzalcitabine. Both stavudine and zalcitabine have the potential to cause peripheral neuropathy and pancreatitis. Combined use of drugs causing these serious adverse effects should be closely monitored (see also NRTIs + Drugs that cause pancreatitis , p.797). US guidelines say that the combination of stavudine and zalcitabine should not be recommended at any time because of additive peripheral neuropathy. ... 

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