Neuropathy caused toxicity

The major toxic effect of exposure to 2-hexanone is neuropathy. Neuropathy can be caused by both 2-hexanone and its metabolite 2,5-hexanedione. A reduction of the neuropathy caused by exposure to 2-hexanone could theoretically be achieved through shunting of metabolism to less toxic metabolites. However, as discussed above, the toxicity of those other metabolites, and the effect of the treatment on metabolism of other potential toxicants, would have to be clearly assessed. 

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also can cause toxic myopathy, cardiopathy, and peripheral neuropathy these reactions improve if the drug is withdrawn promptly.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. 

Meicuiy (quicksilver [CAS 7439-97-6]) Acute exposures to high vapor levels reported to cause toxic pneumonitis and pulmonary edema. Well absorbed by inhalation. Skin contact can produce irritation and sensitization dermatitis. Mercury salts but not metallic mercury are primarily toxic to the kidneys by acute ingestion. High acute or chronic overexposures can result in CNS toxicity (erythrism), chronic renal disease, brain injury, and peripheral neuropathies. Some inorganic mercury compounds have adverse ettects on total development in test animals. See also p 254. 

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). 

However, not all effects of NRTls on mitochondria can be explained by the DNA polymerase y hypothesis. Other mechanisms, either secondary to or independent of inhibition of DNA polymerase y are involved in NRTI toxicity (Moyle 2000a, 2000b Lewis et al. 2003). AZT is a potent inhibitor of mitochondrial DNA polymerase y but does not cause neuropathy in HIV patients (Dalakas 2001). Keswani and colleagues showed that NRTls caused direct mitochondrial toxicity through... 

Each category of chemotherapy drugs has similar side effects. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. 

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