Antiretroviral drugs are associated with a variety of adverse effects on the central and peripheral nervous systems. The frequency and severity of neuropsychiatric adverse events is highly variable, with differences between the antiretroviral classes and amongst the individual drugs in each class. In the developing world, where the nucleoside reverse transcriptase inhibitor (NRTI) stavudine remains a commonly prescribed antiretroviral, peripheral neuropathy is an important complication of treatment. Importantly, this clinical entity is often difficult to distinguish from human immunodeficiency virus (HIV)-induced peripheral neuropathy. Several clinical trials have addressed the efficacy of various agents in the treatment of NRTI-induced neurotoxicity. NRTI-induced neurotoxicity is caused by inhibition of mitochondrial DNA polymerase. This mechanism is also responsible for the mitochondrial myopathy and lactic acidosis that occur with zidovudine. NRTIs, particularly zidovudine and abacavir, may also cause central nervous system (CNS) manifestations, including mania and psychosis. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is perhaps the antiretroviral most commonly associated with CNS toxicity, causing insomnia, irritability and vivid dreams. Recent studies have suggested that the risk of developing these adverse effects is increased in patients with various cytochrome P450 2B6 alleles. Protease inhibitors cause perioral paraesthesias and may indirectly increase the relative risk of stroke by promoting atherogenesis. HIV integrase inhibitors, C-C chemokine receptor type 5 (CCR5) inhibitors and fusion inhibitors rarely cause neuropsychiatric manifestations.
Clinical and epidemiologic characteristics of disease associated with a newly described nonhalophilic Vibrio species, Vibrio mimicus, were identified by studying isolates from 21 patients referred to the Centers for Disease Control between 1977 and 1981. Two isolates were from the ears of patients with otitis who had recently been exposed to seawater. Nineteen isolates were from stool samples; these patients generally had diarrhea, nausea, vomiting, and abdominal cramps, with fever, headache, and bloody diarrhea occurring in fewer than half. Persons with diarrhea were more likely than age- and sex-matched controls to have eaten raw oysters (p = 0.013). Although most cases were sporadic, three were associated with a single outbreak. Only two isolates produced toxin found by enzyme-linked immunosorbent assay or the Y-1 adrenal cell assay for heat-labile toxin, and none produced heat-stable toxin found by the infant mouse assay. Vibrio mimicus should be considered in the differential diagnosis of acute gastroenteritis occurring after recent ingestion of seafood (especially raw oysters) and in acute otitis after exposure to seawater.
Nervous system toxicity with current antituberculosis pharmacotherapy is relatively uncommon, although the frequency of the usage of antituberculosis therapy requires that physicians be aware of such toxicity. Antituberculosis therapy manifests both central and peripheral nervous system effects, which may compromise patient compliance. Among the traditional forms of first-line antituberculosis therapy, isoniazid is most often associated with nervous system effects, most prominently peripheral neuropathy, psychosis and seizures. Adverse events are reported with other antituberculosis therapies, the most prominent being optic neuropathy with ethambutol and ototoxicity and neuromuscular blockade with aminoglycosides. The second-line agent with the most adverse effects is cycloserine, with psychosis and seizures, the psychosis in particular limiting its usage. Fluoroquinolones are rare causes of seizures and delirium. Newer forms of therapy are under development, but to date no significant neurotoxicity is documented with these agents. Future needs include the development of surveillance mechanisms to increase recognition of nervous system toxicities. It is also hoped that the development of new pharmacogenomic assays will help with the identification of patients at risk for these toxicities.
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