Cycloserine adverse effects

Cycloserine This orally effective tuberculostatic agent appears to antagonize the steps in bacterial cell wall synthesis involving D-alanine. It distributes well throughout body fluids, including the CSF. Cycloserine [sye kloe SER een] is metabolized, and both parent and metabolite are excreted in urine. Accumulation occurs with renal insufficiency. Adverse effects involve CNS disturbances epileptic seizure activity may be exacerbated. Peripheral neuropathies are also a problem. 

A report describes both an increase and a decrease in serum cycloserine levels in some subjects, which were apparently caused by isoniazid however, the mean level of cycloserine was not significantly changed. Only one out of 11 patients taking cycloserine alone developed adverse effects (drowsiness, dizziness, unstable gait), but when isoniazid was added, 9 of the 11 developed these effects. The manufacturers recommend monitor-... 

Nervous system The adverse effects of antituberculosis drugs on the nervous system have been reviewed [1 ]. Isoniazid is most often associated with nervous system reactions, most prominently peripheral neuropathy, psychosis, and seizures. Optic neuropathy can occur with ethambutol and ototoxicity and neuromuscular blockade with aminoglycosides. Cycloserine can cause psychosis and seizures, and the psychosis in particular limits its use. Fluoroquinolones are rare causes of seizures and delirium. Significant neurotoxicity has not been documented with newer forms of therapy under development. 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

The adverse CNS effects of cycloserine are increased by isoniazid. Dapsone + Clofozimine... 

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