Cycloserine (seromycin) is a broad-spectrum antibiotic that is used with other drugs in the treatment of tuberculosis when primary agents have failed. Cycloserine is d-4-amino-3-isoxazolidone.
Cycloserine inhibits M. tuberculosis in concentrations of 5—20 mg/mL in vitro. There is no cross-resistance between cycloserine and other tuberculostatic agents.
mechanism of action
Cycloserine and d-Ala are structural analogs; thus, cycloserine inhibits reactions in which d-Ala is involved in bacterial cell-wall synthesis.
absorption, distribution, and excretion
When given orally, 70—90% of cycloserine is rapidly absorbed. Cycloserine is distributed throughout body fluids and tissues. CSF concentrations are comparable to those in plasma. About 50% of a parenteral dose of cycloserine is excreted unchanged in the urine in the first 12 hours; a total of 65% is recoverable in the active form over a period of 72 hours. Very little of the antibiotic is metabolized. The drug may reach toxic concentrations in patients with renal insufficiency; it is removed from the circulation by hemodialysis.
Cycloserine is used only when retreatment is necessary or microorganisms are resistant to other drugs. It must be given together with other effective agents. The usual dose for adults is 250—500 mg twice daily.
Side effects typically affect the CNS, appearing within 2 weeks of therapy and disappearing after drug withdrawal. They include: somnolence, headache, tremor, dysarthria, vertigo, confusion, nervousness, irritability, psychotic states, paranoid reactions, catatonic reactions, twitching, ankle clonus, hyperreflexia, visual disturbances, paresis, and seizures. Large doses or concomitant ingestion of alcohol increases the risk of seizures. Cycloserine is contraindicated in individuals with a history of epilepsy and should be used with caution in individuals with a history of depression.
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