Nervous System Effects of Antituberculosis Therapy

Abstract

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.

Psicosis inducida por fármacos antituberculosos: un caso asociado a cicloserina.

“…Su mecanismo de acción antituberculosa es la inhibición de la formación de la pared celular del Mycobacterium por su estructura similar al aminoácido D-alanina, constituyente natural de dicha estructura y al que suplanta en los procesos enzimáticos de síntesis del péptido-glucano. De las dos formas isómeras existentes de cicloserina, se atribuyen las propiedades psicofarmacológicas relevantes a la forma D- (4,5).…”

“…Pese a que la cicloserina posee prominente capacidad para cruzar la barrera hematoencefálica y carece de resistencia cruzada con otros fármacos antituberculosos, su margen terapéutico es sumamente estrecho y esto la ha relegado a agente antituberculoso de segunda línea (5). Desde los primeros años de su uso fueron reportados numerosos efectos secundarios de la cicloserina a nivel del sistema nervioso periférico y central, así por ejemplo: cefalea, vértigo, disartria y neuropatías distales, además de cuadros de convulsiones, ansiedad, depresión y psicosis.…”

Treatment of cutaneous infections caused by Mycobacterium tuberculosis

“…Among all the drugs used in anti-tuberculosis therapy, isoniazid exhibits the greatest toxicity towards both the central and peripheral nervous system. During treatment with isoniazid, such nervous system complications were observed as polyneuritises, psychoses and peripheral paraesthesias [20].…”

Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

“…Ancak bu toksisite boyutlarının elektron mikroskopi ve immünohistokimyasal yöntemlerle araştırıl-masına gereksinim vardır. 3,5 Tüberküloz tedavisinde İNH ile birlikte kullanılan streptomisin nadiren ensefalopatiye neden olabilmektedir. 6 Ancak, İNH ve streptomisin birlikte kullanımının nörotoksik etkiyi artırıp artırmadığı henüz bilinmemektedir.…”