A review of the use of ethionamide and prothionamide in childhood tuberculosis.
Tuberculosis (Edinb)
; 97: 126-36, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26586647
ABSTRACT
Ethionamide (ETH) and prothionamide (PTH), both thioamides, have proven efficacy in clinical studies and form important components for multidrug-resistant tuberculosis treatment regimens and for treatment of tuberculous meningitis in adults and children. ETH and PTH are pro-drugs that, following enzymatic activation by mycobacterial EthA inhibit InhA, a target shared with isoniazid (INH), and subsequently inhibit mycolic acid synthesis of Mycobacterium tuberculosis. Co-resistance to INH and ETH is conferred by mutations in the mycobacterial inhA promoter region; mutations in the ethA gene often underlie ETH and PTH monoresistance. An oral daily dose of ETH or PTH of 15-20 mg/kg with a maximum daily dose of 1000 mg is recommended in children to achieve adult-equivalent serum concentrations shown to be efficacious in adults, although information on optimal pharmacodynamic targets is still lacking. Gastrointestinal disturbances, and hypothyroidism during long-term therapy, are frequent adverse effects observed in adults and children, but are rarely life-threatening and seldom necessitate cessation of ETH therapy. More thorough investigation of the therapeutic effects and toxicity of ETH and PTH is needed in childhood TB while child-friendly formulations are needed to appropriately dose children.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Protionamida
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Tuberculose
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Etionamida
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Mycobacterium tuberculosis
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Antituberculosos
Tipo de estudo:
Diagnostic_studies
Limite:
Adolescent
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Adult
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Animals
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Child
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Child, preschool
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Humans
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Infant
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article