ATC Group: J04A Drugs for treatment of tuberculosis

Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid.

Bedaquiline is a diarylquinoline. Bedaquiline specifically inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, an essential enzyme for the generation of energy in Mycobacterium tuberculosis. The inhibition of ATP synthase leads to bactericidal effects for both replicating and non-replicating tubercle bacilli.

Capreomycin is active against human strains of Mycobacterium tuberculosis.

Cycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis.

The pharmacological mode of action of delamanid involves inhibition of the synthesis of the mycobacterial cell wall components, methoxy-mycolic and keto-mycolic acid. The identified metabolites of delamanid do not show anti-mycobacterial activity.

Ethambutol is bacteriostatic. It is effective against Mycobacterium tuberculosi and M.bovis with an MIC of 0.5–8µg per ml. The exact mechanism of action is unknown. While it has activity against some atypical mycobacteria including M.Kansasii, activity against other micro-organisms has not yet been reported.

Ethionamide is bacteriostatic against M. tuberculosis at therapeutic concentrations, but may be bactericidal at higher concentrations. The exact mechanism of action of ethionamide has not been fully elucidated, but the drug appears to inhibit peptide synthesis in susceptible organisms. Drug resistance develops rapidly when ethionamide is given as monotherapy.

Isoniazid is used mainly in the treatment of pulmonary tuberculosis but it appears to be effective also in the treatment of extrapulmonary lesions, including meningitis and genito-urinary disease.

The mechanism of action of pretomanid is thought to involve inhibition of the synthesis of cell wall lipids under aerobic conditions and generation of reactive nitrogen species under anaerobic conditions. Reductive activation of pretomanid by a mycobacterial deazaflavin (F420)-dependent nitro-reductase is required for activity under both aerobic and anaerobic conditions.

Pyrazinamide exhibits tuberculostatic activity. Pyrazinamide is active only at an acid pH, and it is therefore active mainly on the tubercle bacilli located within the cell.

Rifabutin is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex.

Rifampicin is an active bactericidial antituberculosis drug which is particularly active against the rapidly growing extracellular organisms and also has bactericidial activity intracellularly. Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.

Rifampicin and isoniazid are active bactericidial antituberculosis drugs which are particularly active against the rapidly growing extracellular organisms and also have bactericidal activity intracellularly. Rifampicin has activity against slow- and intermittently-growing M. tuberculosis. Isoniazid acts against actively growing tubercle bacilli.

Rifapentine, a cyclopentyl rifamycin, is an antimycobacterial agent. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis but not in mammalian cells. At therapeutic levels, rifapentine exhibits bactericidal activity against both intracellular and extracellular M. tuberculosis organisms.