Which ATT is most hepatotoxic?
PZA has been shown to induce greater hepatotoxicity than other first-line anti- TB drugs (3, 11). Although the incidence of PZA-induced hepatotoxicity decreased considerably after reducing the recommended standard dose, PZA is still considered the most frequent cause of anti-TB DIH (11, 12, 13, 14).
Which is more hepatotoxic isoniazid and pyrazinamide?
Conclusions. Preventive treatment with rifampin-pyrazinamide causes severe hepatotoxicity more often than does preventive treatment with isoniazid or curative treatment for tuberculosis.
Which is more hepatotoxic rifampicin and isoniazid?
In a meta-analysis, isoniazid was more likely to be associated with hepatotoxicity (odds ratio (OR) 1.6) even in the absence of rifampicin, but the combination of these two drugs was associated with higher rate of hepatotoxicity (OR 2.6) when compared to each drug on its own.
How does rifampin cause hepatotoxicity?
The mechanism of rifampin hepatotoxicity is not well known, but it is extensively metabolized by the liver and induces multiple hepatic enzymes including CYP 3A4 and ABC C2 (MRP2).
Does isoniazid cause nephrotoxicity?
Isoniazid/rifampicin-induced nephrotoxicity was further confirmed by the recorded histological alterations including atrophy of glomerular tuft, dysplastic renal tubules and inflammatory cells infiltration, as we recently reported [13]. Concomitant administration of either dose of R.
Does ethambutol affect liver?
Ethambutol therapy has been associated with minor, transient and asymptomatic elevations in serum aminotransferase levels, and is a reported but rare cause of clinically apparent acute liver injury.
Which TB drugs cause hepatotoxicity?
Abstract. Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity.
Which Antitubercular drug is hepatotoxic?
* First-line antituberculous drugs include isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid, rifampin, and pyrazinamide are potentially hepatotoxic; ethambutol is not hepatotoxic.
What is isoniazid toxicity?
The ingestion of toxic amounts of isoniazid causes recurrent seizures, profound metabolic acidosis, coma and even death. In adults, toxicity can occur with the acute ingestion of as little as 1.5 g of isoniazid. Doses larger than 30 mg per kg often produce seizures.
Why does isoniazid cause hepatotoxicity?
Chronic INH hepatotoxicity results in the induction of hepatocyte apoptosis, with associated disruption of mitochondrial membrane potential and DNA strand breaks. The most likely biochemical mechanism is that the metabolism of INH produces reactive metabolites that bind and damage cellular macromolecules in the liver.
What factors influence the combination of novel drugs in tuberculosis clinical trials?
A number of factors might have influenced the choice of combining novel drugs in clinical trials: in vitro data and findings from murine TB models about efficacy of certain combinations (table 2), concerns about life-threatening arrhythmia during concurrent use of novel (bedaquiline, delamanid) and existing (moxifloxacin, clofazimine) QT-prolo…
Which antituberculosis medications are used to treat drug-resistant tuberculosis?
After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials.
What is the burden of anti-TB drug-related hepatotoxicity?
Burden of anti-TB drug related hepatotoxicity is based not only on its prevalence or incidence, but also on its severity and outcome.
What is the biotransformation of TB drugs?
Most first line anti-TB drugs are lipophilic and their biotransformation involves their conversion into water soluble compounds and subsequent elimination. Hepatotoxicity appears to involve reactive metabolite formation and accumulation rather than the direct effect of the parent drug itself.8,31