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).
How 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 is the mechanism of action of tuberculosis?
Mechanisms of Action of Current TB Drugs Thioamides, Nitroimidazoles, Ethambutol, and Cycloserine act on cell wall synthesis. Diarylquinoline inhibits ATP synthase. PAS, Fluoroquinolones, Cyclic Peptides and Aminoglycosides act on the DNA.
How does pyrazinamide cause hepatotoxicity?
The mechanism of hepatic injury by pyrazinamide is not known, but the drug is extensively metabolized by the liver and injury may be caused by a metabolic intermediate. Hepatotoxicity from pyrazinamide appears to be more frequent with higher doses, suggesting a direct toxic effect, at least in part.
Which TB drugs are nephrotoxic?
Acute kidney injury (AKI) is a rare and severe complication that can interrupt treatment and cause permanent kidney damage. Although isoniazid (INH) and ethambutol (EMB) have been associated with AKI,[5,6] rifampin (RIF) is the most common anti-TB drug responsible for AKI identified by most studies.
What is the mechanism of action of isoniazid?
Mechanism of action — The antimicrobial activity of INH is selective for mycobacteria, likely due to its ability to inhibit mycolic acid synthesis, which interferes with cell wall synthesis, thereby producing a bactericidal effect [1].
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.
Is TB droplet or airborne?
Mycobacterium tuberculosis is transmitted in airborne particles called droplet nuclei that are expelled when persons with pulmonary or laryngeal TB cough, sneeze, shout, or sing. The tiny infectious particles can be carried by air currents throughout a room or building.
Can TB drugs cause jaundice?
In patients with tuberculosis when a rifampicin containing ant TB treatment is instituted, jaundice occurring within 1 week should suggest rifampicin toxicity.
What is the mechanism of action of ciprofloxacin?
Mechanism of Action Ciprofloxacin is a bactericidal antibiotic of the fluoroquinolone drug class. It inhibits DNA replication by inhibiting bacterial DNA topoisomerase and DNA-gyrase.
What are the mechanisms of action of tuberculosis drugs?
Mechanisms of Action of TB Drugs Under Development. Tuberculosis drugs target various aspects of Mycobacterium tuberculosis biology, including inhibition of cell wall synthesis, protein synthesis, or nucleic acid synthesis. For some drugs, the mechanisms of action have not been fully identified.
What are the Inhibitors of ATP synthase in tuberculosis?
Diarylquinoline inhibits ATP synthase. PAS, Fluoroquinolones, Cyclic Peptides and Aminoglycosides act on the DNA. Tuberculosis drugs target various aspects of Mycobacterium tuberculosis biology, including inhibition of cell wall synthesis, protein synthesis, or nucleic acid synthesis.
What is the second line treatment for XDR tuberculosis (TB)?
Kanamycin, Capreomycin and Amikacin are injectable second-line. XDR TB occurs when a Mycobacterium tuberculosis strain is resistant to isoniazid and rifampin, two of the most powerful first-line drugs, as well as key drugs of the second line regimen—any fluoroquinolone and at least one of the three injectable drugs shown above.
What is the mechanism of action of nitroimidazole?
For some drugs, the mechanisms of action have not been fully identified. Nitroimidazoles, SQ-109,, Meropenem, and Benzothiazinones act on cell wall synthesis.