Anti TB Flashcards
What is the mechanism of action of Rifampicin?
Rifampicin inhibits the gene transcription of mycobacteria by blocking the DNA- dependent RNA polymerase, which prevents the bacillus from synthesizing messenger RNA and protein, causing cell death.
How does resistance to rifampicin occur?
mutations in the gene, which encodes the RNA polymerase beta chain.
What is Rifampicin used for?
Active and latent TB
ROA of Rifampicin?
Oral
Which out of RIPE is hepatotoxic?
R, I, P. P is the most hepatotoxic
Can Rifampicin be used in pregnancy? What must be given to the mother and neonate?
Rifampicin is a category C drug. It has been used during pregnancy, and no teratogenic effects have been reported. As a precaution, mothers, and neonates born to mothers who have been under treatment with rifampicin should be given vitamin K, in order to avoid postpartum haemorrhage (as an adverse effect associated with rifampicin is thrombocytopenia).
Which out of RIPE are safe for the kidney?
R and I.
Use of Rifampicin in kidney failure?
No dose adjustment needed
Use of Rifampicin in liver failure?
Used when benefits outweighs risk. Liver functioning must be closely monitored
Does Rifampicin have DDI?
Yes, it INDUCES cyp450 enzymes
What are the adverse effects of Rifampicin?
- Hepatitis
- Drug interactions due to induction of CYP enzymes
- Orange discolouration of bodily fluids
What is the mechanism of action of isoniazid?
Isoniazid is a prodrug. It is activated by the catalase-peroxidase enzyme of M. tuberculosis. The activation of isoniazid produces oxygen-derived free radicals that can inhibit the formation of mycolic acids of the bacterial cell wall, cause DNA damage and, subsequently, the death of the bacillus.
What are the mechanisms of resistance to Isoniazid?
mutations to the catalase-peroxidase enzyme, and mutations of the regulatory genes involved in mycolic acid synthesis.
What is Isoniazid used for?
Active and latent TB
How is isoniazid administered?
Oral
How is isoniazid metabolized?
Metabolized in the liver through acetylation by N-acetyltransferase. Excreted by the kidney as mainly inactive metabolites.
The acetylation rate is related to genetic polymorphisms.
Use of isoniazid in liver failure?
These patients should be closely monitored and should undergo clinical examination and laboratory tests more frequently than is necessary for patients without liver disease.
Use of isoniazid in kidney failure?
No dose adjustment is needed in patients with renal impairment
What is pyridoxine used for?
Together with isoniazid to prevent pyridoxine deficiency and peripheral neuropathy
What should isoniazid not be taken with?
Isoniazid should NOT be taken concomitantly with foods rich in tyramine and histamine
Does isoniazid have DDI?
Yes, it inhibits CYP450.
Key adverse effects of isoniazid?
- Peripheral neuropathy - take pyridoxine
2. Hepatitis
What is pyrazinamide useful against?
Persisters. This activity of pyrazinamide allows the duration of the treatment with rifampicin, isoniazid and pyrazinamide to be reduced to six months.
MOA of pyrazinamide
Pyrazinamide is a prodrug that needs to be converted into its active form, pyrazinoic acid, by the microbial enzymes pyrazinamidase.
It is supposed that pyrazinamide enters the bacillus passively, is converted into pyrazinoic acid by pyrazinamidase, and reaches high concentrations in the bacterial cytoplasm. The accumulation of pyrazinoic acid decreases the intracellular pH to levels that cause the inactivation of critical pathways necessary for the survival of the bacteria.
