Anti TB

Question 1

What is the mechanism of action of Rifampicin?

Answer 1

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.

Question 2

How does resistance to rifampicin occur?

Answer 2

mutations in the gene, which encodes the RNA polymerase beta chain.

Question 3

What is Rifampicin used for?

Answer 3

Active and latent TB

Question 4

ROA of Rifampicin?

Answer 4

Oral

Question 5

Which out of RIPE is hepatotoxic?

Answer 5

R, I, P. P is the most hepatotoxic

Question 6

Can Rifampicin be used in pregnancy? What must be given to the mother and neonate?

Answer 6

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).

Question 7

Which out of RIPE are safe for the kidney?

Answer 7

R and I.

Question 8

Use of Rifampicin in kidney failure?

Answer 8

No dose adjustment needed

Question 9

Use of Rifampicin in liver failure?

Answer 9

Used when benefits outweighs risk. Liver functioning must be closely monitored

Question 10

Does Rifampicin have DDI?

Answer 10

Yes, it INDUCES cyp450 enzymes

Question 11

What are the adverse effects of Rifampicin?

Answer 11

1. Hepatitis
2. Drug interactions due to induction of CYP enzymes
3. Orange discolouration of bodily fluids

Question 12

What is the mechanism of action of isoniazid?

Answer 12

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.

Question 13

What are the mechanisms of resistance to Isoniazid?

Answer 13

mutations to the catalase-peroxidase enzyme, and mutations of the regulatory genes involved in mycolic acid synthesis.

Question 14

What is Isoniazid used for?

Answer 14

Active and latent TB

Question 15

How is isoniazid administered?

Answer 15

Oral

Question 16

How is isoniazid metabolized?

Answer 16

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.

Question 17

Use of isoniazid in liver failure?

Answer 17

These patients should be closely monitored and should undergo clinical examination and laboratory tests more frequently than is necessary for patients without liver disease.

Question 18

Use of isoniazid in kidney failure?

Answer 18

No dose adjustment is needed in patients with renal impairment

Question 19

What is pyridoxine used for?

Answer 19

Together with isoniazid to prevent pyridoxine deficiency and peripheral neuropathy

Question 20

What should isoniazid not be taken with?

Answer 20

Isoniazid should NOT be taken concomitantly with foods rich in tyramine and histamine

Question 21

Does isoniazid have DDI?

Answer 21

Yes, it inhibits CYP450.

Question 22

Key adverse effects of isoniazid?

Answer 22

1. Peripheral neuropathy - take pyridoxine

2. Hepatitis

Question 23

What is pyrazinamide useful against?

Answer 23

Persisters. This activity of pyrazinamide allows the duration of the treatment with rifampicin, isoniazid and pyrazinamide to be reduced to six months.

Question 24

MOA of pyrazinamide

Answer 24

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.

Question 25

Resistance to pyrazinamide

Answer 25

mutations in the gene, which encodes the pyrazinamidase enzyme and prevents pyrazinamide from being converted into its active form.

Question 26

What is pyrazinamide used for

Answer 26

Active TB

Question 27

Use of pyrazinamide in liver and kidney failure?

Answer 27

Avoid in patients with liver disease. Dose adjust for kidney failure

Question 28

Adverse effects of pyrazinamide

Answer 28

1. Hepatotoxicity
2. Hyperuricemia and arthralgia: Pyrazinoic acid, the principal metabolite of
   pyrazinamide, inhibits the renal tubular secretion of uric acid and results in
   gout like symptoms. (Observed more with pyrazinamide then with
   ethambutol.)

Question 29

MOA of ethambutol?

Answer 29

Ethambutol inhibits the arabinosyltransferase enzyme encoded by the embB gene and interferes with the polymerization of arabinose into arabinogalactan, the principal polysaccharide on the mycobacterial cell wall.
This affects the integrity of the Mycobacterium tuberculosis cell wall and thus facilitates the entry of lipophilic antibiotics, like rifampicin and levofloxacin.

Question 30

Adverse effects of ethambutol

Answer 30

1. Visual toxicity

2. Hyperuricemia/gout

Question 31

Use of ethambutol for liver failure and kidney failuRe

Answer 31

Use in patients with liver failure : Ethambutol can be used at full doses in patients with liver failure

Use in patients with kidney failure: Dose reduction. Ethambutol and its metabolites can accumulate in patients with kidney failure.