Drugs for Tuberculosis (TB)

Question 1

1st line agents(drug names)

Answer 1

RIFAMPICIN
ISONIAZIDE
PYRAZINAMIDE
ETHAMBUTOL
(Mnemonic: RIPE)

Question 2

2nd line agents(drug names)

Answer 2

STREPTOMYCIN
AMIKACIN
CIPROFLOXACIN
LEVOFLOXACIN
CLARITHROMYCIN

Question 3

ISONIAZIDE

Answer 3

MOA:
inhibit the mycolic acid synthesis in the CW (bactericidal)
prodrug, activated by KatG (catalase-peroxidase enzyme)
resistance develops by downregulation of KatG
can be used in monotherapy for latent TB
inhibitor of CYP450 enzyme
metabolized by N-acetylatyltransferase (liver) -> excreted in urine

SE:
drug-induced lupus
hepatotoxicity (increase in liver test functions)
seizures (esp. ISONIAZIDE)
neuropathy (vit.B6 def., bcs induces excretion of vit.B6, therefore better to adm. both Vit.B6 w/ ISONIAZIDE
metabolic acidosis

Question 4

Treatment plan

Answer 4

4 drugs -> 2 months
2 drugs (usually RIFAMPICIN & ISONIAZIDE) -> 4 months (to avoid reactivation)

Question 5

RIFAMPICIN

Answer 5

MOA:
bind to bacterial DNA dependent, RNA polymerase enzyme and inhibit it
resistance develops in case of RNA polymerase mutation
inducer of CYP450
used alone for prophylaxis in H. infl. & Neis. Meningitidis

SE:
hepatotoxicity
orange discoloration of body fluids (feces, urine, sputum) -> non-hazard

Question 6

ETHAMBUTOL

Answer 6

MOA:
inhibit the arabinosyl transferase enzyme -> inhibition of carbohydrate formation at the CW -> inhibition of polymerization (bacteriostatic!!!)

SE: non-liver toxic(!!!)
optic neuritis (red-green color discoloration)

Question 7

PYRAZINAMIDE

Answer 7

MOA:
prodrug
inhibit the FAS enzyme (fatty acid synthetase)-> inhibit fatty acid synthesis

SE:
hyperuricemia -> gout
hepatotoxicity
arthralgia