TB Drugs

Question 1

3 Is of treatment challenge

Answer 1

Impermeable cell wall
Intrinsic resistance d/t efflux pumps
Inaccessible d/t intracellular nature

Question 2

Streptomycin

Answer 2

Oldest TB drug, cannot enter cells.
Resistance has developed
Use in severe cases

Question 3

Preferred TB regimens

Answer 3

Latent: INH 9 months or RIF 4 months
Active: 2 months of RIPE, 4 months of INH/RIF

Question 4

Isoniazid

Answer 4

MOA: inhibits mycolic acid synth, bactercidal
AE: hepatic tox (35+), peripheral neuropathy (d/t B6 def), drug induced SLE
AE worse in slow acetylators
CYP inducer/inhibitor

Question 5

CYP induction effects of INH

Answer 5

Acetaminophen -> hepatotoxicity

Question 6

CYP inhibition effects of INH

Answer 6

Diazepam (resp depression)
Phenytoin (neurotoxin)
Warfarin (inc bleeding)

Question 7

How does resistance develop against RIPE drugs?

Answer 7

R: rpoB mutation
I: inhA overexpression, KatG deletion
P: pcnA mutation
E: embB mutation

Question 8

Pyrazinamide

Answer 8

MOA: inhibits FAS1 - dec mycolic acid synth, CIDAL.
Only active at acidic pH (lesions, macrophages)
AE: hyperuricemia (100%), arthralgia

Question 9

Ethambutol

Answer 9

MOA: inhibits embAB operon - enhances bacterial cell wall permeability. STATIC
AE: optic neuritis, color blindness

Question 10

Rifampin

Answer 10

MOA: inhibits RNA synthesis by binding rpoB (no eukaryotic effect)
AE: turns secretions red orange, n/v
Intxn: induces hepatic metab (HIV and OCP failure)

Question 11

What to do if resistance occurs

Answer 11

MDR (against INH/RIF): 4-6 drugs x 18 months

XDR: resistance to INH, RIF, any FQ and at least one second line drug

Question 12

Bedaquiline

Answer 12

MOA: inhibits mycobacterium ATP synthase
AE: liver, BBW for QT prolong death
DO NOT ADMINISTER WITH RIFAMPIN (inducers)
Resistance: atpE