TB

Question 1

First line

Answer 1

TX for 2 months - rapid growers

Rifampin
Isoniazid
Pyrazinamide
Ethambutol

Followed by 4 months of - slow growers

Rifampin
Isoniazid

Question 2

Isoniazid

Answer 2

Only drug for prophylaxis (HIV)

• MOA – prodrug – requires activation by NAD, leads to inhibitions of INHA which blocks synthesis of mycolic acids – blocks cell wall
• PK – fast and slow acetylators
• SE – peripheral neuropathy due to disruption of B6 and GABA synthesis
o Liver tox – supplement with B6

Question 3

Rifampin

Answer 3

Bactericidal/sterilizing action against TB

MOA - RNAP inhibitor (beta subunit)

Higher doses for shorter durations increase activity while suppressing resistance

Turns urine red

Severe DDI - CYPs – use refabutin (more $$$)

Question 4

Ethambutol

Answer 4

Bacteriostatic against active growing TB

MOA - Cell wall inhibitions (targets arabinosyltransferase

SE - dose dependent optic neuritis – not given in kids

DDI - low

Question 5

Pryazinamide

Answer 5

Weakly bactericidal, but potent sterilizing activity – shortens TX time

MOA - Trans-translation inhibitor (process for managing damaged proteins and rescuing non-functioning ribosomes)

Prodrug - activated by PNCA (TB amidase)

Vd variable depending on pts weight

SE - GI, gout (requiring Tx with allopurinol)

Question 6

MDR-TB

Answer 6

No rifampin or isoniazid

Pyrazinamide, ethambutol - primary

Fluoroquinolones (TOPO/gyrase inhibitors) - secondary

Question 7

Amikacin (aminoglycoside)

Answer 7

Bactericidal against active TB

MOA - 30s

SE - oto/vestibulo/nephrotoxicity

Question 8

Ofloxacin (Fluroquinolone)

Answer 8

Most important 2nd line

bactericidal - good for pts who can’t take isoniazid/rifampin

MOA - DNA gyrase/TOPO inhibitor

Question 9

Ethionamide (thioamide)

Answer 9

Bactericidal - much less potent than isoniazid

MOA - same as isoniazid (cross resistance)

prodrug - activation is different than isoniazid

Blocks cell wall