AntiMYCObacterials

Question 1

1st Line TB Drugs

Answer 1

Isoniazid, Rifampin / Rifabutin, Ethambutol, Pyrazinamide

Question 2

2nd Line TB Drugs

Answer 2

Streptomycin, Ethionamide, Levofloxacin, Amikacin (used to all be 1st line but there was resistance developed), more severe SEs

Question 3

Isoniazid (Inh)

Answer 3

Spectrum: M. tuberculosis only
MOA: prodrug activated by KatG in the bacterium, analogue of pyridoxine that targets enoyl acyl carrier protein reductase (InhA) and B-ketoacyl-ACP synthase (KasA)
PK: potent (bacteriostatic if bacilli are stationary, bactericidal in rapidly dividing bacilli)
Use: 1st line tx as combo therapy for active infection, sole drug in tx of latent infection
Resistance: if used alone in active infection resistant organisms rapidly emerge (NO cross-resistance)

Question 4

Isoniazid PK and SE

Answer 4

PK: PO, IV, IM; high Vd
Metabolism: acetylation
SE: peripheral neuritis (corrected by pyridoxine supplementation), hepatotoxicity, CYP450 inhibitor, SLE-like syndrome

Question 5

Rifampin

Answer 5

Antimicrobial, antimycobacterial, bactericidal
*1st line, usually given in combination to tx TB
MOA: binds DNA-dependent RNA polymerase
Effect: inhibits RNA synthesis
Spectrum: M. tuberculosis, M. kansasii, G+ve, G-ve, MRSA
Use: active TB, latent TB in isoniazid intolerant pt, Leptosy, meningitis prophylaxis, H. influenzae prophylaxis, MRSA infections
Resistance: altered target, decreased permeability

Question 6

Rifampin PK and SE

Answer 6

PK: PO and IV, high Vd; strong CYP450 inducer+
Elimination: feces
SE: light chain proteinuria, orange/red bodily fluids

Question 7

Rifabutin

Answer 7

(same as Rifampin except…)

Use: preferred for use in HIV pt’s d/t less inuction of CYP450

Question 8

Ethambutol

Answer 8

MOA: inhibits arabinosyltrnsferase
Effect: decreased CHO polymerization of CW
Spectrum: M. tuberculosis and M. kansasii
Use: tx TB in combo w/ Pyrazinamide, Isoniazid and Rifampin
Resistance: occurs if used alone
SE: dose-dependent visual disturbance (red/green color blindness)

Question 9

Pyrazinamide

Answer 9

MOA: prodrug that has to be activated
Resistance: strain lacks enzyme to activate drug or increase efflux pumps
SE: nongouty polyarthralgia, hyperuricemia, acute gouty arthritis (if predisposed),

Question 10

Streptomycin

Answer 10

2nd line (aminoglycoside)
MOA: enters via O2 dependent uptake, binds the 30S subunit
Effect: inhibits transcription
Use: in combo to tx tuberculous meningitis, miliary TB, etc
Resistance: increasing in frequency so the use is limited

Question 11

Amikacin

Answer 11

2nd line
Use: streptomycin resistant or MRD strains
SE: teratogenic

Question 12

Levofloxacin

Answer 12

2nd line
Use: strains resistant to 1st line drugs, should always be used in combo
SE: teratogenic

Question 13

Ethionamide

Answer 13

2nd line, similar to Isoniazid but no cross-resistance

SE: GI sx’s, neuro effects, hepatotoxicity, endocrine effects, teratogenic

Question 14

Dapsone

Answer 14

*structurally similar to Sulfa drugs
MOA: inhibits dihydropteroate synthetase
Effect: bacteriostatic
PK: high Vd, 
Use: Leptosy, tx PCP in HIV +ve pt's
SE: hemolysis (G6PD), erythema nodosum leprosum (tx w/ steroids), CYP450 inhibitor-

Question 15

Clofazimine

Answer 15

Phenazine dye
MOA: binds to DNA and inhibits replication (bactericidal)
Spectrum: M. leprae, MAC
SE: red-brown discoloration of skin

Question 16

Tx M. kansasii

Answer 16

Isoniazid + Rifampin + Ethambutol

Question 17

Tx M. marinum

Answer 17

2 drug combo (Rifampin, Ethambutol, Clarithromycin, Minocycline, Doxycycline, Sulfonamides)

Question 18

Tx MAC

Answer 18

Clarithromycin + Ethambutol +/- Rifabutin