Anti-TB Drugs

Question 1

Ethambutol

Answer 1

first line drug, EMPIRICAL TX
MOA: inhibits mycobacterial arabinosyl transferases (embCAB operon) –> inhibits synthesis of cell wall
resistance: mutations in embB gene
toxicity: retrobulbar neuritis (loss of acuity, red-green color blindness)

Question 2

Isoniazid

Answer 2

first line drug, EMPIRICAL TX
MOA: inhibits synthesis of mycolic acids (cell wall)
forms complex w/ AcpM + KasA
activated by KatG
resistance: mutations in KasA, KatG
toxicity: hepatitis, peripheral neuropathy (prevented w/ pyridoxine admin)

Question 3

Pyrazinamide

Answer 3

first line drug, EMPIRICAL TX
MOA unknown
resistance: mutations in pncA
toxicity: hepatotoxicity, hyperuricemia (joint pain)

Question 4

Rifampin

Answer 4

first line drug, EMPIRICAL TX
MOA: bind to DNA-dep RNA polymerase –> inhibits RNA synthesis (bactericidal)
STRONG P450 inducer (caution in HIV pts w/ PIs or NNRTIs)
resistance: mutations in rpoB gene
toxicity: flu-like sx if admin for less than 2 wks, harmless orange-red urine
prophylaxis for H influenzae type B

Question 5

Streptomycin

Answer 5

first line drug, EMPIRICAL TX
aminoglycoside, ONLY IV/IM
MOA: binds 30S –> irreversible inhibitor of protein synthesis
active against EXTRAcellular mycobacterium
effective against Myco TB, MAC, Myco Kansii
resistance: mutations in rpsL/rrs gene
toxicity: ototoxicity, nephrotoxicity
RELATIVE contraind in pregnancy

Question 6

Amikacin

Answer 6

second line drug
similar to streptomycin
toxicity: hearing loss

Question 7

Kanamycin

Answer 7

second line drug
similar to streptpmycin
toxicity: hearing loss

Question 8

Aminosalicylic acid

Answer 8

second line drug
folate synthesis antagonist
toxicity: SEVERE HS rxns (not usually used d/t this)

Question 9

Capreomycin

Answer 9

second line drug
peptide protein synthesis inhibitor
IM
toxicity: sterile abscess at injection site, ototoxic

Question 10

Cycloserine

Answer 10

second line drug

inhibitor of cell wall synthesis

Question 11

Ethionamide

Answer 11

second line drug
similar to INH, low level cross-resistance w/ INH
blocks synthesis of mycolic acids
toxicity: hepatotoxicity, neurologic effects (reversed w/ pyridoxine)

Question 12

Rifabutin

Answer 12

second line
substrate and inducer of CYP450 enzymes
resistance: mutations in rpoB

Question 13

rifapentine

Answer 13

second line drug
long acting analog of rifampin
cross-reactive w/ RIF

Question 14

latent TB infxn (LTBI)

Answer 14

INH for 9 mo