antimicrobials II

Question 1

List the anti-mycobacterials

Answer 1

isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin. May require addition of aminoglycosides, cycloserine and p-aminosalicylic acid

Question 2

Why do you need multiple drugs for TB treatment?

Answer 2

synergy, mixed infections and resistant bacteria

Question 3

Describe common TB treatment

Answer 3

isoniazid and rifampin for 6-9months. Pyrazinamide and ethambutol (or streptomycin) for first 2 months.

Question 4

Structure of TB

Answer 4

cell wall contains mycolic acids, arabinogalactan and peptidoglycan. RNA polymerase is required for TB survival

Question 5

Isoniazid MOA

Answer 5

Inhibits mycolic acid synthesis: isoniazid binds covalently to the adenine nucleotide of nicotinamide in enoyl-acyl carrier protein reductase-InhA. Bacteriostatic for resting organisms, bactericidal for growing mycobacteria. High selective toxicity

Question 6

Isoniazid resistance

Answer 6

develops rapidly due to alterations in inhA and katG targets

Question 7

isoniazid toxicities

Answer 7

INH injures neurons and hepatocytes: peripheral and optic neuritis, hepatic damage. Plus rash, fever, pregnancy category C

Question 8

isoniazid uses

Answer 8

mycobacteria only

Question 9

Rifampin (rifampacin) MOA

Answer 9

Inhibits DNA-dependent RNA polymerase initiation. Bactericidal. Synergistic with INH and streptomycin

Question 10

Rifampin uses

Answer 10

TB, leprosy, H. flu

Question 11

Rifampin toxicity

Answer 11

minor hepatotoxicity, induces CYP 450 (rifampin ramps up CYP450 but rifabutin does not). Orange body fluids.

Question 12

Ethambutol MOA

Answer 12

Inhibits cell wall biosynthesis through arabinosyltransferase inhibition. Concentrates in lungs. Tuberculostatic, mycocidal.

Question 13

Ethambutol toxicities

Answer 13

Optic neuritis (loss of green vision), gout (decreased renal clearance of uric acid). Renal excretion

Question 14

ethambutol uses

Answer 14

mycobacteria only

Question 15

Pyrazinamide MOA

Answer 15

Unknown- bactericidal. Enters cells/macrophages. Prodrug is hydrolyzed to pyrazinoic acid by pyrazinamidase (pncA). Effective at low pH in caseous lesions

Question 16

Pyrazinamide toxicity

Answer 16

hepatic damage, hyperuricemia (gout), GI upset, arthralgias

Question 17

pyrazinamide uses

Answer 17

mycobacteria only

Question 18

Streptomycin MOA

Answer 18

Inhibits protein synthesis (30S). Aminoglycoside selective toxicity

Question 19

streptomycin uses

Answer 19

mycobacteria and gram negative

Question 20

streptomycin toxicity

Answer 20

vestibular/auditory toxicity, nephrotoxicity

Question 21

Bedaquiline MOA and toxicity

Answer 21

New TB drug- inhibits ATP synthase. Hepatotoxicity, hyperuricemia, arthralgia, prolonged QT interval

Question 22

Treatment of M. leprae

Answer 22

Dapsone or amithizone + rifampin +/- clofazimine

Question 23

dapsone MOA and toxicities

Answer 23

Bacteriostatic- PABA antagonist (anti metabolite). Hemolytic anemia with G6PD deficiency

Question 24

Clofazimine MOA

Answer 24

phenazine dye that binds to DNA. Bactericidal. Acts slowly

Question 25

Mycobacterium avium complex (MAC) treatment

Answer 25

macrolides (clarithromycin > azithromycin) + ethambutol +/- rifabutin. Can add fluoroquinolones, clofazimine or amikacin.

Question 26

MAC prophylaxis in AIDs

Answer 26

macrolide + ethambutol or rifabuten.

Question 27

M. kansasii treatment

Answer 27

isoniazid + rifampin + ethambutol

Question 28

M. fortuitum treatment

Answer 28

Fluoroquinolones + doxycycline