antimycobacterials Flashcards Preview

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Flashcards in antimycobacterials Deck (30):
1

challenges of antimycobacterial therapy

difficult to kill, slow growth, lengthy therapy, intracellular forms, chronic disease

2

first-line drugs used in TB therapy

isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin

3

cidal, inhibits synthesis of mycolic acids. activated by KatG protein, targets enoyl-acyl carrier protein reductase (InhA protein)

isoniazid

4

isoniazid resistance due to

mutations in KatG, mutations in InhA

5

isoniazid use

for all infected with INH-sensitive strains. given in combination for active TB treatment (alone for latent)

6

genetic polymorphism associated with INH

N-acetyltransferase-2: can be fast and slow acetylators

7

INH side effects

neurotoxicity, especially peripheral neuritis (slow acetylators), improves with B6 administration. hepatotoxicity (acetylhydrazine. esp with increased age)

8

inhibits DNA-dependent RNA polymerase, suppressing RNA synthesis. cidal.

rifampin. spontaneous mutation in RNA pol B subunit

9

Rifampin side effects

hepatotoxicity, potent CYP inducer --> increased metabolism of other drugs (3A4, 2C9, 2C19, etc). orange red color to tears, urine, saliva, etc.

10

interferes with arabinosyl transferase, blocking cell wall synthesis (prevents arabinoglycan polymerization). tuberculostatic when used alone.

ethambutol

11

ethambutol side effects

generally well tolerated but optic neuritis possible. (decreased visual acuity, red/green color blindness, often reversible) not hepatotoxic.

12

blocks mycolic acid synthesis by inhibiting fatty acid synthase I. cidal. important component of short-term therapy. helpful for CNS involvement.

pyrazinamide

13

pyrazinamide side effects

hepatic damage, especially when combined with rifampin

14

aminoglycoside, binds to several ribosomal sites to stop initiation and cause mRNA misreading. used for most serious TB forms

streptomycin

15

streptomycin side effects

ototoxicity, nephrotoxicity

16

short-course TB treatment

isoniazid + rifampin (6 mo) + pyrazinamide (first 2 months)

17

disseminated TB treatment

isoniazid + rifampin (9-24 mo) + pyrazinamide + ethambutol (1st 2 mo)

18

cidal, intracellular and extracellular treatment of conventional TB strains

isoniazid, rifampin, pyrazinamide

19

atypical mycopacterial infections + treatment

MAC. less fatal than TB so use anti-TB regimen until agent ID'd

20

single-agent prophylaxis of MAC in AIDS patients, alternate to rifampin for multi-drug treatment

rifabutin

21

rifabutin adverse effects

similar to rifampin but less frequent. drug interactions also similar to rifampin but to a lesser extent (less potent CYP inducer)

22

part of multi-drug treatment for MAC in AIDS patients, also for MAC prophylaxis. cidal in this case.

clarithromycin (avoids CYP induction)

23

MAC treatment regimens

clarithromycin + rifabutin, rifabutin synergistic in vitro with clarithromycin

24

for leprosy. structural analog of para-aminobenzoic acid, inhibits synthesis of folic acid, bacteriostatic. used in combination. alternative for prophylaxis and treatment of pneumocystis jiroveci in AIDS patients. slow & fast acetylators

dapsone

25

dapsone adverse effects

hemolytic anemia, methemoglobinemia

26

leprosy drug. binds to DNA, interfering with reproduction and growth, only used in combination therapy. no cross resistance.

clofazimine

27

clofazimine side effects

red-brown pigmentation of skin, eyes, urine

28

antibiotic used for leprosy treatment

rifampin. hepatotoxicity!

29

lepromatous disease treatment

dapsone + clofazimine + rifampin (2 yr)

30

tuberculoid disease treatment

dapsone + rifampin (1 yr)