Antimicrobials

Question 1

what composes mycobacterias cell wall

Answer 1

lipid-rich

mycolic acids

Question 2

how do you treat active TB

Answer 2

4 drugs for 2 months

continuation phase for 18 weeks - reduce to 2 drugs

INH, Rif, PZA, EMB

Question 3

how do you treat latent TB

Answer 3

Isoniazid - 9 months

Rifampin - 4 motnhs

INH and Rifapentne for 3 months

Question 4

what is the most active drug used in the treatment of acute and latent TB

Answer 4

Isoniazid

Question 5

Isoniazid:

1 (bacterostatic/cidal) for actively growing bacilli
Penetrates into 2. Active against both extracellular and intracellular organisms
Less effective against treating 3
Structural similarity to 4

Answer 5

1. bacteriocidal
2. macrophages
3. atypical mycobacterial infections (M. avium complex)
4. pyridoxine (vit. B6)

Question 6

MOA of isoniazid

Answer 6

inhibits synthesis of mycolic acid

delivered as prodrug, activated by a mycobacterial catalase-peroxidase enzyme (Kat G)

activated INH forms a covalent bond with at least 2 proteins involved in mycolic acid synthesis and impedes function

Question 7

how is resistance developed against INH

Answer 7

mutation in Kat G gene - lack of prodrug activation

overexpression of Inh A protein - enzyme involved in mycolic acid synthesis

Question 8

what is necessary when treating TB to prevent emergence of drug resistance during therapy

Answer 8

at least 2 antituberculosis agents are used

Question 9

INH is readily absorbed from the 1

Achieves peak plasma concentration in 2 hours - diffuses into all body fluids and tissues (including CNS)

INH is acetylated to acetyl-INH in the 2. Slow acetylators are prone to develop 3. (peripheral neuropathy)

Answer 9

1. GI tract
2. liver, bowel, kidney
3. toxicity

Question 10

Adverse rxns to INH

Answer 10

Hepatitis - risk increases with age and greater in individuals with alcohol dependence

peripheral neuropathy - results from structural similairty to pyridoxine; slow metabolism of drug; malnourished, alcoholic, diabetic, or suffers AIDs
- reverse with low doses of pyridoxine

Question 11

first line tx for active TB

alternative to INH tx of latent TB

Answer 11

rifampin

Question 12

MOA of rifampin

Answer 12

inhibits RNA synthesis

binds to bacteria DNA dependent RNA polymerase

bactericidal

penetrates most tissues as well as phagocytic cells - kill intracellular

Question 13

resistance to rifampin

Answer 13

point mutation in bacterial RNA polymerase gene (target)

Question 14

Rifampin is well absorbed from ___ and is widely distributed to all tissues/fluids

Answer 14

GI tract

Question 15

Adverse rxns to rifampin

Answer 15

GI

Nervous system: HA, dizziness, fatigue

hepatitis - most common in those with underlying liver condition, INH slow acetylators (combo therapy)

harmless red-orange color in urine, feces, sweat, tears, and saliva

Question 16

Rifampin drug interactions

Answer 16

strong inducer of cytochrome p450

increase elimination of many drugs

Question 17

In HIV patients what drug is used instead of rifampinfor treated TB

Answer 17

rifabutin

Question 18

essential component of multidrug regimens used in treating active TB

synthetic analogue of nicotinamide

Answer 18

Pyrazinamide

Question 19

MOA of pyrazinamide

Answer 19

inhibit mycolic acid synthesis

activity is dependent on an acidic environemtn

prodrug - pyrazinamidase enzyme –> active form

Question 20

resistance to pyrazinamide

Answer 20

mutation in pyrazinamidase enzyme

Question 21

Pyrazinamide

Well absorbed from the 1

Widely distributed throughout the body, can enter 2 and 3

Answer 21

1. GI tract
2. macrophages
3. TB cavities

Question 22

Adverse reactions to pyrazinamide

Answer 22

Hepatoxicity

hyperuricemia - nearly all patients

Question 23

___ is essential component in tx of combo therapy used to treat active TB and infections caused by M. avium

Answer 23

Ethambutol

Question 24

MOA of ethambutol

Answer 24

inhibits arabinosyl transferases (involved in mycobacterial cellw all synthesis)

Question 25

resistance to ethambutol

Answer 25

point mutations in genes encoding arabinosyl transferases should always be given in combo with other drugs

Question 26

Adverse reactions to ethambutol

Answer 26

retrobulbar neuritis - reversible following discontinuation hyperuicemia - less than pyradinazole

Question 27

aminoglycoside antibiotic used in tx of TB caused by strains resistant to first line drugs - used in combo with other drugs to prevent resistance

Answer 27

Streptomycin

Question 28

MOA of streptomycin

Answer 28

interferes with bacterial protein synthesis

Question 29

streptomycin effective against intracellular, extracellular or both?

Answer 29

extracellular - penetrates cells poorly

Question 30

what does streptomycin have antimicrobial activity against

Answer 30

M. tuberculosis M. avium

Question 31

resistance to streptomycin

Answer 31

point mutations in ribosomal proteins

Question 32

Streptomycin: delivered as a _1_ distributed in most _2_ penetrates _3_ poorly

Answer 32

1. injectable 2. body fluids 3. cells and tissues

Question 33

adverse reactions to streptomycin

Answer 33

1. ototoxic - vertigo, hearing loss | 2. nephrotic

Question 34

what is rifabutin active against?

Answer 34

M. tuberculosis and M. avium complex MAC organisms more that rifampin

Question 35

Rifabutin is a less potent induced of _____

Answer 35

cytochrome p450

Question 36

how do you treat M. avium complex (MAC)

Answer 36

combination therapy 1. macrolide (clarithromycin or azithromycin) - protein synthesis inhibitor 2. rifampin 3. ethambutol 4. (+/-) streptomycin

Question 37

drugs used for prophylaxis of MAC in HIV pts (CD4<50)

Answer 37

Clarithromycin or azithromycin

Question 38

tx of leprosy

Answer 38

multidrug regimen: - dapsone - clofazimine - rifampin therapy last for years: 1-2 years for tuberculoid 5 years for lepromatous

Question 39

Dapsone is a competitive inhibitor of what

Answer 39

folic acid synthesis

Question 40

Adverse effects of Dapsone

Answer 40

non-hemolytic anemia acute hemolytic anemia in pts with G6P deficiency

Question 41

what drug for leprosy can cuase skin to turn red-brown to black

Answer 41

Clofazimine