51: Antimycobacterial

Question 1

key characteristics of mycobacteria

Answer 1

mycolic acid lipid-rich cell walls

acid-fast stain

intracellular in macrophages

slow-growing

Question 2

describe latent TB (not a case of TB)

Answer 2

inactive- contained tubercel bacilli in body

TST.blood test positive but chest x ray and sputum smears negative

no symptoms and not infectious

Question 3

describe active TB disease

Answer 3

active multiplying tubercle acilli in the body

blood test positive and chest x-ray and sputum smears abnormal

symptomatic with cough, fever and weight loss

infectious before treatment

Question 4

MAC =

Answer 4

m. avium complex (includes m. avium, m. intracellulare and others)

cause pulmonary disease in normal ppl; acquired through respiratory droplet

disseminated disease in AIDS pts

Question 5

first line treatment drugs for active TB (4)

Answer 5

RIPE - active TB is ripe for treatment

Rifampin
Isoniazid
Pyrazinamide
Ethambutol

Question 6

treatment for latent TB

Answer 6

isoniazid first-line

or isoniazid and firapentine or rifampin

Question 7

MOA isoniazid

Answer 7

inhibits the synthesis of mycolic acid, an essential component of the mycobacterial cell wall

delivered as prodrug, which is activated by a mycobacterial catalase-peroxidase enzyme (Kat g)

activated isoniazid forms a covalent bond with at least two prtns involved in mycolic acid synthesis and impedes their function

Question 8

resistance to isoniazid mechanisms

Answer 8

mutation in Kat G gene –> lack of pro drug activation

overexpression of the Inh A prtn –> an enzyme involved in mycolic acid synthesis

Question 9

2 key adverse reactions for isoniazid

Answer 9

hepatitis

peripherphal neuropathy

Question 10

MOA rifampin

Answer 10

inhibits RNA synthesis by binding to bacterial DNA-dependent RNA polymerase

Question 11

resistance mechanism of rifampin

Answer 11

point mutations in the bacterial RNA polymerase gene

Question 12

key adverse reactions of rifampin

Answer 12

hepatitis, red-orange color imparted to urine, feces, sweat, tears, and saliva

Question 13

drug interactions for rifampin

Answer 13

• strong induced of cytochrome P450 which increases the elimination of many drugs and drug classes
• in HIV infected patients rifabutin should be substituted for rifampin

Question 14

in HIV infected patientes ________ should be substituted for ribampin in treatment of active of latent TB

Answer 14

rifabutin

Question 15

purpose of pyrazinambe

Answer 15

used in combo therapy treatment for active TB

Question 16

MOA pyrazinamide

Answer 16

prodrug converted to active form by bacterial pyrazinamidase enzyme; antimicroial activity is dependent on acidic environment

Question 17

adverse reactions pyrazinamide

Answer 17

hepatotoxicity

hyperuricemia - gouty

Question 18

MOA ethambutol

Answer 18

inhibits arabinosyl transferase (involved in mycobacteria cell wall synthesis)

Question 19

should you give ethambutol alone?

Answer 19

should always be given in combination with other drugs

Question 20

adverse reactions of ethambutol

Answer 20

retrobulbar neuritis

hyperuricemia (less than pyrazinamide)

Question 21

MOA streptomycin

Answer 21

interferes with bacterial prtn synthesis

Question 22

adverse reactions streptomycin

Answer 22

ototoxic

nephrotic

Question 23

combo therapy for m. avium

Answer 23

macrolide (clarithromycin or azithromycin)
rifampin/firamycin
ethambutol

Question 24

m. avium prophylaxis in HIV pts

Answer 24

clarithroycin or azithromycin

Question 25

two different types of leprosy (m. leprae)

Answer 25

lepromatous form (disfiguring skin leisons, skin test negative, large numbers of organisms)

tuberculoid form (hypopigmented plaques, milder form, skin test positive)

Question 26

treatment of leprosy

Answer 26

dapsone
clofazimine
rifampin

therapy last for years

Question 27

MOA dapsone

Answer 27

structural analog of para-amino-benzoic acid

- a competitive inhibitor of folic acid synthesis

Question 28

MOA clofazimine

Answer 28

bactericidal dye with uncertain MOA

leaves a red-brown/black skin discoloration

Question 29

what drugs should be started for treatment of presumptive pulmonary tb?

Answer 29

RIPE

Question 30

alcoholism is a risk factor with traditional tb treatment why?

Answer 30

increased risk of developing hepatotoxicity from both isoniazid and pyrazinamide

Question 31

if HIV/AID use which “r” drug?

Answer 31

use rifabutin, don’t use rifampin