C.2. Antimycobacterial drugs

Question 1

list the 1st line antimycobacterial agents

Answer 1

'RIPE'
Rifampin
Isoniazid (INH)
Pyrazinamide
Ethambutol

Question 2

list the 2nd line antimycobacterial agents

Answer 2

streptomycin 
Amikacin
Kanamycin 
Cycloserine
Ciprofloxacin
Ofloxacin
linezolid

Question 3

what is the MoA of Isoniazid?

Answer 3

inhibits synthesis of mycolic acid

bactericidal effect

Question 4

what is the mechanism of resistance of Isoniazid?

Answer 4

deletions in katG gene

Question 5

what is the most important drug used in TB treatment?

Answer 5

Isoniazid

Question 6

what are the indications for TB prophylaxis (3)?

Answer 6

1. TB exposure in young children, TST negative
2. TST conversion in the past 2 years
3. TST reactors with high risk (diabetes, HIV positive, immunosuppressive treatment, leukemia)

Question 7

what is the MoA of Rifampin?

Answer 7

inhibits DNA-dependent RNA polymerase (transcription inhibitor)
bactericidal effect

Question 8

what is the mechanism of resistance of Rifampin?

Answer 8

alteration of the polymerase enzyme

Question 9

which agents are given prophylaxis TB?

Answer 9

Isoniazid (INH) or Rifampin

Question 10

how are TB and leprosy drugs given?

Answer 10

Orally

Question 11

what are the other indications for Rifampin other than TB?

Answer 11

1. leprosy
2. in combination with vancomycin–>active against MRSA and PRSP
3. Prophylaxis: N.meningitidis, H. influenza, staphylococci

Question 12

what is the MoA of Ethambutol?

Answer 12

inhibits synthesis of arabinogalactan

Question 13

what is the mechanism of resistance of Ethambutol

Answer 13

alteration of drug target

Question 14

which TB drug is an inhibitor of CYP450 enzymes?

Answer 14

Isoniazid

Question 15

which TB drug is an inducer of CYP450 enzymes?

Answer 15

Rifampin

Question 16

mechanism of action of Pyrazinamide

Answer 16

unknown

bacteriostatic

Question 17

mechanism of resistance of Pyrazinamide

Answer 17

mutations in gene encoding enzymes involved in drug activation

Question 18

which drugs T1/2 ↑ in renal/hepatic impairment?

Answer 18

pyrazinamide

Question 19

which TB drug should be avoided in pregnancy?

Answer 19

pyrazinamide

Question 20

which TB agents are prodrugs (activation by catalase)?

Answer 20

isoniazid

pyrazinamide

Question 21

how long is the phase I TB treatment? (‘RIPE’)

Answer 21

2 months

Question 22

how long is the phase II TB treatment? (‘RI’)

Answer 22

4-7 months

Question 23

what is the T1/2 of Isoniazid ?

Answer 23

fast acetylators–> 60-90 min’

slow acetylatos–> 3-4 h’

Question 24

SE of Isoniazid (6)

Answer 24

1. Neurotoxicity due to B₆ deficiency- insomnia, muscle twitching, peripheral neuritis
2. sideroblastic anemia
3. hepatotoxicity
4. drug-induced lupus
5. acute hemolysis in G6PD deficient patients
6. AG metabolic acidosis

Question 25

SE of Rifampin (5)

Answer 25

1. nephrotoxicity 2. skin rash 3. thrombocytopenia 4. hepatotoxicity 5. orange colored secretions (saliva, tears, urine)

Question 26

SE of ethambutol (2)

Answer 26

1. dose-dependent visual disturbances | 2. headache, confusion

Question 27

SE's of pyrazinamide (4)

Answer 27

1. non-gout polyarthralgia 2. hyperuricemia 3. hepatotoxicity 4. skin rash

Question 28

when do we give 2nd line agents for TB?

Answer 28

when the TB is resistant to the 1st line agents

Question 29

which drug is used for the treatment of life-threatening associated diseases in TB (meningitis, miliary dissemination, end -organ TB)?

Answer 29

streptomycin

Question 30

which agents are used when TB is resistant to streptomycin?

Answer 30

Amikacin | Kanamycin

Question 31

what are streptomycin, Amikacin and kanamycin?

Answer 31

Aminoglycosides | protein synthesis inhibitor

Question 32

what is Cycloserine?

Answer 32

cell wall active Ab | cyclic analogue of D- ala--> inhibits peptidoglycan synthesis

Question 33

what is Ciprofloxacin and Oflxacin?

Answer 33

2nd gen' fluoroquinolones | nucleic acid synthesis inhibitor

Question 34

what is Linezolid?

Answer 34

protein synthesis inhibitor

Question 35

what does MDR TB mean?

Answer 35

multidrug resistant M. Tuberculosis | resistant to at lease Isoniazid and Rifampin

Question 36

what does XDR TB mean?

Answer 36

extensively drug-resistant M. Tuberculosis | resistant to fluoroquinolones and at least 1 additional 2nd line drugs

Question 37

how do we treat MDR -TB and XDR-TB and for how long?

Answer 37

extensive use of 2nd line agents 18-24 months +12 months after sputum culture is negative maybe surgery for lung abscess

Question 38

what are the drugs used for leprosy?

Answer 38

Dapsone+Rifamin +/- Clofazimine

Question 39

which drug is also used as an alternative treatment for Pneumocystis jirovecii pneumonia in AIDS patients

Answer 39

Dapsone

Question 40

what is the T1/2 of Clofazimine?

Answer 40

up to 2 m'

Question 41

what is the mechanism of Dapsone?

Answer 41

inhibits folic acid synthesis | bacteriostatic

Question 42

what is the mechanism of clofazimine?

Answer 42

unknown | bacteriostatic

Question 43

what are the side effects of Dapsone?

Answer 43

GI symptoms skin rash, fever methemoglobinemia acute hemolysis in G6PD deficient patients

Question 44

what are the drugs used against M. avium complex?

Answer 44

Clarithromycin +Ethambutol +/-Rifabutin *prophylaxis treatment in AIDS patients