Antimycobacterial Drugs

Question 1

mycobacerium tuberulosis

• structural characteristics
• stain
• diagnostic hallmark

Answer 1

• lipid rich wall (mycolic acid)
• acid-fast stain
• histological hallmark: caseating granulomas

Question 2

dx of active tuberculosis?

Answer 2

tuberculin skin test

Question 3

what is the standard therapy (what drugs are taken and for how long) for active TB?

Answer 3

• 6-month combination therapy:
  
  • inititiation phase (2 mos):
    
    • rifampin + isoniazid + pyrazinamide + ethambutol (“RIPE”)
  • continuation phase (remaining 4 mos):
    
    • rifampin + isoniazid

Question 4

which of the RIPE drugs are the most effective?

Answer 4

rifampin, isoniazid

Question 5

what is the second line treatment for active TB?

Answer 5

• streptomycin
• amikacin
• flouroquinilones - moxifloxacin, levofloxicin

Question 6

rifampin:

• MOA
• uses
• pharmokinetics
• AES

Answer 6

rifampin:

• MOA: blocks DNA dependent RNA Polymerase –> inhibits RNA synthesis (bacteriacidal)
• uses: prophylaxis / latent / active TB
• PK:
  
  • must be taken on empty stomach - food dec absorption
  • induces:
    
    • 3A4, 2D6, 1A2, BC9
• AES:
  
  • hepatotoxicity
  • thrombocytopenia
  • red tear, sweat, urine
  • inactivation of oral contraceptives

“hate the rich, okay”

Question 7

how to microbes develop resistance to rifampin?

Answer 7

via mutating the rpoB gene coding DNA Dependent RNA Polymase.

new polymerase not inhibited tby rampin

Question 8

isoniazid

• MOA
• uses
• pharmokinetics
• AEs

Answer 8

• MOA: inhibits cell wall (mycolic acid) synthesis (bactericidal)
  
  • is a prodrug that must be activated by mycobacterial catalase-peroxidase (KatG) ennzyme
• uses: prophylasis / latent / active TB
• PK:
  
  • prodrug
  • metbolized in liver –> byproduct (acetylhydralazine ) = toxic
    
    • binds hepatic proteins, reduces glutathione lvel
• AEs:
  
  • peripheral neuropathy: iso lowers Vit B6 levels, needed myelin & GABA synhesis
    
    • –> seizures
  • hepatotoxicity: iso lowers glutathione

Question 9

what remedy is given for isoniazid induced peripheral neuropathy?

Answer 9

piroxidine (Vit B6)

Question 10

pyrazinamide

• MOA
• uses
• pharmokinetics
• AEs

Answer 10

• MOA - inhibits FA synthesis
• uses - active TB
• PK - best CNS penetration of TB drugs
• AEs:
  
  • Hepatotoxicity
  • Hyperuricemia
    
    • –> Gout, arthralgia
      
      • ​“pyrates go arghhh”

Question 11

ethambutol

• MOA
• uses
• PK
• AE

Answer 11

• MOA - inhibits cell wall (arabinogalactan) synthesis
• uses - active TB
• AEs:
  
  • optic neuritis: irreversible lesions in optic nerve/chiasm
  • red-green color blindless

E = eyes - side effects related to vision: lesions, color blindness

Question 12

list the first line TB drugs and what types of TB (prophylaxis, latent, active) they can treat

Answer 12

• rifampin/isoniazid: prophylaxis, latent, active
• pyrazinamide, ethambutol: active

Question 13

what first line TB drug has the best CNS penetration?

Answer 13

pyrazinamide

Question 14

what 1st line TB drug can cause thrombocytopenia?

Answer 14

rifampin

Question 15

what 1st line rifampin agent causes urate retention & what can this do?

Answer 15

pyrazinamide - gout, arthralgia

Question 16

what 1st line TB drug can cause peripheral neuropathy?

Answer 16

iaoniazid - causes Vit B deficiency –> dec myelin, GABA

tx: piroxidine (Vit B6)

Question 17

what 1st line TB drug has visual side effects and what are they?

Answer 17

• ethambutol (e = eye):
  
  • optic neuritis: irreversible lesions on optic nerve
  • red-green color blindness

Question 18

which 1st line drugs for TB can cause hepatotoxicity & which one is the most severe?

Answer 18

all (rifampin, isoniazid, pyrazinimide) except for ethambutol

• isoniazid worst hepatotoxicity: when metabolized by liver, toxic byproduct (acetylhydralizine) product –> reduces glutathione levels
• pyrazinimde = dose dependent

Question 19

tx for TB resistant to isoniazid only?

Answer 19

1. give 3 other 1st drugs (rifamin, pyriazinamide, ethabumol) for longer, or
2. flouroquinilones

Question 20

tx for TB resistant to rifampin only?

Answer 20

• tx with other 3 1st line drugs
• add streptomycin / amikacin

Question 21

what 2nd ilne TB drug can cross the BBB?

Answer 21

cycloserine

Question 22

tx for TB resistant to both rifampin and isonizid?

Answer 22

AKA: MDR-TB

• dont use other 1st line drugs
• use
  
  • 2nd line: streptomycin, amikacin, flouroquinilones
  • beaquelline

Question 23

bedaquiline

• indications
• MOA
• AEs

Answer 23

• use: for MDR-TB in adults/children
• MOA: ATP synthase inhibitor
• AE:
  
  • nausea
  • QT prolongation

Question 24

what is extensive drug resistant (TB) and how it is treated?

Answer 24

• TB resistant to rifampin, isoniazid AND flouroquinolones + either
  
  • aminoglycosides
  • caprreomycin
• tx - expertion consultation needed
  
  • BPaL: bedaquiline + pretomanid + linezolid
    
    • pretty bad lineup
  • possible surgery

Question 25

what drugs should and should not be used for latent TB?

Answer 25

* should - rifampin, isoniazid * should not - pyrazinimide , ethambutol

Question 26

tx for HIV-TB co-infection?

Answer 26

* 1st choice --\> rifampin +/- isoniazid * 2nd choice --\> isoniazid monotherapy. do if * HIV pt has latent TB * rifamycin C/I

Question 27

tx regmin for TB in pregnancy?

Answer 27

* 9 month regimen * 2 mos: rifampin + isoniazid + **_e_**thambutol (same as normal regimen only you dont use it _p_) * 7 mos: rif + iso

Question 28

leprosy * etiologic agent * tx?

Answer 28

* *mycobacterium leprae* * tx based on form * tuberuloid form: **dapsone** + rifampin * lepromatous form: **dapsone** + **clofazimine** + rifampin

Question 29

dapsone * MOA * uses * AEs?

Answer 29

* MOA: inhibits **folic acid synthesis** (bacteriostatis) * use: **leprosy** - both tubercoid/lepromatous form * AE * hemolytic anemia in GPD deficiency

Question 30

clofazamine * MOA * uses * AEs

Answer 30

* inhibits **DNA template function** * use: leprosy * dapsrone resistant * in combo w/ dapsone for lepromatous form * AE: brown skin dislocoration

Question 31

tx for *mycobacterium avium complex* (MAC)?

Answer 31

* prophylaxis: azithromycin * active disease: azithromycin + ethambutol + rifabutin (*not rifampin*)

Question 32

which 1st line tx for tuberculosis MUST be taken on an empty stomach?

Answer 32

rifampin