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Pharmacology > Antimycobacterial Drugs > Flashcards

Antimycobacterial Drugs Flashcards

1
Q

mycobacerium tuberulosis

  • structural characteristics
  • stain
  • diagnostic hallmark
A
  • lipid rich wall (mycolic acid)
  • acid-fast stain
  • histological hallmark: caseating granulomas
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2
Q

dx of active tuberculosis?

A

tuberculin skin test

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3
Q

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

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

which of the RIPE drugs are the most effective?

A

rifampin, isoniazid

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5
Q

what is the second line treatment for active TB?

A
  • streptomycin
  • amikacin
  • flouroquinilones - moxifloxacin, levofloxicin
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6
Q

rifampin:

  • MOA
  • uses
  • pharmokinetics
  • AES
A

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”

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7
Q

how to microbes develop resistance to rifampin?

A

via mutating the rpoB gene coding DNA Dependent RNA Polymase.

new polymerase not inhibited tby rampin

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8
Q

isoniazid

  • MOA
  • uses
  • pharmokinetics
  • AEs
A
  • 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
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9
Q

what remedy is given for isoniazid induced peripheral neuropathy?

A

piroxidine (Vit B6)

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10
Q

pyrazinamide

  • MOA
  • uses
  • pharmokinetics
  • AEs
A
  • MOA - inhibits FA synthesis
  • uses - active TB
  • PK - best CNS penetration of TB drugs
  • AEs:
    • Hepatotoxicity
    • Hyperuricemia
      • –> Gout, arthralgia
        • ​“pyrates go arghhh”
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11
Q

ethambutol

  • MOA
  • uses
  • PK
  • AE
A
  • 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

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12
Q

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

A
  • rifampin/isoniazid: prophylaxis, latent, active
  • pyrazinamide, ethambutol: active
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13
Q

what first line TB drug has the best CNS penetration?

A

pyrazinamide

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14
Q

what 1st line TB drug can cause thrombocytopenia?

A

rifampin

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15
Q

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

A

pyrazinamide - gout, arthralgia

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16
Q

what 1st line TB drug can cause peripheral neuropathy?

A

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

tx: piroxidine (Vit B6)

17
Q

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

A
  • ethambutol (e = eye):
    • optic neuritis: irreversible lesions on optic nerve
    • red-green color blindness
18
Q

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

A

all (rifampin, isoniazid, pyrazinimide) except for ethambutol

  • isoniazid worst hepatotoxicity: when metabolized by liver, toxic byproduct (acetylhydralizine) product –> reduces glutathione levels
  • pyrazinimde = dose dependent
19
Q

tx for TB resistant to isoniazid only?

A
  1. give 3 other 1st drugs (rifamin, pyriazinamide, ethabumol) for longer, or
  2. flouroquinilones
20
Q

tx for TB resistant to rifampin only?

A
  • tx with other 3 1st line drugs
  • add streptomycin / amikacin
21
Q

what 2nd ilne TB drug can cross the BBB?

A

cycloserine

22
Q

tx for TB resistant to both rifampin and isonizid?

A

AKA: MDR-TB

  • dont use other 1st line drugs
  • use
    • 2nd line: streptomycin, amikacin, flouroquinilones
    • beaquelline
23
Q

bedaquiline

  • indications
  • MOA
  • AEs
A
  • use: for MDR-TB in adults/children
  • MOA: ATP synthase inhibitor
  • AE:
    • nausea
    • QT prolongation
24
Q

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

A
  • TB resistant to rifampin, isoniazid AND flouroquinolones + either
    • aminoglycosides
    • caprreomycin
  • tx - expertion consultation needed
    • BPaL: bedaquiline + pretomanid + linezolid
      • pretty bad lineup
    • possible surgery
25
Q

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

A
  • should - rifampin, isoniazid
  • should not - pyrazinimide , ethambutol
26
Q

tx for HIV-TB co-infection?

A
  • 1st choice –> rifampin +/- isoniazid
  • 2nd choice –> isoniazid monotherapy. do if
    • HIV pt has latent TB
    • rifamycin C/I
27
Q

tx regmin for TB in pregnancy?

A
  • 9 month regimen
    • 2 mos: rifampin + isoniazid + ethambutol (same as normal regimen only you dont use it p)
    • 7 mos: rif + iso
28
Q

leprosy

  • etiologic agent
  • tx?
A
  • mycobacterium leprae
  • tx based on form
    • tuberuloid form: dapsone + rifampin
    • lepromatous form: dapsone + clofazimine + rifampin
29
Q

dapsone

  • MOA
  • uses
  • AEs?
A
  • MOA: inhibits folic acid synthesis (bacteriostatis)
  • use: leprosy - both tubercoid/lepromatous form
  • AE
    • hemolytic anemia in GPD deficiency
30
Q

clofazamine

  • MOA
  • uses
  • AEs
A
  • inhibits DNA template function
  • use: leprosy
    • dapsrone resistant
    • in combo w/ dapsone for lepromatous form
  • AE: brown skin dislocoration
31
Q

tx for mycobacterium avium complex (MAC)?

A
  • prophylaxis: azithromycin
  • active disease: azithromycin + ethambutol + rifabutin (not rifampin)
32
Q

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

A

rifampin

Pharmacology (4 decks)

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