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Flashcards in Antimycobacterials Deck (44)
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1

describe the image below 

  • Mycobacterium tuberculosis
  • Small, aerobic, non-motile, bacillus
  • Can lead to serious infections of the lungs, genitourinary tract, skeleton & meninges

2

list 1st line TB drugs

"RIPE"

  • Rifampin
    • Rifabutin (1st line in HIV pts)
  • Isoniazid
  • Pyrazinamide
  • Ethambutol

3

list 2nd line TB drugs

"SALE"

  • Streptomycin
  • Amikacin
  • Levofloxacin
  • Ethionamide

4

describe people who are at high risk of TB/need prophylaxis 

  • Persons who have been recently infected with TB bacteria
  • Persons with medical conditions that weaken the immune system

5

describe isoniazid 

  • Synthetic analog of pyridoxine
  • First-line agent
  • Most potent antitubercular drug
  • Part of COMBINATION THERAPY for active infection

6

___ is the sole drug in treatment of latent infection

Isoniazid is the sole drug in treatment of latent infection

7

Isoniazid is converted to its active form via ___ and targets enzymes required in _____ synthesis such as: 

Isoniazid is converted to its active form via catalase- peroxidase - KatG and targets required in mycolic acid synthesis such as: 

  • enoyl acyl carrier protein reductase (InhA)
  • b-ketoacyl-ACP synthase (KasA)

8

what happens if INH is used alone? 

resistant organisms rapidly emerge 

9

how does TB create resistance against INH? 

  • Chromosomal mutations resulting in:
    • mutation of deletion of KatG
    • mutations of acyl carrier proteins
    • overexpression of inhA
  • Cross-resistance between other anti-tuberculosis drugs DOES NOT OCCUR

10

describe adverse effects of INH

  • Peripheral neuritis: corrected by pyridoxine supplementation
  • Hepatotoxicity: clinical hepatitis & idiosyncratic
  • CYP P450 inhibitor
  • Lupus-like syndrome: rare

11

is INH safe in pregnany? 

yes, use pyridoxine supplementation 

12

describe Rifamycins 

  • Rifampin & rifabutin
  • 1st drugs for treatment of all susceptible forms of TB
  • Part of COMBINATION THERAPY for active infections
  • Sole drug in treatment of latent infection (2nd line)

13

Rifampin is usually given in ____

Rifampin is usually given in combination

14

what is Rifampins MOA? 

Blocks transcription: binds to B subunit of bacterial DNA-dependent RNA polymerase → inhibition of RNA synthesis

15

describe resistance to Rifampin

  • Point mutations in rpoB (gene for B subunit of RNA polymerase) → decreased affinity of bacterial DNA-dependent RNA polymerase for drug
  • Decreased permeability

16

what are the clinical applications of Rifampin? 

  • Active TB infections
  • Latent TB in isoniazid intolerant patients
  • Leprosy (delays resistance to dapsone)
  • Prophylaxis for:
    • individuals exposed to meningitis
    • contacts of children with H.influenzae type B
  • MRSA (with vancomycin)

17

Rifampin is a strong ____ inducer

Rifampin is a strong CYP450 inducer

18

list the AEs with Rifampin 

  • Light chain proteinuria
  • GI distress
  • Occasional effects: thrombocytopenia, rashes, nephritis, liver dysfunction
  • Imparts harmless orange/red color to bodily fluids
  • Strongly induces CYP P450
  • SAFE IN PREGNANCY

19

describe what caused this

Rifampin! 

AE: yellow/orange bodily fluids 

20

___ is the referred drug for use in HIV patients (due to less induction of CYP enzymes)

Rifabutin is the referred drug for use in HIV patients (due to less induction of CYP enzymes)

 

Rifampin substitute to those that are intolerant

21

describe Ethambutol 

  • 1st line for all susceptible forms of TB
  • Specific for most strains of M.tuberculosis & M.kansasii
  • Used in combination with pyrazinamide, izoniazid & rifampin
  • Resistance occurs rapidly if used alone
    • mutations in emb gene

22

Ethambutol inhibits ____ leading to decreased carbohydrate polymerization of cell wall

Ethambutol inhibits arabinosyltransferase leading to decreased carbohydrate polymerization of cell wall

23

Ethambutol AEs

  • Dose-dependent visual disturbances (eg, red/green color blindness) – cannot be used in children too young to receive sight tests
  • Headache, confusion, hyperuricemia, peripheral neuritis (rare)
  • Safe in pregnancy

24

describe Pyrazinamide 

  • First-line agent
  • Used in combination with isoniazid, rifampin & ethambutol
  • Must be enzymatically hydrolysed to active pyrazinoic acid. Mechanism of action remains unclear
  • Resistant strains lack pyrazinamidase or have increased efflux of drug

25

Pyrazinamide AEs

  • Nongouty polyarthralgia (~ 40%)
  • Acute gouty arthritis (rare unless predisposed)
  • Hyperuricemia
  • Hepatotoxicity, myalgia, GI irritation, porphyria, rash, photosensitivity
  • Recommended for use in pregnancy when benefits outweigh risks

26

The aminoglycoside ____ is used for drug-resistant strains and is used in combinations for treatment of life-threatening tuberculous disease

The aminoglycoside streptomycin is used for drug-resistant strains

  • Life-threatening tuberculous disease:
    • meningitis
    • miliary dissemination
    • severe organ tuberculosis
  • Increasing frequency of resistance to streptomycin limits use of drug

27

what is the duration of treatment with INH for latent TB?

6-9 months

28

what is the duration of treatment with Rifampin with latent TB?

4 months 

29

describe the 2nd line TB drugs:

Amikacin

Levofloxacin

Ethionamide

What AE do they all have in common? 

  • Amikacin
    • Used for streptomycin- or multi-drug-resistant strains. Similar AE to streptomycin
  • Levofloxacin
    • Recommended for use against first-line drug- resistant strains. Always use in combination.
  • Ethionamide
    • Congener of INH (no cross-resistance). Severe GI irritation, adverse neurologic effects, hepatotoxicity & endocrine effects.
  • Common AE: Teratogenic 

30

describe standard regimens for empiric treatment of pulmonary TB: