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PR3124 > Anti-Tuberculosis Agents > Flashcards

Anti-Tuberculosis Agents Flashcards

1
Q

What is the regimen like for Anti-TB Agents

A

2mth intensive: R-I-P-E/S

4mth continuation: R-I (Daily/3x week)

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2
Q

What is an ADE common across all the 1st line Anti-TB agents?

A

Cutaneous reaction (Self-limiting, give anti-histamines)

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3
Q

MOA of Rifampicin

A

Blocks DNA-dependent RNA polymerase, prevents bacillus from synthesising mRNA & protein -> Cell Death

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4
Q

How does resistance against Rifampicin come about?

A

Mutations in gene

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5
Q

Clinical indications for Rifampicin

A

Active/Latent TB (~4mths)

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6
Q

Metabolism of Rifampicin

A

Hepatic

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7
Q

Use of Rifampicin in liver/kidney impairment?

A

Kidney: Ok
Liver: When benefit > risk

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8
Q

ADE of Rifampicin

A

1) Cutaneous reactions (Give anti-histamine)
2) Hepatitis
3) DDI (CYP450 inducer)
4) Orange discolouration of bodily fluids
5) Flu-like syndrome
6) Respiratory syndrome

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9
Q

How are Anti-TB agents administered?

A

Orally (Streptomycin: IM)

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10
Q

Can Rifampicin be given to pregnant women?

A 
If needed (Category C)
- Give Vitamin K to both neonates & mother to avoid postpartum haemorrhage
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11
Q

MOA of Isoniazid

A

Bactericidal effect
- Prodrug activated by catalase-peroxidase enzyme -> Produces O2-derived free radicals -> Inhibit formation of mycolic acids of bacterial cell wall

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12
Q

Resistance to Isoniazid

A

1) Mutations to catalase-peroxidase enzyme

2) Mutations of regulatory genes involved in mycolic acid synthesis

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13
Q

Clinical indications of Isoniazid

A

Active/Latent TB (~6-9mths)

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14
Q

Metabolism of Isoniazid

A

Liver through acetylation by N-acetyltransferase (Genetic Polymorphism)

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15
Q

CSF Penetration of Anti-TB

A

R: 10-20%
I: Good
P: Good, similar to that in plasma

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16
Q

Which Anti-TB agent should be taken with pyridoxine?

A

Isoniazid

17
Q

Why should Isoniazid be taken with pyridoxine

A

Peripheral neuropathy

  • Pyridoxine (Natural form of Vit B6)
  • Isoniazid interferes competitively with Pyridoxine metabolism -> Inhibit formation of active form of Vit B6
18
Q

Which drugs should not be taken with tyramine/histamine rich foods?

A

Isoniazid

Linezolid

19
Q

ADE of Isoniazid

A

1) Peripheral neuropathy (Pyridoxine)
2) Hepatitis
3) DDI (CYP450 Inducer)

20
Q

MOA of Pyrazinamide

A

MOST EFFECTIVE in eliminating persisters
Bactericidal (Potent sterilising effect)
- Prodrug converted to pyrazinoic acid by pyrazinamidase -> Accumulation of pyrazinoic acid decrease intracellular pH -> Inactivate critical pathways for bacterial survival

21
Q

Use of Pyrazinamide

A

Active TB

22
Q

Elimination of Pyrazinamide

A

Renal (Metabolites eliminated by kidney)

23
Q

ADE of Pyrazinamide

A

1) Hepatotoxicity** (MOST)
2) Photosensitivity
3) Hyperuricemia & arthralgia (gout-like symptoms)
4) Exanthema (widespread rash) & puritus
5) GIT

24
Q

MOA of Ethambutanol

A

Bacteriostatic
- Inhibits arabinosyltransferase enzyme encoded by embB gene -> Interferes with polymerization of arabinose into arabinogalactan (in c.w)

25
Q

Resistance to Ethambutanol

A

Mutations in embB gene

26
Q

Use of Ethambutanol

A

Pri TB (Combi with other Anti-TB agents)

27
Q

ADE of Ethambutanol

A

1) Visual toxicity
2) Risk with Kidney impairment & elderly (Prolonged treatment > 2 mths)
3) Hyperuricemia/gout

  • Toxicity is dose-dependent
28
Q

Caution for use of Ethambutanol

A 
Young children (visual acuity difficult to evaluate)
Kidney failure (Dose reduction)
29
Q

Which anti-TB agent should be taken apart from antacids (2h)

A

Ethambutanol

30
Q

Which Anti-TB agent is safe for kidney impairment?

A

R-I

31
Q

Which Anti-TB agent is safe for liver dysfunction?

A

Ethambutanol

32
Q

Which Anti-TB agent causes visual toxicity?

A

Ethambutanol

33
Q

Which Anti-TB agent causes peripheral neuropathy?

A

Isoniazid (Give pyridoxine)

34
Q

Which Anti-TB agent causes Hepatotoxicity?

A

R-I-P (Most hepatotoxicity)

35
Q

MOA of Aminoglycosides

A

Block formation of initiation complex -> Misreading of codon

36
Q

ADE of Aminoglycosides

A

Nephrotoxicity
Ototoxicity
Neuromuscular Paralysis

PR3124 (16 decks)

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