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PR3151 Antibiotics + Antifungals > Anti-Tuberculosis > Flashcards

Anti-Tuberculosis Flashcards

1
Q

Is Mycobacterium Tuberculosis aerobic or anaerobic?

A

Aerobic, rod shaped, acid-fast bacilli

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2
Q

According to MOH guidelines, what tests must be done prior to TB tx initiation?

A
  1. Liver enzymes
  2. Visual acuity
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3
Q

According to MOH guidelines, what must be monitored at each visit?

A
  • Weight, drug dosages adjusted accordingly
  • Risk factors for drug-induced hepatitis
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4
Q

How long is the standard TB tx?

A

6 months
- 2 months intensive phase: daily RIPE
- 4 months continuation phase: daily/3x per week RI

*Restart therapy if non-compliance for 2 weeks

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5
Q

What are common adverse effects among all first line anti-TB drugs?

A
  1. Cutaneous reactions (pruritus, rash) - be alert for SJS, DRESS, TEN

RIP only:
2. GI symptoms: anorexia, nausea, abdominal discomfort
3. Hepatitis (*monitor infant for jaundice if breastfeeding)

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6
Q

Which of the 4 drugs in RIPE require dose adjustment in renal and hepatic impairment?

A

Renal impairment: PE
Hepatic impairment: RIP

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7
Q

Which drugs (RIPE) are batericidal?

A

Bactericidal: RIP
Bacteriostatic: E

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8
Q

Pyrazinamide is only indicated for ____ TB

A

Active

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9
Q

Which drugs (RIPE) have good CSF penetration?

*All are given oral

A

Good CSF penetration: IP
Poor CSF penetration: RE

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10
Q

Rifampicin is indicated for Tuberculosis caused by Mycobacterium Tuberculosis and _____ caused by __________

A

Leprosy caused by Mycobacterium leprae

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11
Q

Rifampicin inhibits gene transcription by blocking which enzyme?

A

DNA-dependent RNA polymerase

=> thus, prevent synthesis of mRNA and proteins, cause cell death

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12
Q

How is Rifampicin eliminated?

A

Hepatic metabolism, rapidly excreted in bile

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13
Q

Which of the 4 RIPE drugs can be used in pregnancy?

A

All are Cat C but weight risk and benefit

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14
Q

Mothers and neonates born to mothers under treatment with Rifampicin should be given _____ to prevent _________

A

Vitamin K

Prevent postpartum hemorrhage
*Because Rifampicin can cause thrombocytopenia

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15
Q

Rifampicin is a CYP450 ______, while Isoniazid is a CYP450 ______

A

Rifampicin: CYP450 inducer
Isoniazid: CYP450 inhibitor

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16
Q

What are Rifampicin Adverse effects?

A
  1. GI
  2. Cutaneous
  3. Hepatitis
  4. Flu-like syndrome (fever, chills, malaise)
  5. Orange discoloration of body fluids (e.g., sweat, urine, tears)
  6. (RARE) respiratory syndrome - SOB
  7. (RARE) thrombocytopenia, hemolytic anemia, acute renal failure *if these occur, stop and never give again as they are severe immune mediated reactions
17
Q

Which of the 4 RIPE can be used for prophylaxis?

A

Isoniazid

18
Q

Isoniazid is a prodrug activated by ________ enzyme.
This causes production of ___________ that can inhibit formation of _______ and causes _________.

A

Catalase-peroxidase enzyme

Activation of isoniazid produces oxygen-derived free radicals

Inhibit formation of mycolic acid of the bacterial cell wall and causes DNA damage

19
Q

Isoniazid resistance can be due to
1. Mutation of catalase peroxidase enzyme
2. Mutation of ______

A

Mutation of the regulatory genes involved in mycolic acid synthesis

20
Q

Isoniazid undergoes metabolism in the liver through __________

A

Acetylation by N-acetyltransferase

*Inactive metabolites are excreted by kidneys

21
Q

Explain why Isoniazid can cause hepatotoxicity

A

Two metabolic pathways of isoniazid

  1. NAT2 pathway => acetylhydrazine
  2. Amidase pathway => hydrazine (hepatotoxic metabolite)
22
Q

Pregnant women receiving Isoniazid should receive ________ because Isoniazid ___________________

A

Pyridoxine (Vit B6) supplementation 10mg daily

Isoniazid interferes competitively with pyridoxine metabolism

Isoniazid metabolites can also react with pyridoxine to deactivate it

23
Q

What is the role of pyridoxine?

A

Pyridoxine metabolised in the liver to active Vit B6, pyridoxal phosphate

Pyridoxal phosphate is involved in metabolic processes + CNS function

Hence, Vit B6 deficiency causes risk of peripheral neuropathy

24
Q

Explain the food-drug and drug-drug interactions of Isoniazid

A

Food-drug:
- Carbohydrates decrease absorption
- Avoid tyramine and histamine rich food as Isoniazid as MAO and histaminase inhibitory activity => flushing headache, serotonin syndrome

DDI:
- Antacids (incr pH) decrease absorption (*E as well)
- Isoniazid is a CYP450 inhibitor

25
Q

Isoniazid has similar structure to ______, but no cross-resistance of Mycobacterium Tuberculosis

A

Pyrazinamide

26
Q

Pyrazinamide is most effective in eliminating _______

Pyrazinamide also has potent sterilizing effect

A

Persisters (these persistent bacilli can cause relapse)

27
Q

Pyrazinamide is a prodrug converted by pyrazinamidase to _______ which acts by ___________

A

Pyrazinoic acid, accumulation of pyrazinoic acid decreases intracellular pH to levels that inactivate critical pathways for survival

28
Q

Pyrazinamide metabolites are eliminated by _______

When is dose adj required?

A

Kidneys

Therefore can accumulate in kidney impairment require dose adj

Also require dose adj in liver failure since it is a hepatotoxic drug (usually avoid in these pt)

29
Q

Which of the 4 drugs RIPE cause photosensitivity?

A

Pyrazinamide

30
Q

Which of the 4 RIPE drugs cause hyperuricemia and gout-like symptoms (arthralgia)?

A

Pyrazinamide and Ethambutol

P: inhibit tubular secretion of uric acid
E: reduce renal excretion of uric acid

31
Q

Ethambutol inhibits the arabinosyltransferase enzyme encoded by the embB gene.

This enzyme is involved in ________

A

The polymerization of arabinose to arabinogalactan, a principal polysaccharide on the mycobacterial cell wall

Therefore Ethambutol interferes with this, affecting the intergrity of mycobacterial cell wall, causing entry of lipophilic antibiotics

32
Q

How is ethambutol eliminated?

A

25% metabolized in liver
24% excreted unchanged in feces
50% excreted unchanged in urine

33
Q

There is higher risk of visual toxicity caused by Ethambutol in patients who:

A
  • have kidney failure
  • elderly
  • prolonged treatment >2months
  • taking higher dose of the drug
34
Q

Can Ethambutol be used in breastfeeding?

A

Yes, compatible

(RIP => must monitor for baby jaundice)

35
Q

Ethambutol serum conc. may be reduced by concomitant _____

A

Antacids - increase in pH

36
Q

Which drug may be used to replace Ethambutol as 1st line anti-TB?

A

Streptomycin (IM) - aminoglycoside

37
Q

High index of suspicion of drug resistant TB in patients who:

A
  1. Previously treated for TB
  2. Failed TB treatment
  3. Known contacts of pt with drug resistant TB
  4. Visited country with high prevalence of drug resistant TB
38
Q

What drugs are second line for MDR-TB?

A

Respiratory quinolones (Levo and Moxifloxacin)

39
Q

How is cure for TB demonstrated?

A

Negative sputum spear or culture in the last month of treatment (6th month) and on at least one previous occasion (usually in the 5th month)

*Tx failure:
- Positive sputum at or after 5 months
- Nonconversion of sputum cultures after 2 months (means likely risk of relapse)

**Recall usually after 2 months or RIPE majority should have been eliminated

PR3151 Antibiotics + Antifungals (5 decks)

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