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Anti-microbes > TB drugs > Flashcards

TB drugs Flashcards

1
Q

What are the 4 anti-TB drugs?

A

Rifampicin, Isoniazid, Pyrazinamide & Ethambutol

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2
Q

What is the recommended 6-month regimen?

A

2 months daily RI
4 months RIPE daily/3x a week

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3
Q

Why is anti-TB treatment so prolonged?

A

In an active TB patient, there are several subpopulations of Mycobacterium tuberculosis.

Hence, TB treatment has to be prolonged to reduce transmission and to ensure killing of slowly growing/semi-dormant organisms

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4
Q

Why is monotherapy avoided in active TB?

A

Monotherapy may select for a drug resistant subpopulation of Mycobacterium tuberculosis

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5
Q

What is an adverse effect exhibited by all first-line anti-TB drugs?

A

Cutaneous reactions

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6
Q

Which anti-TB drugs cause GI symptoms?

A

RIP

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7
Q

Which anti-TB drug may cause visual toxicity?

A

Ethambutol

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8
Q

What is a major concern for all first-line anti-TB drugs?

A

Hepatotoxicity

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9
Q

What is the mechanism of action of rifampicin?

A

Rifampicin inhibits gene transcription of mycobacteria by blocking the DNA-dependent RNA polymerase, preventing the bacillus from synthesizing mRNA & proteins

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10
Q

What is the main cause of resistance to rifampicin?

A

Mutations in the gene that encodes the RNA polymerase beta chain

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11
Q

What is the route of administration of rifampicin?

A

Oral

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12
Q

How is rifampicin eliminated?

A

Hepatic metabolism and eliminated in bile

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13
Q

What is an important DDI caused by rifampicin?

A

Rifampicin is a CYP450 enzyme inducer

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14
Q

What are the important adverse effects when taking rifampicin?

A
  1. Cutaneous syndrome
  2. Hepatotoxicity
  3. Orange discolouration of bodily fluids
  4. DDI caused by induction of CYP450 enzymes
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15
Q

Is rifampicin safe to use in pregnancy?

A

Cat C. Don’t give unless bopes.

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16
Q

If rifampicin treatment is necessary during pregnancy, what should be given alongside to prevent postpartum haemorrhage?

A

Vit K

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17
Q

What is the mechanism of action of isoniazid?

A

It is a prodrug activated by the catalase-peroxidase enzyme of Mycobacterium tuberculosis

Activation produces O2-derived free radicals that inhibit the formation of mycolic acids of the bacterial cell wall, cause DNA damage and hence cell death

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18
Q

What is the route of administration of isoniazid?

A

Oral

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19
Q

How is isoniazid eliminated?

A

Metabolized in the liver & excreted by the kidney

20
Q

What are the 2 main mechanisms of resistance against isoniazid?

A
  1. Mutations to the catalase-peroxidase enzyme
  2. Mutations in the regulatory genes involved in mycolic acid synthesis
21
Q

Is isoniazid safe for use in pregnancy?

A

Cat C. Don’t give unless bopes

22
Q

What should be given alongside isoniazid to prevent peripheral neuropathy secondary to B6 deficiency?

A

Pyridoxine

23
Q

What foods should be avoided with isoniazid?

A

Eat on empty stomach and avoid tyramine & histamine-rich foods

24
Q

What are the potential DDI caused by isoniazid?

A

Isoniazid is a CYP450 enzyme inhibitor

25
Q

Isoniazid is a MAO inhibitor.

True/False

A

True. Avoid taking tyramine-rich foods with isoniazid

26
Q

What are the adverse effects when taking isoniazid?

A
  1. Peripheral neuropathy
  2. Hepatotoxicity
  3. DDI interactions
27
Q

Which anti-TB drug is the least hepatotoxic?

A

Rifampicin

28
Q

What is the mechanism of action of pyrazinamide?

A

Pyrazinamide is a prodrug that is converted to its active form by the microbial enzymes pyrazinamidase.

It is converted into pyrazinoic acid in the bacterial cytoplasm and decreases the intracellular pH to levels that cause the inactivation of critical pathways necessary for the survival of the bacteria

29
Q

What is the main mechanism of resistance against pyrazinamide?

A

Mutations in the gene encoding the pyrazinamidase enzyme preventing pyrazinamide from being converted to its active form

30
Q

What is the route of administration of pyrazinamide?

A

Oral

31
Q

Is pyrazinamide safe for use during pregnancy?

A

Cat C. WHO says safe.

32
Q

How is pyrazinamide eliminated?

A

Metabolized in liver and excreted by kidney

33
Q

What is an important DDI of pyrazinamide?

A

Rifampicin & isoniazid can potentiate the hepatotoxic & nephrotoxic effects of pyrazinamide

34
Q

Which anti-TB drug is the most hepatotoxic?

A

Pyrazinamide

35
Q

What are the adverse effects when taking pyrazinamide?

A
  1. GI symptoms
  2. Photosensitivity
  3. Hyperuricemia & arthralgia (gout-like symptoms)
  4. Exanthema
36
Q

What is the mechanism of action of ethambutol?

A

Ethambutol inhibits the arabinosyltransferase enzyme encoded by the embB gene and interferes with the polymerization of arabinose into arabinogalactan, affecting the integrity of the Mycobacterium tuberculosis cell wall and thus facilitates the entry of lipphilic antibiotics

37
Q

What is the main mechanism of resistance against ethambutol?

A

Mutations in the embB gene

38
Q

What is the route of administration of ethambutol?

A

Oral

39
Q

How is ethambutol eliminated?

A

25% metabolized in liver and 50% excreted unchanged in the urine

40
Q

Which anti-TB drugs require dose-adjustment in patients with liver failure?

A

RIP

41
Q

Which anti-TB drugs require dose-adjustments in patients with renal dysfunction?

A

PE

42
Q

Is ethambutol safe for use during pregnancy?

A

Cat C. WHO says non-teratogenic

43
Q

What are the adverse effects when taking ethambutol?

A
  1. Visual toxicity
  2. Hyperuricemia/gout
44
Q

What is the mechanism of action of streptomycin?

A

It binds to the 30S subunit, causing a conformational change in the ribosome. This prevents the formation of the initiation complex and causes the misreading of codons as wrong amino acyl tRNAs can bind to the A site without matching codon present in the mRNA and inhibit translocation

45
Q

What are the adverse effects when taking streptomycin?

A

PONS

46
Q

What is the route of administration of streptomycin?

A

IM

47
Q

How is streptomycin eliminated?

A

Renal clearance

Anti-microbes (9 decks)

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