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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
Isoniazid is a MAO inhibitor. True/False
True. Avoid taking tyramine-rich foods with isoniazid
26
What are the adverse effects when taking **isoniazid**?
1. Peripheral neuropathy 2. Hepatotoxicity 3. DDI interactions
27
Which anti-TB drug is the least hepatotoxic?
Rifampicin
28
What is the mechanism of action of **pyrazinamide**?
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
What is the main mechanism of resistance against **pyrazinamide**?
**Mutations in the gene encoding the pyrazinamidase enzyme** preventing pyrazinamide from being converted to its active form
30
What is the route of administration of **pyrazinamide**?
Oral
31
Is **pyrazinamide** safe for use during pregnancy?
Cat C. WHO says safe.
32
How is **pyrazinamide** eliminated?
Metabolized in liver and excreted by kidney
33
What is an important DDI of **pyrazinamide**?
Rifampicin & isoniazid can potentiate the hepatotoxic & nephrotoxic effects of pyrazinamide
34
Which anti-TB drug is the most hepatotoxic?
Pyrazinamide
35
What are the adverse effects when taking **pyrazinamide**?
1. GI symptoms 2. Photosensitivity 3. Hyperuricemia & arthralgia (gout-like symptoms) 4. Exanthema
36
What is the mechanism of action of **ethambutol**?
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
What is the main mechanism of resistance against **ethambutol**?
Mutations in the embB gene
38
What is the route of administration of **ethambutol**?
Oral
39
How is **ethambutol** eliminated?
25% metabolized in liver and 50% excreted unchanged in the urine
40
Which anti-TB drugs require dose-adjustment in patients with liver failure?
RIP
41
Which anti-TB drugs require dose-adjustments in patients with renal dysfunction?
PE
42
Is **ethambutol** safe for use during pregnancy?
Cat C. WHO says non-teratogenic
43
What are the adverse effects when taking **ethambutol**?
1. Visual toxicity 2. Hyperuricemia/gout
44
What is the mechanism of action of **streptomycin**?
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
What are the adverse effects when taking **streptomycin**?
PONS
46
What is the route of administration of **streptomycin**?
IM
47
How is **streptomycin** eliminated?
Renal clearance

Anti-microbes (9 decks)

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