Anti-TB

Question 1

metabolism and excretion of rifampicin

Answer 1

liver; bile

Question 2

the adverse effect of rifampicin

Answer 2

cutaneous rxn: pruritis, flush

flu-like symptoms: fever, chills

hepatitis

orange discoloration of bodily fluids: tears, sweat, urine

Question 3

DDI of rifampicin (which CYP)

Answer 3

cyp450 inducer: decrease levels of warfarin, CS, hormonal contraceptives, HIV protease inhibitors

Question 4

CNS penetration of rifampicin

Answer 4

10-20%

Question 5

How does resistance to rifampicin is acquired?

Answer 5

mutations in gene, encoding the RNA polymerase beta chain

Question 6

How does resistance to isoniazid is acquired?

Answer 6

mutations to catalase-oxidase enzymes converting isoniazid, regulatory genes of the mycolic acid synthesis

Question 7

which is the toxic and non-toxic metabolite formed via the amidase and NAT2 pathway respectively?

Answer 7

hydrazine; acetyl hydrazine

Question 8

why is pyridoxine given along with isoniazid

Answer 8

isoniazid competitively inhibits pyridoxal phosphate formation (active form of it B6) -> causes peripheral neuropathy

Question 9

which two anti-TB drugs should be given 2 hours spaced apart from antacids?

Answer 9

isoniazid (delay absorption) and ethambutol (decreases level of E)

Question 10

adverse effect of isoniazid?

Answer 10

peripheral neuropathy, GI effects, hepatitis

Question 11

DDI of isoniazid

Answer 11

CYP450 inhibitor: increase phenytoin and carbamazepine

Question 12

which drug allows the TB treatment to become 6 months? also the most effective drug

Answer 12

Pyrazinamide

Question 13

MOA of pyrazinamide

Answer 13

converted into pyrazinoic acid by pyrazinamidase -> decrease intracellular pH

Question 14

adverse effects of pyrazinamide?

Answer 14

Hepatotoxicity (higher risk when + Isoniazid)

Hyperuricaemia and arthralgia

GI effects: N/V

Photosensitivity

Exanthema (widespread rashes) and pruritis

Question 15

How does resistance to pyrazinamide occur?

Answer 15

mutation to the gene encoding, pyrazinamidase enzyme

Question 16

How does resistance to ethambutol occur?

Answer 16

mutation to embB gene

Question 17

adverse effect of ethambutol

Answer 17

visual toxicity (higher risk if kidney failure and elderly)

• toxicity is dose-dependent
• monitoring for young required

hyperuricemia/gout

Question 18

what is MDR in TB treatment?

Answer 18

resistant to first line anti-TB, esp rifampicin and isoniazid
treatment requires second line anti-TB drugs (more toxic and $$)

Question 19

what is XDR in TB treatment

Answer 19

resistant to second line: FQ and injectables

Question 20

what is cure

Answer 20

negative sputum in the last month of treatment

Question 21

what is treatment failure

Answer 21

positive sputum at or after 5months of treatment

Question 22

what is a good marker to indicate risk of relapse

Answer 22

nonconversion of sputum culture at 2 months

Question 23

Which anti-TB drugs have GI sx such as nausea, anorexia, abdominal discomfort

Answer 23

RIP

Question 24

Which anti-TB drugs have cutaenous rxns which are usually self-limiting (pruritus)?

Answer 24

RIPE (all first anti-TB drug)

Question 25

before active TB treatment is started, what needs to be done

Answer 25

1. test for baseline level of liver enzyme for the patient
2. have to measure weight at each visit to dose adjust when needed
3. 2 month of RIPE, and 4 months of RI

Question 26

who is susceptible to TB?

Answer 26

HIV/diabetes, visited at TB-prone country, , age, nutrition