Anti-Tuberculosis Flashcards
(39 cards)
Is Mycobacterium Tuberculosis aerobic or anaerobic?
Aerobic, rod shaped, acid-fast bacilli
According to MOH guidelines, what tests must be done prior to TB tx initiation?
- Liver enzymes
- Visual acuity
According to MOH guidelines, what must be monitored at each visit?
- Weight, drug dosages adjusted accordingly
- Risk factors for drug-induced hepatitis
How long is the standard TB tx?
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
What are common adverse effects among all first line anti-TB drugs?
- 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)
Which of the 4 drugs in RIPE require dose adjustment in renal and hepatic impairment?
Renal impairment: PE
Hepatic impairment: RIP
Which drugs (RIPE) are batericidal?
Bactericidal: RIP
Bacteriostatic: E
Pyrazinamide is only indicated for ____ TB
Active
Which drugs (RIPE) have good CSF penetration?
*All are given oral
Good CSF penetration: IP
Poor CSF penetration: RE
Rifampicin is indicated for Tuberculosis caused by Mycobacterium Tuberculosis and _____ caused by __________
Leprosy caused by Mycobacterium leprae
Rifampicin inhibits gene transcription by blocking which enzyme?
DNA-dependent RNA polymerase
=> thus, prevent synthesis of mRNA and proteins, cause cell death
How is Rifampicin eliminated?
Hepatic metabolism, rapidly excreted in bile
Which of the 4 RIPE drugs can be used in pregnancy?
All are Cat C but weight risk and benefit
Mothers and neonates born to mothers under treatment with Rifampicin should be given _____ to prevent _________
Vitamin K
Prevent postpartum hemorrhage
*Because Rifampicin can cause thrombocytopenia
Rifampicin is a CYP450 ______, while Isoniazid is a CYP450 ______
Rifampicin: CYP450 inducer
Isoniazid: CYP450 inhibitor
What are Rifampicin Adverse effects?
- GI
- Cutaneous
- Hepatitis
- Flu-like syndrome (fever, chills, malaise)
- Orange discoloration of body fluids (e.g., sweat, urine, tears)
- (RARE) respiratory syndrome - SOB
- (RARE) thrombocytopenia, hemolytic anemia, acute renal failure *if these occur, stop and never give again as they are severe immune mediated reactions
Which of the 4 RIPE can be used for prophylaxis?
Isoniazid
Isoniazid is a prodrug activated by ________ enzyme.
This causes production of ___________ that can inhibit formation of _______ and causes _________.
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
Isoniazid resistance can be due to
1. Mutation of catalase peroxidase enzyme
2. Mutation of ______
Mutation of the regulatory genes involved in mycolic acid synthesis
Isoniazid undergoes metabolism in the liver through __________
Acetylation by N-acetyltransferase
*Inactive metabolites are excreted by kidneys
Explain why Isoniazid can cause hepatotoxicity
Two metabolic pathways of isoniazid
- NAT2 pathway => acetylhydrazine
- Amidase pathway => hydrazine (hepatotoxic metabolite)
Pregnant women receiving Isoniazid should receive ________ because Isoniazid ___________________
Pyridoxine (Vit B6) supplementation 10mg daily
Isoniazid interferes competitively with pyridoxine metabolism
Isoniazid metabolites can also react with pyridoxine to deactivate it
What is the role of pyridoxine?
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
Explain the food-drug and drug-drug interactions of Isoniazid
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
