Anti-Tuberculosis Agents Flashcards
What is the regimen like for Anti-TB Agents
2mth intensive: R-I-P-E/S
4mth continuation: R-I (Daily/3x week)
What is an ADE common across all the 1st line Anti-TB agents?
Cutaneous reaction (Self-limiting, give anti-histamines)
MOA of Rifampicin
Blocks DNA-dependent RNA polymerase, prevents bacillus from synthesising mRNA & protein -> Cell Death
How does resistance against Rifampicin come about?
Mutations in gene
Clinical indications for Rifampicin
Active/Latent TB (~4mths)
Metabolism of Rifampicin
Hepatic
Use of Rifampicin in liver/kidney impairment?
Kidney: Ok
Liver: When benefit > risk
ADE of Rifampicin
1) Cutaneous reactions (Give anti-histamine)
2) Hepatitis
3) DDI (CYP450 inducer)
4) Orange discolouration of bodily fluids
5) Flu-like syndrome
6) Respiratory syndrome
How are Anti-TB agents administered?
Orally (Streptomycin: IM)
Can Rifampicin be given to pregnant women?
If needed (Category C) - Give Vitamin K to both neonates & mother to avoid postpartum haemorrhage
MOA of Isoniazid
Bactericidal effect
- Prodrug activated by catalase-peroxidase enzyme -> Produces O2-derived free radicals -> Inhibit formation of mycolic acids of bacterial cell wall
Resistance to Isoniazid
1) Mutations to catalase-peroxidase enzyme
2) Mutations of regulatory genes involved in mycolic acid synthesis
Clinical indications of Isoniazid
Active/Latent TB (~6-9mths)
Metabolism of Isoniazid
Liver through acetylation by N-acetyltransferase (Genetic Polymorphism)
CSF Penetration of Anti-TB
R: 10-20%
I: Good
P: Good, similar to that in plasma
Which Anti-TB agent should be taken with pyridoxine?
Isoniazid
Why should Isoniazid be taken with pyridoxine
Peripheral neuropathy
- Pyridoxine (Natural form of Vit B6)
- Isoniazid interferes competitively with Pyridoxine metabolism -> Inhibit formation of active form of Vit B6
Which drugs should not be taken with tyramine/histamine rich foods?
Isoniazid
Linezolid
ADE of Isoniazid
1) Peripheral neuropathy (Pyridoxine)
2) Hepatitis
3) DDI (CYP450 Inducer)
MOA of Pyrazinamide
MOST EFFECTIVE in eliminating persisters
Bactericidal (Potent sterilising effect)
- Prodrug converted to pyrazinoic acid by pyrazinamidase -> Accumulation of pyrazinoic acid decrease intracellular pH -> Inactivate critical pathways for bacterial survival
Use of Pyrazinamide
Active TB
Elimination of Pyrazinamide
Renal (Metabolites eliminated by kidney)
ADE of Pyrazinamide
1) Hepatotoxicity** (MOST)
2) Photosensitivity
3) Hyperuricemia & arthralgia (gout-like symptoms)
4) Exanthema (widespread rash) & puritus
5) GIT
MOA of Ethambutanol
Bacteriostatic
- Inhibits arabinosyltransferase enzyme encoded by embB gene -> Interferes with polymerization of arabinose into arabinogalactan (in c.w)
Resistance to Ethambutanol
Mutations in embB gene
Use of Ethambutanol
Pri TB (Combi with other Anti-TB agents)
ADE of Ethambutanol
1) Visual toxicity
2) Risk with Kidney impairment & elderly (Prolonged treatment > 2 mths)
3) Hyperuricemia/gout
- Toxicity is dose-dependent
Caution for use of Ethambutanol
Young children (visual acuity difficult to evaluate) Kidney failure (Dose reduction)
Which anti-TB agent should be taken apart from antacids (2h)
Ethambutanol
Which Anti-TB agent is safe for kidney impairment?
R-I
Which Anti-TB agent is safe for liver dysfunction?
Ethambutanol
Which Anti-TB agent causes visual toxicity?
Ethambutanol
Which Anti-TB agent causes peripheral neuropathy?
Isoniazid (Give pyridoxine)
Which Anti-TB agent causes Hepatotoxicity?
R-I-P (Most hepatotoxicity)
MOA of Aminoglycosides
Block formation of initiation complex -> Misreading of codon
ADE of Aminoglycosides
Nephrotoxicity
Ototoxicity
Neuromuscular Paralysis
