Integrative Pharmacology of MTB Flashcards
What TB patients get the extra 7 months of therapy?
- cavitary pul TB still positive after 2 months
- initial phase did not contain PZA
- Pts receiving 1 weekly INH + rifa whose sputum still positive
What is the MOA of Isoniazid (INH)?
Pro drug that messes with cell wall synthesis
How is Isoniazid metabolized?
liver-N-acetyltransferase! watch out for different degrees of acetylators
When is INH induced hepatotoxicity most common?
4-8 weeks into therapy
What are two Adverse Drug Effects of INH?
Hepatotoxicity
Dose Related Peripheral Neuropathy
What role does INH have on phenytoin levels?
INH decreases metabolism so increases levels of phenytoin
What is the MOA of Rifampin?
Inhibits bacterial RNA synthesis by binding to bacterial DNA dependent RNA polymerase
What is a side effect of Rifampin (minor)?
Red secretions
What is a major adverse effect of Rifampin?
Hepatitis!
What levels are elevated in Rifampin toxicity?
hepatotoxicity, increased bilirubin and increased alkaline phosphatase
What levels are increased in INH toxicity?
hepatotoxicity, increased aminotransferase levels
What effect does Rifampin have on CYP 450 (3A4)?
inducer of cyps!! so DDI due to decreased levels of other drugs
What is the MOA of Pyrazinamide (PZA)?
unknown!! but we do know it’s a prodrug
What are the adverse drug effects of PZA?
Nausea + vomiting
Dose-dependent hepatotox
increased serum uric acid (non gouty polyarthragia)
What is the MOA of ethambutol?
Inhibits cell wall synthesis
What is the major toxicity of ethambutol?
retrobullar optic neuritis
VISION impairments
Whats the MOA of streptomycin?
Aminoglycoside antibiotic (30s ribosome protein synthesis inhibitor)
What are the adverse drug effects of streptomycin?
otoVESTIBULAR
nephrotoxicity
What is the major place in therapy for Rifabutin?
substitute for rifampin in patients treated w/ protease inhibitors for HIV!! (avoid the cyp 3A4 DDI)
What are the two second line agents for TB therapy?
Fluroquinolones and Linezolid
How do we manage the ADE of GI disturbance?
First step is to rule out hepatotox! check LFT, if normal try taking with food
How do we manage ADE of Rash
manage symptomatically with antihistamines. if severe, stop ALL meds and reintroduce one by one 2-3 day intervals
How do we manage ADE of hepatitis?
increase LFT without symptoms- do not stop regimen but monitor more. WITH symptoms discontinue therapy and reintroduce meds 1 week intervals.
Elevated bilirubin and alkaline phosphatase strongly suggest WHAT?
rifampin toxicity