Antitubercular agents Flashcards
What 4 medications are used in treatment of TB?
Isoniazid (INH)
Rifampin
Ethambutol
Pyrazinamide (PZA)
What are the 3 subpopulations of TB?
Intracellular in caseating granulomas
Extracellular, rapidly dividing
Intracellular in macrophages
Which TB drugs are working on which subpopulations of TB?
Intracellular in caseating granulomas- rifampin and isoniazid
Extracellular - rifampin, isoniazid, and streptomycin
Intracellular in macrophages - pyrazinamide, isoniazid, rifampin
Which drug is dropped after susceptibility is established?
Drop ethambutol if there is no resistance OR drop PZA if patient has PZA intolerance but keep ethambutol
How long does initial therapy last?
8 weeks
Continuation therapy occurs after initial therapy. How long does it last and what drugs are used?
18 weeks of INH and rifampin
What is the initial treatment of latent TB?
Isoniazid + rifapentine weekly x 12 weeks
Alternative treatment for latent TB?
Rifampin daily x 4 months
Latent TB treatment for pregnant or HIV patients?
INH x 6-9 months
Treatment for multidrug resistant latent TB?
PZA + fluoroquinolone OR ethambutol
Adverse reactions of isoniazid?
Neuritis
Hepatotoxicity
drug drug interactions vis inhibition of CYP450
allergic reactions
What should patients take to prevent neuritis?
pyridoxine (vitamin B6)
Mechanism of action of isoniazid?
Inhibits mycolic acid synthesis and cell wall formation
Mechanism of action of rifampin?
Inhibits RNA synthesis by binding to RNA polymerase
Rifampin works synergistically with what drug?
INH
Does rifampin enhance or inhibit metabolism of drugs?
Enhances metabolism of drugs via P450 metabolism
Adverse reactions to rifampin?
Hepatotoxicity
GI upset, rashes,
Imparts orange color to urine, sweat and tears
What drug can HIV patients take instead of rifampin and why?
Rifabutin - weaker inducer of CYP450 metabolism
What rifampin-like drug can patients take once weekly for latent TB infections?
Rifapentine - 5x longer half life than rifampin
Which TB drugs are bactericidal?
INH, rifampin, (pyrazinamide in acidic environment of macrophages or edges of necrotic TB cavities)
Adverse reactions to pyrazinamide?
hepatotoxicity
drug rash (most common of first line agents)
Hyperuricemia (gout)
Which TB drugs are bacteriostatic?
Ethambutol, PZA
Mechanism of action of ethambutol?
Inhibits synthesis of mycobacterial cell wall component arabinogalactan
