Tuberculosis Drugs Flashcards
Isoniazid: Mechanism of Action
Inhibits synthesis of mycolic acid, an important component of the Mycobacterial cell wall (bactericidal)
What enzyme activates Isoniazid? What type of drug does this make Isoniazid?
The bacterial enzyme encoded by the KatG gene; this makes Isoniazid a prodrug
Isoniazid: Adverse Effects
- Peripheral neuritis (can be alleviated by giving pyridoxine/vitamin B6)
- Hepatitis (age-related)
Isoniazid: Drug Interactions
Inhibits the metabolism of other drugs
Rifampin: Mechanism of Action
Inhibits bacterial RNA polymerase (bactericidal)
Rifampin: Adverse Effects
Hepatotoxicity
Rifampin: Drug Interactions
Induces a time-dependent expression of drug metabolizing enzymes
- Results in increased metabolism (decreased half-life) of many different drugs (i.e. oral contraceptives and oral anticoagulants
- This requires changes in the selections or dose of other drugs
Rifampin: Other uses (besides TB)
Elimination of N. meningitidis (meningococcus) carrier state
Pyrazinamide: Mechanism of Action
Unclear, but is different than other TB drugs (bactericidal)
What type of drug is Pyrazinamide? What is it activated by?
Prodrug; activated by bacterial enzyme pyrazinamidase to pyrazinoic acid
Pyrazinamide: Adverse Effects
- Liver toxicity
- Inhibits secretion of urate which may lead to hyperuricemia and gout
Ethambutol: Mechanism of Action
Blocks assembly of cell wall by a different mechanism than isoniazid
- Affects arabinogalactan biosynthesis, a component of the mycobacterial cell wall (bactericidal)
Ethambutol: Adverse Effects
- Optic neuritis (red/green color blindness)
According to the CDC, what are the guidelines for TB treatment?
- Initial phase: 2 months with INH, Rifampin, Pyrazinamide, Ethambutol
- Continuation phase therapy: 4 months with INH and Rifampin
