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What are first line drugs for TB?
Isoniazid, rofampin, ethambutol, pyrazinamide (IREP)
What's the treatment regimine for Active TB
What's the MoA of Isoniazid?
Inhibit synthesis of mycolic acids (myco cell wall)
What are the absorption/metabolism of isoniazid?
- Absorption: GI --> body fluids/tissues
- Activation: KatG enzyme
- Inactivation: acetylation
What drug interactions exist for isoniazid?
Inhibits hydroxylation of phenytoin
What are toxicities of Isoniazid?
Neurotoxicity, hepatotoxicity (with EtOH), allergic reactions
What's common resistance mechanism for isoniazid?
Mutation of KatG gene (prevent activation)
What's the MoA of Rifampin?
- Inhibits bacterial DNA dependent RNA polymerase
What are the Absorption/excretion of Rifampin?
- Absorption: GI
- Excretion: orange-red coloration of urine
What are clinical uses of rifampin?
- first line TB with isoniazid
- Menigococcal prophylaxis, HiB meningitis
What are SE/interactions of rifampin?
- SE: well tollerated; jaundice, rashes, thromocytopenia, flu-like illness
- Interactions: induce CYP450 enzymes
What is a resistance mechanism for Rifampin?
mutation in DNA dependend RNA polymerase
What's the MoA of Ethambutol?
Inhibit synthesis of arabinogalactan
What's the absorption/excretion of ethambutol?
- Absorption: GI
- Excretion: Kidney-Urine
What are SE of ethambutol?
Few; neuritis (color blindness)
What's the resistance process for ethambutol?
What's the MoA of Pyrazinamide?
Inhibit fatty acid synthase I (mycolic acid synthesis)
What are pharmacokinetics/SE of Pyrazinamide?
- SE: Hepatotoxicity (not for gout pts)
- Activation/resistance: pyrazinamidase
What are guidelines for TB chemotherapy?
2+ drugs for 6+ months
When are second line TB agents used?
- First line resistance
- Failed response
- Expert toxcicity management
What are secondline TB drugs?
- Aminosalicytic Acid
What are Rx for Mycobacterium Complex?
Clarithromycin or Azithromycin AND ethamutol
What's Rx for Hansen's Disease (Leprosy)
- Dapsone + Rifampin
- Multibacillary: Dapsone + Rifampin + Clofazimine
- Paucibacillary: rifampin, minocycline, and ofloxacin
What's the SE of Dapsone?
What's SE of Clofazimine?
GI, red coloring of skin
What's SE of Thalidomide?
What are the SE of Streptomycin?
Ototoxicity and nephrotoxicity
What are SE of Ethionamide?
Gastric irritation, metallic taste, neurologic symptoms
What are SE of Aminosalicylic Acid (PAS)?
GI Symptoms, Drug fever
What are SE of Cycloserine?
CNS dysfuntions and psychotic reactions