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