Updated: 9/23/2019

Anti-Mycobacterial Drugs

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Introduction
  • Drugs
    • rifamycins
    • isoniazid
    • pyrazinamide
    • ethambutol
    • dapsone
    • clofazimine
    • streptomycin
  • Clinical use
Classic Treatment Paradigm for Mycobacteria
Organism Prophylaxis
Treatment

Mycobacterium tuberculosis

  • Isoniazid
  • Active infection: RIPE therapy
    • Rifampin
    • Isoniazid
    • Pyrazinamide
    • Ethambutol
  • Latent infection:
    • isoniazid x 9 months
Mycobacterium avium-intracellulare
  • Azithromycin
  • Rifabutin
  • Azithromycin + ethambutol
  • Can also add rifabutin or ciprofloxacin
Mycobacterium leprae
-
  • Tuberculoid: dapsone + rifampin
  • Lepromatous: dapsone + rifampin + clofazimine
 
Anti-Mycobacterial Medications
Drug Mechanism of Action
Adverse Effects
Notes

Rifamycins (rifampin and rifabutin)

  • Inhibits DNA-dependent RNA polymerase
  • Hepatotoxicity
  • Red or orange body fluids
  • CYP450 inducer
  • Cutaneous flushing
  • Rifabutin has less CYP450 effect, thus favored for HIV patients
  • Mutations occur due to decreased binding to RNA polymerase
  • Resistance occurs rapidly if used as monotherapy
Isoniazid
  • Inhibits synthesis of mycolic acids
  • Hepatotoxicity
  • Inhibits CYP450
  • Drug-induced systemic lupus erythematosus
  • Vitamin B6 deficiency
    • peripheral neuropathy
    • sideroblastic anemia
    • co-administer with pyridoxine (B6) to reduce side effects
  • May be used as monotherapy for prophylaxis and latent TB
  • Mutations occur due to underexpression of enzyme required to convert drug into active metabolite
Pyrazinamide
  • Unknown but may work through host phagolysosomes
  • Hepatotoxicity
  • Hyperuricemia
  • Arthralgias
-
Ethambutol
  • Inhibits arabinosyltransferase and disrupts cell wall carbohydrate polymerization
  • Optic neuropathy
    • red-green color blindness
  • Drug resistance due to increased production of arabinosyltransferase
Dapsone
  • Inhibits dihydropteroate synthesis (anti-folate)
  • Methemoglobinemia
  • Hemolysis (G6PD deficiency patients)
-
Clofazimine
  • Disrupts DNA
  • Gastrointestinal upset
  • Dry skin
  • Pink/brown skin and body fluid dyspigmentation
-
Streptomycin
  • Interacts with 30S ribosomal subunit
  • Tinnitus
  • Vertigo
  • Ataxia
  • Renal toxicity
  • Second-line treatment for M. tuberculosis
 

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