TB

• 5 main drugs used to treat TB

  • Ethambutol
  • Streptomycin
  • Pyrazinamide
  • Rifampin
  • Isoniazid
• Anti-TB therapy duration using 5 main anti-TB drugs

  24 weeks
• Regimen for option 1 treatment using 5 main anti-TB drugs

  1. Pyrazinamide, Rifampin, Isoniazid, and Ethambutol (or Streptomycin) for the first 8 weeks (Once daily)

  2. Isoniazid and Rifampin for the next 16 weeks (Daily or 2-3x weekly)
• Regimen for option 2 treatment using 5 main anti-TB drugs

  1. Pyrazinamide, Isoniazid, Rifampin and Ethambutol (or Streptomycin) for the first 2 weeks (Daily)

  2. Same drugs for 6 more weeks (2x weekly)

  3. Isoniazid and Rifampin for the final 16 weeks (2x weekly)
• Regimen for option 3 treatment using 5 main anti-TB drugs

  Pyrazinamide, Isoniazid, Rifampin, Ethambutol (or Streptomycin) for 24 weeks
• Rifamate

  Combination drug containing Rifampin and Isoniazid
• Rifater

  Combination drug containing Rifampin, Isoniazid, and Pyrazinamide
• Mechanism of action of Isoniazid

  Interferes with mycolic acid synthesis
• Isoniazid is NEVER used alone
• Two main adverse effects associated with Isoniazid

  • Liver Toxicity
  • Peripheral Neuropathy
• How peripheral neuropathy side effect of Isoniazid is corrected

  Vitamin B6 use
• Mechanism of action of Rifampin

  Inhibition of RNA synthesis
• Rifampin is never used alone
• Anti-TB drugs distributed to breast milk

  • Rifampin
  • Ethambutol
• Anti-TB drugs that must be dose adjusted for renal toxicity

  • Ethambutol
  • Cycloserine
• Two major side effects with Rifampin

  • Hepatotoxicity
  • Discoloration of bodily fluids
• Mechanism of action of Ethambutol

  Inhibition of RNA and cell wall synthesis
• Bacilli must be actively dividing for Ethambutol to work properly
• Anti-TB drugs that cause hyperuricemia (and possibly gout)

  • Ethambutol
  • Pyrazinamide
• Reversible, adverse effect associated with Ethambutol


  Optic Neuritis
• Mechanism of action of Pyrazinamide

  Converted to active pyrazinoic acid by bacilli, then decreases pH below the threshold of bacterial growth
• Rifampin is considered first line anti-TB drug
• Mechanism of action of Cycloserine

  Blocks cell wall synthesis at an early stage
• Cycloserine is considered second line anti-TB drug
• Cycloserine is NOT protein bound and DOES get into the CNS, even without inflamed meninges
• Cycloserine is contraindicated in Epilepsy
• Capreomycin is considered last line anti-TB drug
• Main 3 adverse effects with Capreomycin

  • Nephrotoxicity
  • Ototoxicity
  • Vestibular disturbance
• Mechanism of action of Ethionamide

  Inhibits peptide synthesis
• 3 toxicities associated with Ethionamide

  • GI
  • Hepatic
  • Thyroid
• Capreomycin is effective in multi drug-resistant TB therapy
• First line drugs for TB

  • Isoniazid
  • Rifampin
  • Pyrazinamide
  • Ethambutol
  • Streptomycin
• Second line drugs for TB

  • Aminoglycosides
  • Fluoroquinolones
  • Rifapentin & Rifabutin
  • Cycloserine
  • Paraminosalicylic acid
  • Thioamides
• First line timeline for TB pharmacotherapy

  1. 9 months

  First 2 months: 4 major drugs

  Next 4 months: 2 major drugs
• Second line timeline for TB pharmacotherapy

  18-24 months
• MDR TB

  Resistance to 2 first line drugs
• XDR TB

  Resistant to 2 first line + 3 second line drugs
• Drug treatment for latent TB

  Isoniazid or Rifampin
• Latent TB is the only time when single drug therapy can be used
• DOTS

  Directly Observed Tx Short course - 6 month course of TB meds w/ supervised swallowing