26. Treatment of Pulmonary Infections

• (Isoni) Isoniazid

  • only active against mycobacteria
  • bactericidal
  • penetrate into macrophage
• Isoni MOA

  • inhibit mycolic acid synthesis
  • prodrug needs to be converted into active form - KatG
  • active form inhibit enzyme - InhA and KasA - involve in mycolic acid synthesis
  • inhibit cell wall synthesis
• Isoni - ADE - hepatitis
• Isoni metabolized by N-acetyltransferase
• Isoni ADE

  • slow acetylator - peripheral neuropathy
  • fast acetylator - hepatotoxicity due to metabolites - acetylhydrazine
• Isoni ADE

  • lupus
  • seizure in high dose
• How dose isoni cause seizure?

  • depleting GABA by
  • deficiency of pyridoxine by inhibiting pyridoxine phosphokinase
  • PLP (pyridoxal 5 phosphate) - cofactor in conversion to GABA
• What to give to pts suffering from seizure and peripheral neuropathy due to isoni?

  pyridoxine - vitamin B6
• Isoni is CYP enzyme inhibitor - decrease metabolism of drugs - leading to toxicity
• Rifampin MOA

  • inhibit DNA dependent RNA polymerase --> suppress RNA synthesis
  • nucleic aid synthesis inhibitor
• Rifa ADE

  • hepatitis
  • orange red discoloration of urine or other body fluids
• Rifa - CYP inducers

  • increase metabolism of drugs
  • leading to therapeutic failure of
  • OCP
  • antiepileptic
  • warfarin
• (pyra) Pyrazinamide

  • bactericidal - for treatment of TB
• Pyra MOA

  • prodrug - converted to pyrazinoic acid by mycobacteria
  • disrupt cell membrane metabolism and transport function
• Resistance to pyra due to

  • impaired uptake of drugs
  • mutation in pncA
• Pyra ADE

  • hepatitis
  • hyperuricemia - gout
  • phototoxicity
  • increase porphyrin synthesis
• Etham MOA

  • bacteriostatic
  • inhibit arabinosyl transferase - inhibit cell wall synthesis
• Etham ADE

  • retrobulbar neuritis - red-green blindess
  • hyperuricemia - gout
• etham - eye exam needed due to decrease visual acuity
• Atypical mycobacteria treatment - combination of drugs given: to prevent resistance

  • macro
  • sulfona
  • tetra
• Dapsone MOA

  • bacteriostatic
  • inhibit folate synthesis
• Dapsone - use

  • prevent prevent jiroveci pneumonia in AIDS
  • leprosy
• Dapsone ADE

  • sulfone hypersensitivity syndrome
  • treatment - corticosteroid
  • hemolysis in G6PD deficiency
• Treatment of leprosy - for 6 months

  • dapsone - daily
  • rifa - every month
• Treatment of leprosy - for 1 year

  • dapsone
  • rifa
  • clofa
• Treatment of type 1 reaction of leprosy

  • NSAID
  • prednisone (steroid) \