Chloramphenicol

Question 1

Chloramphenicol

Answer 1

Bacteriostatic

Target:

• very effective against anaerobic/aerobic Gram - and Gram + organisms

Indications:

• rarely used in US (ophthalmic usage for bacterial conjunctivitis)
• alternative to beta-lactams for meningicoccal meningitis
  
  • PCN hypersensative individuals
  • PCN resistant pneumococci
• can be used for Yersinia pestis infection (severe), brain abscesses, bacterial meningitis

Mechanism:

• binds 50S subunit of ribosome
• inhibits peptidyltransferase activity
  
  • does not appreciably interact w/ euk 80S ribosomes
  • can interfere with euk mito ribosomes
    
    • inhibit aerobic metabolism = decrease ATP = cell death

Route of Administration:

• PO

Absorption:

• rapid on oral administration

Distribution:

• large volume of distribution, penetrates CNS and CSF
• crosses placenta/present in breast milk

Metabolism:

• in liver
  
  • dose reduction required in hepatic failure
  • can inhibit CYP2C, CYP3A P450 (durg interactions!)

Excretion:

• via urine primarily (feces, bile lesser extent)
  
  • active drug (10% of total)
  • inactive metabolites (90% of total)

Toxicities:

• Hematological effects
  
  • bone marrow suppression
    
    • anemia, leukopenia, thrombocytopenia
    • dose-related
    • reversible
    • cause mito toxicity?
• aplastic anemia
  
  • idiosyncratic
  • not dose-related
  • irreversible
  • can be fatal
  • cause = inhibition of mito protein synthesis, prevents iron incorporation into heme?
• “Gray Baby Syndrome” (infants lack UGT and cannot excrete drug and therefore deactive it)

Drug Interaction potential!

• inhibits hepatic cytochrome P450 enzymes
• increased t1/2 of Warfarin, pheytoin, antiretroviral protease inhibitors

Pt considerations:

• Pregnancy Category D
• infants - caution in dosing
  
  • <25-50 mg/kg/d