Chloramphenicol Flashcards
What is the mechanism of action of chloramphenicol?
- chloramphenicol reversibly bind to the 50S ribosomal subunit.
- It inhibits the peptidyl transferase activity and thus blocks peptide bond formation between the P and the A site.
- Binds near the site for erythromycin and clindamycin –> competitive binding interaction occur among these drugs
What is the therapeutic use for chloramphenicol?
It’s broad spectrum but really only used in third world countries due to its toxicities.
What is the relationship between chloramphenicol sodium succinate to chloramphenicol?
Prodrug to active drug
Describe the solubility of chloramphenicol:
- lipid soluble
- remains unbound to plasma protein
- penetrates into all tissues – including the brain
What are the resistance mechanisms against chloramphenicol?
- reduced membrane permeability
- mutation of 50S subunit
- elaboration of chloramphenicol acetyltransferase which then forms metabolites that do not bind to the 50S ribosomal subunit
How is chloramphenicol metabolized in the liver?
Metabolized to an inactive glucuronide and then gets excreted by the kidneys.
UDPGA attacks the OH on the left side of the molecule
What is the most serious toxicity of chloramphenicol?
- aplastic anemia
- keep chloramphenicol concentrations less than 25 ug/mL
risk for this is extremely low for the eye drop formulation
Is chloramphenicol bone marrow suppression a predictor of aplastic anemia?
No
After what cumulative dose of chloramphenicol is bone marrow suppression likely to occur?
20 g
What is the relationship between childhood leukemia and chloramphenicol?
Risk of childhood leukemia increases with the length of treatment
What is the cause of the drug interactions chloramphenicol causes?
Chloramphenicol inhibits CYP450
How does inflammation of the meninges impact brain concentrations of chloramphenicol?
- When the meninges are not inflamed –> 30-50% of that of the plasma
- Inflamed –> 89%
