Cushman Chloramphenicol Flashcards
Chloramphenicol MOA
Binds reversibly to the 50S ribosome subunit and inhibits the peptidyl transferase activity of the ribosome and blocks peptide formation between the P site and A site
Chloramphenicol indication
Chloramphenicol sodium succinate is a prodrug for IV or IM administration that is hydrolyzed to chloramphenicol in the liver
Meningitis
Typhoid fever
Rickettsial infections
Intraocular infections
Chloramphenicol resistance mechanisms (bacteria metabolism)
- Reduced membrane permeability
- Mutation of the 50S ribosomal subunit
- Elaboration of chloramphenicol acetyltransferase, which acetylates one or both hydroxy groups to form metabolites that do not bind to the 50S subunit
Human metabolism
Metabolized to its glucuronide in the liver. The glucuronide is inactive and readily excreted by the kidneys
Chloramphenicol is also metabolized by reduction of the nitro group to an amino
Chloramphenicol toxicity
Aplastic anemia
This occurs weeks or months after treatment has been stopped.
The highest risk is with oral use and the lowest risk is eyedrops
It is recommended that blood levels be monitored to keep chloramphenicol concentrations less than 25 ug/mL
Chloramphenicol and bone marrow suppression
Bone marrow suppression is common due to impairment of mitochondrial function resulting from inhibition of protein synthesis
This is reversible once the drug is stopped, and does not predict future development of aplastic anemia
This effect occurs once a cumulative dose of 20 g has been given
Chloramphenicol and child-hood leukemia
Increases risk of development and increases risk with length of treatment
Chloramphenicol drug interactions
CYP450 inhibitor
Chloramphenicol distribution
Concentration in brain is 30-50% that of plasma when meninges are not inflamed; this increases to 89% when meninges are inflamed
