Antibiotics 3.1 - Chloramphenicol Flashcards
Choramphenicol obtained from _____
Streptomyces venezuelae
Choramphenicol MOA
Binds reversibly to the 50S subunit
(near the site for erythromycin and clindamycin)
Inhibits the peptidyltransferase step and blocks peptide formation between the P and A sites
Primary use for Choramphenicol
ointment/eyedrops for bacterial conjunctivitis
Choramphenicol prodrug for IV/IM administration?
Metabolism?
Choramphenicol sodium succinate
hydrolyzed to Choramphenicol in the liver
CSS is specifically indicated for what diseases?
Bacterial meningitis
Typhoid fever
Rickettsia
Intraocular infections
Chloramphenicol PK (solubility, bound to, penetration)
Lipid solule
bound to plasma proteins
penetrates into all tissues including brain
Three mechanisms for Choramphenicol resistance
Reduced membrane permeability
50S subunit mutation
production of Choramphenicol Acetyltransferase
How does Choramphenicol Acetyltransferase work?
It acetylates one or both hydroxy groups to form non-binding metabolites
Most serious Choramphenicol AE
Aplastic anemia
**occurs weeks or months after adminstration
Choramphenicol AE that is slightly less serious but more common
bone marrow suppression
d/t impairment of mitochondrial function from the inhibition of protein synthesis
Reversible AE from Choramphenicol
bone marrow suppression
**Does NOT predict the occurrence of aplastic anemia in future
Bone marrow suppression is predicted after a cumulative Choramphenicol dose of ____
20g
Childhood Choramphenicol use comes with an increased risk for ________
Childhood leukemia
Choramphenicol is metabolized to ______ in the liver
Reaction?
its glucuronide conjugate
Less hindered primary alcohol attack on UDPGA, catalyzed by glucuronyl transferase
Excretion of Choramphenicol metabolite?
Kidney
