Chloramphenicol

Question 1

MOA

Answer 1

Reveribly binds to the 50s subunit at A site and inhibits the peptidyl transferase activity of the ribosome thus blocking peptide bond formation

Question 2

Therapeutic use

Answer 2

Prodrug for IV or IM

Bacterial meningitis, typhoid fever, rickettsial infection, intraocular infections

Question 3

Resistance mechanism

Answer 3

3 ways
1. reduce membrane permability
2. Mutation of the 50S ribosomal subunit
3. elaboration of chloramphenicol acetyltransferase, which acetylates one or both of the hydroxy groups to form metabolites that do not bind to the 50S ribosomal subunit.

Question 4

Metabolism

Answer 4

Metabolized to glucuronide in the liver which is inactive and is readily excreted by the kidneys
glucoronidation of the second hydroxyl group

Question 5

Toxicity

Answer 5

Aplastic anemia - highest risk with oral and lowest risk occurs with eye drops - Monitor levels always want to be lower than 25

bone marrow supression is common due to impaired mitochondrial functions due to inhibition of protein synethesis

Reversible once drug is stopped

Increased risk of childhood leukemia with longer treatment durations

Question 6

Drug interactions

Answer 6

inhibit cytochrome p450

Question 7

distribution

Answer 7

The concentration achieved in brain and CSF is about 30 to 50% that of the plasma even when the meninges are not inflamed; this increases to as high as 89% when the meninges are inflamed.