CHLORAMPHENICOL ppt
Transcript of CHLORAMPHENICOL ppt
-
7/27/2019 CHLORAMPHENICOL ppt
1/28
Chloramphenicol
First isolated from Streptomyces venezuelae
in 1947, this antibiotic has a very broad
spectrum including Gram +ve, Gram -ve and
a special use against typhoid.
This agent is now produced by total
synthesis.
-
7/27/2019 CHLORAMPHENICOL ppt
2/28
Mechanism of action
It inhibits protein biosynthesis in both Gram(+)
and Gram(-)bacteria.
It is a bacteriostatic agent.
-
7/27/2019 CHLORAMPHENICOL ppt
3/28
Metabolism
Metabolism is mainly through the formation of
the C3-glucuronide metabolite that is the soluble
excretable metabolite (Phase 2).
The reduction of the nitro compound to the
amine, dechlorination and the hydrolysis of the
amide bond may also occur (Phase 1).
All these metabolites are inactive.
-
7/27/2019 CHLORAMPHENICOL ppt
4/28
Pharmacokinetic Properties
It is well absorbed then well distributed to
tissues.
It shows about 60% protein binding.
It has a bitter taste, which can be masked by the
use of the palmitate ester at the 3-hydroxyl group
in pediatric oral suspensions.
-
7/27/2019 CHLORAMPHENICOL ppt
5/28
-
7/27/2019 CHLORAMPHENICOL ppt
6/28
-
7/27/2019 CHLORAMPHENICOL ppt
7/28
Structure Activity Relationship
-
7/27/2019 CHLORAMPHENICOL ppt
8/28
-
7/27/2019 CHLORAMPHENICOL ppt
9/28
-
7/27/2019 CHLORAMPHENICOL ppt
10/28
-
7/27/2019 CHLORAMPHENICOL ppt
11/28
Structure Activity Relationship
-
7/27/2019 CHLORAMPHENICOL ppt
12/28
Replacement of the primary or secondary
alcohol by alkyl group decreases activity.
-
7/27/2019 CHLORAMPHENICOL ppt
13/28
-
7/27/2019 CHLORAMPHENICOL ppt
14/28
Extending the length or branching of the side
chain leads to loss of activity.
-
7/27/2019 CHLORAMPHENICOL ppt
15/28
-
7/27/2019 CHLORAMPHENICOL ppt
16/28
Toxicity
It can cause a dose-related bone marrow
depression and may precipitate leukemia.
-
7/27/2019 CHLORAMPHENICOL ppt
17/28
Toxicity
A very small percent of patients (one in every
25,000 to 40,000 cases of therapy) may develop
aplastic anemia and results from loss of both
white and red cells precursors.
-
7/27/2019 CHLORAMPHENICOL ppt
18/28
-
7/27/2019 CHLORAMPHENICOL ppt
19/28
Heme :
C34H32O4N4FeOH
-
7/27/2019 CHLORAMPHENICOL ppt
20/28
-
7/27/2019 CHLORAMPHENICOL ppt
21/28
-
7/27/2019 CHLORAMPHENICOL ppt
22/28
Resistance
Enzymes that cause acetylation of the hydroxyl
groups (especially the secondary alcohol),
resulting in a decreased ability of binding to
the ribosomes.
-
7/27/2019 CHLORAMPHENICOL ppt
23/28
Acetylation of the secondary Alcohol
-
7/27/2019 CHLORAMPHENICOL ppt
24/28
-
7/27/2019 CHLORAMPHENICOL ppt
25/28
-
7/27/2019 CHLORAMPHENICOL ppt
26/28
-
7/27/2019 CHLORAMPHENICOL ppt
27/28
-
7/27/2019 CHLORAMPHENICOL ppt
28/28