Antibiotic Chloramphenicol history,classification,mechanism of action and adverse effect

1. Chloramphenicol
AMIR SOHAIL

2. Chloramphenicol
• Chloramphenicol is a bacteriostatic
antimicrobial that became available in 1949.
• Chloramphenicol was originally derived from
the bacterium Streptomyces venezuelae,
isolated by David Gottlieb, and introduced
into clinical practice in 1949, under the trade
name Chloromycetin.
• It was the first antibiotic to be manufactured
synthetically on a large scale.

3. Chloramphenicol
• Chloramphenicol is active against a wide
range of gram-positive and gram-negative
organisms.
• However, because of its toxicity, its use is
restricted to life-threatening infections for
which no alternatives exist.

4. Chloramphenicol
• Chloramphenicol inhibits protein synthesis
in susceptible microorganisms and ,to a
lesser extent,in mammalian cells.
• Host ribosomes do not bind effectively as
do bacterial ribosome.

5. Chloramphenicol
• Chloramphenicol readily penetrates into
bacterial cells,probably both passive and
facilitated diffusion.

6. A. Mechanism of action

7. A. Mechanism of action
• Once inside bacterial cell,the drug binds
reversibly to the bacterial 50S ribosomal
subunit and inhibits protein synthesis at
the peptidyl transferase reaction.This
interferes with transfer of elongating
polypeptide chain in the newly attached
aminoacyl t-RNA at ribosome-mRNA
complex.

9. Mechanism of action
• Chloramphenicol prevents protein chain
elongation by inhibiting the peptidyl
transferase activity of the bacterial
ribosome
• It binds to 50S ribosomal subunit,
preventing peptide bond formation.

10. Mechanism of action
• Chloramphenicol
↓
• Binds reversibly to 50 S ribosomal subunit
↓
• Prevents the formation of peptide bond
↓
• Inhibits protein synthesis

12. Antimicrobial spectrum

13. B. Antimicrobial spectrum
• Chloramphenicol has a very broad
spectrum of activity: it is active against
Gram-positive bacteria , Gram-negative
bacteria and anaerobes.

14. B. Antimicrobial spectrum
• Chloramphenicol, a broad-spectrum
antibiotic, is active rickettsiae.
• Pseudomonas aeruginosa is not affected,
nor are the chlamydiae.

15. Antimicrobial spectrum
• Chloramphenicol has excellent activity
against anaerobes. The drug is either
bactericidal or (more commonly)
bacteriostatic, depending on the organism.
• Chloramphenicol is bacteriostatic against
Gram negative rods and bacteriocidal for
pneumococci.

16. Therapeutic uses
• Because of the risk of bone marrow
toxicity and availability of safer drugs,
chloramaphenicol is not generally
preferred.
The indication include
• Rickettsial infection
• Eye infection
• Typhoid fever

17. Therapeutic uses
• Because of its excellent BBB penetration
(far superior to any of the cephalosporins),
chloramphenicol remains the first choice
treatment for staphylococcal brain
abscesses. It is also useful in the
treatment of brain abscesses due to mixed
organisms or when the causative
organism is not known.

18. Therapeutic uses
• Chloramphenicol is active against the
three main bacterial causes of meningitis:
Neisseria meningitidis, Streptococcus
pneumoniae and Haemophilus influenzae.

19. C. Resistance
• Acetyl transferase and other metabolizing
enzymes inactivates chloramphenicol.
• Another mechanism for resistance is
associated with an inability of the antibiotic
to penetrate the organism. This change in
permeability may be the basis of multidrug
resistance.
• Lowered affinity of bacterial ribosome for
chloramphenicol

20. D. Pharmacokinetics
• Chloramphenicol may be administered
either intravenously or orally . It is
completely absorbed via the oral route
because of its lipophilic nature, and is
widely distributed throughout the body. It
readily enters the
normal CSF.

21. D. Pharmacokinetics
• It is metabolised in the liver by reduction
and glucuronide conjuction.
• The metabolites are excreted in the urine.

23. E. Adverse effects
• Anemias: Hemolytic anemia occurs in
patients with low levels of glucose 6-
phosphate dehydrogenase.
• Other types of anemia occurring as a side
effect of chloramphenicol include reversible
anemia, which is apparently dose-related and
occurs concomitantly with therapy, and
chloramphenicol may inhibit the uptake of
iron by erythrocytes and slow their rate of
maturation in bone marrow.

24. E. Adverse effects
Aplastic anemia
• The most serious side effect of
chloramphenicol treatment is aplastic
anaemia. This effect is rare, idiosyncratic and
generally fatal: there is no treatment and
there is no way of predicting who may or may
not get this side effect. The effect usually
occurs weeks or months after
chloramphenicol treatment has been stopped
and there may be a genetic predisposition.

25. Adverse effects
• Bone marrow suppression
It is common for chloramphenicol to cause
bone marrow suppression during treatment:
this is a direct toxic effect of the drug on
human mitochondria. This effect manifests
first as a fall in hemoglobin levels and occurs
quite predictably once a cumulative dose of
20 g has been given. This effect is fully
reversible once the drug is stopped and does
not predict future development of aplastic
anaemia.

26. Adverse effects
• GIT disturbance
Nausea,vomiting and diarrhoea

27. Adverse effects
• Gray baby syndrome: This adverse effect occurs
in neonates if the dosage regimen of
chloramphenicol is not properly adjusted. Neonates
have a low capacity to glucuronylate the antibiotic,
and they have underdeveloped renal function.
Therefore, neonates have a decreased ability to
excrete the drug, which accumulates to levels that
interfere with the function of mitochondrial
ribosomes. This leads to poor feeding, depressed
breathing, hypotension, cyanosis (hence the term
gray baby ), and death.
• Adults who have received very high doses of the
drug can also exhibit this toxicity.

28. Adverse effects
• Hypersensitivity reactions like rashes
• Superinfection