Chloramphenicol
Content
Chloramphenicol
• Mechanism
of action
• Pharmacokinetics
• Drug
interactions
• Adverse
effects
• Clinical
uses
Objectives
At the end of this session, students will be able to:
• Describe
the mechanism of action of Chloramphenicol
• Outline
the pharmacokinetics of Chloramphenicol
• Explain
the drug interactions and clinical uses of Chloramphenicol
Chloramphenicol
• Broad
spectrum antibiotic
• Isolated
from Streptomyces venezuelae
• Contains
nitro group as nitrobenzene moiety
Mechanism of action
• Inhibits bacterial protein synthesis
• Binds 50S subunit and block
elongation
• Inhibits the formation of initiation
complexes and peptidyltransferase;
• Binding site overlaps with that of
macrolides and clindamycin
• Primarily bacteriostatic
• May be bactericidal to some strains
of microorganisms even at lower concentration
Binding site of chloramphenicol
Mechanism of resistance
• Selection of permeability mutants
• Results in impaired penetration of
the drug to target site
• Production of chloramphenicol acetyltransferase,
a plasmid-encoded enzyme that inactivates the drug
Antimicrobial spectrum
• active against a broad range of
organisms, including G+ and G-bacteria (including anaerobes)
• Effects on G- bacteria is better
than on G+ bacteria, especially Salmonella typhi
• At low concentration effective
against H. influenzae, N. meningitidis and N. gonorrhoeae
Pharmacokinetics
• Administration
in crystalline form
• Parenteral
– Chloramphenicol sodium succinate
• Oral
– Chloramphenicol palmitate
• Oral – rapid and complete absorption
• Widely
distributed
• Metabolized
by glucuronyl transferase and aryl amide
• 30-60%
protein bound
• Secreted
in breast milk
• 75-90%
excreted in inactive form through kidneys
• Small
amount in bile
Adverse effects
Bone
marrow Disturbance
• Reversible bone marrow depression
• Chloramphenicol inhibits protein
synthesis in the mitochondria of human cells
• Dose dependent toxicity of drug to
bone marrow
Toxicity
for Newborn Infants (Gray-baby syndrome)
• In neonates, especially premature
infants
• Given relatively large doses of
chloramphenicol
• Cyanosis, respiratory irregularities
• Abdominal distention, loose green
stool, and an ashen-gray color
• Gastrointestinal reaction. nausea,
vomiting, diarrhea
• Super infections such as Oropharyngeal
candidiasis and acute Staphylococcal enterocolitis
• Hypersensitivity reactions
• A rare anaemia, probably
immunological in origin but often fatal
Drug interactions
• Paracetamol
increases the bioavailbility of chloramphenicol
• Cloramphenicol
– enzyme inhibitor
• Inhibits
the metabolism of morphine, chlorpropamide and warfarin
Clinical uses
• Meningitis
• Typhoid
fever
• Sepsis
caused by gram negative organisms
• Bacterial
fragilis
• Rickettsial
disease
• Topically
used for eye and ear infection
Summary
• Chloramphenicol
is a broad spectrum antibiotic isolated from Streptomyces venezuelae and
it contains nitro group as nitrobenzene moiety
• Binds 50S subunit, block elongation
and inhibits the formation of initiation complexes by inhibiting
peptidyltransferase
• Used
for the treatment of bacterial fragilis, meningitis, Typhoid fever
• Associated
with sever adverse effects like gray baby’s syndrome and bone marrow depression
