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�Chloramphenicol

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Content

Chloramphenicol

Mechanism of action
Pharmacokinetics
Drug interactions
Adverse effects
Clinical uses

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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

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Chloramphenicol

Broad spectrum antibiotic
Isolated from Streptomyces venezuelae
Contains nitro group as nitrobenzene moiety

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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

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Binding site of chloramphenicol

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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

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Mechanism of resistance

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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

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Pharmacokinetics

Administration in crystalline form
Parenteral – Chloramphenicol sodium succinate
Oral – Chloramphenicol palmitate
Oral - rapid and complete absorption
Widely distributed

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Pharmacokinetics

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

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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

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Adverse effects

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

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Adverse effects

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

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Drug interactions

Paracetamol increases the bioavailbility of chloramphenicol
Cloramphenicol - enzyme inhibitor
Inhibits the metabolism of morphine, chlorpropamide and warfarin

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Clinical uses

Meningitis
Typhoid fever
Sepsis caused by gram negative organisms
Bacterial fragilis
Rickettsial disease
Topically used for eye and ear infection

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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

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Faculty of Pharmacy