Chloramphenicol

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

 

 

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