Amphenicols:

• These are group of broad-spectrum antibiotic which are primarily bacteriostatic.
• It function by blocking protein synthesis of susceptible bacteria.
• These include chloramphenicol and its congeners thiamphenicol, florfenicol and azidamphenicol.

Chloramphenicol:

• It is broad-spectrum bacteriostatic antibiotic.
• It was initially obtained from Streptomyces venezuelae in 1947, but now manufactured synthetically.
• It is used in a variety of infections in human and veterinary medicine, those caused by anaerobic bacteria.
• It is highly lipid soluble antibiotic
• It is derivative of nitrobenzene and dichloroacetic acid.
• Though chloramphenicol exists in 4 stereoisomers, only D-threo form has antibacterial activity.

Mechanism of action:

• It inhibits protein synthesis in susceptible microorganism and to lesser extent in mammalian cells.

Chloramphenicol readily penetrates bacterial cell both by passive & facilitated diffusion

Binds reversibly to 50S ribosomal subunit

Prevents activity of peptidyl transferase enzyme

Interference in transfer of elongating peptide chain in newly attached aminoacyl t-RNA at ribosome-mRNA complex.

Inhibition of protein synthesis

Antimicrobial spectrum:

• It is broad-spectrum antimicrobial agent
• It is active against both gram +ve and gram -ve aerobes and anaerobes including Staphylococcus, Streptococcus, Salmonella, Brucella, Shigella, Neisseria and Haemophilus species.
• It is also active against gram -ve anaerobes, Clostridium, Bacteroides, Fusobacterium &
• Nocardia, Rickettsia, Chlamydia and Mycoplasma are also sensitive to chloramphenicol.

Bacterial resistance:

• Most bacteria are capable of developing resistance to chloramphenicol.
• Resistance develops slowly in a graded manner.
• Three mechanism are important in acquiring bacterial resistance:

1. Elaboration of chloramphenicol acetyltransferase
2. Reduced membrane permeability

• Mutation of 50S ribosomal subunit

Pharmacokinetics:

• They are rapidly and efficiently absorbed after oral administration
• Peak plasma concentration is generally achieved within 30 minutes
• It diffuses throughout the body after oral administration
• It binds to plasma proteins to about 30-60%
• Eliminates by hepatic metabolism via glucuronide conjugation
• Excreted mainly in urine by glomerular filtration and tubular secretion.

Side effects/Adverse effects:

• It produces dose dependent and dose independent bone marrow depression
• It produces vomiting, diarrhoea & anorexia in animals
• Rapid IV infusion may result in collapse, hemolysis and death in large animals.
• Some animals may show hypersensitivity.

Contraindications & precautions:

• In hypersensitive animals
• In patients with hematological disorders
• It should be used cautiously with impaired hepatic and renal functions
• In pregnant animals and nursing bitches and queens.

Indications:

• In infection caused by anerobic bacteria like Salmonellosis & Bacteroides species.
• In chronic respiratory infections and otitis externa

Dose:

Dogs & cats: 40-50 mg/kg, PO, IM or slow IV, 2 times daily

Cats: 12.5-20 mg/kg, PO, IV or IM, 2 times daily

Horses: 50mg/kg, PO, 3-4 times daily

Birds: 30-50mg/kg, PO, 3-4 times daily