Chloramphenicol (Pharmacokinetics, pharmacodynamics)

Chloramphenicol

1. Chloramphenicol is a bacteriostatic broad-spectrum antibiotic, active against both aerobic and anaerobic gram +ve & gram –ve organisms.
2. It is also active against rickettsiae but not chlamydiae.
3. Isolated from the cultures of Streptomyces venezuelae in 1947.
4. It is a unique compound that contains a nitrobenzene moiety, which is probably responsible for the antibacterial activity.

Molecular structure

Pharmacokinetics

1. Administration: Oral, parenteral
2. Absorption: Rapidly and completely absorbed
3. Distribution: Widely distributed throughout the tissues and body fluids( 30-50% plasma protein-bound, half-life is approximately 2 hours, freely penetrates BBB )
4. Metabolism: Primarily conjugated with glucuronic acid in the liver
5. Excretion: Metabolite is excreted mainly in the urine

Mechanism of action

Therapeutic uses

1. Bacterial as well as rickettsial infections.
2. Has excellent activity against anaerobes.
3. Either bactericidal or (more commonly) bacteriostatic, depending on the organism.
4. Also used against Salmonella typhi, Brucella species.
5. Infections caused by Haemophilus influenza resistance to other drugs.
6. Used in meningitis in whom penicillin cannot be used.

Resistance

Bacteria produce an enzyme, chloramphenicol acetyltransferase

which can degrade the drug

bacteria become chloramphenicol resistance

Adverse effects

1)Bone marrow

• pancytopenia

• leukopenia,

• thrombocytopenia 

• aplasia of the bone marrow

• aplastic anemia

2)Gastrointestinal

• Nausea, Vomiting

• Unpleasant taste

3)Toxicity in neonates

• Gray baby syndrome

Gray baby syndrome

1. Most of the chloramphenicol is conjugated (in the liver) with glucuronic acid and the process is called glucuronidation.
2. In the case of neonates & very young babies, the glucuronidation enzyme is deficient resulting in the accumulation of chloramphenicol in the body.
3. This leads to various symptoms including anemia, CVS collapse, cyanosis.