Antibiotics - chloramphenicol Flashcards
Chloramphenicol was originally obtained from …
It was the first antibiotic to be …
obtained from streptomycin venezuelae
it was the first to be manufactured synthetically on a large scale
Use of chloramphenicol (general)
Use was waned due to considerable toxicities
Used in west when benefits clearly outweigh the risks
Use is more prevalent in third-world countries b/c it is inexpensive
Mechanism of action of chloramphenicol
binds reversible to the 50S ribosomal subunit at a site that is near the site for erythromycin and clindamycin
(competitive binding interactions occur among these drugs)
it inhibits the peptidyl transferase activity of the ribosome and thus blocks peptide bond formation b/t the P and A sites
Therapeutic use of chloramphenicol
Main use is ointment or eye drops to treat bacterial conjunctivitis
Chloromycentin succinate for bacterial meningitis, typhoid fever, rickettsial infections, intraoccular infections and other serious infections
Chloramphenicol properties
It is lipid soluble and remains relatively unbound to plasma proteins
Penetrates effectively into all tissues of the body, including the brain
Chloramphenicol resistance mechanisms
- reduced membrane permeability
- mutation of the 50S ribosome
- elaboration of the chloramphenicol acetyltransferase, which acetylates one or both of the hydroxyl groups to form metabolites that do not bind to the 50S ribosomal subunit
Toxicity of chloramphenicol
- Most serious toxicity is aplastic anemia (weeks or months after); rare, but generally fatal
- Bone marrow suppression - due to impairment of mitochondrial fxn resulting from inhibition of protein synthesis
- Increased risk of childhood leukemia
- Nausea, vomiting,
Chloramphenicol metabolism
Metabolized to glucuronide in the liver (which is pharmacologically inactive is readily excreted by the kidneys) - catalyzed by glucuronyl transferase
Can neonates receive chloramphenicol?
No! They cannot metabolized it
