Chloramphenicol
INTRODUCTION
Broad spectrum
(aerobic, anaerobic, gram +, gram -, rickettsiae)
Bacteriostatic
Bactericidal (H.influenzae, Neisseria meningitidis)
30S
P A
PROTEIN SYNTHESIS
50S
Step 1 – AA binds to A Step 2 – transpeptidation
Step 3 – tRNA leaves P site Step 4 – translocation
X
Inhibits protein synthesis
Binds reversibly to 50S; Inhibits peptidyl transferase
Inhibits transfer of elongating peptide chain to newly
attached aminoacyl tRNA at A site
30S
PROTEIN
SYNTHESIS
P A
XX
PHARMACOKINETICS
Dose : 50 - 100 mg/kg/day
Chloramphenicol palmitate (oral)
Chloramphenicol succinate (Parenteral)
THROUGH ORAL ROUTE – COMPLETELY & RAPIDLY ABSORBED
Wide tissue distribution ( body fluids, CSF )
Inactivated by glucuronide conjugation
Eliminated in urine, bile, feces
1-10µg/ml - inhibits Gram +ve bacteria
O.2-5µg/ml - inhibits Gram -ve bacteria
Resistance due to
chloramphenicol acetyl transferase
decreased permeability into bacterial cells
Cross resistance seen between
Chloramphenicol, Macrolides, Lincosamide
Clinical uses
Typhoid
Typhus
Rocky Mountain Spotted Fever
Meningococcal meningitis
Topically for eye infections
HEPATIC FAILURE
NEW BORNS (<1WK)
PREMATURE INFANTS
When
chloramphenicol
should not be
prescribed ?
Adverse effects
Nausea, vomiting, diarrhoea,
oral/vaginal candidiasis
Bone marrow disturbances:
dose related reversible suppression of
RBCs
aplastic anemia (idiosyncratic),
irreversible, prolonged use
Gray Baby Syndrome
Gray baby syndrome
stops feeding Vomiting Hypotonic Hypothermic Distended abdomen Irregular respiration Ashen gray cyanosis Cardiovascular
collapse Death
Why Gray baby syndrome occurs in neonates ?
Inability of neonate to metabolise
& excrete chloramphenicol due to
deficiency of glucuronosyl
transferase
At higher concentration it inhibits
electron transport in liver, heart,
skeletal muscle
Avoided by dose reduction
< 50 mg/kg/day ( full term
infants )
< 25 mg/kg/day ( pre term
infants )
Gray baby syndrome
DRUG INTERACTION
Inhibits hepatic enzymes
Increases serum level of
Phenytoin, tolbutamide, warfarin
Antagonises action of penicillins,
aminoglycosides
Why it is rarely used?
potential toxicity,
bacterial
resistance &
availability of
effective
alternatives
Top Related