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