Chloramphenicol
CHLORAMPHENICOL
- Broad spectrum antibiotic.
- Active against nearly same range of organisms (gram-positive & negative bacteria, rickettsiae, mycoplasma, chlamydia).
Gram-positive:
- Streptococcus sp., Staphylococcus sp., Enterococcus sp., Bacillus anthracis, Listeriamonocytogenes.
Gram- negative:
- H. influenzae, M. catarrhalis, N. meningitides, E. coli, P. mirabilis, Salmonella sp., Shigella sp., Stenotrophomonasmaltophilia.
Against anaerobes:
- More commonly bacteriostatic.
- Bactericidal against H. influenzae, Neisseria meningitides, & S. pneumoniae.
MOA:
- Protein synthesis inhibitor in bacteria.
- Inhibits protein by binding irreversibly to bacterial 50s ribosome subunit.
- Hinders aminoacyl-tRNA access to acceptor site for amino acid incorporation by acting as peptide analogue.
- Prevents peptide bond formation.
- Thus inhibits protein synthesis at peptidyl transferase reactio.
PHARMACOKINETICS:
- Administered either intravenously or orally.
- Rapidly and completely absorbed via oral route.
- Due to lipophilic nature.
- Widely distributed throughout the body.
- Volume of distribution 1 L/kg
- 50-60% bound to plasma proteins.
- Freely penetrates serous cavities.
- BBB: CSF concentration is nearly equal to that of unbound drug in plasma.
- It crosses placenta & is secreted in bile and milk.
- Hepatic metabolism to inactive glucuronide is major route of elimination.
USES:
- Treatment of serious rickettsial infections such as typhus & rocky mountain spotted fever.
- Alternative to β-lactam antibiotic for treatment of meningococcal meningitis.
- Mainly in patients with major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci.
- Topically in treatment of eye infections.
- Due to its broad spectrum & its penetration of ocular tissues & aqueous humour.
- Ineffective for chlamydial infections.
- Brucellosis: If tetracyclines are contraindicated, chloramphenicol is recommended.
- Rare: Typhoid, when third-generation cephalosporins & quinolones are contraindicated.
ADVERSE EFFECTS:
Anaemia
- Hemolytic anaemia –less glucose 6-phosphate dehydrogenase.
- Reversible anaemia- side effect, dose-related
- Aplastic anaemia – rare – idiosyncratic – usually fatal
Hypersensitivity reaction
- Rashes,
- fever,
- atrophic glossitis
- angioedema
Gastrointestinal irritative effects
- Nausea
- vomiting
- diarrhoea
Gray baby syndrome
- Neonates with low capacity to glucuronate the antibiotic with underdeveloped renal function.
- Hence, decreased ability to excrete drug, which accumulates to levels interfering with mitochondrial ribosomal function.
- This leads to poor feeding, depressed breathing, cardiovascular collapse, cyanosis & death.
- Adults receiving very high drug doses exhibit this toxicity.
INTERACTIONS:
- Inhibits metabolism of warfarin, phenytoin, tolbutamide, & chlorpropamide.
- Hence, elevating their concentrations.
- Concurrent administration of CYP’s inducers phenobarbital or rifampin.
- Shortens chloramphenicol’s t1/2 resulting in subtherapeutic drug concentrations.
Exam Question
- A young male presents with meningococcal meningitis and allergy to penicillin can be treated with chloramphenicol.
- Chloramphenicol resistance in Pseudomonas aeruginosa is due to active efflux pumping out of drug.
- Gray baby syndrome is caused by Chloramphenicol.
Don’t Forget to Solve all the previous Year Question asked on Chloramphenicol