Chloramphenicol

• Broad spectrum Antibiotic
• Usage limited due to bone marrow suppression
• Isolated from Streptomyces Venezualae

• Primarily Bacteriostatic
• Bactericidal against H.influenzae,N.meningitides and S.pneumoniae

1. Chloramphenicol ≫≫≫ Binds reversibly to 50 s ribosomal subunit ≫≫ Prevents peptide bond formation ≫≫ Inhibits protein synthesis
2. Also inhibits mitochondrial protein synthesis in Mammalian cells by acting on 70s ribosomal subunit.

• Production of inactivating enzymes
• Acetyltransferase by H.influenzae,S.typhii,S.aureus
• Decreased permeability of Microbial Cell wall
• Ribosomal Mutation

• Available in Oral, topical and intravenous formulations
• Commonly used as oral tablets
• Syrup has bitter taste
• Chloramphenicol Palmitate developed for Pediatric use
• Is A Pro-drug, activated to chloramphenicol by pancreatic lipase
• Is Less bitter
• Available as suspension
• Completely absorbed through GIT
  
• Widely distributed in the body
• Freely crosses the Blood Brain Barrier (BBB) and attains almost equal concentration in the CSF as in Plasma.
• Freely crosses the placental barrier and achieves high concentration in breast milk.
• Metabolised in the liver, undergoes conjugation by Glucoronyl Transferase and is excreted in the Urine.

• Hypersensitivity reactions: Itching, rashes, rarely Angioedema
• Bone Marrow suppression:
• Most important and serious adverse effect
• Incidence: 1:30,000
• Of 2 Types:
• Dose dependent reversible suppression presenting as leucopenia, anemia and thrombocytopenia
• Idiosyncratic non-dose related irreversible aplastic anemia
• Periodic Blood picture examination is a must
• Gastrointestinal Side effects: Nausea, vomiting, superinfections
• Grey Baby syndrome:
  
• Rare
• Seen in Neonates, especially premature newborns
• Due to deficiency of glucoronyl transferase
• Manifests as dehydration, hypotension, circulatory failure and cyanosis - Ashen grey skin color
• 40% mortality

1. Bacterial Meningitis:
1. Alternate agent in combination with ampicillin for H.influenzae,N.meningitides and S.pneumoniae meningitis
2. Preferred drugs are 3^rd generation Cephalosporins like Cefotaxime/ceftriaxone.
2. Anaerobic Infections:
1. Very effective against anaerobes including B.Fragilis
2. Combined with Metronidazole, especially, in anaerobic abcesses
3. Typhoid (Enteric Fever):
1. Was the preferred drug earlier but replaced due to bacterial resistance, making a comeback now.
   
2. Preferred drug now is Ciprofloxacin
1. Tab.Ciprofloxacin _750mg 12^th hourly for 10 days. Eradicates carrier state as well.
3. Other drugs
1. Fluoroquinolones: Pefloxacin,Ofloxacin
2. 3^rd Generation cephalosporins: Ceftriaxone,Cefoperazone
3. Ampicillin
4. Co-trimoxazole
5. Azithromycin
4. In multi drug resistant cases: Ceftriaxone _{1-4gm/day i.m/i.v} is given for 10 days.
4. Rickettsial Infections:
1. Drug of choice is Doxycycline
2. Chloramphenicol is used when tetracyclines are contraindicated
5. Brucellosis: Alternative to tetracyclines and streptomycin
6. Topically used in eye and ear infections due to susceptible organisms.

Category: Pharmacology Notes