Protein synthesis inhibitor, chloramphenicol, and thiamphenicol

1. Chloramphenicol
Jagir R. Patel
Asst Professor
Dept.: pharmacology

2. • Chloramphenicol was initially obtained from Streptomyces Venezuela
• It was soon synthesized chemically and the commercial product now is all
synthetic
• It has a nitrobenzene substitution, which is probably responsible for the
antibacterial activity and its intensely bitter taste.

3. • Chloramphenicol is primarily bacteriostatic, though high concentrations Have
been shown to exert cidal effect on some bacteria.
• Chloramphenicol was highly active against Salmonella including S. typhi, but
resistant strains are now rampant.
• It is more active than tetracyclines against H. influenzne (though many have
now developed resistance), B. pertussis, Klebsiella, N.meningitidis and
anaerobes including Bact. fragilis.
• It is less active against gram-positive cocci, spirochetes, certain
Enterobacteriaceae and Chlamydia. Entamoeba and Plasmodia are not inhibited.

5. Inhibits protein synthesis
Prevents formation of peptide bond
Binds reversibly to 50s ribosome subunit
Chloramphenicol

6. • Resistance to chloramphenicol is caused by
Resistance
Ribosomal
mutation
Decreased permeability of drug to
microbial cell wall
Production of inactivating enzyme,
acetlytransferase, e.g. H.influenza, S.typhi S.aureus

7. • Duration: Typhoid: 8-10 days; meningitis: 7-10 days; brain abscess: Up to 4 wk.
• Absorption: Readily absorbed with peak plasma concentrations after 1 or 2 hr
(oral).
• Distribution: Distributed widely into tissues and fluids, CSF, eye, crosses the
placenta and enters the breast milk. Protein-binding: 60%.
• Metabolism: Hydrolysed to the free drug in the GI tract (palmitate); liver by
conjugation with glucuronic acid, lungs and kidneys after parenteral admin
(sodium succinate).
• Excretion: Via the urine, via the bile (3%), via the faeces (1% as inactive form);
1.5-4 hr (elimination half-life).

8. • Hypersensitive reactions: sin rashes, fever, and angioedema
• GIT: nausea, vomiting, diarrhoea
• Anemias: Patients may experience dose-related anemia, hemolytic anemia (seen in patients
with glucose-6-phosphate dehydrogenase deficiency), and aplastic anemia. [Note: Aplastic
anemia is independent of dose and may occur after therapy has ceased.]
• Bone marrow suppression:
• The most serious ADV of chloramphenicol, is on bone marrow, it occurs in two ways
 Dose dependent reversible suppression, which manifests
anemia, leukopenia, and thrombocytopenia.
 Non dose related: which is fatal

9. • Gray baby syndrome (also termed Gray or Grey syndrome) is a rare but
serious side effect that occurs in newborn infants
• Pathophysiology
• Due to lack of The UDP- glucuronyl transferase enzyme system of infants,
especially premature infants, is immature and incapable of metabolizing the
excessive drug load.
• Insufficient renal excretion of the unconjugated drug.

10. • Loss of appetite
• Vomiting
• Ashen gray color of the skin
• Hypotension (low blood pressure)
• Cyanosis (blue discolouration of lips and skin)
• Hypothermia
• Cardiovascular collapse
• Abdominal distension
• Irregular respiration
• Increased blood lactate

11. 1. Paracetamol + chloramphenicol = enhances bioavailability of
chloramphenicol by 28 %
2. Chloramphenicol is potent enzyme inhibitor and inhibits metabolism of
3. warfarin = increase risk of bleeding
4. Morphine = respiratory depression
5. Chorpropamide = increase hypoglycaemia
6. Chloramphenicol + Penicillins can cause antibiotic antagonism.

12. • Anaerobic infections: B.fragilis, in combination with metronidazole for treatment of
brain, lungs, intra abdominal, or pelvic abscess
• Eye and ear infections
• Brucellosis
• Because of its toxic side effects, chloramphenicol is used only to suppress
infections that cannot be treated effectively with other antibiotics. Such
infections typically include
• (1) Typhoid fever
• (2) Meningococcal infections in cephalosporin-allergic patients
• (3) Serious H. influenzae infections, particularly in cephalosporin-allergic patients
• (4) Anaerobic infections (e.g., those originating in the pelvis or intestines) Anaerobic
or mixed infections of the CNS
• (6) Rickettsial infections in pregnant patients, tetracycline-allergic patients, and
renally impaired patients
• Oral : 50mg/kg, ear drops: 5% 2-3 drops, eye drops: 0.5% drops

13. 1. Chloramphenicol can cause bone marrow suppression (dose-related) with
resulting pancytopenia; rarely, the drug leads to aplastic anemia (not related to
dose).
2. Hypersensitivity reactions may include skin rash and, in extremely rare
cases, angioedema or anaphylaxis.
3. Chloramphenicol therapy may lead to gray baby syndrome in neonates
(especially premature infants). This dangerous reaction, which stems partly
from inadequate liver detoxification of the drug, is manifested by vomiting,
gray cyanosis, rapid and irregular respirations, vasomotor collapse, and in
some cases death.

15. • Thiamphenicol (also known as thiophenicol and dextrosulphenidol) is
an antibiotic.
• It is the methyl- sulfonyl analogue of chloramphenicol and has a similar spectrum
of activity, but is 2.5 to 5 times as potent.
• Pharmacokinetics
• Absorption: Peak serum concentrations: 2 hr.
Distribution: Diffuses into the CSF, across the placenta, into breast milk and into
the lungs. Protein binding: 10%. Half-life: 2-3 hr, increased in renal impairment.
Metabolism: Undergoes little or no conjugation with glucuronic acid in the liver.
Excretion: Excreted in the urine mainly as unchanged drug (70%); small amount
excreted in bile and faeces.

16. • Interactions: Drugs that depress bone marrow function.
• Indications oral only 1.5gm daily divided dose
• Sexually transmitted diseases; Susceptible infections
• Gonorrhoea

17. • Adverse effects of Chloramphenicol-
BIG Super Hypersensitivity
B- Bone marrow depression
I- Irritative effects like nausea, vomiting, diarrhoea, pain on injection
G- Gray baby syndrome
Super- super infections
Hypersensitivity reactions like rashes, fever, angioedema