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Chloramphenicol<br />
introduction<br /><ul><li> Broad spectrum </li></ul>(aerobic, anaerobic, gram +, gram -, rickettsiae) <br /><ul><li> Bacte...
 Bactericidal (H.influenzae, Neisseria meningitidis)</li></li></ul><li>Step 1 – AA binds to A<br />Step 2 – transpeptidati...
<ul><li>Inhibits protein synthesis </li></ul>	Binds reversibly to 50S; Inhibits peptidyl transferase<br />X<br />Protein s...
Pharmacokinetics <br />Chloramphenicol palmitate (oral)<br />Chloramphenicol succinate (Parenteral) <br />through oral rou...
 1-10µg/ml   -  inhibits Gram +ve bacteria<br /> O.2-5µg/ml - inhibits Gram -ve bacteria<br />Resistance due to <br />chlo...
Clinical uses <br /><ul><li> Typhoid
Typhus
 Rocky Mountain Spotted Fever
 Meningococcal meningitis
 Topically for eye infections </li></li></ul><li>When chloramphenicol should not be prescribed ?<br />	hepatic failure <br...
Adverse effects<br />Nausea, vomiting, diarrhoea, <br />oral/vaginal candidiasis<br />Bone marrow disturbances: <br /><ul>...
 aplastic anemia (idiosyncratic), irreversible, prolonged use</li></ul>Gray Baby Syndrome<br />
Gray baby syndrome <br />stops feeding <br />Vomiting<br />Hypotonic<br />Hypothermic <br />Distended abdomen<br />Irregul...
Why Gray baby syndrome occurs in neonates ?<br />Inability of neonate to metabolise & excrete chloramphenicol due to defic...
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Chloramphenicol

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Chloramphenicol

  1. 1. Chloramphenicol<br />
  2. 2. introduction<br /><ul><li> Broad spectrum </li></ul>(aerobic, anaerobic, gram +, gram -, rickettsiae) <br /><ul><li> Bacteriostatic
  3. 3. Bactericidal (H.influenzae, Neisseria meningitidis)</li></li></ul><li>Step 1 – AA binds to A<br />Step 2 – transpeptidation <br />X<br />Protein synthesis <br />50S<br />30S<br />P<br />A<br />Step 4 –translocation <br />Step 3 – tRNA leaves P site<br />
  4. 4. <ul><li>Inhibits protein synthesis </li></ul> Binds reversibly to 50S; Inhibits peptidyl transferase<br />X<br />Protein synthesis <br />X<br />P<br />A<br />30S<br />Inhibits transfer of elongating peptide chain to newly attached aminoacyl tRNA at A site <br />
  5. 5. Pharmacokinetics <br />Chloramphenicol palmitate (oral)<br />Chloramphenicol succinate (Parenteral) <br />through oral route – completely & rapidly absorbed<br />Dose : 50 - 100 mg/kg/day <br />Wide tissue distribution ( body fluids, CSF )<br />Inactivated by glucuronide conjugation<br />Eliminated in urine, bile, feces<br />
  6. 6. 1-10µg/ml - inhibits Gram +ve bacteria<br /> O.2-5µg/ml - inhibits Gram -ve bacteria<br />Resistance due to <br />chloramphenicol acetyl transferase<br />decreased permeability into bacterial cells<br />Cross resistance seen between Chloramphenicol, Macrolides, Lincosamide<br />
  7. 7. Clinical uses <br /><ul><li> Typhoid
  8. 8. Typhus
  9. 9. Rocky Mountain Spotted Fever
  10. 10. Meningococcal meningitis
  11. 11. Topically for eye infections </li></li></ul><li>When chloramphenicol should not be prescribed ?<br /> hepatic failure <br /> new borns (<1wk)<br /> premature infants <br />
  12. 12. Adverse effects<br />Nausea, vomiting, diarrhoea, <br />oral/vaginal candidiasis<br />Bone marrow disturbances: <br /><ul><li> dose related reversible suppression of RBCs
  13. 13. aplastic anemia (idiosyncratic), irreversible, prolonged use</li></ul>Gray Baby Syndrome<br />
  14. 14. Gray baby syndrome <br />stops feeding <br />Vomiting<br />Hypotonic<br />Hypothermic <br />Distended abdomen<br />Irregular respiration<br />Ashen gray cyanosis <br />Cardiovascular collapse <br />Death <br />
  15. 15. Why Gray baby syndrome occurs in neonates ?<br />Inability of neonate to metabolise & excrete chloramphenicol due to deficiency of glucuronosyl transferase<br />At higher concentration it inhibits electron transport in liver, heart, skeletal muscle<br />
  16. 16. Gray baby syndrome <br />Avoided by dose reduction <br /><ul><li>< 50 mg/kg/day ( full term infants )
  17. 17. < 25 mg/kg/day ( pre term infants )</li></li></ul><li>Drug interaction<br /><ul><li> Inhibits hepatic enzymes
  18. 18. Increases serum level of </li></ul>Phenytoin, tolbutamide, warfarin<br /><ul><li>Antagonises action of penicillins, aminoglycosides</li></li></ul><li>Why it is rarely used?<br />potential toxicity, <br />bacterial resistance & <br />availability of effective alternatives <br />

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