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  1. 1. Tetracyclines and Chloramphenicol (broad spectrum antibiotics)
  2. 2. Source- Soil actinomycetes Chlortetracycline- introduced in 1948 Divided into three groups: Group I- Tetracycline Chlortetracycline Oxytetracycline Group II- Demeclocycline Methacycline Lymecycline
  3. 3. <ul><li>Group III </li></ul><ul><li>Doxycycline </li></ul><ul><li>Minocycline </li></ul><ul><li>Mechanism of action- </li></ul><ul><li>Bacteriostatic </li></ul><ul><li>Inhibit protein synthesis by binding at 30 S ribosomes in </li></ul><ul><li>susceptible organism </li></ul><ul><li>Attachment of aminoacyl-t-RNA to the mRNA-ribosome </li></ul><ul><li>complex is interferred </li></ul><ul><li>as a result peptide chain fails to grow </li></ul>
  4. 4. <ul><li>The sensitive organism have an energy dependent active transport </li></ul><ul><li>process which concentrates tetracyclines intracellularly. </li></ul><ul><li>Gram negative bacteria –diffuses through porin channels </li></ul><ul><li>The carrier involved in active transport of tetracycline is absent in </li></ul><ul><li>the host cells </li></ul><ul><li>Doxycyclin and minocyclin (more lipid soluble)- enter by passive diffusion. </li></ul><ul><li>SPECTRUM </li></ul><ul><li>Broad spectrum </li></ul><ul><li>Cocci - All gram+ve and –ve cocci were originally sensitive </li></ul><ul><li>now Sterp.pyogens,Staph.aureus and Enterococci have </li></ul><ul><li>become resistant. </li></ul>
  5. 5. 2. Most gram positive bacilli- Clostridia, Listeria & Corynebacteria are inhibited but not Mycobacteria . 3. Sensitive gram negative bacilli- H.ducreyi,V .cholerae, Yersinia pestis etc. 4. Spirochetes 5. Rickettsiae and Chlamydiae are highly sensitive 6. Entamoeba histolytica and plasmodia - at high concentration
  6. 6. <ul><li>RESISTANCE </li></ul><ul><li>- Tetracycline concentrating mechanism become less efficient or the bacteria acquire capacity to pump it out. </li></ul><ul><li>Plasmid mediated synthesis of a ‘protection’ protein which protects the ribosomal binding site from tetracycline. </li></ul>
  7. 7. Group I Tetracycline(T) Oxytetracycline (oxyT) Group II Demeclocycline (Deme) Group III Doxycycline(Doxy) Minocycline(Mino) Source T- semisynthetic OxyT- S.rimosus S.aureofaciens Doxy- semisynthetic Mino- semisynthetic Potency Low Intermediate High Intestinal absorption T- intermediate OxyT- intermediate intermediate Complete, no interference by food Plasma protein binding OxyT- Low T- intermediate High High Elimination Rapid renal excretion Partial metabolism, Slower renal excretion Doxy- faeces Mino- urine and bile Plasma 6-10 hrs 16-18 hrs 18-24 hrs Dosage 250-500 mg QID or TDS 300-600 mg BD 200 mg initially, 100-200 mg OD
  8. 8. Group I Tetracycline(T) Oxytetracycline (oxyT) Group II Demeclocycline (Deme) Group III Doxycycline(Doxy) Minocycline(Mino) Alteration of intestinal flora Marked Moderate Least Incidence of diarrhoea High Intermediate Low Phototoxicity Low Highest Low Specific toxicity OxyT-less tooth discolouration More phototoxic Doxy-low renal toxicity
  9. 9. <ul><li>PRECAUTIONS </li></ul><ul><li>Should not be used during pregnancy,lactation and in children,unless there is no other choice. </li></ul><ul><li>They should be avoided in patients on diuretics: blood urea may rise in such patients. </li></ul><ul><li>Do not mix injectable tetracycline with penicillins-inactivation occurs. </li></ul><ul><li>Should be cautiously used in renal and hepatic insufficiency. </li></ul>
  10. 10. <ul><li>USES </li></ul><ul><li>Treatment of serious/life threatening infections. </li></ul><ul><li>2. Drug of first choice in: </li></ul><ul><li>a) venereal diseases </li></ul><ul><li>Lymphogranuloma venereum </li></ul><ul><li>Granuloma inguinale </li></ul><ul><li>b) Atypical pneumonia due to Mycoplasma pneumoniae </li></ul><ul><li>c) Cholera </li></ul><ul><li>d) Plague </li></ul><ul><li>e) Relapsing fever </li></ul><ul><li>f) Rickettsial infections </li></ul>
  11. 11. <ul><li>3. Second choice: </li></ul><ul><li>To penicillin/ampicillin for tetanus,anthrax,actinomycosis & </li></ul><ul><li>listeria infections. </li></ul><ul><li>To ciprofloxacin or ceftriaxone for gonorrhoea. </li></ul><ul><li>To cotrimoxazole for chancroid </li></ul><ul><li>To ceftriaxone for syphilis. </li></ul><ul><li>4. Other situations </li></ul><ul><li>UTI </li></ul><ul><li>Chronic obstructive lung disease </li></ul>
  12. 12. CHLORAMPHENICOL Source- Streptomyces venezuelae in 1947 Mechanism of action- inhibits bacterial protein synthesis By interferring with transfer of elongating peptide chain to the newly attached aminoacyl-tRNA at the ribosome-mRNA complex. It binds to 50S ribosome Probably by acting as peptide analogue, it prevents formation of peptide bonds
  13. 13. <ul><li>SPECTRUM </li></ul><ul><li>Bacteriostatic </li></ul><ul><li>High concentrations have been shown to exert </li></ul><ul><li>bacrericidal effect on some bacteria, e.g . H . influenzae. </li></ul><ul><li>- Active against gram +ve and gram –ve bacteria, </li></ul><ul><li>rickettsiae, mycoplasma </li></ul><ul><li>Difference from tetracycline is: </li></ul><ul><li>Highly active against Salmonella including S.typhi </li></ul><ul><li>b) It is more active than tetracycline against H.influenzae, </li></ul><ul><li>B.pertussis,klebsiella and N.meningitidis. </li></ul>
  14. 14. <ul><li>c) It is less active against gram+ve cocci,spirochetes, </li></ul><ul><li>certain enterobacteriaceae and clamydia . </li></ul><ul><li>It is ineffective against Mycobacteria, Pseudomonas, </li></ul><ul><li>many Proteus,viruses and fungi. </li></ul><ul><li>RESISTANCE </li></ul><ul><li>Due to transfer of R factor by conjugation. </li></ul><ul><li>Resistance among gram-ve bacteria is generally due to </li></ul><ul><li>Acquisition of R-plasmid encoded for an acetyl transferase. </li></ul>