QUINOLONES Synthetic antimicrobials having a quinolone structure Active against gram-ve bacteria First member was  Nalidix...
<ul><li>Nalidixic acid </li></ul><ul><li>It is active against gram –ve bacteria specially coliforms: </li></ul><ul><li>E.c...
<ul><li>Pharmacokinetics </li></ul><ul><li>A- oral </li></ul><ul><li>D- plasma protein bound </li></ul><ul><li>M- partly i...
<ul><li>Prolonged use- parkinsonism like symptoms,leucopenia </li></ul><ul><li>and biliary stasis. </li></ul><ul><li>Indiv...
FLUOROUINOLONES These are quinolone antimicrobials having one or more Fluorine substitutions. First generation Fluoroquino...
<ul><li>-Antimicrobial activity  extending to gram +ve cocci and anaerobes. </li></ul><ul><li>MOA </li></ul><ul><li>Inhibi...
FQs binds to A subunit with high affinity and interfere with  its strand cutting and resealing function. In gram +ve bacte...
<ul><li>RESISTANCE </li></ul><ul><li>chromosomal mutation producing DNA gyrase or  </li></ul><ul><li>Topoisomerase IV with...
MIC  - < 0.1 µg/ml for  Neisseria  and   enterobacteriaceae. Gram +ve are inhibited at relatively higher concentrations. H...
<ul><li>Microbiological features  </li></ul><ul><li>Rapidly bactericidal activity and high potency: MBCs are close  </li><...
PHARMACOKINETICS A-  oral, but food delays absorption and first pass metabolism  occurs.  D - plasma protein bound Promine...
<ul><li>ADVERSE EFFECTS </li></ul><ul><li>Gastrointestinal- nausea,vomiting,bad taste,anorexia </li></ul><ul><li>CNS- dizz...
<ul><li>USES </li></ul><ul><li>UTI </li></ul><ul><li>Gonorrhoea </li></ul><ul><li>Chancroid </li></ul><ul><li>Bacterial ga...
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Quinolones and misc. antibiotics

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Quinolones and misc. antibiotics

  1. 1. QUINOLONES Synthetic antimicrobials having a quinolone structure Active against gram-ve bacteria First member was Nalidixic acid introduced in 1960’s There usefulness is limited to urinary and g.i tract infections because of -Low potency -Modest blood and tissue levels -Limited spectrum -High frequency of bacterial resistance
  2. 2. <ul><li>Nalidixic acid </li></ul><ul><li>It is active against gram –ve bacteria specially coliforms: </li></ul><ul><li>E.coli,Proteus,Klebsiella,Enterobacter,Shigella </li></ul><ul><li>but not Pseudomonas </li></ul><ul><li>Bactericidal </li></ul><ul><li>MOA </li></ul><ul><li>Inhibit bacterial DNA gyrase </li></ul>
  3. 3. <ul><li>Pharmacokinetics </li></ul><ul><li>A- oral </li></ul><ul><li>D- plasma protein bound </li></ul><ul><li>M- partly in liver </li></ul><ul><li>E- urine </li></ul><ul><li>Plasma t 1/2 ̴ 8 hrs </li></ul><ul><li>Adverse effects </li></ul><ul><li>Infrequent, mostly of g.i. upset and rashes. </li></ul><ul><li>Most important is neurological- headache,drowsiness, </li></ul><ul><li>visual disturbances,occasionally seizures(children). </li></ul>
  4. 4. <ul><li>Prolonged use- parkinsonism like symptoms,leucopenia </li></ul><ul><li>and biliary stasis. </li></ul><ul><li>Individuals with G-6PD deficiency may develop haemolysis. </li></ul><ul><li>USE </li></ul><ul><li>1. Urinary antiseptic </li></ul><ul><li>2. Diarrhoea caused by Proteus,E.coli,Shigella or salmonella. </li></ul>
  5. 5. FLUOROUINOLONES These are quinolone antimicrobials having one or more Fluorine substitutions. First generation Fluoroquinolones (introduced in 1980s) Norfloxacin Ofloxacin Ciprofloxacin Pefloxacin Second generation Fluoroquinolones (1990s) Lomefloxacin Levofloxacin Sparfloxacin Gatifloxacin Moxifloxacin
  6. 6. <ul><li>-Antimicrobial activity extending to gram +ve cocci and anaerobes. </li></ul><ul><li>MOA </li></ul><ul><li>Inhibit DNA gyrase </li></ul><ul><li>DNA gyrase- nicks double stranded DNA,introduces negative </li></ul><ul><li>Supercoils and then reseals the nicked ends. </li></ul><ul><li>Consists of two A and two B subunits </li></ul><ul><li>A subunit- carries out nicking of DNA </li></ul><ul><li>B subunit- introduces negative supercoils </li></ul><ul><li>A subunit reseals the strands </li></ul>
  7. 7. FQs binds to A subunit with high affinity and interfere with its strand cutting and resealing function. In gram +ve bacteria -inhibit Topoisomerase IV which nicks and seperates daughter DNA strands after DNA replication. In host cell topoispmerase II is present which has very low affinity for FQs- hence low toxicity to host cells.
  8. 8. <ul><li>RESISTANCE </li></ul><ul><li>chromosomal mutation producing DNA gyrase or </li></ul><ul><li>Topoisomerase IV with reduced affinity for FQs </li></ul><ul><li>-due to reduced permeability/increased efflux of these drugs </li></ul><ul><li>across bacterial membrane. </li></ul><ul><li>Ciprofloxacine </li></ul><ul><li>Most potent first generation FQ </li></ul><ul><li>Active against broad range of bacteria most susceptible </li></ul><ul><li>are aerobic gram-ve bacilli- enterobacteriaceae and </li></ul><ul><li>Neisseria </li></ul>
  9. 9. MIC - < 0.1 µg/ml for Neisseria and enterobacteriaceae. Gram +ve are inhibited at relatively higher concentrations. Highly susceptible E.Coli Enterobacter Salmonella typhi Shigella Proteus Moderately susceptible P.Aeruginosa S. Aureus S. Epidermidis Listeria Brucella
  10. 10. <ul><li>Microbiological features </li></ul><ul><li>Rapidly bactericidal activity and high potency: MBCs are close </li></ul><ul><li>to MICs. </li></ul><ul><li>Relatively long post-antibiotic effect on enterobacteriaceae, </li></ul><ul><li>Pseudomonas and Staph. </li></ul><ul><li>Low frequency of bacterial resistance. </li></ul><ul><li>Active against many β lactam and aminoglycoside resistant </li></ul><ul><li>bacteria. </li></ul>
  11. 11. PHARMACOKINETICS A- oral, but food delays absorption and first pass metabolism occurs. D - plasma protein bound Prominent feature- high tissue penetrability: concentrates in lung, sputum, muscle, bone. but CSF and aqueous levels are lower. E - urine
  12. 12. <ul><li>ADVERSE EFFECTS </li></ul><ul><li>Gastrointestinal- nausea,vomiting,bad taste,anorexia </li></ul><ul><li>CNS- dizziness,headache,restlessness,insomnia </li></ul><ul><li>Skin- rash,photosenstivity,utricaria </li></ul><ul><li>INTERACTIONS </li></ul><ul><li>Plasma concentration of theophylline, caffeine and warfarin </li></ul><ul><li>are increased by ciprofloxacin. </li></ul><ul><li>NSAIDs may enhance the CNS toxicity of FQs </li></ul><ul><li>Antacids,sucralfate and iron salts reduce absorption of FQs </li></ul>
  13. 13. <ul><li>USES </li></ul><ul><li>UTI </li></ul><ul><li>Gonorrhoea </li></ul><ul><li>Chancroid </li></ul><ul><li>Bacterial gastroenteritis </li></ul><ul><li>Typhoid </li></ul><ul><li>Bone, soft tissue, gynaecological and wound infections </li></ul><ul><li>Respiratory infections </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Gram –ve septicaemias </li></ul><ul><li>Meningitis </li></ul><ul><li>Conjuctivitis </li></ul>

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