UTI Agents
- 1. URINARY TRACT ANTI-INFECTIVE AGENTS BY KENCHA SWATHI ASSISTANT PROFESSOR Swathi Pharma Jnan
- 2. URINARY TRACT ANTI-INFECTIVE AGENTS Definition: Antibacterial agents that fail to achieve adequate concentrations in the plasma or tissues for the treatment of systemic infections following oral or parentral administration are concentrated in the urine,where they can be effective for eradicating urinary tract infections. Swathi Pharma Jnan
- 3. CLASSIFICATION Based on chemical structure: 1.Quinolone derivatives – Nalidixic acid,Norfloxacin,Ciprofloxacin 2.Nitrofuran derivatives – Nitrofurantoin 3.Methenamine and its salts – Hexamine(Hexa methylene Tetramine) 4.Urinary analgesics – Phenyl azo pyridine Swathi Pharma Jnan
- 4. QUINOLONE DERIVATIVES • These are isosteric heterocyclic groupings which includes – a.Quinolones –Norfloxacin Ciprofloxacin,Sparfloxacin,Lomefloxacin,O-floxacin b.Naphthyridines(1,8-Napthyridines) – Nalidixic acid,Enoxacin c.Cinnolines(1,2-Napthyridines) – Cinnoxacin Quinolone derivatives contain isosteric substitution of carbon by nitrogen. Swathi Pharma Jnan
- 5. SAR OF QUINOLONES • 1,4-dihydro 4-oxo pyridine 3-carboxylic acid is essential for anti-bacterial activity. • Pyridone should be fused with aromatic ring for showing activity. Swathi Pharma Jnan
- 6. • Isosteric replacements of nitrogen for carbon atoms at position 2(cinnolines),position 5(1,5-naphthyridines),position 6(1,6- naphthyridines),position 8(1,8-naphthyridines) are consistent with retained antibacterial activity. • 1,7-naphthyridines and 1,3-naphthyridines are not active. • 1,2-Naphthyridines(Cinnolines) are showing better activity. Eg: Swathi Pharma Jnan
- 7. • 1,5-naphthyridines have isosteric substitution of carbon with nitrogen at 5th position. Eg: • 1,8-Naphthyridines shows better activity compared to other napthyridines. Eg: Nalidixic acid Swathi Pharma Jnan
- 8. • Introduction of substituents at position 2 greatly abolishes the activity. • Introduction of substituents at position 5,6,7 (especially at 8) of anneulated ring will result in compounds with good activity. • Normally at 7th position piperazinyl (saturated pyrazine)structure is common. • 3-Amino pyrrolidinyl(saturated pyrrole) substituents at position 7 enhances the activity of quinolone class against “Pseudomonas aerogenosa”. Eg: Enoxacin Swathi Pharma Jnan
- 9. • F atom substitution at position 6 also significantly enhances the antibacterial activity. • Alkyl substitution at position 1 is essential for activity with lower alkyl groups like methyl,ethyl,cyclopropyl group containing compounds have progressively greater potency. Eg:Ciprofloxacin Swathi Pharma Jnan
- 10. • If we have aryl substitution at position 1 is also consisting with the antibacterial activity with 2,4-difluorogroups produces optimum activity. • Ring condensation compounds are active Eg: Cinnoxacin - 6,7-fusion & O-Floxacin -1,8 condensation Swathi Pharma Jnan
- 11. • 6-Fluoro quinolones having basic moieties like 1-piperidino-3-amino,1-pyrrolidino or similar basic moiety at the 7th position will have some CNS effects such as irritability,tremors,sleep disorders,vertigo,anxiety,agitation and convulsions etc., Eg: O-Floxacin • Quinolones possessing additional halogen atom at 8th position shows along with CNS effects they also exihibit phototoxicity. • One more F at 8th position causes sensitive towards photolight. Eg: Lomefloxacin Swathi Pharma Jnan
- 12. • Quinolone derivatives having an amino group or methoxy group either at 5th or 8th position will have lowest incidence of photo light. Eg: Sparfloxacin Swathi Pharma Jnan
- 13. NORFLOXACIN USES: In the treatment of UTI’s caused by E.Coli,Pneumonia,Enterobacter species,Proteus species and staphylococcus aureus. Swathi Pharma Jnan
- 14. SPARFLOXACIN USES: To treat skin and soft tissue infections. To treat lower respiratory tract infetions like bronchitis and bacterial pneumonia,pelvic inflammatory disease caused by gonorrhoea,chlamydia species. Swathi Pharma Jnan
- 15. CIPROFLOXACIN Swathi Pharma Jnan USES: To treat bacterial gastroenteritis caused by gram –ve bacteria . It is widely used for the treatment of respiratory tract infections such as pneumonia caused by gram –ve bacteria. To treat UTI ,venereal disease. For post exposure treatment of inhalation anthrax.
- 16. LOMEFLOXACIN USES: To treat Urinary tract infections Swathi Pharma Jnan
- 17. O-FLOXACIN USES: To treat lower respiratory tract infections and pelvic inflammatory disease. To treat UTI’s caused by gram-ve bacteria and for prostatitis caused by E.Coli. To treat soft tissue /skin infections caused by staphylococcus,streptococci .Swathi Pharma Jnan
- 18. NALIDIXIC ACID USES:In the treatment of UTI’s in which gram –ve bacteria predominates. Swathi Pharma Jnan
- 19. ENOXACIN USES: To treat urinary tract infections Swathi Pharma Jnan
- 20. CINNOXACIN USES: To treat UTI infection in which gram-ve bacteria is susceptible . Swathi Pharma Jnan
- 21. NITROFURANTOIN USES: To treat bacterial infections. Antiprotozoal drug Swathi Pharma Jnan
- 22. METHENAMINE(HEXAMETHYLENE TETRAMINE) Uses: Used as urinary antiseptic and for the treatment of chronic UTI’s. Swathi Pharma Jnan
- 23. PHENYL AZO PYRIDINE USES: Used as local analgesic which acts on the mucosa of urinary tract. Swathi Pharma Jnan
- 24. MOA OF QUINOLONES • Quinolones produces their antibacterial activity by inhibiting the synthesis of DNA due to the inhibition of bacterial DNA gyrase(topoisomerase-2),an enzyme responsible for introducing negative supercoils into circular duplex DNA. • Negative supercoiling relieves torsional stress of unwinding helical DNA and there by allows transcription and replication to occur . Swathi Pharma Jnan
- 25. MOA OF NITROFURANTOIN Swathi Pharma Jnan
- 26. SYNTHESIS OF NITROFURANTOIN Swathi Pharma Jnan 5-Nitrofurfural 1-Amino hydantoin Nitrofurantoin NaOH -H₂O