Urinary tract anti infective agents

UTI and Drugs fro 6 sem B.Pharm as per new PCI Syllabus 2018

1. URINARY TRACT ANTI-INFECTIVE AGENTS

2. Urinary tract infections mainly caused by E -coli , Staphulococcus etc It affects the various part of urinary system kidney , urethra , bladder . symptoms Burning senation during urination pain in pelvic area Red or pink coloured urine Continuous urge to urinate

3. Urinary tract infections can be treated with many drugs like sulfoamides , quinolones and other agents . These agents are mainly concentrated in urine after administration Effective in eradicating urinary tract infections

4. Classification QUNINOLONES Nalidixic acid Norfloxacin Ciprofloxacin Sparfloxacin Ofloxacin Gemifloxacin

5. Quinolones constitute a large class of synthetic antimicrobial agents that are highly effective in the treatment of many types of infectious diseases, particularly those caused by bacteria. Quinolones are poten t, broad-spectrum antibacterial agents.

6. Mode of action: Quinolones inhibit the action of bacterial DNA gyrase enzyme. This enzyme is responsible for supercoiling and compacting bacterial DNA molecules into the bacterial cell during replication. This action is accomplished by modifying the topology of DNA via supercoiling and twisting of these macromolecules to permit DNA replication or transcription.

7. QNINOLONES 4-OXO,1,4- DIHYDROQUNILONE MOIETY SAR

8. (8-aza-4-quinoline) Prototype drug is Nalidixic acid

9. 1,4-Dihydro-4-oxa-3-pyridine carboxylic moiety Presence of -COOH group at C3 is essential for Gyrase binding and bacterial transport. Modification or removal of this group abolishes the activity. Introduction of fluorine at C-6 & Piprazine ring at C-7 gives highly potent drugs. For ex: Norfloxacin , Ciprofloxacin ,

10. Substitution at C-7 & C-8 controls potency and Pharmacokinetic of the drug. Introduction of Fluorine at C-6 and C-8 gives Sparfloxacin . Which has broad spectrum of activity.

11. Substitution at positions 5.6.7. and 8 of the annulated ring produced good effects. Substitution at position 6 with fluorine atom significantly enhance the activity. Alkly substitution at position 1 is essential for activity by lower alkyl groups have greater potency. Aryl substitution at position 1 is consistent with activity and 2.4-di fluoro phenyl group has optimum potency.

12. Ring condensations at (1,8), (5,6), (6,7) positions leads to active compounds.

13. MOA Quninolines acts as a anti- infectives agents and treats UTI By Inhibiting the A – subunit of DNA gyrase enzyme ( topoisomerase ) which is required for reproduction of bacterial DNA. The agents inhibits DNA replication pathway. DNA gyrase causes unwinding of DNA in the bacteria. Quinolines inhibit this enzyme by binding to its A-subunit as a result of which bacteria is not able to replicate.

14. NALIDIXIC ACID 1-ETHYL- 7 METHYL-1,4-OXO ( 1,8) NAPH THYRIDINE- 3 CARBOXYLIC ACID

15. MOA It inhibits bacterial replication by binding to the A – subunit of the enzyme DNA gyrase . USES used for lower UTI caused by E-Coli

16. 1-ETHYL -6-FLURO—1,4-DIHYDRO-4-OXO-7-(1-PIPERAZINYL) -3-QUINOLINE CARBOXYLIC ACID NORFLOXACIN

17. MOA It inhibit the enzymes topoisomerase II and IV ( DNA gyrase ) Essential for replication, transcription, repair and recombination of bacterial DNA.

18. USES Treatment of UTI’s caused by E-Coli Gasteroenteritis Enzyme inhibitor Nucleic acid synthesis inhibitor

19. Enoxacin MOA: Enoxacin functions by inhibiting bacterial  DNA gyrase  and  topoisomerase IV . The inhibition of these enzymes prevents bacterial DNA replication, transcription, repair and recombination USES: It is used in UTI infection caused by E coli. It is used in the treatment of Diarrhoea and respiratory tract Infections.

20. 1-cyclopropyl -6-fluoro- 1,4-dihydro-4-oxo-7-(1- piperazinyl )-3-quinoline carboxylic acid CIPROFLOXACIN

21. USES Recurrent UTI Chronic Prostatitis Pneumonia Skin infection Meningitis Combination with Metronidazole ( for Complicated abdominal infection )

22. Sparfloxacin 5-AMINO-1-CYCLOPROPYL-7-(3R,5S)-3,5-DIMETHYLPIPERAZIN-1-YL) -6,8-DIFLUORO-4-OXO-QUINOLINE-3- CARBOXYLIC ACID

23. MOA It inhibit the enzymes topoisomerase II and IV ( DNA gyrase ) Essential for replication, repair and recombination of bacterial DNA. Inhibition of cell growth cell lysis .

24. USES UTI Bacterial infection Bronchitis Lower respiratory tract infections

25. OFLOXACIN 9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-2 H-[1,4] oxazino [2,3,4-ij]quinoline-6-carboxylic acid

26. It is one of the most promising newer members of the fluoroquionolone family. In this product, N-methyl moiety has been made rigid by incorporation into a heterocyclic ring. It is useful in the treatment of genitourinary, respiratory, gastrointestinal, skin, soft tissue infections, periodonitis , and gonorrhoea .

27. GATIFLOXACIN inhibits the  bacterial   enzymes   DNA gyrase  and  topoisomerase IV .

28. oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial infections In chronic bronchitis and mild-to-moderate pneumonia.

29. LOMEFLOXACIN It inhibits the  bacterial   enzymes   DNA gyrase  and  topoisomerase IV . USES: It is used in UTI infection caused by E coli. It is used in the treatment of Diarrhoea and respiratory tract Infections.

30. MOXIFLOXACIN It inhibits the  bacterial   enzymes   DNA gyrase  and  topoisomerase IV . USES: It is used in UTI infection. It is used in the treatment of conjuctivitis

31. FURAZOLIDINE MOA: It exerts its effect by cross linking with bacterial DNA USES: It is used to treat diarrhoea and enteritis caused by bacterial infection including travelers diaahoea and cholera Furazolidine has also been used for treating giardiasis amoebiasis Being antibacterial it is also used in the treatment of UTI’s

32. NITROFURANTOIN MOA: It causes inhibition of DNA, RNA, protein, and cell wall synthesis. This leads to inhibition of bacterial growth or cell death USES: it is used in the prophylaxis of UTI

33. METHENAMINE MOA: It gets converted into formaldehyde in the body which has an antibacterial action USES: it is used in the prophylaxis of UTI