Quinolones , folic acid antagonists and urinary tract antiseptics

1. Quinolones, folic acid antagonists and urinary tract antiseptics

2. Drugs that inhibit bacterial DNA/RNA synthesis Fluoroquinolones Ciprofloxacin Norfloxacin Ofloxacin Lomefloxacin Trovafloxacin Levofloxacin Sparfloxacin Gatifloxacin Quinolones Nalidixic acid Urinary tract antiseptics Methenamine Nitrofurantoin

3. Mafenide Silver sulfadiazine Succinylsulfathiazole Sulfacetamide Sulfadiazine Sulfamethoxazole Sulfasalazine sulfisoxazole Inhibitors of folate synthesis

4. Pyrimethamine trimetoprim Inhibitors of folate reduction

5. Co-trimoxazole Combination of inhibitors of folate synthesis and reduction

6. First generation –nalidixic acid Second generation—ciprofloxacin, norfloxacin, ofloxacin Third gen—gatifloxacin, levofloxacin, moxifloxacin, sparfloxacin Fourth—trovefloxacin. Classification of fluoroquinolones

7. Inhibit replication of bacterial DNA by blocking the action of DNA gyrase(topoisomerase-II) and topoisomerase IV resulting in death of the bacteria. Are bactericidal and exhibit concentration dependent killing FLUORO QUINOLONES

8. First generation: restricted to the treatment of infections of the urinary tract Second generation: gram-ve, some gram +ve and atypical organisms Third generation: gram-ve, some gram+ve and atypical organisms Fourth generation: gram+ve, some gram-ve and anerobes They are effective against gonorrhea but not syphilis. Antimicrobial spectrum

9. Ciprofloxacin-- Anthrax Pseudomonal infections UTI Gonorrhea Traveller’s diarrhea

11. ROUTE : ORAL , IV ORAL –absorption Decreased by sucralfate, calcium, antacids containing Mg , iron supplements, zinc… DISTRIBUTION : CSF LESS Exception – OFLOXACIN EXCRETION : RENAL FLUORO QUINOLONES

12. NORFLOXACIN-Effective against both Gram positive and G negative organisms Useful in treating UTIS and prostatitis. LEVOFLOXACIN- An isomer of ofloxacin and has largely replaced it. Useful in treatment of prostatitis due to E coli. STDs including gonorrhea EXCEPT syphilis Good against respiratory infections due to S. Pneumonia and skin infections

13. Mutation in bacterial DNA gyrase → decreased affinity for fluoroquinolones Decreased intracellular concentration due to the presence of an efflux pump Decreased number of porin proteins in the outer membrane resistance

14. Ciprofloxacin, ofloxacin can increase the serum levels of theophylline, warfarin and cyclosporin Cimetidine interferes with the elimination of the fluoroquinolones Drug interaction

15. NAUSEA, HEADACHE, DIARRHEA NEPHROTOXICITY PHOTO TOXICITY Liver toxicity-Trovafloxacin CNS – CARE FOR EPILEPSY Sparfloxacin and moxifloxacin- prolongs QT interrval –CI in arrhythmias Cartilage erosions(in children) and increase risk of tendon injury with previous Tendonitis(adults). CI : preg, lactating, children SE

16. FOLATE ANTAGONISTS

17. Inhibition of DNA/RNA synthesis/function through interference with folic acid production

18. MECH : analogs of PABA that COMPETES WITH PABA ENZY : inhibits DIHYDRO-PTEROATE SYNTHETASE AB SPECTRUM : BACTERIOSTATIC SULFONAMIDES

19. SILVER SULFA DIAZINE SULFACETAMIDE MAFENIDE SULFASALAZINE SULFISOXAZOLE SULFAMETHOXAZOLE

20. ROUTE : MOSTLY ORAL • TOPICAL: CREAMS OF MAFENIDE ACETATE AND SILVER SULFADIAZINE USED IN BURNS • DISTRIBUTION : BBB, PLACENTA • EXCRETION : RENAL

21. HYPERSENSITIVITY reaction: rashes, angioedema, steven-Johnson syndrome Cyrstalluria: due to depressed kidney function NEPHROTOXICITY BLOOD: hemolytic anemia in pts def in G6PD, granulo and thrombocytopenia KERNICTERUS CI ; infants and newborns(< 2months of age), PREGNANT(at term). SE

22. Potentiation of the hypoglycemic effect of tolbutamide as well as the anticoagulant effect of warfarin due to their displacement from binding sites on albumin Drug interactions

23. USES • SILVER SULFA DIAZINE • SULFACETAMIDE • MAFENIDE • SULFASALAZINE • SULFISOXAZOLE • BURNS • IBD

24. Other uses NOCARDIOSIS-Nocardia asteroides UTI TRACHOMA

25. TRIMETHOPRIM PYRIMETHAMINE - in combination with sulfadiazine used to treat toxoplasmosis and and chloroquine resistant malaria) METHOTREXATE – carcinoma USES : UTI, PROSTATITIS, vaginitis SE : blood disorders RX ; FOLINIC ACID(leucovorin) to reverse the blood disorder. INHIBITORS OF FOLATE REDUCTION enzyme- dihydrofolatereductase

26. TRIMETHOPRIM + SULFAMETHOXAZOLE PNEUMOCYSTIS CARINII (JIROVECI) PNEUMONIA MOA—Inhibition of 2 sequential steps in the synthesis of tetrahydrofolic acid Sulfamethoxazole inhibits incorporation of PABA into folic acid and trimethoprim prevents reduction of dihydrofolate to tetrahydofolate USES : UTI, GENITAL, PROSTATE Shigellosis, nontyphoid salmonella, H-influenza and alternative to Legionella and PCP in AIDS pts CO TRIMOXAZOLE

27. DERMATOLOGICAL GIT—glossitis and stomatitis BLOOD- Anemia, Leukopenia, Thrombocytp. Reverse using folinic acid(leucovorin) DRUG INTERACTIONS- increased PT in Pts taking warfarin. SE

28. Methenamine Needs acidic pH Mostly combined with mandelic acid Decomposes to Form formaldehyde which is toxic for bacteria CI : hepatic failure, renal failure, catheterized pt. & also with Sulfonamides. U T Antiseptics

29. Methenamine Route – oral Excretion – urine (renal) SE- GIT distress, at higher doses albuminuria, hematuria and rashes.

30. Bacteriostatic Antibiotic activity is greater in acidic urine Sensitive bacteria reduce the drug to an active agent that Inhibits various bacterial enzymes & damages DNA Route – oral Excretion – renal ( brown urine ) Nitrofurantoin

31. SE GIT Pneumonitis Anemia : G 6 PD DEF. NEURO : DEMYELINATION. CI : Pregnant & children