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Fluoroquinolones Ciprofloxacin Norfloxacin Ofloxacin Lomefloxacin Trovafloxacin Levofloxacin Sparfloxacin Gatifloxacin Quinolones Nalidixic acid Urinary tract antiseptics Methenamine Nitrofurantoin 2

 Mafenide  Silver sulfadiazine  Succinylsulfathiazole  Sulfacetamide  Sulfadiazine  Sulfamethoxazole  Sulfasalazine  sulfisoxazole 3

 Pyrimethamine  trimetoprim 4

 Co-trimoxazole 5

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

 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 7

 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. 8

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

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

 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 12

 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 13

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

 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 15

FOLATE ANTAGONISTS 16

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

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

 SILVER SULFA DIAZINE  SULFACETAMIDE  MAFENIDE  SULFASALAZINE  SULFISOXAZOLE  SULFAMETHOXAZOLE 19

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

 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). 21

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

 SILVER SULFA DIAZINE  SULFACETAMIDE  MAFENIDE  SULFASALAZINE  SULFISOXAZOLE  BURNS  IBD 23

 Other uses  NOCARDIOSIS-Nocardia asteroides  UTI  TRACHOMA 24

 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. 25

 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 26

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

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. 28

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

 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 ) 30

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