SULFONAMIDES SULFONAMIDES TREATMENT OF URINARY TRACT INFECTIONS TREATMENT OF URINARY TRACT INFECTIONS DRUGS USED TO TREAT UTI S
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1 TREATMENT OF URINARY TRACT INFECTIONS Most acute lower urinary tract infections (acute bacterial cystitis) are uncomplicated. E.coli causes 75-90% of episodes of acute uncomplicated cystitis. Staph saprophyticus is the 2 nd most common pathogen and the remaining cases are due to Proteus and other gram negative rods. TREATMENT OF URINARY TRACT INFECTIONS In most settings they can be safely treated on basis of the clinical history with a 3 day course of trimethoprim/sulfamethoxazole In areas where resistance is prevalent a FQ or nitrofurantoin could be substituted. DRUGS USED TO TREAT UTI S Sulfamethoxazole/trimethoprim Fluoroquinolones Fosfomycin Nitrofurantoin Amoxicillin Cephalosporins SULFONAMIDES Recognized since In clinical usage since First compounds found to be effective antibacterial agents in safe dose ranges. Mainstay of therapy before penicillins. SULFONAMIDES Now largely superceded by antibiotics and trimethoprim-sulfamethoxazole. They continue to occupy a small place in therapy. 1
2 ANTIBACTERIAL ACTIVITY Broad spectrum UTI s THERAPEUTIC USES Parasitic diseases (combined with other antimicrobials)- malaria, toxoplasmosis, PCP. PHARMACOKINETICS BLOOD Protein Bound Kidney Oral Topical Parenteral Metabolites Free Other-Sweat, Saliva, Prostatic fluid, Stool Body Fluids & Tissues CSF KERNICTERUS IN THE NEWBORN Displacement of bilirubin from plasma protein binding sites. 2
3 METABOLISM 3 HC O C N SO 2 N H R EXCRETION They are excreted in the urine partly as the parent and partly as the metabolite. Acetylated sulfonamides-inactive, toxic, and less soluble Some sulfonamides are very insoluble in the acid urine. EXCRETION Half life of the sulfonamides depends on renal function. Dosage should be modified or the sulfonamides should not be used in renal failure. SULFONAMIDE PREPARATIONS Rapidly absorbed and rapidly eliminated (prototype- sulfisoxazole). Poorly absorbed sulfonamides (sulfasalazine). Topical sulfonamides (sulfacetamide, silver sulfadiazine). Long-acting sulfonamides (sulfadoxine). ADVERSE EFFECTS Hypersensitivity reactions -common allergic rashes photosensitivity drug fever Stevens-Johnson syndrome 3
4 CONTRAINDICATIONS 4
5 DRUG-DRUG INTERACTIONS Inhibit metabolism of some drugs. Displace certain drugs from plasma albumin. TRIMETHOPRIM- SULFAMETHOXAZOLE 2 HN CH 2 80 mg TRIMETHOPRIM OCH 3 OCH 3 OCH 3 2 HN SO 2 NH N CH 3 O 400 mg SULFAMETHOXAZOLE COTRIMOXAZOLE Synergism Optimal ratio of the two drugs is 5:1 sulfa :trimethoprim. 5
6 Expanded number of organisms inhibited. Bactericidal. Decreased resistance. Decreased toxicity. ADVANTAGES THERAPEUTIC USES Oral cotrimoxazole is used in the treatment of acute uncomplicated or chronic urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) due to susceptible organisms (E coli, Klebsiella-Enterobacter, Proteus mirabilis, indole-positive proteus species). ADVERSE REACTIONS Dermatological reactions including skin rashes. GI (nausea and vomiting). HEMATOLOGICAL EFFECTS Leukopenia, thrombocytopenia and megaloblastosis. Most likely in patients with preexisting folate deficiency or in patients taking prolonged therapy. DRUG INTERACTIONS Same as with sulfonamides FLUOROQUINOLONES Now the most common class of antibiotics used for UTI s (especially ciprofloxacin). Due to concerns about cost-effectiveness and emerging resistance, routine use is not advised. 6
7 THERAPEUTIC USES Given as a single dose for the treatment of uncomplicated UTIs. FOSFOMYCIN Although approved as single-dose therapy for uncomplicated urinary tract infections, it appears to be less effective in eradicating bacteriuria than ofloxacin as single-dose therapy, ciprofloxacin as 7-day therapy, or trimethoprim-sulfamethoxazole (TMP-SMX) as 10-day therapy. PHARMACOKINETICS Available as both oral and parenteral preparations. Primarily excreted unchanged in the urine. May be useful for the treatment of TMP-SMXresistant uncomplicated UTI s. NITROFURANTOIN Nitrofurantoin is used in the treatment of UTI s caused by susceptible microorganisms; Also useful for longterm suppressive therapy. It is not indicated for the treatment of pyelonephritis or perinephric abscess. NITROFURANTOIN Adverse effects-nausea, vomiting and diarrhea are most common. Not effective in systemic infections. 7
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