Urinary Antiseptics, Drugs used in STDs and UTI

Urinary Antiseptics, Drugs used in STDs and UTI

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  URINARY ANTISEPTICS, DRUGS USEDIN UTI & STDs Anusha Shaji, B.Pharm, M.Pharm Assistant Professor Department of Pharmacology Nirmala College of Pharmacy, Muvattupuzha, Ernakulam
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  URINARY TRACT ANTISEPTICS/ANTIMICROBIALS Escherichiacoli is the most common pathogen, causing about 80% of uncomplicated upper and lower UTIs. Staphylococcus saprophyticus is the second most common bacterial pathogen causing UTIs Other common causes including Klebsiella pneumoniae and Proteus mirabilis. These infections may be treated with any one of a group of agents called urinary tract antiseptics, including methenamine, nitrofurantoin, and the quinolone nalidixic acid.
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  These drugs donot achieve antibacterial levels in the circulation ↓ But because they are concentrated in the urine ↓ Microorganisms at that site can be effectively eradicated. Methenamine It is hexamethylene- tetramine Inactive as such Decomposes slowly in acidic urine → to release formaldehyde ↓ Which inhibits all bacteria
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  Mechanism of action Toact, methenamine must decompose at an acidic pH of 5.5 or less in the urine → thus producing formaldehyde Which acts locally and is toxic to most bacteria Methenamine should not be used in patients with indwelling catheters. Bacteria do not develop resistance to formaldehyde. Methenamine is frequently formulated with a weak acid, such as mandelic acid or hippuric acid. Ascorbic acid (vitamin C), and cranberry juice have been used to reduce urinary pH.
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  Antibacterial spectrum Methenamine isprimarily used for chronic suppressive therapy. Urea-splitting bacteria that alkalinize the urine, such as Proteus species, are usually resistant to the action of methenamine. Methenamine is used to treat lower UTIs but is not effective in upper UTIs. It is most useful when the causative organism is E. coli, however it can suppress other organisms.
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  Pharmacokinetics Methenamine is administeredorally. In addition to formaldehyde, ammonium ion is produced in the bladder. Because the liver rapidly metabolizes ammonia to form urea Methenamine is contraindicated in patients with hepatic insuffi ciency In which elevated levels of circulating ammonium ions would be toxic to the CNS. Methenamine is distributed throughout the body fluids But no decomposition of the drug occurs at pH 7.4. → thus, systemic toxicity does not occur The drug is eliminated in the urine.
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  Adverse effects The majorside effect of methenamine treatment is gastrointestinal distress Although at higher doses, albuminuria, hematuria, and rashes may develop. Methenamine mandelate is contraindicated in patients with renal insufficiency → because mandelic acid may precipitate. Sulfonamides, such as cotrimoxazole, react with form aldehyde and must not be used concomitantly with methenamine. ↓ The combination increases the risk of crystalluria and mutual antagonism.
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  Nitrofurantoin It is primarilybacteriostatic, but may be cidal at higher concentrations and in acidic urine → its activity is enhanced at lower pH. It inhibits many gram-negative bacteria, but due to development of resistance, activity is now restricted largely to E. coli. Resistance to nitrofurantoin develops slowly and no cross resistance with any other AMA is known. It antagonizes the bactericidal action of nalidixic acid. Susceptible bacteria appear to enzymatically reduce nitrofurantoin to generate reactive intermediates which damage DNA.
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  Pharmacokinetics Nitrofurantoin is wellabsorbed orally Rapidly metabolized in liver and other tissues Less than half is excreted unchanged in urine Plasma t½ is 30–60 min. Antibacterial concentrations are not attained in blood or tissues. Probenecid inhibits its tubular secretion and reduces the concentration attained in urine- may interfere with its urinary antiseptic action. Renal excretion is reduced in azotaemic patients → effective concentrations may not be reached in urine → while toxicity increases Contraindicated in renal failure; also during pregnancy and in neonates.
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  Adverse effects Commonest isgastrointestinal intolerance- nausea, epigastric pain and diarrhoea. An acute reaction with chills, fever and leucopenia occurs occasionally. Peripheral neuritis and other neurological effects are reported with long-term use. Haemolytic anaemia is rare. Liver damage and a pulmonary reaction with fibrosis on chronic use are infrequent events. Urine of patients taking nitrofurantoin turns dark brown on exposure to air.
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  Use The only indicationfor nitrofurantoin is uncomplicated lower urinary tract infection, but it is infrequently used now. Acute infections due to E. coli can be treated with 50–100 mg TDS, given for 5–10 days. Suppressive long-term treatment has been successful with 50 mg BD. It is also employed for prophylaxis of urinary tract infection when catheterization or instrumentation of the lower urinary tract is performed.
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  TREATMENT OF URINARYTRACT INFECTIONS Most UTIs are caused by gram-negative bacteria, especially coliforms.
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  The status ofAMAs (other than urinary antiseptics) in urinary tract infections is; Sulfonamides Dependability in acute UTIs has decreased: not used now as single drug. May occasionally be employed for suppressive and prophylactic therapy. Cotrimoxazole Employed empirically in acute UTI without bacteriological data ↓ Because majority of urinary pathogens, including C. trachomatis, are covered by cotrimoxazole. It should not be used to treat UTI during pregnancy.
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  Quinolones The first generationFQs, especially norfloxacin and ciprofloxacin are highly effective Nalidixic acid is also employed. FQs are particularly valuable in complicated cases, those with prostatitis or indwelling catheters and for bacteria resistant to cotrimoxazole/ampicillin. The FQs should not be given to pregnant women. Cloxacillin Use is restricted to penicillinase producing staphylococcal infection, which is uncommon in urinary tract.
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  Cephalosporins Use is increasing,especially in women with nosocomial Klebsiella and Proteus infections Gentamicin Very effective against most urinary pathogens including Pseudomonas. However, because of narrow margin of safety and need for parenteral administration, it is generally used only on the basis of in vitro bacteriological sensitivity testing. The newer aminoglycosides may be needed for hospital-acquired infections.
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  TREATMENT OF SEXUALLYTRANSMITTED DISEASES (STDs) The effectiveness of various AMAs in treating different STDs is described with the individual drugs. The preferred drugs and regimens for important STDs are;