Urinary Antiseptics

Organisms  Escherichia coli  Proteus  Pseudomonas species  streptococci  Klebsiella  Enterococcus  Staphylococcus epidermidis

Introduction Oral agents have antibacterial activity in urine but have little or no systemic antibacterial activity Oral agents have antibacterial activity in urine but have little or no systemic antibacterial activity Usefulness is limited to lower UTI Usefulness is limited to lower UTI Effective antibacterial concentration reach the renal pelvis and bladder. Effective antibacterial concentration reach the renal pelvis and bladder. Used in chronic UTI where eradication of infection by short term systemic therapy has not been possible Used in chronic UTI where eradication of infection by short term systemic therapy has not been possible

Drugs that act as urinary antiseptics are as follows: Nalidixic Acid & CinoxacinNalidixic Acid & Cinoxacin NitrofurantionNitrofurantion MethenamineMethenamine PhenazopyridinePhenazopyridine

Nalidixic Acid & Cinoxacin Introduction: One of the earlier quinolones, did not achieve systemic antibacterial levels therefore were useful only for treatment of lower UTI Pharmacokinetics: Well absorbed orally. BA % Widely distributed in body fluids and tissues. Plasma Half life 3-10 hrs permitting once daily dosing.

Oral absorption is impaired by divalent cations including those in antacids. Serum concentration of I/V administration is equal to orally administered drug. Excretion is renal either GF or Tubular secretion

MOA inhibit DNA gyrase Therapeutic Uses : - Many gm –ve organisms. Many gm –ve organisms. Lower urinary tract infections. Lower urinary tract infections.

Adverse Effects Adverse Effects GIT irritation GIT irritation Glycosurea Glycosurea Skin rashes. Skin rashes. Photo sensitization. Photo sensitization. Visual disturbances Visual disturbances CNS stimulation. CNS stimulation. Hepatic failure Hepatic failure

Nitrofurantion Bacteriostatic and bactericidal for many Gm +ive and Gm –ive bacteria Second line agent for treatment of UTI Pharmakokinetics Well absorbed orallyWell absorbed orally Rapidly metabolized and excreted through kidneysRapidly metabolized and excreted through kidneys glomerular filtration and tubular secretion. glomerular filtration and tubular secretion. No systemic antibacterial activityNo systemic antibacterial activity Brown discoloration of urine.Brown discoloration of urine.

Mechanism of Action: Complex Rapid intracellular conversion into highly reactive intermediates by bacterial reductase This intermediate then reacts non-specifically with many ribosomal proteins and disrupt synthesis of proteins, RNA, DNA and metabolic processes.

Anti bacterial spectrum: E. coli, enterococci. Most species of Proteus and Pseudomonas, Enterobacter and Klebsiella are resistant. E. coli, enterococci. Most species of Proteus and Pseudomonas, Enterobacter and Klebsiella are resistant. Therapeutic Uses : - Active against many urinary tract pathogens (but not proteus or pseudomonas)Active against many urinary tract pathogens (but not proteus or pseudomonas) Uncomplicated urinary tract infectionsUncomplicated urinary tract infections Daily dose for adults is 100 mg orally 6 hourly with food or milkDaily dose for adults is 100 mg orally 6 hourly with food or milk

It is desirable to keep urinary pH below 5.5, which greatly enhances drug activity

Adverse Effects :- GIT irritation, anorexia, nausea, vomitingGIT irritation, anorexia, nausea, vomiting Skin rashes and hypersensitivity reactionsSkin rashes and hypersensitivity reactions NeuropathiesNeuropathies Hemolysis in patients with G6PD deficiencyHemolysis in patients with G6PD deficiency Acute pneumonitis (fever, chills, leucopenia)Acute pneumonitis (fever, chills, leucopenia)Resistance Resistance emerges slowlyResistance emerges slowly No cross resistance between Nitrofurantion and other antimicrobial agentsNo cross resistance between Nitrofurantion and other antimicrobial agents

Contraindications Pregnant woman Pregnant woman Individuals with impaired renal function. Individuals with impaired renal function. Children younger than 1 month of age. Children younger than 1 month of age.

Methenamine Chemistry: Chemistry: It is hexamethylenetetramine. The compound decomposes in water to form formaldehyde which is responsible for antibacterial activity. Acidification of urine is required for this decomposition. Methenamine mandelate is salt of mendelic acid and methenamine Methenamine Hippurate is salt of huppuric acid and methenamine

 Taken orally excreted unchanged in urine where these drugs are bactericidal for some Gm –ive bacteria when pH is less than 5.5   Acidifying agents (Ascorbic acid 4-12 gm / day) may be needed to lower urinary pH below 5.5   Combination with sulfonamide lead to mutual antagonism.   Microorganisms such as proteus that make a strongly alkaline urine through release of ammonia from urea are usually resistant

Therapeutic uses and status: Not a primary drug, effective for chronic suppressive treatment. Effective against E. coli, S. aureus, S epidermidis and common gram negative bacteria.

Phenazopyridine Phenazopyridine hydrochloride has an analgesic action in urinary tract’ Phenazopyridine hydrochloride has an analgesic action in urinary tract’ Dysuria Dysuria Frequency Frequency Burning Burning Urgency Urgency

Treatment of urinary tract infections Most UTIs are caused by gram negative bacteria specially coliforms. Most UTIs are caused by gram negative bacteria specially coliforms. Acute infections are self limiting, high urine flow rate with frequent bladder voiding. Acute infections are self limiting, high urine flow rate with frequent bladder voiding. Upper UTIs require more aggressive and longer treatment. Upper UTIs require more aggressive and longer treatment.

Bacteriological investigations---- direct choice of drug Bacteriological investigations---- direct choice of drug Upper UTI dose of the drug is as for systemic infections Upper UTI dose of the drug is as for systemic infections If recurrences are frequent, chronic suppressive treatment is needed. If recurrences are frequent, chronic suppressive treatment is needed.

Sulfonamides, Cotrimoxazole, Quinolones, Ampicillin, Cloxacillin, Piperacillin, cephalosporins, gentamicin, Chloramphenicol, Tetracyclines. Sulfonamides, Cotrimoxazole, Quinolones, Ampicillin, Cloxacillin, Piperacillin, cephalosporins, gentamicin, Chloramphenicol, Tetracyclines.