Urinary Antiseptics. Organisms Escherichia coli Proteus Pseudomonas species streptococci ...
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Transcript of Urinary Antiseptics. Organisms Escherichia coli Proteus Pseudomonas species streptococci ...
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Urinary AntisepticsUrinary Antiseptics
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Organisms Organisms
Escherichia coliEscherichia coli ProteusProteus Pseudomonas speciesPseudomonas species streptococcistreptococci KlebsiellaKlebsiella Enterococcus Enterococcus Staphylococcus epidermidisStaphylococcus epidermidis
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IntroductionIntroduction
Oral agents have antibacterial activity in urine but Oral agents have antibacterial activity in urine but have little or no systemic antibacterial activityhave little or no systemic antibacterial activity
Usefulness is limited to lower UTIUsefulness is limited to lower UTI Effective antibacterial concentration reach the Effective antibacterial concentration reach the
renal pelvis and bladder. renal pelvis and bladder. Used in chronic UTI where eradication of Used in chronic UTI where eradication of
infection by short term systemic therapy has not infection by short term systemic therapy has not been possiblebeen possible
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Drugs that act as urinary Drugs that act as urinary antiseptics are as follows:antiseptics are as follows:
•Nalidixic Acid & CinoxacinNalidixic Acid & Cinoxacin•NitrofurantionNitrofurantion•MethenamineMethenamine•Phenazopyridine Phenazopyridine
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Nalidixic Acid Nalidixic Acid & Cinoxacin& Cinoxacin
IntroductionIntroduction: One of the earlier quinolones, did : One of the earlier quinolones, did not achieve systemic antibacterial levels not achieve systemic antibacterial levels therefore were useful only for treatment of therefore were useful only for treatment of lower UTI lower UTI
PharmacokineticsPharmacokinetics: Well absorbed orally. BA 80-: Well absorbed orally. BA 80-95%95%
Widely distributed in body fluids and tissues. Widely distributed in body fluids and tissues. Plasma Half life 3-10 hrs permitting once daily Plasma Half life 3-10 hrs permitting once daily dosing.dosing.
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Oral absorption is impaired by divalent cations Oral absorption is impaired by divalent cations including those in antacids. Serum including those in antacids. Serum concentration of I/V administration is equal to concentration of I/V administration is equal to orally administered drug. Excretion is renal orally administered drug. Excretion is renal either GF or Tubular secretioneither GF or Tubular secretion
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MOA MOA inhibit DNA gyraseinhibit DNA gyrase
Therapeutic UsesTherapeutic Uses: -: - Many gm –ve organisms.Many gm –ve organisms. Lower urinary tract infections.Lower urinary tract infections.
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Adverse EffectsAdverse Effects GIT irritationGIT irritation GlycosureaGlycosurea Skin rashes.Skin rashes. Photo sensitization.Photo sensitization. Visual disturbancesVisual disturbances CNS stimulation.CNS stimulation. Hepatic failureHepatic failure
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NitrofurantionNitrofurantionBacteriostatic and bactericidal for many Gm +ive and Bacteriostatic and bactericidal for many Gm +ive and
Gm –ive bacteriaGm –ive bacteria
Second line agent for treatment of UTISecond line agent for treatment of UTI
PharmakokineticsPharmakokinetics• 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.
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Mechanism of Action:Mechanism of Action:
ComplexComplex
Rapid intracellular conversion into highly Rapid intracellular conversion into highly reactive intermediates by bacterial reductasereactive intermediates by bacterial reductase
This intermediate then reacts non-specifically with This intermediate then reacts non-specifically with many ribosomal proteins and disrupt synthesis of many ribosomal proteins and disrupt synthesis of proteins, RNA, DNA and metabolic processes.proteins, RNA, DNA and metabolic processes.
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Anti bacterial spectrum:Anti bacterial spectrum: E. coli, enterococci. Most species of Proteus and E. coli, enterococci. Most species of Proteus and
Pseudomonas, Enterobacter and Klebsiella are Pseudomonas, Enterobacter and Klebsiella are resistant. resistant.
Therapeutic UsesTherapeutic Uses: -: -• Active against many urinary tract pathogens (but not Active against many urinary tract pathogens (but not
proteus or pseudomonas)proteus or pseudomonas)
• Uncomplicated urinary tract infectionsUncomplicated urinary tract infections
• Daily dose for adults is 100 mg orally 6 hourly with food Daily dose for adults is 100 mg orally 6 hourly with food or milkor milk
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It is desirable to keep urinary pH below 5.5, which greatly enhances drug activity
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Adverse EffectsAdverse 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)
ResistanceResistance• Resistance emerges slowlyResistance emerges slowly• No cross resistance between Nitrofurantion and No cross resistance between Nitrofurantion and
other antimicrobial agentsother antimicrobial agents
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Contraindications Contraindications
Pregnant womanPregnant 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.
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Methenamine 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
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Taken orally excreted unchanged in urine where these drugs Taken orally excreted unchanged in urine where these drugs are bactericidal for some Gm –ive bacteria when pH is less are bactericidal for some Gm –ive bacteria when pH is less than 5.5than 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
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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.
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Phenazopyridine Phenazopyridine
Phenazopyridine hydrochloride has an Phenazopyridine hydrochloride has an analgesic action in urinary tract’analgesic action in urinary tract’
Dysuria Dysuria Frequency Frequency Burning Burning Urgency Urgency
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Treatment of urinary tract Treatment of urinary tract infectionsinfections
Most UTIs are caused by gram Most UTIs are caused by gram negative bacteria specially coliforms.negative bacteria specially coliforms.
Acute infections are self limiting, Acute infections are self limiting, high urine flow rate with frequent high urine flow rate with frequent bladder voiding.bladder voiding.
Upper UTIs require more aggressive Upper UTIs require more aggressive and longer treatment.and longer treatment.
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Bacteriological investigations---- Bacteriological investigations---- direct choice of drugdirect choice of drug
Upper UTI dose of the drug is as for Upper UTI dose of the drug is as for systemic infectionssystemic infections
If recurrences are frequent, chronic If recurrences are frequent, chronic suppressive treatment is needed.suppressive treatment is needed.
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Sulfonamides, Cotrimoxazole, Sulfonamides, Cotrimoxazole, Quinolones, Ampicillin, Cloxacillin, Quinolones, Ampicillin, Cloxacillin, Piperacillin, cephalosporins, Piperacillin, cephalosporins, gentamicin, Chloramphenicol, gentamicin, Chloramphenicol, Tetracyclines.Tetracyclines.