Download Urinary Antiseptics

Urinary Antiseptics
Organisms
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Escherichia coli
Proteus
Pseudomonas species
streptococci
Klebsiella
Enterococcus
Staphylococcus epidermidis
Introduction
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Oral agents have antibacterial activity in urine but
have little or no systemic antibacterial activity
Usefulness is limited to lower UTI
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
Drugs that act as urinary
antiseptics are as follows:
•Nalidixic Acid & Cinoxacin
•Nitrofurantion
•Methenamine
•Phenazopyridine
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 8095%
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: 
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Many gm –ve organisms.
Lower urinary tract infections.
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Adverse Effects
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GIT irritation
Glycosurea
Skin rashes.
Photo sensitization.
Visual disturbances
CNS stimulation.
Hepatic failure
Nitrofurantion
Bacteriostatic and bactericidal for many Gm +ive and
Gm –ive bacteria
Second line agent for treatment of UTI
Pharmakokinetics
• Well absorbed orally
• Rapidly metabolized and excreted through kidneys
glomerular filtration and tubular secretion.
• No systemic antibacterial activity
• 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.
Therapeutic Uses: • Active against many urinary tract pathogens (but not
proteus or pseudomonas)
• Uncomplicated urinary tract infections
• Daily dose for adults is 100 mg orally 6 hourly with food or
milk
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It is desirable to keep urinary pH below 5.5,
which greatly enhances drug activity
Adverse Effects:•
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GIT irritation, anorexia, nausea, vomiting
Skin rashes and hypersensitivity reactions
Neuropathies
Hemolysis in patients with G6PD deficiency
Acute pneumonitis (fever, chills, leucopenia)
Resistance
• Resistance emerges slowly
• No cross resistance between Nitrofurantion and
other antimicrobial agents
Contraindications
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Pregnant woman
Individuals with impaired renal function.
Children younger than 1 month of age.
Methenamine
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
are bactericidal for some Gm –ive bacteria when pH is less
than 5.5
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Acidifying agents (Ascorbic acid 4-12 gm / day) may be
needed to lower urinary pH below 5.5
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Combination with sulfonamide lead to mutual antagonism.
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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
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Phenazopyridine hydrochloride has an
analgesic action in urinary tract’
Dysuria
Frequency
Burning
Urgency
Treatment of urinary tract
infections
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Most UTIs are caused by gram
negative bacteria specially coliforms.
Acute infections are self limiting,
high urine flow rate with frequent
bladder voiding.
Upper UTIs require more aggressive
and longer treatment.
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Bacteriological investigations---direct choice of drug
Upper UTI dose of the drug is as for
systemic infections
If recurrences are frequent, chronic
suppressive treatment is needed.
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Sulfonamides, Cotrimoxazole,
Quinolones, Ampicillin, Cloxacillin,
Piperacillin, cephalosporins,
gentamicin, Chloramphenicol,
Tetracyclines.