Chemotherapy

of
Urinary tract infections
&
Sexually transmitted diseases

Unit-III
Pharmacology III 6th Sem
B.Pharm
 Urinary Tract Infection (UTI)
• A urinary tract infection(UTI)is an infection in any part of your
urinary system – your kidney , uteres , bladder, and urethra .
• Most infections involve the lower urinary tract .
• A urinary tract infection (UTI) occurs when bacteria (germs) get
into the urinary tract and multiply .
• The upper urinary tract is composed of the kidneys and
ureters. Infection in the upper urinary tract generally affects
the kidneys (pyelonephritis), which can cause fever , chills ,
nausea , vomiting , and other severe symptons.
• The lower urinary racts consists of the bladder and the urethra.
• Infection in the lower urinary tract can affect the urethra
(urethritis)or the bladder (cystitis).
 Risk Factors For UTI
• Most common infection diseases.
• Affects all ages.
• Males predominate in the new born period , beyond this age ,
female predominate.
• More common in adults than in children .
• Pregnancy.
• Diabetic.
• Immunosuppressed individual.
• Calculi.
• Men with an enlarged prostate.
• Any medical condition which cause incomplete bladders emptying
( spinal cord injury).
• The most common cause of UTI are bacteria.
 Common symptoms
• Frequent urination
• Painful burning sensation before , during , and
after urinating.
• Urinating blood.
• Urgent need to urinate
• Cloudy or foul smelling urine.
• Fever.
• Severe pain in the lower abdominal region.
 Etiological agents of urinary
tract infections
• Bacteria-
• Gram-negative bacilli – E-coli, Proteus species, Klebsiella,
enterobacter , Pseudomonas.
• Gram-positive cocci- Staphylococcus aureus, Staphylococcus
epidermidies, Staphylococcus, saprophyticus Enterococcus
species.
• Others – Mycobacterium tuberculosis. Salmonella species,
Gardnella Vaginallis.
• Viruses – Adenovirus.
• Fungi – Candida albicans.
• Parasites – Tricomonas vaginalis , Schistosomia hematobium ,
Enterobius vermicularis.
Classification of Drugs for UTI
 URINARY ANTISEPTICS
• Some orally administered AMAs attain antibacterial
concentration only in urine, with little or no systemic
antibacterial effect.
• Like many other drugs, they are concentrated in the kidney
tubules, and are useful mainly in lower urinary tract infection.
• They have been called urinary antiseptics because this may be
considered as a form of local therapy.
• Nitrofurantoin and methenamine are two such agents;
infrequently used now.
• Nalidixic acid can also be considered to be a urinary
antiseptic.
 Nitrofurantoin
• NITROFURANTOIN:
• Primarily bacteriostatic Activity limited to E. coli
• Mechanism of Action: Sensitive bacteria reduce
the drug to an active agent that inhibits various
enzymes damage bacterial DNA. Antibacterial
concentration is not attained in blood or
tissues. Not to be used with Probenecid,
azotemic patients: interferes with tubular
secretion of drug.
 Nitrofurantoin
• Adverse effects-
• Gastrointestinal Intolerance: Nausea, epigastric
pain, diarrhoea
• Hypersensitivity : fever, chills
• Peripheral neuritis and other neurological
effects with long term use
• Hematologic disorders: leukopenia,
granulocytopenia, Hemolytic anemia in G6PD
deficient patients
 Nitrofurantoin
• Use- The only indication for nitrofurantoin is
uncomplicated lower urinary tract infections,
but it is infrequently used now.
• Used to treat acute infections due to E. coli
• Employed for prophylaxis of urinary tract
infection or for catheterization prophylaxis.
 Methenamine (Hexamine)
• It is hexamethylene-tetramine, which is inactive as such;
decomposes slowly in acidic urine to release formaldehyde
which inhibits all bacteria.
• This drug exerts no antimicrobial activity in blood and
tissues, including kidney parenchyma.
• Acidic urine is essential for its action; urinary pH must be
kept below 5.5 by administering an organic acid which is
excreted as such, e.g. mandelic acid or hippuric acid or
ascorbic acid.
• Methenamine is administered in enteric coated tablets to
protect it from decomposing in gastric juice.
 Methenamine (Hexamine)
• Mandelic acid, given as methenamine mandelate, is
excreted in urine →lowers urinary pH and promotes
decomposition of methenamine.
• It is not an effective drug for acute urinary tract infections or
for catheterization prophylaxis. Its use is restricted to
chronic, resistant type of urinary tract infections.
• Resistance to formaldehyde does not occur, but
methenamine is rarely used now.
• Gastritis can occur due to release of formaldehyde in
stomach. Chemical cystitis and haematuria may develop
with high doses given for long periods. CNS symptoms are
produced occasionally.
 NALIDIXIC ACID
• Nonfluorinated quinolone
• Bactericidal. Mechanism of Action:Inhibit the replication
of bacterial by interfering with the action of DNA gyrase
during bacterial growth and development. Resistance
Develops rather rapidly
• Uses: Second Line Drugs for UTI Recurrent cases- On the
basis of Sensitivity Reports  ADR: Infrequent: GI upset,
rashes  Headache drowsiness, vertigo, visual
disturbances  Seizures in children, Nausea ,Vomiting
and abdominal pain, Photosensitivity, urticaria and
Fever Contraindicated in infants
 TREATMENT OF URINARY TRACT
INFECTIONS
• The general principles of use of AMAs for urinary tract
infections (UTIs) are:
• Most UTIs are caused by gram-negative bacteria,
especially coliforms.
• Majority of acute infections involve a single organism
(commonest is E. coli); chronic infections may be mixed
infections.
• Many single dose antimicrobial treatments have been
sufficient for lower UTIs.
• Upper UTIs require more aggressive and longer treatment.
 Commonly used Antimicrobial regimens for
acute UTI (all given orally for 3-5 days)*
• 1. Ciprofloxacin 250-500 mg 12 hourly
• 2. Ofloxacin 20G-400 mg 12 hourly
• 3. Cotrimoxazole 960 mg 12 hourly
• 4. Cephalexin 250-500 mg 6 hourly
• 5. Cefpodoxime proxetil 200 mg 12 hourly
• 6. Amoxicillin + clavulanic acid (500 + 125 mg) 8
hourly
• 7. Nitrofurantoin 50 mg 8 hourly or 100 mg 12
hourly x 5- 7 days
STATUS OF ANTIMICROBIAL AGENTS OTHER
THAN URINARY ANTISEPTICS IN UTI
• 1. Sulfonamides- occasionally used for
suppressive and prophylactic therapy.
• 2. Cotrimoxazole- used for prophylaxis of
recurrent cystitis in women, as well as in
catheterized patients. It should not be used to
treat UTI during pregnancy.
• 3. Quinolones-The first generation FQs, especially
norfloxacin and ciprofloxacin are highly effective
and currently the most popular drugs
STATUS OF ANTIMICROBIAL AGENTS OTHER
THAN URINARY ANTISEPTICS IN UTI
• 4. Ampicillin/Amoxicillin- Parenteral
coamoxiclav is often combined with
gentamicin for initial treatment of acute
pyelonephritis.
• 5. Cephalosporins- Use in women with
Klebsiella and Proteus infections. Alternative
drug for prophylaxis of recurrent cystitis.
• 6. Gentamicin- Very effective against most
urinary pathogens including Pseudomonas.
 Urinary pH in relation to use of AMAs
• Certain AMAs act better in acidic urine, while
others in alkaline urine.
• Administering acidifying or alkalinizing agents is
seldom required (except for methenamine),
because most drugs used in UTI attain high
concentration in urine and minor changes in
urinary pH do not affect clinical outcome.
• In complicated cases, measurement of urinary pH
and appropriate corrective measure may help.
 Favourable urinary pH for antimicrobial
action
Acidic Alkaline pH
immaterial
Nitrofurantoin Cotrimoxazole Chloramphenicol
Methenamine Aminoglycosides Ampicillin
Tetracyclines (Gentamicin, etc.)
Cloxacillin Cephalosporins
Fluoroquinolones
 Urinary infection in patients with
renal impairment
• Difficult to treat because most AMAs attain lower urinary
concentration in the presence of renal impairment.
• Methenamine mandelate, tetracyclines (except
doxycycline) and certain cephalosporin are contraindicated.
• Nitrofurantoin, nalidixic acid and aminoglycosides are
avoided.
• Bacteriological testing and follow up cultures are a must to
select the appropriate drug and to ensure eradication of
the pathogen.
• Potassium salts and acidifying agents are contraindicated.
 Prophylaxis for urinary tract infection

• Needed in-
• Catherised,
• Uncorrectable anatomical abnormalities
• Inoperable prostate,
• Septicemia,
• Immuno-compromised,
• Trauma
• The most frequently used drugs for prophylaxis of lower
UTI are:
• Cotrimoxazole, Nitrofurantoin, Norfloxacin, Cephalexin