The current presentation includes the pharmacology of urinary antiseptics, Drugs used in STDs and UTI. Reference: Essentials of Medical Pharmacology, K D Tripathi, Seventh Edition

1. URINARY ANTISEPTICS,
DRUGS USED IN UTI &
STDs
Anusha Shaji, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam

2. URINARY TRACT ANTISEPTICS/ANTIMICROBIALS
Escherichia coli 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.

3. These drugs do not 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

4. Mechanism of action
To act, 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.

5. Antibacterial spectrum
Methenamine is primarily 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.

6. Pharmacokinetics
Methenamine is administered orally.
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.

7. Adverse effects
The major side 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.

8. Nitrofurantoin
It is primarily bacteriostatic, 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.

9. Pharmacokinetics
Nitrofurantoin is well absorbed 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.

10. Adverse effects
Commonest is gastrointestinal 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.

11. Use
The only indication for 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.

12. TREATMENT OF URINARY TRACT INFECTIONS
Most UTIs are caused by gram-negative bacteria, especially
coliforms.

13. The status of AMAs (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.

14. Quinolones
The first generation FQs, 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.

15. 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.

16. TREATMENT OF SEXUALLY TRANSMITTED 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;