Urinary Antiseptics

URINARY ANTISEPTICS

Some AMAs, in orally tolerated doses, 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

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.

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.

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, except in G6PD deficiency. 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.

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. These doses should not be used for > 2 weeks at a time. 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.

FURADANTIN 50, 100 mg tab, 25 mg/5 ml susp. TRIFURAN: nitrofurantoin 50 mg + trimethoprim 40 mg + deglycyrrhizinised liquorice 200 mg tab.

Methenamine  (Hexamine)

It is hexamethylenetetramine; 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 some organic acid which is excreted as such, e.g. mandelic acid or ascorbic acid.

Methenamine is administered in enteric coated tablets to protect it from decomposing in gastric juice. Mandelic acid itself is a urinary antiseptic in high doses, also lowers pH of urine. However, the amount taken with methenamine (as methenamine mandelate) is inadequate in its own right: serves only to promote decomposition of methenamine.

MANDELAMINE 0.5 g, 1 g tab: 1 g TDS or QID with fluid restriction (daily urine volume between 1–1.5 L) to ensure adequate concentration of formaldehyde in urine.

It is not a good drug for acute urinary tract infections or for catheterization prophylaxis. Its use is restricted to chronic, resistant type of urinary tract infections, not involving kidney substance. Resistance to formaldehyde does not occur, but methenamine is not popular now.

Adverse Effects

Gastritis can occur due to release of formaldehyde in stomach—patient compliance is often poor due to this.

Chemical cystitis and haematuria may develop with high doses given for long periods. CNS symptoms are produced occasionally.

Methenamine mandelate is contraindicated in renal failure (mandelic acid accumulates in blood → acidosis) and in liver disease (the released NH₃ is not detoxified).

Sulfonamides combine chemically with methenamine in urine resulting in antagonism.

Phenazopyridine

It is an orange dye which exerts analgesic action in the urinary tract and affords symptomatic relief of burning sensation, dysuria and urgency due to cystitis. It does not have antibacterial property. Side effects are nausea and epigastric pain.

Dose: 200–400 mg TDS: PYRIDIUM 200 mg tab.