Urinary tract antiseptics methenamine

The prodrug methenamine, described above in this chapter (Scheme S-17), can be considered a site-specific chemical delivery system for the urinary tract antiseptic agent fotmal-dehyde. The low pH of the urine promotes the hydrolysis... 

Methenamine is a urinary tract antiseptic and prodmg that owes its activity to its capacity to generate formaldehyde. Methenamine is hexamethylenetetramine (hexamethylenamine). 

Methenamine mandelate, 1 g four times daily, or methen-amine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4-12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites. 

Topical antibiotics with a narrow spectrum of action and low toxicity (eg, bacitracin and mupirocin) can be used for temporary control of bacterial growth and are generally preferred to antiseptics. Methenamine mandelate releases formaldehyde in a low antibacterial concentration at acid pH and can be an effective urinary antiseptic for long-term control of urinary tract infections. 

Intermittent self-catheterization with or without a concomitant anticholinergic agent is recommended in patients with large postvoid urine residual volumes (>100 mL) or when the urinary problem is hyporeflexic in nature (failure to empty). Patients with large postvoid residual volumes are at risk for developing urinary tract infections and often are prescribed urinary acidifiers such as vitamin C or antiseptics such as methenamine mandelate to prevent infections. 

Formaldehyde has antiseptic properties and can be employed in the treatment of urinary tract infections due to its ability to react with nucleophiles present in urine. However, formaldehyde can be toxic when exposed to other regions of the body. Therefore, the use of formaldehyde as an antiseptic agent requires a method for selective delivery to the urinary tract. This can be accomplished by using a prodrug called methenamine ... 

Hexamethylenetetramine is a well known urinary antiseptic for the treatment of pyelitis, cystitis, and other diseases of the urinary tract. Its action apparently resides in the hydi-oMic liberation of formaldehyde in acid urine, and for this reason acidity is often insured by gh ing the patient alternate doses of hexamethA lenetetramine and sodium acid phosphate. TlTien prescribed for medicinal use hexamethyleneteti amine is gi en the name of methenamine, formin, or utropine. 

Methenamine mandelate is a salt of mandelic acid and methenamine and both of these possess property of urinary antiseptic. It is rapidly absorbed in gastrointestinal tract and excreted unchanged in urine, where it broken down in acidic pH (< 5) of urine and formaldehyde is released, which inhibits most of the bacteria. It is administered with sodium biphosphate, mandelic acid or ascorbic acid to keep the urinary pH below 6. Its use is restricted to chronic, resistant type of UTI. 

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