Methenamine (hexamethylenetetramine) is an aromatic acid that is hydrolyzed at an acid pH (<6) to liberate ammonia and the active alkylating agent formaldehyde, which denatures protein and is bactericidal. Meth-enamine is usually administered as a salt of either man-delic (Mandelamine) or hippuric (Hiprex, Urex) acid. Not only do these acids acidify the urine, which is necessary to generate formaldehyde, but also, the resulting low urine pH is by itself bacteriostatic for some organisms.
Methenamine is administered orally and is well absorbed from the intestinal tract. However, 10 to 30% decomposes in the stomach unless the tablets are protected by an enteric coating. The inactive form (methenamine) is distributed to virtually every body fluid. Almost all of the methenamine moiety is excreted into the urine by 24 hours, having reached the urine by both glomerular filtration and tubular secretion.
Methenamine is primarily used for the long-term prophylactic or suppressive therapy of recurring UTIs. It is not a primary drug for therapy of acute infections. It should be used to maintain sterile urine after appropriate antimicrobial agents have been employed to eradicate the infection.
Gastric distress (nausea and vomiting) is one of the most frequently reported adverse reactions. Bladder irritation (e.g., dysuria, polyuria, hematuria, and urgency) may occur. The mandelic salt can crystallize in urine if there is inadequate urine flow and should not be given to patients with renal failure. Patients with preexisting hepatic insufficiency may develop acute hepatic failure due to the small quantities of ammonia formed during methenamine hydrolysis.
The coadministration of methenamine with certain sulfonamides (sulfamethizole or sulfathiazole) can form a urine precipitate resulting in drug antagonism.
^ Study Questions
1. A 24-year-old AIDS patient is interested in starting chemoprophylaxis for Pneumocystis pneumonia (PCP) and cerebral toxoplasmosis. He has no drug allergies. Which of the following prophylactic agents is appropriate for the prevention of both PCP and cerebral toxoplasmosis?
(E) Nalidixic acid
2. Urinalysis of a 38-year-old woman with recurrent UTIs revealed pH 6.8,30 to 50 WBC per highpower field, and gram-negative bacilli identified as Proteus mirabilis. Which of the following produces a bacteriostatic urinary environment for P. mirabilis?
(A) Urease enzyme
(B) Hippuric acid
(C) Catalase enzyme
(D) Folic acid
(E) Coagulase enzyme
3. A 3-day-old baby is given a presumptive diagnosis of kernicterus. Which of the following mechanisms is involved in sulfonamide-induced kernicterus?
(A) Competes for the bilirubin-binding sites on plasma proteins
(B) Defective bilirubin hepatic conjugation and metabolism
(C) Physiological jaundice due to destruction of fetal red blood mass
(D) Pregnancy-induced hepatic congestion and cholestasis
(E) Primary biliary cirrhosis of the liver
4. A 6-year-old relatively healthy boy is diagnosed with external otitis and was prescribed a 7-day course of TMP-SMX. Which of the following is the basic mechanism of action of the sulfonamides?
(A) Selective inhibition of incorporation of PABA into human cell folic acid synthesis.
(B) Competitive inhibition of incorporation of PABA into microbial folic acid.
(C) Inhibition of transpeptidation reaction in bacterial cell wall synthesis.
(D) Changes in DNA gyrases and active efflux transport system resulting in decreased permeability of drug.
(E) Structural changes in dihydropteroate synthase and overproduction of PABA.
5. Evaluation of a yearly chest radiograph of a 73-year-old patient taking nitrofurantoin prophylacti-cally for recurrent UTIs revealed new findings of bilateral interstitial fibrosis. What is the possible explanation for the patient's pulmonary presentation and what is the next step?
(A) Acute urosepsis; add a broad-spectrum antibiotic to nitrofurantoin.
(B) Possible allergic reaction to nitrofurantoin; stop it immediately.
(C) Nitrofurantoin-resistant E. coli infection; stop it immediately.
(D) Acute community-acquired streptococcal pneumonia; treat accordingly.
(E) Nitrofurantoin-induced hemolysis; requires permanent urinary catheter.
6. A 16-year-old girl, a cystic fibrosis patient, is diagnosed with a ciprofloxacin-resistant Pseudomonas aeruginosa lower respiratory tract infection. Bacteria acquire quinolone resistance by which of the following mechanisms?
(A) Overproduction of PABA
(B) Changes in the synthesis of DNA gyrases
(C) Plasmid-mediated changes in efflux transport system
(D) Inhibition of synthesis of peptidoglycan sub-units in bacterial cell walls
(E) Inhibition of folic acid synthesis by blocking different steps
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