Drugs for Urinary Tract Disorders

Acute cystitis, a lower UTI, frequently occurs in female patients because of their shorter urethra. It is more common in women of childbearing age, older women, and young girls. Acute cystitis is commonly caused by Escherichia coli. Other bacterial causes include the gram-positive Staphylococcus saprophyticus and gram-negative Klebsiella, Proteus, and Pseudomonas. Symptoms of cystitis include pain and burning on urination and urinary frequency and urgency. A urine culture is usually obtained before the start of any antiinfective/antibiotic drug therapy. In male patients, a lower UTI is most likely prostatitis with symptoms similar to cystitis.

Acute pyelonephritis, an upper UTI, is commonly seen in women of childbearing age, older women, and young girls. E. coli is the most common organism causing pyelonephritis. Symptoms include chills, high fever, flank pain, pain during urination, urinary frequency and urgency, and pyuria. The bacterial count in the urine is greater than 100,000 bacteria/mL. In severe cases, the patient may be hospitalized and receive intravenous (IV) antibiotics (e.g., an aminoglycoside, ticarcillin/clavulanic acid, or piperacillin/tazobactam).

The most commonly used agents for treating UTIs are nitrofurantoin (Macrodantin); trimethoprim-sulfamethoxazole (Bactrim, Septra); and fluoroquinolones such as nalidixic acid (NegGram), norfloxacin (Noroxin), and ciprofloxacin (Cipro). Treatment may consist of a single double-strength dose of the chosen drug, a 3-day course, or the traditional method of 7 to 14 days of drug dosing. Fosfomycin tromethamine (Monurol), a nitrofurantoin prototype drug, is effective for UTIs as a single-dose treatment. Other agents used to treat UTIs include oral amoxicillin/clavulanic acid (Augmentin) and oral third-generation cephalosporins (cefixime, cefpodoxime proxetil, or ceftibuten). With severe UTIs, IV drug therapy followed by oral drug therapy is usually recommended.

Urinary Antiseptics/Antiinfectives and Antibiotics

Urinary antiseptics/antiinfectives are limited to the treatment of UTIs. Drug action occurs in the renal tubule and bladder, where it is effective in reducing bacterial growth. A urinalysis, as well as a culture and sensitivity test, is usually performed before the initiation of drug therapy. The groups of urinary antiseptics/antiinfectives are nitrofurantoin, methenamine, trimethoprim, and the fluoroquinolones.

Nitrofurantoin

Nitrofurantoin (Macrodantin) was first prescribed to treat UTIs in 1953. Nitrofurantoin is bacteriostatic or bactericidal, depending on the drug dosage, and is effective against many gram-positive and gram-negative organisms, especially E. coli. It is used to treat acute and chronic UTIs. The drug data for nitrofurantoin are given in Prototype Drug Chart 34-1.

Prototype Drug Chart 34-1

Nitrofurantoin

Drug Class	Dosage
Urinary antiinfective Trade Names: Macrodantin Pregnancy Category: B	A: PO: 50-100 mg q.i.d. (with meals and h.s.); take with food; max: 7 mg/kg/d C >1 mo: PO: 1.25-1.75 mg/kg/d q6h; max: 7 mg/kg/d
Contraindications	Drug-Lab-Food Interactions
Hypersensitivity, moderate to severe renal impairment, oliguria, anuria, infants <1 mo, term pregnancy, lactation with infant suspected of having G-6-PD deficiency Caution: Vitamin B deficiency, electrolyte imbalance, diabetes mellitus	Drug: Decreased renal clearance with probenecid leading to toxicity; decreased absorption with antacids; decreased effectiveness of fluoroquinolones; decreased effectiveness of oral contraceptives
Pharmacokinetics	Pharmacodynamics
Absorption: Well absorbed from GI tract; enhanced with food Distribution: PB: 20%-60%, crosses placenta, excreted in breast milk Metabolism: : 20 min Excretion: In urine; small amounts in bile	PO: Onset: UK Peak: 30 min Duration: UK
Therapeutic Effects/Uses
To treat acute and chronic UTIs
Mode of Action: Inhibits bacterial enzymes and metabolism, also inhibits bacterial cell wall formation
Side Effects	Adverse Reactions
Anorexia, nausea, vomiting, abdominal pain, rust/brown discoloration of urine, diarrhea, rash, pruritus, chills, dizziness, headache, drowsiness, confusion, depression, alopecia, nystagmus	Superinfection, angioedema, peripheral neuropathy, hemolytic anemia, aplastic anemia, thrombocytopenia, agranulocytosis Life-threatening: Anaphylaxis, hepatotoxicity, Stevens-Johnson syndrome

A, Adult; C, child; CLcr, creatinine clearance; G-6-PD, glucose-6-phosphate dehydrogenase; GI, gastrointestinal; h.s., at bedtime; min, minute; mo, month; PB, protein-binding; PO, by mouth; q.i.d., four times a day; , half-life; UK, unknown; UTI, urinary tract infection; y, year; <, less than.

Pharmacokinetics

Nitrofurantoin is well absorbed from the gastrointestinal (GI) tract. The drug is usually taken with food to decrease GI distress. Decreased absorption occurs when the drug is taken with antacids. Nitrofurantoin is moderately protein-bound. With normal renal function, the drug is rapidly eliminated because of its short half-life of 20 minutes; however, it accumulates in the serum with urinary dysfunction.

Pharmacodynamics

When nitrofurantoin is given in low doses for prophylactic use, the drug has a bacteriostatic effect. High concentration of nitrofurantoin causes a bactericidal effect. Nitrofurantoin is effective against many gram-positive and gram-negative organisms such as E. coli, Neisseria, streptococci, Staphylococcus aureus, and others. It is not as effective against Pseudomonas aeruginosa, Proteus species, and some species of Klebsiella. The onset and duration of action are unknown. Peak action occurs 30 minutes after absorption. If sudden onset of dyspnea, chest pain, cough, fever, and chills develops, the patient should contact the health care provider. Symptoms resolve after discontinuing the drug.

The nursing process for nitrofurantoin is applicable to the other urinary antiseptics/antiinfectives.

Methenamine

Methenamine (Hiprex) produces a bactericidal effect when the urine pH is less than 5.5. Methenamine is available as hippurate salt. It is effective against gram-positive and gram-negative organisms, especially E. coli and P. aeruginosa. It is used for chronic UTIs. Methenamine should not be taken with sulfonamides, because crystalluria is likely to occur. It is absorbed readily from the GI tract, and approximately 90% of the drug is excreted in the urine unchanged. Methenamine forms ammonia and formaldehyde in acid urine; therefore the urine needs to be acidified to exert a bactericidal action. Cranberry juice (several 8-ounce glasses per day), ascorbic acid, and ammonium chloride can be taken to decrease the urine pH.

Nursing Process

Patient-Centered Collaborative Care

Urinary Antiinfective: Nitrofurantoin

Assessment

Obtain a history from patient of clinical problems with UTI, incontinence, or other urinary tract disorders.

Assess patient for signs and symptoms of UTI: pain or burning sensation on urination, frequency and urgency of urination.

Monitor complete blood count (CBC) on patients with long-term therapy; monitor regularly.

Monitor urine culture and sensitivity results.

Assess renal and hepatic function.

Determine urine pH. A pH of 5.5 is desired. However, alkalinization of the urine is not recommended.

Nursing Diagnoses

Risk for infection related to insufficient knowledge to avoid invasion of pathogens

Planning

Patient will be free of signs and symptoms of UTI within 10 days.

Nursing Interventions

Monitor patient's urinary output and urine specific gravity. Careful attention to output is required when administering urinary antiseptics to patients with anuria and oliguria. Report promptly any decrease in urine output.

Obtain urine culture to identify infecting organism before initiation of drug therapy to treat UTI.

Observe patient for side effects and adverse reactions to urinary antiseptic drugs. Peripheral neuropathy (tingling, numbness of extremities) may result from renal insufficiency (inability to excrete drug) or long-term use of nitrofurantoin. Peripheral neuropathy may be irreversible.

Patient Teaching

General

Teach patient not to crush tablets or open capsules.

Advise patient to rinse mouth thoroughly after taking oral nitrofurantoin. Drug can stain teeth.

Encourage patient to avoid antacids because they interfere with drug absorption.

Teach patient to shake suspension well before administration and protect from freezing.

Warn patient not to drive a motor vehicle or operate dangerous machinery; drug may cause drowsiness.

Advise female patient to immediately report pregnancy to health care provider.

Diet

Inform patient to increase fluids and take drug with food to minimize GI upset.

Side Effects

Alert patient that urine may turn a harmless brown color.

Encourage patient to report any signs of secondary fungal or bacterial infection (superinfection), such as stomatitis or anogenital discharge or itching.

Methenamine

Educate patient to drink cranberry juice, eat plums, or take vitamin C (with approval of health care provider) to keep urine acidic. Foods that are alkaline, such as milk and some vegetables, may increase urine pH. Urine pH should be less than 5.5 for the antiseptic to be effective.

Fluoroquinolones

Warn patient to avoid operating hazardous machinery or driving a car while taking drug, especially if dizziness is present.

Encourage patient to take drug with food and avoid antacids, because they interfere with drug absorption.

Alert patient that drug may turn urine a harmless brown color.

Direct patient to report any signs of superinfection or secondary fungal or bacterial infection.

Tell patient to avoid excessive exposure to sunlight.

Cultural Considerations

Alleviate fear or concerns of patient from a different cultural background. Use culturally consistent communication when explaining the treatment regimen for a UTI. An interpreter may be necessary. The use of pamphlets in the language patient reads or speaks most easily can facilitate patient understanding.

Evaluation

Evaluate the effectiveness of the urinary antiinfectives in alleviating the UTI. Patient is free of side effects and adverse reactions to drug.

Trimethoprim and Trimethoprim-Sulfamethoxazole

Trimethoprim (Proloprim) can be used alone for the treatment of UTIs, although it is usually used in combination with a sulfonamide, sulfamethoxazole (the combined preparation is generically called TMP/SMZ), to prevent the occurrence of trimethoprim-resistant organisms. This drug combination produces slow-acting bactericidal effects against most gram-positive and gram-negative organisms. TMP/SMZ (Bactrim, Septra) is discussed in Chapter 31. Trimethoprim is used in the treatment and prevention of acute and chronic UTIs. The amount of trimethoprim in the prostatic fluid is about two to three times greater than the amount in the vascular fluid. The half-life of trimethoprim is normally 8 to 11 hours, but it is longer in patients with renal dysfunction.

Fluoroquinolones (Quinolones)

Fluoroquinolones are one of the groups of urinary antibacterials that are effective against lower UTIs; they include nalidixic acid (NegGram), norfloxacin (Noroxin), ciprofloxacin hydrochloride (Cipro), and ofloxacin . , Norfloxacin, ciprofloxacin, and ofloxacin, are effective against a wide variety of UTIs. The drug dosage must be decreased when renal dysfunction is present. The half-lives of these drugs are ordinarily 2 to 8 hours, but are prolonged in patients with renal dysfunction. Table 34-1 lists the urinary antiseptics/antiinfectives and their dosages, uses, and considerations.

TABLE 34-1

ANTISEPTICS AND URINARY ANTIINFECTIVES

GENERIC (TRADE) NAME	ROUTE AND DOSAGE	USES AND CONSIDERATIONS
fosfomycin tromethamine (Monurol)	A: PO: 3-g packet dissolved in 4 oz water, as a single dose	For uncomplicated UTIs in women. Has a bactericidal effect against most gram-negative and gram-positive bacteria. Side effects include headaches and diarrhea. Pregnancy category: B; PB: 0%; : 3-8.5 h
methenamine hippurate (Hiprex, Urex)	Hippurate: A: PO: 1 g b.i.d. C 6-12 y: PO: 0.5-1 g q12h	For chronic UTIs. Urine pH should be acidic (<5.5). Do not use with sulfonamides. May cause crystalluria, so push fluids. May cause GI irritation, so give with meals. Pregnancy category: C; PB: UK; : 4 h
nitrofurantoin (Macrodantin)	See Prototype Drug Chart 34-1.
trimethoprim (Proloprim)	A: PO: 100 mg b.i.d. or 200 mg/d for 10-14 d	For prevention and treatment of acute and chronic UTIs in both men and women. High doses can cause GI upset. Drug can be combined with sulfamethoxazole (Bactrim). Pregnancy category: C; PB: 45%; : 8-10 h
ertapenem (Invanz)	A/Adol: IM/IV: 1 g/d for 10-14 d C >3 mo: IM/IV: 15 mg/kg b.i.d. for 10-14 d	To prevent recurring UTIs, acute pelvic infections, and diabetic foot infections. Effective against gram-positive and gram-negative bacteria. Commonly causes diarrhea, nausea, and headache. Pregnancy category: B; PB: 95%; : 4.5 h
Sulfonamides
trimethoprim-sulfamethoxazole (TMP-SMZ, Bactrim, Septra)	See Prototype Drug Chart 31-1 in Chapter 31.	Effective for serious UTIs and otitis media. Pregnancy category: C; PB: 44%-70%; : 6-12 h
Quinolones (Fluoroquinolones)
ciprofloxacin (Cipro)	A: PO: Mild to moderate: 250 mg q12h for 3 d A: PO: ER: 500 mg/d for 3 d A: IV: 200 q12h A: PO: severe/complicated: 500 mg q12h for 7-14 d; 1 g/d XRfor 7-14 d C: PO: 10-20 mg/kg q12h for 10-21 d A: IV: 400 mg q12h for 7-14 d; dilute and infuse over 1 h C: IV: 6-10 mg/kg q8h for 10-21 d	Has broad-spectrum antibacterial effect. For UTI, skin and soft-tissue infections, bone and joint infections, and anthrax infection. Antacid inhibits drug absorption. Use with caution in patients with seizure disorders. Can be taken without food. Photosensitivity can occur. Avoid excessive exposure to sunlight. Pregnancy category: C; PB: 20%-40%; : 4 h
nalidixic acid (NegGram)	A: PO: 1 g q.i.d. for 1-2 wk; 500 mg q.i.d. for long-term use; max: 4 g/d C >3 mo: PO: 55 mg/kg/d in 4 divided doses for 1-2 wk; 33 mg/kg/d for long-term use	For acute and chronic UTIs. Resistance to drug may occur. Highly protein-bound. Not distributed in prostatic fluid. Give with food to avoid GI upset. Photosensitivity can occur. Have patient contact health care provider if seizures or severe headaches occur. Pregnancy category: C; PB: 93%; : 1-2.5 h
norfloxacin (Noroxin)	A: PO: 400 mg q12h for 3-21 d on empty stomach	For acute and chronic UTIs. Most potent drug of the quinolone group. Food may inhibit drug absorption. Pregnancy category: C; PB: 10%-15%; : 3-4 h
ofloxacin	A: PO: 200 mg q12h for 3-10 d	For UTIs, respiratory tract infections, and skin infections. May cause headaches, dizziness, and insomnia. Pregnancy category: C; PB: UK; : 4-8 h
Other
aztreonam (Azactam)	A: IM/IV: 500 mg–1 g q8-12h C >9 mo: IM/IV: 30 mg/kg q6-8h	Treatment of UTIs caused by gram-negative organisms. Also useful for lower respiratory tract infections and septicemia. Pregnancy category: B; PB: 56%-60%; : 1.5-2 h
imipenem/cilastatin sodium (Primaxin)	A: IV: 250 mg q6-8h; max: 4 g/d or 50 mg/kg/d, whichever is less	Treatment of serious UTIs. Also useful for lower respiratory tract, bone, and joint infections; septicemia; and endocarditis. Pregnancy category: C; PB: imipenem 20%/cilastatin 40%; : 1 h
polymyxin B SO₄	A/C: IV: 15,000-25,000 units/kg/d in divided doses q12h	Effective for UTIs and prevention of bacteruria from Foley catheter. Can cause nephrotoxicity. Monitor renal function (BUN, serum creatinine). Pregnancy category: B; PB: UK; : 4-6 h

A, Adult; Adol, adolescent; b.i.d., twice a day; BUN, blood urea nitrogen; C, child; CLcr, creatinine clearance; d, day; ER, extended-release; GI, gastrointestinal; h, hour; IM, intramuscular; IV, intravenous; min, minute; mo, month; PB, protein-binding; p.c., after meals; PO, by mouth; q.i.d., four times a day; , half-life; t.i.d., three times a day; UK, unknown; UTI, urinary tract infection; wk, week; y, year; >, greater than; <, less than.

Side Effects and Adverse Reactions

Nitrofurantoin. Side effects of nitrofurantoin use include (1) GI disturbances such as anorexia, nausea, vomiting, diarrhea, and abdominal pain and (2) pulmonary reactions such as dyspnea, chest pain, fever, and cough.

Methenamine. Methenamine use has GI side effects, including nausea, vomiting, and diarrhea. Allergic reactions to the dye in Hiprex have occurred. Bladder irritation and crystalluria (when taken in large doses) may occur.

Trimethoprim. GI symptoms (including nausea and vomiting) and skin problems (including rash and pruritus) can accompany trimethoprim use.

Fluoroquinolones. Nalidixic acid use can have the following side effects: headaches, dizziness, syncope (fainting), peripheral neuritis, visual disturbances, and rash. Nausea, vomiting, diarrhea, headaches, and visual disturbances can occur with cinoxacin and norfloxacin use. Photosensitivity is a common side effect associated with fluoroquinolones.

Drug-Drug Interactions

The following drug-drug interactions can occur with the use of urinary antiseptics/antiinfectives:

• Antacids decrease nitrofurantoin absorption.

• Sodium bicarbonate inhibits the action of methenamine.

• Methenamine mandelate taken with sulfonamides increases the risk of crystalluria.

• Nalidixic acid enhances the effects of warfarin (Coumadin).

• Most urinary antiseptics cause false-positive Clinitest results.

Urinary Analgesics

Phenazopyridine

Phenazopyridine hydrochloride (Pyridium), an azo dye, is a urinary analgesic (relieves urinary pain and burning) that has been available for almost 40 years. It is used to relieve the pain, burning sensation, and frequency and urgency of urination that are symptomatic of lower UTIs. The drug can cause GI disturbances, hemolytic anemia, nephrotoxicity, and hepatotoxicity. The urine becomes a harmless reddish orange because of the dye. Phenazopyridine can alter the glucose urine test (Clinitest); therefore, a blood test should be used to monitor glucose levels.

Urinary Stimulants

When bladder function is decreased or lost as a result of (1) a neurogenic bladder (a dysfunction caused by a lesion of the nervous system), (2) a spinal cord injury (paraplegia, hemiplegia), or (3) a severe head injury, a parasympathomimetic may be used to stimulate micturition (urination). The drug of choice, bethanechol chloride (Urecholine), is a urinary stimulant, also known as a direct-acting parasympathomimetic (cholinomimetic). The drug action is to increase bladder tone by increasing tone of the detrusor urinal muscle, which produces a contraction strong enough to stimulate urination. Bethanechol is discussed in detail in Chapter 19.

Urinary Antispasmodics/Antimuscarinics

Urinary tract spasms resulting from infection or injury can be relieved with antispasmodics that have a direct action on the smooth muscles of the urinary tract. This group of drugs (dimethyl sulfoxide [also called DMSO], oxybutynin [Ditropan], and flavoxate [Urispas]) is contraindicated for use if urinary or GI obstruction is present or if the patient has glaucoma. Antispasmodics have the same effects as antimuscarinics (agents that block parasympathetic nerve impulses), parasympatholytics, and anticholinergics (see Chapter 19). Side effects include dry mouth, increased heart rate, dizziness, intestinal distention, and constipation. Tolterodine tartrate (Detrol) is an antimuscarinic/anticholinergic drug used to control an overactive bladder, which causes frequency in urination. This drug also decreases urge urinary incontinence. It has the same side effects as antispasmodics/anticholinergics. The patient taking antimuscarinic/anticholinergic drugs should be taught to report urinary retention, severe dizziness, blurred vision, palpitations, and confusion. The patient should be warned to use caution in hot environments to avoid heat prostration. Table 34-2 lists drugs that are urinary analgesics, stimulants, and antispasmodics/antimuscarinics.

TABLE 34-2

URINARY ANALGESICS, STIMULANTS, AND ANTISPASMODICS

GENERIC (BRAND)	ROUTE AND DOSAGE	USES AND CONSIDERATIONS
Urinary Analgesics
phenazopyridine HCl (Pyridium)	A: PO: 200 mg t.i.d. p.c.; max: 600 mg/d	For chronic cystitis to alleviate pain and burning sensation during urination. Urine will be reddish orange. Can be taken concurrently with an antibiotic. Treats only symptoms, not underlying cause. Do not use long-term for undiagnosed urinary tract pain. Pregnancy category: B; PB: UK; : UK
Urinary Stimulants
bethanechol Cl (Urecholine)	A: PO: 10-50 mg t.i.d./q.i.d. 1 h a.c. or 2 h p.c.; max: 200 mg/d A: subQ: 5-mg single dose, may repeat 3-4 times PRN; max: 40 mg/d	For hypotonic or atonic bladder. Do not take if peptic ulcer is present. Can cause epigastric distress, abdominal cramps, nausea, vomiting, diarrhea, and flatulence. Can cause dizziness, lightheadedness, and fainting, especially when standing up from lying or sitting position. Pregnancy category: C; PB: UK; : UK
Urinary Antispasmodics
dimethyl sulfoxide (DMSO, Rimso-50)	Bladder instillation: 50 mL of 50% sol retained for 15 min; repeat q2wk until relief	For cystitis. Administered into the bladder to remain for 15 minutes. Additional effects are antiinflammatory, anesthetic, and bacteriostatic. Can cause garlic-like taste and odor on breath and skin for up to 72 h. Pregnancy category: C; PB: UK; : UK
flavoxate HCl (Urispas)	A: PO: 100-200 mg t.i.d./q.i.d.	For urinary tract spasms. Avoid in patients with glaucoma. Cautious use by older adults. Side effects include nausea, vomiting, dry mouth, drowsiness, blurred vision. Pregnancy category: B; PB: 50%-80%; : 10-20 h
oxybutynin Cl (Ditropan)	A: PO: 5 mg b.i.d./t.i.d.; max: 20 mg/d Older adults: PO: 2.5-5 mg b.i.d.; max: 20 mg/d C >5 y: PO: 5 mg b.i.d.; max: 15 mg/d	For urinary tract spasms and overactive bladder. Contraindicated for patients with cardiac, renal, hepatic, and prostate problems. Side effects include drowsiness, blurred vision, and dry mouth. Pregnancy category: B; PB: UK; : 2-5 h
mirabegron (Myrbetriq)	A:PO: 25 mg qd	For treatment of overactive bladder. Pregnancy category: C; PB: 71%; : 50 h
Antimuscarinics/Anticholinergics
tolterodine tartrate (Detrol, Detrol LA)	A: PO: 2 mg b.i.d.; max: 4 mg/d A: ER: 4 mg/d	To control overactive bladder by decreasing urinary frequency and urgency. Patients with narrow-angle glaucoma should not take this drug. Dry mouth is common. Pregnancy category: C; PB: 96%; : 2-4 h
trospium chloride (Sanctura, Sanctura XR)	A: PO: 20 mg b.i.d.; max: 60 mg/d A: ER: 60 mg/d in morning	To treat overactive bladder by action of a muscarinic-receptor antagonist. Pregnancy category: C; PB: 50%-85%; : 20-35 h
solifenacin succinate (VESIcare)	A: PO: 5 mg/d initially; then up to 10 mg/d if tolerated; max: 10 mg/d	To treat overactive bladder by action of a muscarinic-receptor antagonist. Pregnancy category: C; PB: 98%; : 55 h
darifenacin hydrobromide (Enablex)	A: PO: 7.5-15 mg/d; max: 15 mg/d	To treat overactive bladder by action of a muscarinic-receptor antagonist. Pregnancy category: C; PB: 98%; : 13-19 h