US Pharm. 2007;32(6):34-44.

Urinary incontinence (UI) is best defined as a variety of abnormalities of the urinary tract that result in the inability to experience normal micturition, leading to involuntary loss of bladder control. Approximately 40% of community-dwelling elderly and hospitalized patients are afflicted with this disorder.1-3 Sixty percent of nursing home patients experience this disorder, and it is often the reason for their admittance.4 Due to the social stigma associated with UI, the actual incidence in the community may be underestimated. Urinary incontinence may be associated with significant medical complications, creating issues for both patients and caregivers.1,5,6 The economic impact that results from UI influences both direct and indirect costs, placing a significant burden on the health care system.7,8

The causes of urinary incontinence are numerous and may involve age-related changes in the bladder and urethra, including declines in outlet resistance in females and prostate enlargement in males. Causes may also be secondary to a variety of cerebral insults or diseases, including cerebrovascular disease (strokes), spinal cord lesions, Alzheimer's disease, and Parkinson's disease. Reversible causes are numerous and include urinary tract infections, stool impaction, and numerous other triggers, described by the acronym DIAPPERS in Table 1.9-14 Numerous medication and medication classes can cause or exacerbate an existing incontinence and are described in Table 2 .12,13 Pharmacists should be aware of these potential disease–drug interactions when monitoring their patients' drug therapy.

A basic understanding of the bladder's anatomy and pathophysiology is important in order to understand the various UI types and their pharmacological management.11,14 Figure 1 describes the anatomy and physiology associated with bladder function, including the detrusor muscle in the bladder body and the internal and external sphincters, along with their nervous system connections. The bladder fills when sympathetic nervous system control results in a relaxed detrusor muscle and closed sphincters at the bladder outlet. When the bladder reaches a certain volume (200-400 mL), signals move from the spinal cord to brain centers, resulting in the sensation of urge. During voiding, the parasympathetic nervous system releases acetylcholine, which acts on the bladder detrusor smooth muscle to create contractions, and, concurrently, the sympathetic nervous system and somatic systems allow the sphincters to open. The result of these complex processes is the release of urine (micturition) from the bladder. 14-18

The evaluation and diagnosis of UI requires a complete medical examination to rule out reversible causes and may require the participation of physicians trained in urological evaluation.13 Correct diagnosis is important since drugs utilized for one incontinence type may exacerbate other types. 18,19 From a pharmacist's perspective, a good understanding of the medications used to treat incontinence and the medications (Table 2) that may exacerbate this disorder are important.9-13 In addition, since many urinary incontinent patients are elderly, drug use can be challenging and requires an understanding of the pharmacokinetic and pharmacodynamic changes that occur in this population.20

The various types of UI include those listed in Table 3, although many patients may experience mixed etiologies. This article will provide an overview of the three major types of UI and their treatments, including urge, stress, and overflow types.6,13,21-26

Urge UI is the most common cause of incontinence in the elderly and is best described by features of urgency that result in loss of urine. Urge incontinence is often referred to as overactive bladder (OAB), although an important distinction needs to be made from OAB since approximately two thirds of patients with OAB are not incontinent of urine.13,27-30 The pathophysiology is primarily due to detrusor muscle overactivity, resulting in uncontrolled, uninhibited, or involuntary bladder muscle contractions. 30-32a Clinically, patients describe a sudden desire to urinate, which is difficult to defer and results in leakage of urine occurring at various times during the day and night.6,29,30 The causes may be secondary to neurogenic insults including stroke, trauma, and neurologic diseases in addition to reversible causes such as drugs and infections.6,9-13,26 The treatments for urge incontinence include bladder training, behavioral treatments, pelvic floor exercises (Kegels), pads for temporary support, surgery, and pharmacotherapy.33-35 

Pharmacotherapy with Anticholinergic Drugs
The basis of pharmacotherapy for urge incontinence is controlling bladder detrusor muscle overactivity with drugs that act as acetylcholine (cholinergic) antagonists on bladder muscarinic (M) receptors, specifically the M2 and M3. The result is a reduction in urgency symptoms and improvements in bladder control.36 Since muscarinic receptors are also located in other organ systems throughout the body and since these antimuscarinic drugs are nonselective, numerous other effects and/or adverse effects may result from their use.

Anticholinergic or antimuscarinic side effects include both peripheral and central adverse reactions as noted in Table 4 . These adverse effects, including confusion, delirium, constipation, and urinary retention, are especially concerning in the more vulnerable elderly population.11,36,41,42 Contraindications to these agents are documented elsewhere and include narrow-angle glaucoma, urinary/gastric obstructive disorders, and dementia. Drug interactions include other anticholinergic drugs, acetylcholinesterase inhibitors, and numerous other agents. All of the antimuscarinic agents discussed below, except trospium, are metabolized by the cytochrome P-450 (CYP-450) system, and inhibitors of this system can potentiate their side-effect profiles.11,36 Monitoring for anticholinergic side effects, drug interactions, and potential contraindications, especially in patients who are taking multiple drugs with these properties, is essential for all health care professionals, including pharmacists.

A number of anticholinergic drugs are utilized in the treatment of urge incontinence. Older agents such as propantheline, dicyclomine, and flavoxate are still available but are rarely used because of their questionable efficacy and side-effect profiles. The tricyclic antidepressants (TCAs), including imipramine, have been used in urge incontinence and may have a role in mixed forms of stress and urge due to their duel antimuscarinic and alpha-adrenergic properties.36,43-47 The major agents used today in the treatment of urge incontinence include oxybutynin chloride (OBC), tolterodine (TD), and the three newest agents--trospium chloride (TC), darifenacin (DAF), and solifenacin (SFA)--along with a transdermal formulation of oxybutynin. Results from two large meta-analyses reported similar clinical efficacy among the available agents measured as reductions in episodes of urgency, frequency, daily micturitions, nocturnal awakenings, increase volume per void, and patient satisfaction. 44,48 Comparison trials with these agents are limited, however, and will be discussed below in a brief overview.49-51   

Oxybutynin chloride: Oxybutynin chloride is the oldest of the agents presently used for urge incontinence and is available in regular-release and long-acting oral products, in addition to a patch formulation. Clinical trials indicate similar efficacy to other agents in the class, and the significance of OBC's proposed additional muscle relaxation properties is not clear.52 The oral extended-release formulation and patch formulations may offer improved tolerability, due to less formation of the active metabolite desethyloxybutynin (DES).53-57 The adverse effects include dose-related anticholinergic effects as described above, along with the addition of erythema and pruritus associated with the transdermal patch. Dry mouth with this agent is reported to be as high as 50% to 70% and may be due to greater binding to the parotid gland.52-57 Drug interactions include the expected additive side effects when used with other anticholinergic agents. In addition, CYP-450 2D6 and 3A4 pathway inhibitors (e.g., fluconazole and erythromycin) may potentiate its side-effect profile. Monitoring and reviewing patients' medication profiles are important when oxybutynin is prescribed with other agents.36,52,57

Tolterodine (Detrol, Detrol LA): Tolterodine is available in both regular-release tablets and long-acting products, and they may offer improved tolerability versus regular-release oxybutynin, with similar efficacy and tolerability to the other available agents.57,58 Tolterodine's bioavailability (BA) and elimination is dependent on the CYP-450 2D6 metabolism phenotype, with extensive metabolizers having a lower BA and less excretion of drug in the urine. Drug interactions are similar to those reported with oxybutynin, above.59-62

Newer Agents Released in 2004
The search for drugs with improved tolerability led to the development, approval, and release of three new drugs in 2004.49-51 Although these agents appear equal in efficacy to oxybutynin and tolterodine, they may have some individual advantages in pharmacokinetic profile and/or tolerability, although there is limited evidence to support a clinical advantage.63-65

Trospium (Sanctura): The first of the new agents, trospium chloride, has a quaternary amine structure resulting in a hydrophilic molecule, with less blood–brain barrier penetration and a reduced potential for central nervous system (CNS) side effects. The BA of this agent is poor, and administration should be on an empty stomach. Hepatic metabolism is limited, resulting in lack of CYP-450 involvement and associated drug interactions. Elimination is via tubular secretion, requiring dose adjustments in patients with creatinine clearances (CrCl) less than 30 mL/minute.51,64,65 Trospium's efficacy is reported to be similar to other drugs in the class, although it may be better tolerated in some patients. 64,66-68 Drug interactions may involve competition for tubular secretion (metformin, digoxin) and drugs with an additive anticholinergic side-effect profile. Contraindications are similar to those of other anticholinergic agents as discussed above.51,69-71

Solifenacin (VESIcare): Solifenacin, another of the new antimuscarinics, is dosed once daily and has excellent BA. Solifenacin is metabolized primarily by CYP-450 3A4 and has some dependence on renal clearance, requiring adjustments in patients with a CrCl less than 30 mL/minute.50,72 Efficacy is reported to be similar to that of the other available anticholinergic agents,72-76 with one trial reporting fewer micturitions per 24 hours with solifenacin versus tolterodine.63 Adverse effects are similar to those of the other agents, along with reports of prolonged QTc intervals at higher doses, suggesting caution with patients at risk for this adverse event. As noted with oxybutynin and other drugs mentioned above, drug interactions, adverse effects, and contraindications are similar along with the added QTc concern. 50,77

Darifenacin (Enablex): Darifenacin, the third of the newer agents released in 2004, is also dosed once daily. Darifenacin's BA is poor and depends on the CYP-450 2D6 metabolism phenotype. Extensive metabolizers have a lower BA and more dependence on the CYP-450 3A4 pathway. Dosage adjustments are recommended in patients with hepatic impairment, and caution is suggested in patients with renal disease. 49,78

Darifenacin is reported to have a higher affinity for bladder M3 receptors, suggesting greater selectivity and tolerability, although clinical evidence of this advantage is lacking.78-80 Clinical trials with darifenacin have reported similar efficacy to the other agents, with improved tolerability versus oxybutynin.81-84 As noted with oxybutynin and the others above, metabolism involves the CYP-450 system, and adverse effects and contraindication are also similar.49

The anticholinergic/muscarinic drugs described above have a role in the management of urge incontinence. Doses should be started low, especially in elderly patients, and titrated slowly with careful monitoring for adverse effects and drug interactions. An adequate trial of four to eight weeks is recommended, with no clear advantage in terms of efficacy between the five agents discussed, although tolerability differences may exist.47,48,81,82 Patient counseling when dispensing these agents should include a review of potential side effects, drug interactions, and education on dosing and onset of action.

Stress incontinence, the most common form of UI in elderly women, is primarily a problem with bladder sphincter function, resulting in urine leakage at inappropriate times. Risk factors are numerous, including aging changes, multiple childbirths, medications (Table 2), obesity, trauma, or neurogenic problems.13,26,59,85-88 Although the economic costs are high, the social costs and impact on elderly women are also significant. 89-91 Clinically, patients describe involuntary loss of urine triggered by coughing, sneezing, or rising quickly. Patients with pure stress incontinence may lack urgency and nocturia, although many of these patients may have mixed forms of incontinence with features of urgency.87,88,92,93 The treatment of stress incontinence includes temporary pads for social situations, behavioral interventions, and Kegel exercises, along with a number of surgical options.37,94-99 There are limited agents and data available for the pharmacological management of pure stress incontinence. Unlabeled uses of alpha-adrenergic agonists (e.g., pseudoephedrine and phenylephrine) are based on the urethral smooth-muscle response to alpha stimulation, resulting in improved control of the internal sphincter and reduced urine loss. Lack of proven efficacy with these agents and concerns with adverse effects including insomnia, anxiety, hypertension, arrhythmias, and stroke limits their utility.13,26,59,100-102 The tricyclic antidepressant imipramine has been used in the treatment of stress or mixed incontinence, due to its alpha-adrenergic agonist and anticholinergic properties. Low doses may provide relief in some patients, especially if they have a mixed disorder with stress and urgency symptoms. With its anticholinergic side-effect profile, the use of this agent in elderly patients may be problematic.11,26,36,85,86

Although the loss of estrogen in postmenopausal woman may contribute to symptoms of stress incontinence due to estrogen's influence on sphincter control, there is limited clinical evidence to support its use. Estrogen therapy has been proposed to increase urethral resistance via stimulation of estrogen receptors. If treatment is utilized, local or topical treatments are recommended and include creams (Table 3), vaginal tablets, or elastomer ring formulations, which may be beneficial for improving irritative symptoms and discomfort in some patients. 85,86,103-107 The use of oral estrogen for stress incontinence is not recommended due lack of benefit, along with the small but significant increased risk of other comorbidities.108 

The most recent agent being evaluated for stress incontinence is duloxetine, a dual norepinephrine (NE) and serotonin (5HT) reuptake blocker approved for depression. The proposed mechanism in this disorder is through duloxetine's action on receptors in the Onuf's nucleus of the spinal cord and on the pudendal bladder nerve to improve urethral sphincter muscle contractions and tone.109

Overflow incontinence is best described as an overfilled bladder secondary to obstruction, bladder prolapse, or alignment problems, most commonly seen in males with benign prostatic hyperplasia (BPH).11,13,26,110 Men with BPH are usually found to have an enlarged prostate on physical exam, and in some cases further evaluation may be warranted to rule out prostate cancer or other obstructions.110 The clinical presentation of overflow incontinence is described by lower urinary tract symptoms including difficulty starting urination and/or having a weak urine stream, a sense of incomplete emptying, nocturia, and dribbling. A complicating feature of this disorder is that two thirds of patients with BPH may also have urgency symptoms, which can make diagnosis and treatment challenging.110,111 Treatment for overflow incontinence caused by BPH may include watchful waiting and eliminating potential triggers, including alcohol and/or caffeine. Surgical options may include transurethral resection of the prostate (TURP) or newer, less-invasive laser procedures.110,112-116 

Drug therapy for the treatment of overflow incontinence secondary to BPH includes the peripheral alpha-adrenergic blockers and the 5-alpha-reductase inhibitors.110,112 The alpha-adrenergic blockers include the older, nonselective agents originally approved to treat hypertension and the newer prostate selective agents, which have minimal effects on blood pressure.117-119 The alpha-adrenergic blockers are usually the choice therapy in early mild disease due to their faster onset of action, usually within six weeks.118-121 Their mechanism of action is through their blocking action at the prostate alpha 1A receptor, resulting in improved urine outflow and relief of the symptoms described above.

These agents are metabolized by the hepatic CYP-450 system, and monitoring for drug interactions is necessary. Adverse effects include dizziness, peripheral edema, sedation, ejaculatory dysfunction, flulike symptoms, headaches, and gastrointestinal effects. Contraindications include heart failure, hypotension, and the potential to exacerbate stress incontinence in females. Individual differences between these agents include selectivity, dosing frequency, and cost issues related to brand name products. The selective agents may be better choices in patients without hypertension or in elderly patients at risk for orthostatic hypotension. The nonselective agents may be appropriate choices in younger BPH patients with concurrent hypertension. Patient counseling when dispensing these agents should include a review of potential side effects, especially effects on blood pressure, sedation, and dizziness.110,112,118

Alpha-Reductase Inhibitors
The alpha-reductase inhibitors finasteride and dutasteride are also used to treat overflow incontinence secondary to BPH. Their mechanism of action is through inhibiting the conversion of testosterone to dihydrotestosterone, resulting in reduced androgenic prostate stimulation and leading to reduced gland size and improved urine outflow. Although usually considered a second-line therapy, they may be used first-line in patients with contraindications to the alpha-blockers (hypotension or heart failure) or in combination with alpha-blockers in progressive or more moderate-to-severe disease, e.g., large glands. Although effective in treating the symptoms of BPH, their side-effect profile (e.g., decreased libido, impotence, dry sex, and gynecomastia) and slower onset of action, which may take up to six to 12 months, limits their use in mild disease.110,112,118,122-124 Similar efficacy for both agents has been reported in clinical trials, and potential differences in selectivity for reductase enzymes have not been demonstrated clinically.125 Although these agents are not indicated in women, they are classified as pregnancy category X, and avoidance of drug contact by any potential route (handling broken tablets, semen transfer) with pregnant women or those seeking to become pregnant is recommended. 110,112,118 

Other therapies that have been utilized in the management of overflow incontinence secondary to BPH include the herbal saw palmetto, which is reported to have 5-alpha-reductase inhibitor activity and the cholinergic agonist bethanechol, which may be used for acute management after TURP procedures11,36 Investigational therapies include combinations of anticholinergic drugs with alpha-blockers for patients who have urgency associated with their BPH symptoms.111,126 The use of the erectile dysfunction drugs (e.g., phosphodiesterase inhibitors [sildenafil] and botulinum toxin) are also being evaluated in the treatment of overflow incontinence secondary to BPH.127,128 As noted in Table 3, other types of incontinence include functional incontinence secondary to patients' inability to reach the bathroom due to a physical disability and atonic bladder, where complete loss of bladder innervation and control secondary to various diseases or insults, including stroke or diabetes, requires the use of intermittent catheterizations. Mixed UI may occur in up to 20% to 30% of patients and, due to the various clinical presentations and symptoms, may require extensive evaluation and therapeutic trials to determine appropriate therapies.6,11,13,18,24-26,59,88

The pharmacological management of UI requires appropriate evaluation by qualified clinicians. Pharmacists can offer educational support to patients by questioning and monitoring the effectiveness and tolerability of the various pharmacotherapies. Taking time to get to know your patients in the ambulatory and clinical settings allows the pharmacist the opportunity to provide valuable education, intervention, and recommendations to improve patient care outcomes in the management of this complex disorder.

1. Wilson MM. Urinary incontinence: selected current concepts. Med Clin North Am. 2006;90:825-836.
2. Zarowitz BJ, Ouslander JG. Management of urinary incontinence in older persons. Geriatr Nurs. 2006:265-270.
3. Chutka DS, Takalhashi PY. Urinary incontinence in the elderly. Drugs . 1998;56:587-595.
4. Tannenbaum C, DuBeau CE. Urinary incontinence in the nursing home: practical approach to evaluation and management. Clin Geriatr Med. 2004;20:437-452.
5. American Medical Directors Association (AMDA) Clinical Practice Guideline: Urinary Incontinence, 2005. Available at:
6. AHCPR Urinary Incontinence in Adults Guideline Update Panel. Clinical practice guidelines: managing acute and chronic urinary incontinence. Am Family Physician. 1996;54:1661-1671.
7. Levy R, Muller N. Urinary incontinence: economic burden and new choices in pharmaceutical treatment. Adv Ther. 2006;23:556-573.
8. Wilson L, Brown JS, Shin GP, et al. Annual direct cost of urinary incontinence. Obstet Gynecol. 2001;98:398-406.
9. Thom DH, van den Eeden SK, Brown JS. Evaluation of parturition and other reproductive variables as risk factors for urinary incontinence in later life. Obstet Gynecol. 1997;90:983-989.
10. Thom DH, Brown JS. Reproductive and hormonal risk factors for urinary incontinence in later life: a review of the clinical and epidemiologic literature. J Am Geriatri Soc. 1998;46:1411-1417.
11. Thompson JF. Geriatric urological disorders. In: Koda Kimble MA, Young LL, eds. Applied Therapeutics: The Clinical Use of Drugs. 8th ed. Vancouver, WA: Applied Therapeutics, Inc; 2005:101-1–101-33.
12. Rondorf-Klyn LM, Colling J, Simonson W. Medication use by community-dwelling elderly with urinary incontinence. Urol Nurs. 1998;18:201-206.
13. Abrams P, Andersson KE, Brubaker L, et al; 3rd International Consultation on Incontinence. Recommendations of the International Scientific Committee. Evaluation and treatment of urinary incontinence, pelvic organ prolapse, and faecal incontinence. In: Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence. Vol 2. Plymouth, UK: Health Publication Ltd; 2005:1589-1626.
14. Gosing, JA. The structure of the female lower urinary tract and pelvic floor. Urol Clin North Am. 1985;12:207.
15. Abrams P. Describing bladder storage function: overactive bladder syndrome and detrusor overactivity. Urology. 2003;62:28-37.
16. Elbadawi A, Diokno A, Millard R. The aging bladder: morphology and urodynamics. World J Urol. 1998;16(suppl 1):S10-S34.
17. Chapple CR, Artibani W, Cardozo LD, et al. The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects. BJU Int. 2005;95:335-340.
18. Tannenbaum C, Perrin L, DuBeau C, et al. Diagnosis and management of urinary incontinence in the older patient. Arch Phys Med Rehabil. 2001;82:134-138.
19. Scientific Committee of the First International Consultation on Incontinence. Assessment and treatment of urinary incontinence. Lancet. 2000;355:2153-2158.
20. Linnebur SA, O'Connell MB, Wessell AM, et al. Pharmacy practice, research, education, and advocacy for older adults. Pharmacotherapy. 2005;25:1396-1430.
21. Anderson KE, Hedlund P. Pharmacologic perspective on the physiology of the lower urinary tract. Urology. 2002;605(suppl 1):13-21.
22.Yim PS, Peterson AS. Urinary incontinence. Postgrad Med. 1996;99:137-150.
23. Sandvik H, Hunskaar S, Vanvik A, et al. Diagnostic classification of female urinary incontinence: an epidemiological survey corrected for validity. J Clin Epidemiol. 1995;48:339-343.
24. Bump RC, Norton PA, Zinner NR, et al. Mixed urinary incontinence in women with predominant stress urinary incontinence symptoms: urodynamic findings, incontinence severity measures, and duloxetine treatment response. Obstet Gynecol. 2003;102:76-83.
25. Viktrup L. Addressing the need for a simpler algorithm for the management of women with urinary incontinence. Medscape General Medicine. 2005;7:3. Available at:
26. National Library of Medicine. Urinary incontinence in adults: acute and chronic management. clinical practice guideline number 2 (1996 Update) AHCPR Publication No. 96-0682: March 1996. Available at: 
27. Milsom L, Abrams P, Cardozo L, et al. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int. 2001;87:760-766.
28. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327-336.
29. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology in lower urinary tract function: report from the Standardization Sub-committee of the International Continence Society. Am J Obstet Gynecol. 2002;187:116-126.
30. Wein AJ, Rovner ES. Definition and epidemiology of overactive bladder. Urology. 2002;60(suppl 5A):7-12.
31. Payne CK. Epidemiology, pathophysiology, and evaluation of urinary incontinence and overactive bladder. Urology. 1998;51(suppl 2A):3-10.
32. Fourcroy JL. Urogynecology update: incontinence. Hospital Practice. 1998;33:63-81.
32a. Resnick NM, Blaivas JG, Ostergard DR. Practical pointers on urinary incontinence. Patient Care. 1995;29:103-131.
33.Burgio KL, Locker JL, Goode PS, et al. Behavioral vs drug treatment for urge incontinence in older women: a randomized controlled trial. JAMA. 1998;280:2034-2035.
34.Wyman JE, Fantl JA. Bladder training in ambulatory care management of urinary incontinence. Urol Nurs. 1991;11:11-17.
35. Wyman JF, Fantl JA, McClish DK, et al. Comparative efficacy of behavioral interventions in the management of female urinary incontinence. Continence Program for Women Research Group. Am J Obstet Gynecol. 1998;179:999-1007.
36. Brown JH, Palmer T. Muscarinic receptor agonist and antagonists. In: Goodman & Gilman's The Pharmacolgical Basis of Therapeutics . 9th ed. New York, NY: McGraw-Hill; 1996:141-160.
37. Goode PS, Burgio KL. Pharmacological treatment of  lower urinary tract dysfunction in geriatric patients. Am J Med Sci. 1997;314:262-267.
38. Yasuhiko I. Discussion: functional role of M1, M2 and M3 muscarinic receptors in overactive bladder. Urology. 2000;55:47-49.
39. Caulfield MP, Birdsall NJ. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev. 1998;50:279-290.
40. Andersson KE. Antimuscarinics for treatment of overactive bladder. Lancet Neurol. 2004;3:46-53.
41. Moore AR, O'Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging. 1999;15:15-28.
42. Power AE, McIntyre CK, Litmanovich A, et al. Cholinergic modulation of memory in the basolateral amygdala involves activation of both M1 and M2 receptors. Behav Pharmacol. 2003;14:207-213. 
43. Herbison P, Hay-Smith J, Blis G, et al. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systemic review. BMJ. 2003;326:8414.
44. Andersson KE. Antimuscarinics for treatment of overactive bladder. Lancet Neurol. 2004;3:46-53.
45. Fischer CP, Diokno A, Lapides J. The anticholinergic effects of dicyclomine HCl in uninhibited neurogenic bladder dysfunction. J Urol. 1978;120:328-329.
46. Briggs RS, Castleden CM, Asher MJ. The effect of flavoxate on uninhibited detrusor contractions and urinary incontinence in the elderly. J Urol. 1980;123:665-666.
47. Chapple CR. Muscarinic receptors antagonists in the treatment of overactive bladder. Urology. 2000;55(suppl 5A):33-46.
48. Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis. Eur Urol. 2005;48:5-26.
49. Enablex (darifenacin). East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004.
50. Vesicare (solifenacin) tablets. Yamanouchi Pharma America, Inc., and GlaxoSmithKline; 2004.
51. Sanctura (trospium chloride) tablets. Lexington, MA: Indevus Pharmaceuticals, Inc.; 2004.
52. Yarker Y, Goa KL, Fitton A. Oxybutynin: a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging. 1995;6:243-262.
53. Waldeck K, Larsson B, Andersson KE. Comparison of oxybutynin and its active metabolite, N-desethyl-oxybutynin in the human detrusor and parotid gland. J Urol. 1997;157:1093-1097.
54. Diokno AC, Appell RA, Sand PK, et al. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc. 2003;78:687-695.
55. Davila GW, Daugherty CA, Sanders SW. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol. 2001;166:140-145.
56. Barkin J, Corcos J, Radomski S, et al. A randomized, double-blind, parallel-group comparison of controlled- and immediate- release oxybutynin chloride in urge urinary incontinence. Clin Ther. 2004;26:1026-1036.
57. Dmochowski RR, Sand PK, Zinner NR, et al., for the Transdermal Oxybutynin Study Group. Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. Urology. 2003;62:237-242.
58. Abrams P, Freeman R, Anderstrom C, et al. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol. 1998;81:801-810.
59. Andersson K-E, Appell R, Cardozo L, et al. 3rd International Consultation on Incontinence. Pharmacological treatment of urinary incontinence. In: Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence. Vol 2. Plymouth, UK: Health Publication Ltd.; 2005:809-855.
60. Guay D. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clin Pharmacokinetics. 2003;42:1243-1285.
61. Nilvebrant L, Andersson KE, Gillberg PG, et al. Tolterodine: a new bladder-selective antimuscarinic agent. Eur J Pharmacol. 1997;327:195-207.
62. Nilvebrant L, Glas G, Jonsson A, et al. The in vitro pharmacological profile of tolterodine: a new drug for the treatment of urinary incontinence. Neurourol Urodyn. 1994;13:433-435.
63. Chapple C, Rechberger T, Al-Shukri S, et al. Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int . 2004;93:303-310.
64. Pak RW, Petrou SP, Staskin DR. Trospium chloride: a quaternary amine with unique pharmacologic properties. Curr Urol Rep. 2003;4:436-440.
65. Haab F, Stewart L, Dwyer P. Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol. 2004;45:420-429.
66. Todorova A, Vonderheid-Guth B, Dimpfel W. Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol . 2001;41:636-644.
67. Pietzko A, Dimpfel W, Schwantes U, Topfmeier P. Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. Eur J Clinic Pharmacol. 1994;47:337-343.
68. Madersbacher H, Stöhrer, Richter R, et al. Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia. Br J Urol. 1995;75:452-456.
69. Beckmann-Knopp S, Rietbrock S, Weyenmeyer R, et al. Inhibitory effects of trospium chloride on cytochrome P540 enzymes in human liver microsomes.  Pharmacol Toxicol. 1999;85:299-304.
70. Rovner ES. Trospium chloride in the management of overactive bladder. Drugs. 2004;64:2433-2446.
71. Fusgen I, Hauri D. Trospium chloride: an effective option for medical treatment of bladder overactivity. Int J Clin Pharmacol Ther. 2000;38:223-234.
72. Brunton S, Kuritzky L. Recent developments in the management of overactive bladder: focus on the efficacy and tolerability of once daily solifenacin succinate 5 mg. Curr Med Res Opin. 2005;21:71-80.
73. Chapple CR, Martinez-Garcia R, Selvaggi L, et al. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome; results of the STAR trial. Eur Urol. 2005;48:464-470.
74. Chapple C, Wyndaele JJ, Gronen S, for the Solifenacin Study Group. Solifenacin provided statistically significant and clinically relevant reductions in urgency, a defining symptom of overactive bladder. Neurourol Urodyn. 2004;23:316.
75. Haab F, Cardozo L, Chapple C, Ridder AM, for the Solifenacin Study Group. Long-term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome. Eur Urol. 2005;47:376-384.
76. Cardozo L, Lisec M, Millard R, et al. Randomized, double-blind placebo-controlled trial of the once-daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J Urol. 2004;172:1919-1924.
77. Ikeda K, Kobayashi S, Suzuki M, et al. M(3) receptor antagonist by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. Arch Pharmacol. 2002;366:97-103.
78. Chapple CR. Darifenacin: a novel M3 muscarinic selective receptor antagonist for the treatment of overactive bladder. Expert Opin Invest Drugs . 2004;13:1493-1500.
79. Newgreen DT, Anderson DW, Carter AJ. Darifenacin: a novel bladder-selective agent for the treatment of urge incontinence. Neurourol Urodyn. 1995;14:95-99.
80. Braverman AS, Ruggieri MR, Pontari MA. The M2 muscarinic receptor subtype medicates cholinergic bladder contractions in patients with neurogenic bladder dysfunction. J Urol. 2001;165:36.
81. Haab F, Stewart L, Dwyer P. Darifenacin. an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol. 2004;45:420-429.
82. Foote JE. Darifenacin. A highly M3 selective muscarinic receptor antagonist, is effective and well tolerated by elderly patients with overactive bladder. J Am Geriatr Soc. 2004;52:S126.
83. Zinner N, Tuttle JB, Marks L. Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist, compared with oxybutynin in the treatment of patients with overactive bladder. International Continence Society Meeting; 2004. Paris, France.
84. Khullar V. Darifenacin, an M3 selective receptor antagonist, reduces the frequency of nocturnal awaking, and important symptom of overactive bladder. J Urol. 2004;171(suppl 4):131. Abstract 491.
85. Mushkat Y, Bukovsky I, Langer R. Female urinary stress incontinence--does it have familial prevalence? Am J Obstet Gynecol. 1996;174:617-619.
86. Brown JS, Grady D, Ouslander JG, et al. Prevalence of urinary incontinence and associated risk factors in postmenopausal women. Heart & Estrogen/Progestin Replacement Study (HERS) Research Group. Obstet Gynecol. 1999;94:66-70.
87. Viktrup L, Koke S, Burgio KL, Ouslander JG. Stress urinary incontinence in active elderly women. South Med J. 2005;98:79-89.
88. Urinary Incontinence in Women. Bethesda, Md: National Kidney and Urologic Diseases Clearinghouse. NIH Publication No. 02-4132. May 2002. Available at:
89. Wilson L, Brown JS, Shin GP, et al. Annual direct cost of urinary incontinence. Obstet Gynecol. 2001;98:398-406.
90. Dugan E, Cohen S, Bland DR, et al. The association of depressive symptoms and urinary incontinence among older adults. J Am Geriatr Soc. 2000;48:413-416.
91. Melville JL, Walker E, Katon W, et al. Prevalence of comorbid psychiatric illness and its impact on symptom perception, quality of life, and functional status in women with urinary incontinence. Am J Obstet Gynecol. 2002;187:80-87.
92. Campbell SC, Siegel SW. Female urinary incontinence, current evaluation and management. Consultant. 1992;32:45-52.
93. Artibani W, Andersen JT, Gajewski JB, et al. Imaging and other investigations. In: Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence . 2nd ed. Plymouth, UK: Health Publication Ltd.; 2002:425-477.
94. Wilson PD, Bo K, Hay-Smith J, et al. Conservative treatment in women. In: Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence. 2nd ed. Plymouth, UK: Health Publication Ltd.; 2002:571-624.
95. American Academy of Family Physicians. Urinary incontinence: Kegel exercises for your pelvic muscles. Information from your family doctor. Available at:
96. Bo K, Talseth T, Holme I. Single blind, randomised controlled trial of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine stress incontinence in women. BMJ. 1999;318:487-493.
97. Ulmsten U, Falconer C, Johnson P, et al. A multicenter study of tension-free vaginal tape (TVT) for surgical treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 1998;9:210-213.
98. Weber AM, Walters MD. Burch procedure compared with sling for stress urinary incontinence. A decision analysis. Obstet Gynecol. 2000;96:867-873.
99. Hilton P. Trials of surgery for stress incontinence--thoughts on the ‘Humpty Dumpty principle.' BJOG. 2002;109:1081-1088.
100. Hoffman BB, Lefkowitz RJ. Catecholamines, sympathomimetic drugs and adrenergic receptor antagonists. In: Goodman & Gilman's The Pharmacolgical Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996:199-248.
101. Collset L, Lindskog M. Phenylpropanolamine in the treatment of female stress urinary incontinence: double-blind placebocontrolled study in 24 patients. Urology. 1987;30:398-403.
102. Stier BG, Hennekens CH. Phenylpropanolamine and hemorrhagic stroke in the Hemorrhagic Stroke Project: a reappraisal in the context of science, the Food and Drug Administration, and the law. Ann Epidemiol. 2006;16:49-52.
103. Maloney C. Estrogen in urinary incontinence treatment: an anatomic and physiologic approach. Urol Nurs. 1997;17:88-91.
104. Bernier F, Jenkins P. The role of vaginal estrogen in the treatment of urogenital dysfunction in postmenopausal women. Urol Nurs. 1997;17:92-95.
105. Sartori MG, Baracat EC, Girao MJ, et al. Menopausal genuine stress incontinence treated with conjugated estrogens plus progestogens. Int J Gynaecol Obstet. 1995;49:165-169.
106. Makinen JI, Pitkanen YA, Salmi TA, et al. Transdermal estrogens for female stress urinary incontinence in postmenopause. Maturitas. 1995;22:233-238.
107. Griebling TL, Nygaard IE. The role of estrogen replacement therapy in the management of urinary incontinence and urinary tract infection in postmenopausal women. Endocrinol Metab Clin North Am. 1997;26:347-360.
108. Hendrix SL, Cochrane BB, Nygaard IE, et al. Effects of estrogen with and without progestin on urinary incontinence. JAMA. 2005;293:935-948.
109. Millard RJ, Moore K, Rencken R, et al. Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial. BJU Int. 2004;93:311-318.
110. Lee ML. Management of benign prostatic hyperplasia. In: DiPiro JT, ed. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw-Hill; 2005:1535-1546.
111. Macdiarmid S, Chen A, Tu N, et al. Effects of tamsulosin and extended-release oxybutynin on lower urinary tract symptoms in men. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Ga. Abstract 1638.
112. Walsh PC. Treatment of benign prostate hyperplasia. N Engl J Med. 1996;335;586-587.
113. Gnanapragasam VJ, Kumar V, Langton D, et al. Outcome of transurethral prostatectomy for the palliative management of lower urinary tract symptoms in men with prostate cancer. Int J Urol. 2006;13:711-715.
114.  Mattiasson A, Wagell L, Schelin S, et al. Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study. Urology. 2007;69:91-97.
115. Fried NM. New laser treatment approaches for benign prostatic hyperplasia. Curr Urol Rep. 2007;8:47-52.
116. Harris JL. Treatment of postprostatectomy urinary incontinence with behavioral methods. Clin Nurse Spec. 1997;11:159-166.
117. Saseen JJ, Carter BL.  Hypertension. In: Dipiro JT. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. Connecticut: McGraw-Hill; 2005:18-217.
118. American Urological Association Practice Guidelines Committee. AUA guidelines on management of benign prostatic hyperplasia (2003). Chap 1: Diagnosis and treatment recommendations. J Urol. 2003;170:530-547.
119. Oades GM, Eaton JD, Kirby RS. The clinical role of alpha-blockers in the treatment of benign prostatic hyperplasia. Curr Urol Rep. 2000;1:97-102.
120. Noble AJ, Chess-Williams R, Couldwell C, et al. The effects of tamsulosin, a high affinity antagonist at functional alpha 1A and alpha 1D-adrenoceptor subtypes. Br J Pharmacol. 1997;120:231-238.
121. MacDonald R, Wilt TJ. Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects. Urology. 2005;66:780-788.
122. Anderson JT, Nickel JC, Marshall VR, et al. Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia. Urology. 1997;49:839-845.
123. Lepor H, Willford WO, Barry MJ, et al. The efficacy terazosin, finasteride, or both in benign prostate hyperplasia. N Engl J Med. 1996;335:533-540.
124. Sandhu JS, Te AE. The role of 5-alpha-reductase inhibition as monotherapy in view of the MTOPS data. Curr Urol Rep. 2004;5:274-279.
125. Nickel JC. Comparision of clinical trials with finasteride and dutasteride. Rev Urol. 2004;6(suppl 9):S31-S39.
126. Yang Y, Zhao XF, Li HZ, et al. Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study. Chin Med J. 2007;120:370-374.
127. Hopps CV, Mulhall J. Assessment of the impact of sildenafil citrate on lower urinary tract symptoms (LUTS) in men with erectile dysfunction (ED). J Urol. 2003;169:375A.
128. Chuang YC, Chiang P, Hsien K, et al. Beneficial effects of up to one year with intraprostatic botulinum toxin type A injection on LUTS and quality of life in BPH patients. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Ga. Abstract 1436.

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