Stress urinary incontinence

Explain the pathophysiology of the major types of urinary incontinence (urge, stress, overflow, and functional) and pediatric enuresis. 

Vaginally-administered estrogen plays only a modest role in managing stress urinary incontinence (urethral underactivity), unless it is accompanied by local signs of estrogen deficiency (e.g., atrophic urethritis or vaginitis). 

The use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

ACE-I, angiotensin-converting enzyme inhibitor ADH, antidiuretic hormone (or vasopressin) ARB, angiotensin II receptor blocker, MESNA, sodium 2-mercaptoethanesulfonate TCA, tricyclic antidepressant Ul, urinary incontinence SUI, stress urinary incontinence UUI, urge urinary incontinence. 

CAM, complementary and alternative medications CNS, central nervous system CVA, costovertebral angle OTC, over-the-counter OUI, overflow urinary incontinence SUI, stress urinary incontinence UTI, urinary tract infection UUI, urge urinary incontinence. 

TABLE 50-4. Drugs Used for Stress Urinary Incontinence... 

Guay DRP. Duloxetine for management of stress urinary incontinence. Am J Geriatr Pharmacother 2005 3 25-38. 

ACEIs, angiotensin-ronverting enzyme inhibitors SUI, stress urinary incontinence. 

In addition to treating MDD [51-53], duloxetine was approved as the first agent for the treatment of painful diabetic neuropathy in the U.S. [54-56]. It also has been used for stress urinary incontinence in women in Europe [57,58]. In 2007, duloxetine was approved for the treatment of generalized anxiety disorder in the U.S. 

Unlabeled Uses Treatment of chronic pain syndromes, fibromyalgia, stress incontinence, urinary incontinence... 

Geriatric Considerations - Summary Compared to placebo, duloxetine is effective for the treatent of depression and painful diabetic neuropathy Few head-to-head studies are available comparing duloxetine to other agents in the treatment of depression or painful neuropathy. Because this agent may increase urethral sphincter activity, it is now being assessed as an agent for the treatment of stress urinary incontinence. This same property may increase the risk of urinary retention, although this has not been well documented. Duloxetine has not been well studied with respect to falls. 

Schuessler B, Baessler K. Pharmacologic treatment of stress urinary incontinence expectations for outcome. Urology 2003 62 31-38. 

Some of the growth in antidepressant use may be related to the broad application of these agents for conditions other than major depression. For example, antidepressants have received FDA approvals for the treatment of panic disorder, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). In addition, antidepressants are commonly used to treat pain disorders such as neuropathic pain and the pain associated with fibromyalgia. Some antidepressants are used for treating premenstrual dysphoric disorder (PMDD), mitigating the vasomotor symptoms of menopause, and treating stress urinary incontinence. Thus, antidepressants have a broad... 

The SNRIs include venlafaxine, its metabolite desvenlafaxine, and duloxetine. Another SNRI, milnacipran, is in late clinical trials in the USA but has been available in Europe for several years. In addition to their use in major depression, other applications of the SNRIs include the treatment of pain disorders including neuropathies and fibromyalgia. SNRIs are also used in the treatment of generalized anxiety, stress urinary incontinence, and vasomotor symptoms of menopause. 

Lin AT et al Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan A double-blind, randomized, placebo-controlled trial. BMC Urol 2008 8 2. [PMID 18221532]... 

Process analysis looks at the logical sequence in a model where for instance the forecast for a product can be derived from a set of reasonably hard data (such as epidemiological data sets, perhaps of disease incidence, prevalence or death rates). Knowing the numbers of patients suffering from a particular disease such as stress urinary incontinence (SUI), one can state various assumptions which are either fact-based or logical and from this produce a forecast (see Figure 1.2). 

Dosing for neuropathic pain and fibromyalgia may be similar to that for depression but different from dosing for stress urinary incontinence, but clinical experience is still evolving... 

Well-studied in stress urinary incontinence and approval for this use is expected... 

Zinner NR. Duloxetine a serotonin-noradrenaline re-uptake inhibitor for the treatment of stress urinary incontinence. Expert Opin Investig Drugs 2003 ... 

Purified solubilized bovine collagen is used as biomaterial for the treatment of soft tissue defects and has been used for the treatment of stress urinary incontinence since the late 1980s (1). Injected material precipitates at body temperature, forming a matrix allowing fibroblastic infiltration and formation of new tissue. It has been used for cosmetic purposes by injection in the dermis to correct scars and other contour deformities of the skin. 

Delayed hypersensitivity reactions after bovine collagen injection for stress urinary incontinence have been reported. 

Stothers L, Goldenberg SL. Delayed hypersensitivity and systemic arthralgia following transurethral coUagen injection for stress urinary incontinence. J Urol 1998 159(5) 1507-9. 

Refluxing ureters can be treated endoscopically with sub-ureteric injection of polytetrafluoroethylene paste (Polytef), the STING procedure. However, ureteric obstruction has been described as a complication (8). Urinary incontinence has also been treated by periurethral or submucosal injections of Polytef, but reports of urinary obstruction (9,10) and poor long-term success (11,12) have limited the range of indications for this treatment. Other reported complications of Teflon injection for stress urinary incontinence include periurethral abscess, urethral diverticulum. Teflon granuloma with urethral wall prolapse (13), and microembolization (14). 

Kiilholma PJ, Chancellor MB, Makinen J, Hirsch IH, Klemi PJ. Complications of Teflon injection for stress urinary incontinence. Nenronrol Urodyn 1993 12(2) 131-7. 

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