Medications for Stress Urinary Incontinence

G.Willy Davila

Pharmacologic therapy of stress urinary incontinence (SUI) is directed toward enhancing urethral sphincteric function, especially during times of increased intraabdominal pressure such as coughing or lifting. Appropriate function of the intrinsic and extrinsic urethral sphincteric musculature, along with appropriate urethral support, as well as integrity of the urethral mucosa and submucosal vascular plexus are the key components of the delicate female continence mechanism. The extrinsic muscular support of the urethra is dependent on intact pelvic floor musculature and its innervation. Physiotherapeutic approaches to SUI are discussed in Chapter 12-2. The urethral mucosal and vascular factors are dependent on estrogen availability. In menopausal women, there is a prompt reduction in blood flow to the urethral submucosa and thinning of the urethral mucosa. Usage of local estrogen cream is discussed in Chapter 11-1.

Alpha 1A/1L adrenoceptors are present at the level of the urethra and bladder neck smooth muscle. They are amenable to pharmacologic manipulation in order to enhance urethral sphincteric tone and contractility. Alpha-adrenergic stimulants have therefore been used for many years in the treatment of SUI. These include phenylpropanolamine, pseudoephedrine, ephedrine, and phenylephrine. These medications result in enhanced ure-thral sphincteric tone attributed to a direct effect on the alpha-adrenergic receptors in the urethral smooth muscle. In the United States, phenylpropanolamine was removed from the market in the year 2000, because of the reported occurrence of subarachnoid and intracerebral hemorrhage in adults taking this medication. It was found that in women who were admitted to the hospital with intracere-bral bleeding, the odds ratio was 16.58 for usage of phenylpropanolamine. Before its removal from the market, phenylpropanolamine was widely used for mild SUI symptoms. It was used either as a single-dose extended-release formulation, or three-times-daily 25-mg tablets. The improvement in SUI was mild, but predictable. Previous urodynamic studies have demonstrated an increase in urethral closure pressure with alpha-adrenergic agents.

Importantly, the combination of an alpha-adrenergic oral agent along with local estrogen replacement therapy resulted in a synergistic improvement in SUI symptoms.1 Thus, we recommended the usage of local estrogen cream along with an oral alpha-adrenergic agent before their removal from the market.

Imipramine (Tofranil) is a drug with combined properties as an anticholinergic, alpha-adrenergic, and mild anesthetic agent. It was primarily used as a tricyclic antidepressant and anxiolytic. Its usage for depression has been limited because of the recent availability of serotonin reuptake inhibitors. Because of its combined properties, imipramine can be very useful in mixed urinary incontinence, as well as in SUI. It can be used as a once-a-day 25-to 50-mg tablet, or can be given in multiple daily dosages. Care must be taken in the elderly because of the possibility of cardiovascular side effects. Various studies have demonstrated an improvement in urethral closure as well as SUI symptoms with imipramine. Cure rates are variable but have been shown to be as high as 35%, especially in those patients who demonstrated an increase in urethral closure pressure during therapy.2

Most recently, duloxetine has been studied widely for the treatment of stress as well as mixed urinary incontinence. Although it is not yet approved by the Food and Drug Administration for incontinence, it is available for clinical use for depression, and multiple studies have been completed and data have been reported. Duloxetine's effect in the central nervous system at the level of Onuf's nucleus leads to a stimulation of the external urethral sphincter. Because of this stimulation, reduction in SUI of 50% to 65% has been reported with an approximate 20% cure of SUI symptoms.3 It is also being studied in the treatment of mixed urinary incontinence. Other agents are also being studied with alpha-adrenergic properties. Once duloxetine and other agents are available, they may provide an effective means for addressing SUI pharmacologically.4 As with any nonsurgical treatment modality for urinary incontinence, a multimodal-ity approach, including behavioral modifications and pelvic floor exercises, is likely to be most beneficial for patients.

Herbal Remedies For Acid Reflux

Herbal Remedies For Acid Reflux

Gastroesophageal reflux disease is the medical term for what we know as acid reflux. Acid reflux occurs when the stomach releases its liquid back into the esophagus, causing inflammation and damage to the esophageal lining. The regurgitated acid most often consists of a few compoundsbr acid, bile, and pepsin.

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