http://evolve.elsevier.com/Edmunds/NP/
Top 100 drug; 
Key drug. Key drug because was first marketed for urinary incontinence and remains in popular use.
This chapter discusses genitourinary drugs used to treat urinary incontinence (UI), urinary retention, nocturnal enuresis in children, and urinary tract pain/discomfort. The condition discussed is UI, which occurs primarily in women and is not really a disease but a geriatric syndrome. Some of the drugs that are used to treat symptoms of UI have not been approved by the FDA for UI. For example, SNRIs are being studied for use in stress incontinence. The anticholinergics/antispasmodics, which are FDA approved for UI, are discussed in detail in this chapter. α-Adrenergic agonists, α-adrenergic antagonists, tricyclic antidepressants, sympathomimetics, and estrogens also are used, and information about those drugs may be found in the relevant chapters.
Desmopressin is a medication that is used in children with primary nocturnal enuresis. Phenazopyridine is used on a short-term basis for urinary analgesia, usually resulting from an acute UTI.
Therapeutic Overview
Urinary incontinence is the unintentional leakage of urine. Four basic types of established incontinence are known: stress, urge, mixed, and overflow.
Stress incontinence is leakage of urine that results from a reduction in urethral resistance and increased abdominal pressure associated with physical exertion (e.g., exercise, coughing, and sneezing). Causative factors include weak pelvic floor muscles, prostatectomy, and obesity. It is the most common type of incontinence in women younger than 60 years and also occurs in men who have had prostate surgery.
Urge incontinence, or overactive bladder, is caused by a hyperactive detrusor muscle and is associated with an intense urge to void before the bladder is full. Urge incontinence is associated with localized conditions (e.g., infection, atrophic vaginitis, stones, calculi, or other obstruction), neurologic disorders (e.g., CVA, Parkinson’s, Alzheimer’s), and metabolic conditions (e.g., diabetes, dehydration, vitamin B12 deficiency).
Overflow incontinence results from detrusor muscle underactivity and/or bladder outlet obstruction. Leakage of urine is small in volume and continual. Overflow incontinence is found in women with pelvic organ prolapse and in men with benign prostatic hyperplasia.
Urinary incontinence is a complex syndrome with multiple causes; it is not uncommon for individuals to experience more than one type.
Assessment
A focused history with a careful physical examination is essential for determining the cause of incontinence. Transient or reversible causes should be ruled out (Table 34-1). A bladder diary is a helpful diagnostic tool that reveals toileting habits, fluid intake, and leakage episodes. Urinalysis and postvoid residual are essential laboratory tests. Further evaluation by specialists may involve urodynamic and imaging tests.
TABLE 34-1
Common Contributors to Transient Urinary Incontinence
| Cause | Comment |
| Delirium | Mental status changes; treat underlying medical condition. |
| Infection | Irritated detrusor muscle |
| Atrophic urethritis or vaginitis | May present as dysuria, dyspareunia, burning on urination, urgency, and incontinence; requires a pelvic examination. Treat with estrogen. |
| Pharmaceuticals | Side effect of numerous agents (e.g., diuretics, NSAIDs, antihypertensives) |
| Excessive urine output | Peripheral edema, hyperglycemia |
| Restricted mobility | Cognitive decline, physical weakness |
| Stool impaction | Requires rectal examination |
Mechanism of Action
Anticholinergic drugs have many actions. They block muscarinic actions (a subset of the parasympathetic nervous system). Primary associated adverse effects are blurred vision, urinary retention, constipation, dry mouth, tachycardia, and confusion.
Anticholinergic medications used for urge incontinence include those in this chapter, tricyclic antidepressants (TCAs), and dicyclomine (Bentyl) (discussed in Chapter 29).
Anticholinergic drugs inhibit the action of acetylcholine on bladder smooth muscle. This blocks contraction of the bladder and decreases the urodynamic response of detrusor overactivity—the problem in urge incontinence. These actions result in increased bladder capacity, delayed desire to void, and diminished frequency of involuntary bladder contractions. Oxybutynin has both direct antispasmodic effects and anticholinergic effects on smooth muscle. Its direct relaxant effect on smooth muscle is produced by way of phosphodiesterase inhibition. The two newest drugs, darifenacin and solifenacin, have greater affinity for bladder smooth muscle cells than for salivary gland tissue. Darifenacin may have less affinity for the CNS receptors.
Antispasmodics
Flavoxate acts as a direct smooth muscle relaxant. This effect causes relief of bladder spasticity and thereby produces increased bladder capacity. Flavoxate also exhibits local anesthetic and analgesic actions.
Propantheline effectiveness in UI is based on its anticholinergic properties.
Cholinergic Agonists
Bethanechol has an effect that is opposite that of the anticholinergics. It stimulates the parasympathetic nervous system, causing release of acetylcholine at parasympathetic nerve endings. This increases detrusor muscle tone. Increased tone causes a contraction that initiates voiding and bladder emptying, which is useful in some cases of overflow incontinence from urinary retention.
Biologic Toxin
OnabotulinumtoxinA (Botox) blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering nerve terminals, and inhibiting the release of acetylcholine. This toxin is used in urinary incontinence due to detrusor over activity in patients with an inadequate response or intolerance to an anticholinergic medication. Currently it is used primarily by neurologic specialists but is expected to gain approval for more primary care conditions.
Desmopressin (DDAVP)
Desmopressin (1-deamino-8-d-arginine vasopressin; DDAVP) is a synthetic analog of vasopressin that acts as an antidiuretic. Vasopressin is a naturally occurring antidiuretic hormone. Desmopressin is stronger as an antidiuretic than as a vasopressor in smooth muscle. It decreases urine output for approximately 6 hours.
Urinary Tract Analgesia
Phenazopyridine is an azo dye that is excreted in the urine, where it exerts a topical analgesic effect on the urinary tract mucosa. It is useful only for the relief of pain. Phenazopyridine is compatible with antibacterial therapy. It should be used short term (2 days) for treatment of UTI until antibiotic action reduces the pain.
Treatment Principles
Evidence-Based Recommendations
Cardinal Points of Treatment
Treatment for UI depends on the type of incontinence. Treatment may include nonpharmacologic therapies, biofeedback, electrical stimulation, and surgical options.
Stress Incontinence—Off-Label Treatments
