Symptoms of painless urinary urgency and frequency are often accompanied by nocturia and urge urinary incontinence (UUI) (Box A Case of Urinary Urgency and Incontinence). Standardized terms to describe these symptoms include overactive bladder dry when urgency and frequency occur without UUI, and overactive bladder wet when UUI occurs. Because the dome, or body of the bladder, is comprised of an elastic smooth muscle called the detrusor muscle, symptoms associated with involuntary detrusor contraction during objective bladder testing (urodynamically) are referred to as detru-sor overactivity.
Box A Case of Urinary Urgency and Incontinence
MK is a 48-year-old woman with two children. She began having irregular menses over 2 years, along with a gradual onset of increasing problems with urinary incontinence related to urgency. She has a lifelong history of frequent voiding (10–14 voids per day), including enuresis to age 8, and nocturia, typically two to three times per night. Until recently, she was able to manage her urgency by voiding frequently and modifying fluid intake. However, MK has begun experiencing increasingly intense, painless urgency. Several times a week, she leaks urine before she can reach a restroom. She now wears pads continuously. Her life is beginning to center around finding a bathroom everywhere she goes. MK rarely loses any urine with cough, sneeze, or exercise, is a nonsmoker, has not had urinary tract infections (UTIs), and has never noticed hematuria. She has no neurologic symptoms, such as incoordination, numbness, or tremor. She currently takes no prescription or over-the-counter medications. She has no other pelvic floor problems such as dyspareunia, constipation, or fecal incontinence.
MK’s physical exam is normal. Her body-mass index is 24. On pelvic exam she displays moderate pelvic floor muscle strength and no evidence of prolapse. She has minimal genital atrophy. Her urinalysis and culture are negative.
Primary Care Treatment
As an initial treatment, MK was instructed to try eliminating, or decreasing, bladder irritants such as caffeine, spices, artificial sweeteners, and alcohol. MK also used other behavioral strategies, including regular, measured voiding, monitoring her fluid intake, strengthening her pelvic muscles, and using her muscles to control urgency. Though her symptoms improved, she continued to have unpredictable urine loss. Her bladder is still the focus of her daily life.
MK wants to try a medication. The review of her history indicates that she does not have contraindications to use of antimuscarinic agents or potential for drug–drug interactions. Her prescription drug plan has a tiered formulary of preferred medications. She is prescribed an inexpensive antimuscarinic agent in an extended-release formulation at the lowest recommended dose. Because MK says her biggest problem currently is restriction of her social activities due to daytime urgency, she starts taking the medication immediately on arising, anticipating peak effect in 4–6 hours.
If MK does not notice satisfactory relief within the next 2 weeks of regular use, her symptoms should guide variations in her medication use. She might choose to increase the dose within the recommended range, change agents, or add a second low-dose agent at bedtime if nighttime voiding problems increase. She was encouraged to continue using the behavioral strategies she has learned.
If medication variations do not produce satisfactory symptom relief within the next 2 months, she will be referred to a urogynecology or urology practice for further evaluation.
The incidence of overactive bladder is obscured by the subjective nature of the symptoms, underreporting, and variations in definition. The National Overactive Bladder Evaluation included phone interviews with 5204 adults in the United States and determined that overactive bladder increased with age from approximately 5% in those < age 25 years to approximately 30% in those > age 75 years. Both men and women reported similar prevalence of overactive bladder, but women were more likely to experience overactive bladder wet, in part because of anatomically shorter urethras. In addition, continence may be impaired by external factors, including connective tissue or neuromuscular injury experienced during childbirth. In the United States, the direct and indirect costs of overactive bladder have been estimated to exceed $18 billion yearly.
Pathophysiology of Overactive Bladder
Muscle and nerve changes can both play a role in the development of overactive bladder and are potential targets for pharmacologic treatment. Smooth muscle changes related to overactive bladder include spontaneous or discoordinated muscle fiber f ring or an increased or decreased response to normal stimuli. Skeletal muscle weakness can contribute to overactive bladder wet due to loss of voluntary urethral support. Voluntary control can also be undermined by central or somatic nervous system degeneration. For example, future therapies may have a dual purpose in maintaining the cerebral cortex, where degeneration simultaneously affects both urinary control centers and aged-related dementia.
The main target of pharmacologic treatment for over-active bladder is the autonomic neurons that control the coordinated homeostatic functioning of the bladder and urethra. Figure Autonomic nervous system of the bladder displays the autonomic pathways relating to bladder function. Sympathetic motor pathways are predominantly mediated by the neurotransmitter norepinephrine. Low-level release of norepinephrine stimulates beta-adrenergic receptors in smooth muscle of the bladder dome (detrusor), resulting in relaxation, while higher concentrations of norepinephrine stimulate alpha-adrenergic receptors in the urethral walls and bladder base (trigone), resulting in contraction of their smooth muscle. T is synergistic activity promotes urine storage by allowing urine to fill the bladder without increasing pressure on the bladder walls.
Parasympathetic innervation is mediated by at least two neurotransmitters, acetylcholine and noncholinergic nonadrenergic transmitters. Stimulation of muscarinic cholinergic receptors in the bladder dome results in detrusor contraction and urine elimination. There are five types of muscarinic acetylcholine receptors in the human body (M1–M5). Of these five, M2 and M3 receptors predominate in the detrusor, with M3 more directly affecting detrusor contraction. The primary mechanism of action of first-line medications for overactive bladder is control of detrusor instability via inhibition of cholinergic activity.