Neuropharmacology of the lower urinary tract in women

Abstract

One of the most common gynecologic complaints is urinary incontinence, which afflicts approximately one third of the female population. In urodynamic units, approximately 80 per cent of women with urinary incontinence have detrusor hyperreflexia as the sole reason for, or as a component of, their incontinence problem. Approximately 80 to 85 per cent of patients with detrusor hyperreflexia have a functional neuromuscular disturbance of their detrusor muscle. One to 2 per cent of the patients seen in our urodynamic unit have detrusor hyperreflexia caused by a neurogenic bladder. As our clinic's population ages, this type of functional neuromuscular disturbance--neurogenic bladder problem--will increase. The neuromuscular control of the lower urinary tract is complex and not fully understood, explaining why we are unable to treat the functional neuromuscular disturbance in some patients effectively and why we may have to try several drugs before finding one that is effective in other patients. Although patients may have the same symptoms and even the same urodynamic findings, the cause of the functional neuromuscular disturbance may be different. One patient may respond to drug A and not to drug B, and another patient with virtually the same symptoms and urodynamic findings responds to drug B and not to drug A. The main neurologic control of the lower urinary tract is through the sacral outflow of somatic and (mainly) parasympathetic nerve fibers. There appears to be an "on-off" control mechanism involving the urethrovesical unit wherein there is parasympathetic inhibition of the detrusor muscle and parasympathetic stimulation of the urethral smooth muscle and stimulation of somatic nerves to the urethral striated muscle at rest. Reverse action occurs when the patient voids. For this reason, cholinergic and anticholinergic drugs exert a powerful influence on the lower urinary tract. Adrenergic control through alpha 1- (and indirectly alpha 2-) and beta 2-receptors (with a preponderance of alpha-receptors in urethral smooth musculature and a preponderance of beta-receptors in the detrusor muscle) appears to modulate and modify parasympathetic action. This explains why adrenergic stimulant and blocker drugs, in most women, do not affect the lower urinary tract as much as parasympathomimetic-lytic drugs. However, adrenergic effect seems to be greater in some women than in others, explaining, for example, why some patients with detrusor hyperreflexia respond to beta 2-stimulatory drugs and not to anticholinergic drugs. Also inter-twined in the neuromuscular control of the lower urinary tract are the roles of prostaglandins and calcium-potassium channel changes.(ABSTRACT TRUNCATED AT 400 WORDS)