Pharmacological management of incontinence.

Many patients with incontinence do not need surgery - for these patients symptoms can often be considerably improved by conservative measures, including drugs. Several different pharmacological actions are potentially useful depending on the underlying cause of the incontinence: a) Detrusor instability (DI) responds to drugs reducing bladder contractility: Anticholinergic agents, e.g. oxybutynin and tolterodine, act at postganglionic parasympathetic cholinergic receptor sites on the detrusor muscle, reducing the strength of the detrusor contraction. Tricyclic antidepressants, e.g. imipramine, have anticholinergic effects, block presynaptic uptake of amine neurotransmitters and directly inhibit detrusor muscle. Alpha-adrenergic antagonists may have a role to play by dual actions on bladder overactivity (due to altered receptor function) and by reducing outlet resistance. b) Genuine stress incontinence (GSI) may be treated using alpha-adrenergic agonists, e.g. phenylpropanolamine, to increase outlet resistance by stimulating smooth muscle of the urethra and bladder neck. c) In nocturnal enuresis reduction of nocturnal urine output with the anti-diuretic hormone (ADH) analogue DDAVP (1-deamino, 8-arginine vasopressin) is beneficial. d) Bladder emptying may be facilitated in patients with retention and 'overflow' incontinence by alpha-adrenergic antagonists, which reduce outlet resistance, and perhaps by parasympathomimetics, e.g. bethanecol. e) In postmenopausal women, systemic oestrogen replacement reduces filling symptoms including urge incontinence. Evidence for oestrogen replacement alone in GSI is lacking, but combination with alpha-agonists is beneficial in milder GSI. For the future, tolterodine and other new anticholinergics offer the hope of treatment for DI with fewer of the side effects that limit the use of established drugs. Better understanding of the pathophysiology of DI may provide new targets for drug therapy, such as hyperpolarisation of detrusor muscle membrane. Alpha-agonists may find a greater role in the future, as may ADH analogues for noctural symptoms.