The pharmacological treatment of urinary incontinence

Metabolism classified as disturbances of storage or of emptying. Excretion Failure to store urine may lead to various forms of Physiological Animal models incontinence (mainly urge and stress incontinence), and Clinical phase I failure to empty can lead to urinary retention, which Clinical Trials may result in overflow incontinence. Theoretically, a ‘practice’ disturbed storage function can be improved by agents that decrease detrusor activity, increase bladder capacity and/or increase outlet resistance. Many drugs have been Bladder contraction tried, but the results are often disappointing, partly through poor treatment eBcacy and side-eCects [3]. The Normal bladder contraction in humans is mediated development of pharmacological treatment has been mainly through stimulation of muscarinic receptors in slow, and the use of some of the currently prescribed the detrusor muscle. Atropine resistance, i.e. contraction agents is founded more on tradition than on evidence of isolated bladder muscle in response to electrical nerve based on results from controlled clinical trials [4–8]. stimulation after pretreatment with atropine, has been In the present review of drugs in current use for the shown in most animal species, but seems to be of little treatment of urinary incontinence, agents specifically importance in normal human bladder muscle [1]. used to treat urinary tract infections and interstitial However, atropine-resistant (nonadrenergic, noncholcystitis have not been included. The currently used inergic, NANC) contractions have been reported in terminology conforms with the recommendations of the normal human detrusor and may be caused by ATP ICS. Drugs have been evaluated using diCerent types of [9–11]. A significant degree of atropine resistance may evidence (Table 1). Evidence of pharmacological and/or exist in morphologically and/or functionally changed physiological eBcacy means that a drug has been shown bladders, and has been reported to occur in hypertrophic to have desired eCects in relevant preclinical experiments bladders [12,13], interstitial cystitis [14], and in neuroor in healthy volunteers (or in experimental situations genic bladders [15]. The importance of the NANC compoin patients); the present clinical drug recommendations nent to detrusor contraction in vivo, normally, and in are based on evaluations made using a modification of diCerent micturition disorders, remains to be established. the grading of evidence found in the Agency for Health Care Policy and Research (AHCPR) guidelines (Table 2). Drugs used to treat bladder hyperactivity