Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly.
BACKGROUND
Overactive bladder (OAB) is a widespread problem that has a negative effect on quality of life, particularly among the elderly. Antimuscarinic agents are the only drug class with broad, accepted efficacy in the treatment of OAB. Their clinical usefulness, however, is limited by dose-dependent adverse effects. In the elderly, the most serious of these is central nervous system (CNS) dysfunction, including cognitive impairment.


OBJECTIVE
This article examines currently available antimuscarinic agents for the treatment of OAB in terms of their likelihood of causing CNS dysfunction by crossing the blood-brain barrier (BBB) and blocking muscarinic type 1 (Ml) receptor sites in the brain.


METHODS
Pertinent studies were selected from a comprehensive review of the OAB literature with a focus on muscarinic receptor-associated mechanisms leading to CNS adverse effects and their potential impact on elderly patients. MEDLINE was searched for articles published in the past 10 years, and additional articles were obtained from the reference lists of identified publications. Also searched were abstracts of recent meetings of the International Consultation on Incontinence, International Continence Society, American Urological Association, and European Association of Urology.


RESULTS
Antimuscarinic agents control involuntary detrusor muscle contractions through cholinergic blockade at the muscarinic receptors. The prevalence of OAB is highest in the elderly, the population most likely to be taking multiple anticholinergic medications and most vulnerable to the CNS adverse effects of these agents. Nonselective antimuscarinic agents that bind to the Ml receptor are most likely to cause significant cognitive adverse effects compared with the more selective antimuscarinic agents for the treatment of OAB.


CONCLUSIONS
When considering use of an antimuscarinic agent for the treatment of OAB in elderly patients, prescribers should routinely consider the agent's receptor selectivity and ability to cross the BBB. The medical history should include all current medications that may contribute to the anticholinergic burden and cognitive impairment. Patients and caregivers should be educated to recognize anticholinergic adverse effects.
Kay
Gary G
GG
Georgetown University School of Medicine, Washington, DC, USA. wnimail@aol.com
Granville
Lisa J
LJ
D000368:Aged; D001812:Blood-Brain Barrier / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors; D014549:Urinary Incontinence / Q000188:drug therapy*
D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1