BERKELEY, CA (UroToday Inc.) - Dr. Gary Kay from the Georgetown University School of Medicine and Dr. Lisa Granville from the Florida State University Medical School reviewed the medical literature to determine the published effects of antimuscarinic therapy, when used for the treatment overactive bladder (OAB), on CNS function. Their review was published in the January 2005 edition of Clinical Therapeutics.

They performed a MEDLINE search for articles regarding the use of antimuscarinic therapy in OAB, with special emphasis on those concerning CNS side effects and their potential impact on the elderly. Articles were also obtained from references and abstracts from recent meetings.

They found that the prevalence of OAB might be higher than initially estimated, and it is more common in women and in the elderly. They noted that acetylcholine is the main neurotransmitter implicated in bladder contractility.

There are 5 subtypes of the muscarinic receptor (M₁-M₅), which are found throughout the body. M₂ is the most common muscarinic receptor in the detrusor with the M₃ receptor thought to contribute most to detrusor contraction. The M₁ receptor is the most common in the cerebral cortex and hippocampus. Blocking of acetylcholine receptors in the cerebral cortex can impair memory and cognitive function. The elderly appear to be more vulnerable to these effects.

Nonselective antimuscarinics that cross the blood brain barrier and block the M₁ receptor are more likely to cause CNS dysfunction. Factors that may influence the ability of a drug to cross the blood barrier include liphophilicity, molecular weight, and polarity.

The use of antimuscarinics, especially in the elderly, needs to be carefully administered, as older persons are more susceptible to adverse effects and are more likely to be on other medications that have anticholinergic activity. These mediations may include over the counter medications that are not reported to their physicians.

The authors conclude that although antimuscarinic agents are efficacious in the treatment of OAB, their use can be limited by their side effects. Agents that can cross the blood brain barrier and antagonize M₁ receptors are more likely to cause cognitive dysfunction and therefore should be used with caution, especially in the elderly. Special care should be taken to gain a careful history from older patients regarding all their active medications, as these may adversely augment the effects of antimuscarinics administered to treat OAB.

Clin Ther 205; 27: 127-138