November 2006;22(2)-PharmaNote.pub

Volume 22, Issue 2 November 2006 1 Overactive bladder (OAB) is a chronic and potentially debilitating condition that affects approximately 16% of the adult population in the U.S. and Europe. According to the National Overactive Bladder Evaluation (NOBLE) program, an estimated 34 million Americans have symptoms of OAB. Overactive bladder is a common condition in both men and women of all ages, but is more prevalent in the elderly population. In 2000, the combined direct and indirect costs associated with OAB were $12.6 billion, which is similar to the economic impact of asthma and osteoporosis. However, due to low physician consultation rates, estimated costs are likely to be grossly underestimated, and the economic burden of OAB may be much larger. As the world’s population continues to grow and age, the economic impact of this condition will continue to expand. By the year 2020, population growth estimations predict that there will be 44% more people over the age of 65, and that costs will escalate in line with this aging population. The International Continence Society has defined OAB as urinary urgency with or without urge incontinence, usually with frequency and nocturia without proven infection or other pathology. These symptoms are believed to be caused by inappropriate contractions of the detrusor muscle during the filling phase of the micturition cycle. Muscarinic receptors play important roles in cholinergic mediated functions throughout the body, including stimulating contractions of urinary bladder smooth muscle. Blockade of muscarinic receptors on the detrusor muscle with anticholinergic medications has become the most common and effective pharmacologic treatment for patients suffering from OAB. Anticholinergic therapy results in fewer and less forceful inappropriate bladder contractions, which allows for enhanced bladder capacity. Blockade of other muscarinic receptors located in the GI, CNS, myocardium, salivary glands, and eye, however, are associated with many adverse effects that may affect adherence. For thirty years, immediate release oxybutynin, a nonselective muscarinic antagonist, has been the “gold standard” for treatment of OAB, but its use has been limited by side effects. More selective agents, such as darifenacin, are being marketed for OAB. Newer agents offer a cleaner side effect profile compared to oxybutynin without sacrificing therapeutic efficacy. Darifenacin (dâr ǐ fĕn' ă sǐn)(Enablex®[ĕ nā' blĕks]) is a new M3 selective receptor antagonist approved by the FDA for OAB and its symptoms in December 2004 and is marketed by Novartis. In contrast to oxybutynin, darifenacin demonstrates a higher degree of selectivity for M3 receptors than M1, Volume 22, Issue 2 November 2006 ®