Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin

Clinical Interventions in Aging, Sep 2008

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Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin

Clinical Interventions in Aging Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin Bilal Chughtai 1 Robert Levin 0 Elise De 1 0 Albany College of Pharmacy and Stratton VAMC , Albany, NY , USA 1 Albany Medical College, Division of Urology Overactive bladder (OAB) is a difficult condition to live with and is very costly to the community. OAB affects 16% of the adult population and rises with increasing age. We describe the necessary steps in evaluation and behavioral therapy prior to initiating medical therapy. There are several medications that have been used for the treatment of patients who suffer from OAB. This manuscript discusses the popular agents used for OAB, with a focus on the recent clinical trials on darifenacin. Introduction Overactive bladder (OAB) is a problem characterized by urgency; a sudden desire to urinate that cannot be postponed. According to the International Continence Society (ICS) “urgency, with or without urge incontinence, usually with frequency and nocturia, can be described as the overactive bladder syndrome, urge syndrome, or urgency-frequency syndrome. These terms can be used if there is no proven infection or obvious pathology.” (Wein and Rovner 2002) . It can be associated with frequency and nocturia, and it may occur with urinary incontinence. OAB affects approximately 16% of the adult population in the US and the prevalence increases with age (Wein and Rovner 2002; Beneton and De Parisot 2003) . OAB costs an estimated US$12 billion annually in the US, with US$9 billion incurred in the community (Basra and Kelleber 2007) . The estimate includes both the direct costs of care, protective undergarments, and treatment as well as consequential costs, such as those resulting from urinary tract infections and falls due to urgency to get to the bathroom. There are intangible costs such as pain, suffering, and poor quality of life. The negative impacts on health, the ability to function, and quality of life have been well-documented. The elderly with OAB and subsequent incontinence are more likely to be admitted to nursing homes. Thom et al (1997 ) found at least a 2-fold increase in risk of admission to a nursing facility for patients with incontinence. Urinary incontinence can lead to anxiety, negative self-image, and isolation (Basra and Kelleber 2007) . OAB places individuals at risk for other forms of morbidity. Problems associated with OAB include skin ulceration and urinary tract infections. Nocturia, waking up more than one time per night to void, is common with OAB and is among the most bothersome of lower urinary tract symptoms (Ohelke 2005). In addition to sleep interruption and resulting fatigue, patients with nocturia may be more likely to suffer from falls and fractures, which are associated with high morbidity in elderly patients (33% of patients do not survive beyond 1 year after a hip fracture) (Reeves et al 2006) . The immediate consequences and co-morbidities of OAB can have a negative influence on quality of life, particularly among the elderly. The effect of OAB becomes clearer with the National Overactive Bladder Evaluation (NOBLE) study (Coyne et al 2004) . In this study, OAB was associated with much lower quality-of-life scores, higher scores on depression, and poorer sleep quality when compared to patient controls (Coyne et al 2004) . Although OAB increases with age, it should not be considered a normal consequence of aging by patients or physicians. By using a systematic approach to diagnosing and evaluating OAB followed by instituting appropriate therapy, care providers can improve the health and quality of life of older patients with OAB. Normal bladder physiology Bladder function represents an interplay between the urinary tract and the nervous system. There are two main phases, filling and emptying. The normal bladder stores urine at a low pressure that remains lower than urethral resistance. Micturition is hallmarked by a decrease in urethral resistance and contractions of the detrusor muscle with resultant emptying. There is a complex interplay of neurotransmitters and receptors leading to normal bladder function. Acetylcholine, by acting on muscarinic receptors within the bladder, is the primary neurotransmitter in bladder contraction (Yamanishi et al 2001) . Contraction occurs as a result of increased parasympathetic outflow and relaxation of sympathetic inhibition. There are 5 known muscarinic subtypes (M1 to M5) that are distributed throughout the human body (Table 1). The muscarinic receptor subtypes are located in smooth muscle (bladder), exocrine glands, the nervous system, and the heart. M2 receptors are the predominant subtype within the healthy detrusor muscle; activation of M2 receptors inhibits sympathetically mediated detrusor relaxation. M2 receptors are also located in the heart and central nervous system (CNS). M3 receptors are responsible for detrusor smooth m (...truncated)


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Bilal Chughtai, Robert Levin, Elise De. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin, Clinical Interventions in Aging, 2008, pp. 503-509, DOI: 10.2147/CIA.S3414