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)