Overactive Bladder Disease : Overview of the recent advances in Symptoms, Diagnosis and Treatment

Anandi Krishnan

The ability to hold urine and maintain continence is dependent on normal function of the lower urinary tract, the kidneys, and the nervous system, plus the physical and psychological ability to recognize and appropriately respond to the urge to urinate.

The bladder's ability to fill and store urine requires a functional sphincter (muscle controlling output) and a stable bladder wall muscle (detrusor). The bladder of an infant contracts automatically when a certain volume of urine is reached. As the individual learns to control urination, bladder muscle contraction is prevented by constant inhibition from the cerebral cortex (part of the brain). This allows urination to be delayed until the individual is ready. Undesired bladder muscle contraction may occur as the result of a break in the neurological pathway from the brain to the bladder. It can also occur if the bladder is irritated and the normal neurological impulses to inhibit urination are insufficient to keep the bladder relaxed as it fills. This is called Overactive bladder syndrome or urinary incontinence. This article reviews the recent advances, diagnosis and treatment of this disease state.

 1. Overview:

An overactive bladder is a condition that results from sudden, involuntary contraction of the muscle in the wall of the urinary bladder. Overactive bladder causes a sudden and unstoppable need to urinate (urinary urgency). Overactive bladder is also referred to as urge incontinence and is a form of urinary incontinence (unintentional loss of urine).

Overactive bladder is especially common in older adults. Overactive bladder affects an estimated 1 in 11 adults in the United States. Overactive bladder, however, should not be considered a normal part of aging.

The symptoms of overactive bladder include frequent urination, urgency of urination, and urge incontinence. Overactive bladder may cause significant social, psychological, occupational, domestic, physical, and sexual problems. These symptoms should not be considered a normal part of aging. Involuntary loss of urine is reportedly experienced by upwards of 95% of women in their reproductive and post-menopausal years. This, however, does not mean that this overwhelming majority has urinary incontinence. To qualify as urinary incontinence (UI), the involuntary loss of urine must have a negative impact on the quality of the individual's life, particularly for hygienic and/or social standpoints. As such, the only person who can ultimately determine the presence of UI is the woman herself.

The following sections attempt to unravel the symptoms and the treatment options available to patients suffering from the disease. The review covers the normal functions of the urinary tract, followed by the possible causes that lead to the malfunction of the same. Once the causes are known and understood the treatment options can be availed of.  As can be seen from the recent advances in therapies available new drugs have been approved and so have new dosage forms like patches. On the other hand surgical procedures have also advanced that offer more long term solutions. The patent’s history is one of the most important tools in understanding the underlying causes and choosing the correct treatment option and hence emphasis is laid on the diagnosis too.⁽¹⁾

2. Normal Function of the Urinary Tract:

The urinary tract is made up of the following:

• Kidneys: Two orange-sized organs situated in your back and protected by the rib cage; function to filter blood and produce urine (liquid waste)
• Ureters: Two thin tubes which deliver urine from the kidneys to the bladder
• Bladder: Holding tank for urine
• Urethra: Conduit/valve

The kidneys produce urine and transport it to the bladder through narrow tubes known as ureters. Urine passes from the bladder to the outside of the body through a short tube known as the urethra. Normally, urine flows in only one direction-from the kidneys down to the bladder and out of the body--because valves at the junction of the bladder and the ureters keep urine from flowing back up (or refluxing) to the kidneys. The urethra has two functions: it serves as a passage from the bladder to the outside when the bladder is emptied; also it is a valve that needs to stay closed in order for the bladder to retain urine. ⁽²⁾

Kidney’s

The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. Typically, every human has two kidneys. The kidneys are bean-shaped organs. The kidneys lie in the abdomen, posterior or retroperitoneal to the organs of digestion,

around or just below the ribcage and close to the lumbar spine. The kidneys are surrounded by what is called peri-nephric fat, and situated on the superior pole of each kidney is an adrenal gland. The kidneys receive their blood supply of 1.25 L/min (25% of the cardiac output) from the renal arteries which are fed by the Abdominal aorta. The other attachment of the kidneys are at their functional endpoints the ureters, which lies more medial and runs down to the trigone of the bladder. ⁽³⁾

Functionally the kidney performs a number of tasks. In its role in the urinary system it concentrates urine, plays a crucial role in regulating electrolytes, and maintains acid-base homeostasis. The kidney excretes and re-absorbs electrolytes (e.g. sodium, potassium and calcium) under the influence of local and systemic hormones. pH balance is regulated by the excretion of bound acids and ammonium ions

Humans produce about 1.5 liters of urine over 24 hours, although this amount may vary according to circumstances. Because the rate of filtration at the kidney is proportional to the glomerular filtration rate, which is in turn related to the blood flow through the kidney, changes in body fluid status can affect kidney function. Hormones exogenous and endogenous to the kidney alter the amount of blood flowing through the glomerulus. Some medications interfere directly or indirectly with urine production. Diuretics achieve this by altering the amount of absorbed or excreted electrolytes or osmalites, which causes a diuresis.

Ureter ⁽³⁾

In human anatomy, the ureters are the ducts that carry urine from the kidneys to the urinary bladder, passing anterior to the Psoas major. The ureters are muscular tubes that can propel urine along by the motions of peristalsis. In the adult, the ureters are usually 25-30cm long.

In humans, the ureters enter the bladder through the back, running within the wall of the bladder for a few centimetres. There are no valves in the ureters, backflow being prevented by pressure from the filling of the bladder, as well as the tone of the muscle in the bladder wall.

Urine is stored in the renal pelvis (or pyelum), which overlaps the ureters, which carry urine to the bladder.  Smooth muscular tissue in the walls of the ureters peristaltically force the urine downward. Small amounts of toxic waste are emptied into the bladder from the ureters about every 50 to 60 hours .

Bladder ⁽³⁾

In anatomy, the urinary bladder is a hollow, muscular, and distensible (or elastic) organ that sits on the pelvic floor in mammals and is shaped like a balloon. It is the organ that collects urine excreted by the kidneys prior to disposal by urination. Urine enters the bladder via the ureters and exits via the urethra. In males, the bladder is superior to the prostate, and separated from the rectum by the rectovesical excavation. In females, the bladder is separated from the rectum by the rectouterine excavation, and it is separated from the uterus by the vesicouterine excavation.

The bladder stores urine; it swells into a round shape when it is full and gets smaller when empty. In the absence of bladder disease, it can hold up to 500 mL (17 fl. oz.) of urine comfortably for two to five hours. The epithelial tissue associated with the bladder is called transitional epithelium. It allows the bladder to stretch to accommodate urine without rupturing the tissue. Normally the bladder is sterile.

Sphincters (circular muscles) regulate the flow of urine from the bladder. The bladder itself has a muscular layer (detrusor muscle) that, when contracted, increases pressure on the bladder and creates urinary flow.

Urination is a conscious process, generally initiated by stretch receptors in the bladder wall which signal to the brain that the bladder is full. This is felt as an urge to urinate. When urination is initiated, the sphincter relaxes and the detrusor muscle contracts, producing urinary flow.

Urethra ⁽³⁾

In anatomy, the urethra is a tube which connects the urinary bladder to the outside of the body. The urethra has an excretory function in both genders to pass urine to the outside, and also a reproductive function in the male, as a passage for sperm.

The external urethral sphincter is a smooth muscle that allows voluntary control over urination .

The endpoint of the urinary system is the urethra. Typically the urethra in humans is colonised by commensal bacteria below the external urethral sphincter. The urethra emerges from the end of the penis in males and between the clitoris and vulva in females.

The basic process of normal urination (or "micturition") can be broken down to: ⁽⁴⁾

1. Urine is made in the kidneys
2. Urine is stored in the bladder
3. The sphincter muscles relax
4. The bladder muscle (detrusor) contracts
5. The bladder is emptied through the urethra and urine is removed from the body.

3. Types of urinary incontinence ⁽⁵⁾

Urinary incontinence can be grouped in several distinct categories, although women often have symptoms found in more than one category (i.e., mixed incontinence).

• Stress Incontinence
  Urine leakage occurs with increases in abdominal pressure (hence, mechanical “stress”).
• Urge Incontinence
  Often referred to as “overactive bladder.” Inability to hold urine long enough to reach restroom.
• Mixed Incontinence
  When two or more causes contribute to urinary incontinence. Often refers to the presence of both stress and urge incontinence.
• Overflow Incontinence
  Leakage or “spill-over” of urine when the quantity of urine exceeds the bladder’s capacity to hold it.
• Functional Incontinence
  Leakage (usually resulting from one or more causes) due to factors impairing reaching the restroom in time because of physical conditions (e.g., arthritis)

3.a .Definition of Stress Incontinence:

Stress urinary incontinence (SUI) is loss of urine that occurs simultaneously with (at the same time as) physical activities that increase abdominal pressure (for instance: sneezing, coughing, boisterous laughing, and straining when performing exercises like abdominal "crunches," or lifting objects). Many of the above-described activities lead to increased pressure within the abdominal cavity. This, in turn, increases the pressure within the bladder, which behaves like a balloon filled with liquid. The rise in bladder pressure has a tendency to force the urethra open and urine loss ensues. The amount of urine loss associated with SUI is usually small, ranging from mild seepage to drops to a large squirt. ⁽⁶⁾

3.b. Predisposing Factors to SUI:

• Gender :male versus female
• Genetic: inherited component of connective tissue, connective (supportive tissue and muscle)
• Vaginal birth trauma : for mothers
• Previous pelvic/vaginal surgery
• Radiation therapy
• Menopausal status
• Chronic conditions: respiratory ailments, obesity, constipation, occupation/lifestyle (strenuous lifting)

In general, the causes of SUI are many. Listed above are factors that lead to SUI.  ⁽⁷⁾

3.c. Causes of urinary incontinence

• Prostate problems and male urinary incontinence: Difficulty and unpredictability in passing urine is a common feature of prostate abnormalities. It can also be a side effect of total prostatectomy (surgical removal of the prostate).
• Head injury and spinal cord injury: Damage to the head or spinal cord due to disease or trauma can result in loss of bladder control as messages passing from the brain to the bladder are interrupted or lost. The loss can be either on a temporary or permanent basis.
• Diseases that can cause male urinary incontinence: Neurological diseases, both cancerous and benign, degenerative diseases such as Parkinson's disease and Multiple Sclerosis are just some of reasons for loss of urination control.
• Infection: In urinary tract infection incontinence may be the only symptom of what can be a serious infection. Treatment is with antibiotics.
• The aging process: Organic brain damage that occurs as we get older can affect both the way in which we function and think. Confusion in time and space can result in incontinence. Body parts are also prone to let us down as we age, just normal wear and tear takes its toll.
• Toxins: Too much alcohol is one is one of the commoner causes of temporary or one off types of incontinence. Any toxins that effect human functioning can effect our ability to pass urine.
• Medications: Common to this type of incontinence are the drugs that have a sedating effect especially if given in high doses.
• Mental State : Emotional distress and illness can lead to urinary incontinence.

4. Symptoms of Urinary Incontinence

Urge incontinence involves a strong, sudden need to urinate immediately followed by a bladder contraction, resulting in an involuntary loss of urine. The ability to hold urine and maintain continence is dependent on normal function of the lower urinary tract, the kidneys, and the nervous system. The bladder's ability to fill and store urine requires a functional sphincter and a stable bladder wall muscle (detrusor).

Two phases are involved in the process of urination: the filling and storage phase and the emptying Urge incontinence is basically a storage problem in which the bladder muscle contracts inappropriately. Often these contractions occur regardless of the amount of urine that is in the bladder. Urge incontinence may result from neurological injuries (such as spinal cord injury or stroke), neurological diseases (such as multiple sclerosis), infection, bladder cancer, bladder stones, bladder inflammation, or bladder outlet obstruction. The majority of cases are classified as idiopathic.

Persons suffering form OAB lose control of their bladder function after feeling a sudden urge to urinate. The symptoms of OAB are: ⁽⁸⁾

-Urinary Frequency: Persons suffering form OAB void 13 or more times during the day and 2 or more times during the night

- Urinary Urgency: OAB often causes a strong need to urinate without warning.

-Urinary Incontinence: The sudden strong urge to void may be followed by a leakage or release of urine that the person cannot prevent.

Urinary incontinence is often caused by specific changes in body function due to related or unrelated diseases and/or usage of medications that affect function of the urinary tract (e.g., diuretics or "water pills," anti-hypertensives or “blood pressure pills”). More often than not, UI is more of an annoyance than a sign of a life-threatening condition. Despite the high prevalence, most people with UI are reluctant to seek help. They might be embarrassed to acknowledge that they have a problem, even to themselves. Or, they might have broached the issue with family members, acquaintances, and/or friends who were discouraging or suggested that no truly useful remedies exist. Thus, many sufferers resort to dealing with the progressively worsening leakage by using the many absorbent products available, including pads and/or diapers. This resignation often results in emotional and psychological vulnerability, including depression and social isolation^{. (9)}

4.a .Medications that Can Cause UI ⁽¹⁰⁾

Table: 1

In adults with overactive bladder syndrome, anticholinergic drugs improve symptoms but are associated with increased dry mouth.

4.b.Patient History

As an increasing number of treatment options for urologic disorders become available, patients with these conditions are more often able to be managed in the primary care setting. Primary care physicians, therefore, must become more knowledgeable of the proper urologic terminology and the screening tools that have traditionally been used by urologists. To that end, this article reviews the terminology associated with lower urinary tract symptoms and describes the evaluation and treatment of patients presenting with these symptoms. ⁽¹¹⁾

The patient history should focus on important risk factors, including:

Table: 2

There should be an update of the medical history and a medication review. A focused genitourinary history should take into account:

Table: 3

5. Treatment Options: ⁽¹²⁾

5.a:Behavioral Therapy

Behavioral therapy has been demonstrated to alter a patient’s voiding habits due to overactive bladder. While behavioral therapy and pharmacological therapy each demonstrate statistically significant improvement in the symptoms of overactive bladder, the combination of the two is superior to any one therapy. Behavior modification may include education of the patient regarding modification of fluid intake and lower urinary tract function.

5.b: Catheterization

Patients may be treated temporarily or on a permanent basis with either a urethral catheter or a suprapubic tube. This form of treatment is less favored, due to the associated risks of chronic infection, calculus formation, and, if used for long-term treatment, bladder malignancy.

5.c: Bladder Augmentation

Patients whose bladders have decreased in capacity secondary to injury, or have significant loss of compliance, may benefit from augmentation cystoplasty. In this surgical procedure, either small bowel or colon tissue is added to the bladder to increase its capacity and compliance.

5.d: Percutaneous Tibial Nerve Stimulation

Percutaneous tibial nerve stimulation (PTNS) therapy must be continuous to maintain control of refractory overactive bladder syndrome, according to the findings of a small clinical trial conducted by Dutch researchers. ⁽¹³⁾

There are no data on the effects of interrupting maintenance treatment in patients with refractory overactive bladder symptoms or whether PTNS is still effective after periods of treatment interruption, Dr. John P.F.A. Heesakkers of the University Medical Center Nijmegen and colleagues note in the March issue of BJU International.

Continuous therapy is necessary in patients with OAB treated successfully by PTNS. The efficacy of PTNS can be reproduced in patients formerly treated successfully . ⁽¹⁴⁾

5.e: Sacral Nerve Stimulation:

InterStim® therapy is a reversible treatment for people with urge incontinence caused by overactive bladder who do not respond to behavioral treatments or medication. InterStim is an implanted neurostimulation system that sends mild electrical pulses to the sacral nerve, the nerve near the tailbone that influences bladder control muscles. Stimulation of this nerve may relieve the symptoms related to urge incontinence.

Prior to implantation, the effectiveness of the therapy is tested on an outpatient basis with an external InterStim device. For a period of 3 to 5 days, the patient records voiding patterns that occur with stimulation. The record is compared to recorded voiding patterns without stimulation. The comparison demonstrates whether the device effectively reduces symptoms. If the test is successful, the patient may choose to have the device implanted.

The procedure requires general anesthesia. A lead (a special wire with electrical contacts) is placed near the sacral nerve and is passed under the skin to a neurostimulator, which is about the size of a stopwatch. The neurostimulator is placed under the skin in the upper buttock.

Adjustments can be made at the doctor's office with a programming device that sends a radio signal through the skin to the neurostimulator. Another programming device is given to the patient to further adjust the level of stimulation, if necessary. The system can be turned off at any time.

Possible adverse effects include the following: ⁽¹⁴⁾

• Change in bowel function
• Infection
• Lead movement
• Pain at implant sites
• Unpleasant stimulation or sensation

5.f: Medication Options:

5.f.i: Transdermal Patch of Oxybutynin. ⁽¹⁵⁾

Watson Pharma introduced the first ever Transdermal therapy in the treatment of OAB.  The product is a transdermal patch containing Oxybutynin HCl and is approved in US under the brand name of Oxytrol and in Europe under the brand name of Kentera.

OXYTROL is the first and only transdermal system (skin patch) to treat OAB. OXYTROL's transdermal delivery system delivers oxybutynin, a medication widely accepted and prescribed in oral formulations for over the past 25 years, into the bloodstream. Since the drug is delivered into the bloodstream through the skin, the initial metabolism process in the liver and the stomach as seen with oral therapies is avoided. This helps alleviate side effects.

OXYTROL is a thin, flexible and clear patch that is applied to the abdomen, hip or buttock twice weekly and provides continuous and consistent delivery of oxybutynin over a three to four day interval. OXYTROL can be worn during normal activities, including bathing, swimming, showering, or exercising. OXYTROL offers OAB patients continuous effective bladder control with some of the side effects, such as dry mouth and constipation encountered with and oral formulation. In most patients these side effects however are not a troublesome.
OXYTROL is a transdermal system delivering 3.9 mg oxybutynin per 24 hours and is proposed for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and/or frequency. The proposed posology is one patch applied twice weekly (every 3 to 4 days). Studies have not been performed in children, therefore oxybutynin 3.9 mg per 24 hours transdermal patch is not recommended for use in children. The development of OXYTROL was based on the rationale that a patch could ease the compliance, and that the dose delivery by the transdermal route      would reduce undesirable side effects of the oral administration. It is a thin flexible patch with rounded corners and consists of three layers: a non-removable polyester protective film (backing layer), the adhesive matrix containing the active substance and a polyester removable protective layer (release liner). The backing film is made of polyethylene terephthalate (PET) / ethylene-vinyl acetate (EVA). The matrix adhesive layer is laminated on the PET side. The matrix layer contains Oxybutynin, glycerol triacetate as penetration enhancer and an acrylic pressure sensitive adhesive. The release liner consists of silicone-coated PET. Each transdermal patch is packed in a heat sealed sachet.  Oxytrol is a matrix type transdermal patch. In this type of patch the active         substance is dissolved directly in the adhesive,      which is kept in contact with the intact skin. The matrix formulation is designed specifically to present a sufficiently high concentration of the active substance to the stratum corneum, which is the primary absorption controlling factor.

5.f.ii: Orally administered drugs:

1. Darifenacin: ⁽¹⁶⁾

Enablex, a once-daily medication of darifenacin, is available as extended-release tablets (7.5mg and 15mg) for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency and frequency.  Enablex works by blocking the M3 receptor, which is primarily responsible for bladder muscle contraction. It is a potent muscarinic receptor antagonist that helps reduce incontinence episodes, increases the amount of urine the bladder can hold, reduces the frequency of urination episodes, and decreases the pressure or urgency associated with the urge to urinate.

The FDA approval of Enablex was based on efficacy data from four pivotal studies and safety data from studies in which more than 7,000 patients with a mean age of 58 years were treated with varying doses of Enablex.  In these studies, patients taking Enablex experienced decreased frequency of incontinence and urination episodes, increased bladder capacity, and decreased feelings of urgency.  Enablex was shown to reduce weekly incontinence episodes by up to 83 percent and results were seen within two weeks of beginning treatment. Efficacy was sustained throughout the 12-week treatment period, and long-term safety was studied for up to one year.  

2. Solifenacin: ⁽¹⁷⁾

Vesicare oral tablets contain solifenacin, a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of urinary bladder smooth muscle. Antagonism at these receptors has been shown to reduce tonus (elastic tension) of the urinary bladder and slow parasympathetic contractions.

It is specifically indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Vesicare is administered via an oral tablet of 5 mg once daily, with a possible increase in dosage, to 10 mg once daily, in subjects experiencing good tollerance. Dosing should occur with liquids, and tablets should not be crushed or broken prior to administration.

FDA approval of Vesicare was based upon four 12-week multi-center, double-blind, placebo-controlled, parallel-group studies. The studies enrolled a total of 3027 subjects with at least a 3 month history of increased urinary frequency, urinary urgency, and/or urge or mixed (predominantly urge) incontinence. Subjects in two of the trials received either 5 or 10 mg Vesicare or placebo once daily, and subjects in the other two received exclusively 10 mg or placebo once daily. All patients completing the 12-week studies were eligible to enter an open label long-term extension. All four trials found that Vesicare offered significantly better efficacy than placebo in both primary (mean change from baseline to 12 weeks in number of micturitions/24 hours) and secondary (including mean change from baseline to 12 weeks in number of incontinence episodes/24 hours, and mean volume voided per micturition) endpoints.

Solifenacin acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, urge severity and improving retention, facilitating increased volume per void.

3. Trospium Chloride ⁽¹⁸⁾

TROSPIUM (Sanctura™) tablets help to control an overactive bladder, a chronic condition that can be improved with medication. Trospium may reduce the frequency of bathroom visits and may help to control wetting accidents.

Sanctura is used for the treatment of overactive bladder that causes the following symptoms:

·sudden need to urinate right away (urgency)

·unwanted urine leakage after urgency (urge urinary incontinence)

·having to urinate  often (urinary frequency)

Recently approved for use in the United States , this agent has a reduced probability of crossing a normal blood-brain barrier. With a low biological availability of 5% and a half-life of 12 to 18 hours, the dosage is 20 mg/d bid, and the drug must be taken 1 hour before meals. This agent is not highly metabolized and, for the most part, is renally excreted in an unchanged form; however, for the same pharmacokinetic reasons that this drug does not cross a normal blood-brain barrier, it also will not have a desired direct effect on bladder muscle or urothelium from its mere presence in the urine.

In a randomized, placebo-controlled trial, trospium, 20 mg/d bid, significantly reduced the number of daily urge incontinence episodes by 60% compared with 44% for placebo.⁸ It significantly increased average volume per void and decreased average urge severity and daytime voiding frequency. These findings paralleled an improved patient-perceived quality

4. Tolterodrine tartrate ⁽¹⁹⁾

Tolterodine belongs to a class of drugs called cholinergic (acetyl-choline) receptor blockers. It is used to treat disorders of the urinary bladder that affect urination. The FDA approved tolterodine in 1998. An extended release form of tolterodine, (Detrol LA) was approved by the FDA in 2001

Tolterodine usually is taken twice daily. The starting dose is 2mg twice daily. With the long-acting tolterodine, the starting dose is 4mg daily, and may be reduced to 2mg if the larger dose is not tolerated. The dose may need to be reduced for patients who have impaired function of the liver or kidneys.

Tolterodine acts on M2 and M3 subtypes of muscarinic receptors whereas most antimuscarinic treatments for overactive bladder only act on M3 receptors making them more selective. Tolterodine, although it acts on two types of receptors, has fewer side effects than other antimuscarinics eg. oxybutynin (which is selective for M3 only) as tolterodine targets the bladder more than other areas of the body. This means that less drug needs to be given daily (due to efficient targeting of the bladder) and so there are fewer side effects eg. hyposalivation, constipation, decreased gastric motility.

5. Oxybutynin Chloride ⁽²⁰⁾

Oxybutynin chloride exerts a direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. Oxybutynin chloride exhibits only one fifth of the anticholinergic activity of atropine on the rabbit detrusor muscle, but four to ten times the antispasmodic activity. No blocking effects occur at skeletal neuromuscular junctions or autonomic ganglia (antinicotinic effects).

Oxybutynin chloride relaxes bladder smooth muscle. In patients with conditions characterized by involuntary bladder contractions, cystometric studies have demonstrated that oxybutynin chloride increases bladder (vesical) capacity, diminishes the frequency of uninhibited contractions of the detrusor muscle, and delays the initial desire to void. Oxybutynin chloride thus decreases urgency and the frequency of both incontinent episodes and voluntary urination.

Antimuscarinic activity resides predominately in the R-isomer. A metabolite, desethyloxybutynin, has pharmacological activity similar to that of oxybutynin in in vitro studies.

DITROPAN XL is indicated to help control the symptoms of overactive bladder—urinating 8 or more times a day, sudden urges to urinate, and leaks.

Once-a-day DITROPAN XL is clinically proven to help 24 hours a day. It has been shown to reduce sudden urges, frequent bathroom trips and wetting incidents, all day and all night. In a clinical study, patients who used DITROPAN XL experienced up to a 90% reduction in wetting incidents per week versus patients taking a placebo who experienced a 51% reduction. These are patients known to be responsive to this type of medication.

6. Conclusion

Worldwide, the number of people 65 or older is increasing faster than ever before. Most of this increase is occurring in developed countries. In the United States the percentage of people 65 or older increased from 4 percent in 1900 to about 13 percent in the late 1990s. In 1900, only about 3 million of the nation's citizens had reached 65. By 1998, the number of senior citizens had increased to about 34 million. Population experts estimate that more than 50 million Americans--about 17 percent of the population--will be 65 or older in 2020.

The prevalence of OAB appears to be on the rise considering the demographics of the world’s population.  Older people have limited regenerative abilities and are more prone to disease, syndromes, and sickness than other adults. The predisposing factors and symptoms are well recognised based on the extensive research conducted by the various organisations.  The pharmaceutical industry has concentrated on the disease state not just from the view point of discovering new drugs but also by utilizing the known drugs and inventing newer therapies that help the patients lead as normal lives as possible.  A thorough understanding of the symptoms and causes have enabled the invention of novel dosage forms such as patches and extended release dosage forms that do help the older generation lead dignified lives.

In the years to come better disease management possibilities need to be explored with the growing need for options that are able to improve the life style of the elderly population in their sunset years.

References:

About Authors:

Anandi Krishnan
Ph.D. Student of Prof. (Dr.) R.S. Gaud, School of Pharmacy and Technology Management, NIMIMS
Mrs. Anandi has 14 years work experience in some of the leading Indian pharmaceutical companies. She has a rich experience that encompasses activities from lab set up to USFDA approvals. Started her career with hands on bench scale formulation design and now successfully design patented platform technologies. Anandi has 14 patent applications at various stages to her credit. She is currently pursuing her doctoral programme with NIMIMS under the guidance of Prof. (Dr.) R S Gaud.
Author for correspondence
Address: R. H.-I, F-5, Sector-8, Vashi, Navi Mumbai 400 703
Telephone: +91-22-27820482, +91-22-27825670
Email: anandik@rediffmail.com;

Prof. Dr. R. S. Gaud
Prof R.S.Gaud, M.Pharm., Ph.D, FIPA
Dean,(Faculty of Pharm Sciences)
SVKM’s NMIMS University
[“A”grade Accredited by NAAC]
V L Mehta Marg, Vile Parle(W), Mumbai 400056
Professor R.S.Gaud, is Dean, Faculty of Pharmaceutical Management, NMIMS Deemed University, Mumbai since 28th Feb.2006 and had long 29 years professional experience out of which 24 years teaching and research experience at Holkar College, Shri S.G.S. Institute of Science and Technology, Indore and at Mumbai. He has 5 years national experience as an Adviser-I/II at AICTE, New Delhi and about nine month experience as a principal of Prin.K.M.Kundnani College of Pharmacy(Govt aided). Since last two years he is working as a Dean, SVKM’s NMIMS University, Mumbai .
Prof Gaud has guided Seven Ph.Ds successfully and six candidates are registered under his supervision. He has presented 76 research papers at national and international conferences and published many papers and articles in journals of repute. He has authored 10 pharmacy books.