Diagnosis and treatment of overactive bladder

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Overactive bladder (overactive bladder OAB) is a common disease in September 2001, the International Continence Society (ICS) which is defin


Overactive bladder (overactive bladder OAB) is a common disease in September 2001, the International Continence Society (ICS) which is defined as a new term, which is characterized by urgency, with or without incontinence, usually with frequency and nocturia [1]. The Chinese Medical Association Branch Department of Urology continence group "overactive bladder clinical guideline" is defined as: OAB is a frequent micturition, urgency and urge incontinence etc. the symptoms, these symptoms can appear alone, can also be any form of composite [2]. Urodynamic examination when some patients in the urinary bladder, bladder detrusor contraction caused by involuntary, high intravesical pressure, detrusor overactivity (detrusor overactivity [3]). The two have both connection and difference.

First, epidemiology

OAB is not a local disease in a specific cultural context. Because OAB is often confused with urinary incontinence, the diagnostic criteria used by different doctors are different, so the incidence or prevalence of [4] is very different. But some people think that the popularity of different countries is roughly the same. In France, Italy, Sweden, the United Kingdom, Spain, the incidence rate was 11%~22%. An estimated 17% of adults in the United States and Europe suffer from the disease. The number of people around the world is about 50 million to 100 million [3][5]. The number of females was slightly higher than that of males, and the incidence increased with age. [6]. At present there is no epidemiological data of this disease, but the survey of Peking University Department of Urology Institute in Beijing area shows that: 50 men over the age of incontinence occurred in 16.4% of 18 women over the age of mixed urinary incontinence and urge incontinence. The incidence rate was 40.4%[7]. The correct treatment of OAB will reduce the incidence of urinary incontinence and improve the quality of life of patients.

Two, etiology

The symptoms of OAB is because the bladder filling process of detrusor involuntary contraction induced by [8], its etiology is still not clear, it may be due to inhibition of central efferent pathway, peripheral sensory afferent pathway or muscle damage caused by the bladder itself, these can be either alone or in combination with [9].

Central pontine micturition reflex nerve to inhibit the disease often leads to inadequate suppression, and the incidence of detrusor hyperreflexia is 75%~100%, is generally not accompanied by detrusor external sphincter dyssynergia; and pontine and sacral cord between lesions, manifested as detrusor hyperreflexia and detrusor external sphincter dyssynergia [10]. Diabetic peripheral neuropathy caused by sacral cord, there have been reports of detrusor hyperreflexia, multifocal lesions may be related to the relevant [10]. In addition, bladder outlet obstruction caused by unstable bladder occurrence rate is as high as 50%~80%, it is through the bladder wall nerve and muscle change, resulting in increase of detrusor excitability, OAB symptoms.

Three, diagnosis

Using ICS or the definition of continence group, OAB is an empirical diagnosis. It is important to ask a history carefully, including typical symptoms and symptoms. Medical history should cover the history of diagnosis and treatment of diseases related to internal medicine, neurology and genitourinary system. At the same time, it is necessary to make a detailed diary of urination.

Physical examination focuses on the abdomen, pelvis, rectum, nervous system. Urine routine examination is necessary, if the positive need further bacteriological and cytological examination. For the determination of residual urine after voiding, urodynamic examination, etc., according to the patient's choice of application. The diagnosis of overactive bladder can be made after the infection, stones and bladder cancer were excluded.

Four, treatment

Once the diagnosis of patients may have OAB, it is necessary to seriously consider the need for treatment, to understand whether the patient has treatment requirements. So the initial treatment should focus on how much the patient's symptoms affect their quality of life.

Because OAB is a symptom diagnosis, so its treatment can only relieve symptoms rather than for the cause, it is impossible to achieve cure. Current treatments include behavioral modification, drug therapy, neuromodulation, and surgical procedures.

(I) conduct correction

Behavioral correction includes patient health education, timely or delayed voiding, bladder training, pelvic floor exercises, etc.. Tell the patient about the "working principle" of the lower urinary tract, so that the patient clearly knows the coping strategies. Voiding diary can not only enhance the patient's self awareness, but also allows doctors to clearly understand the incidence and severity of symptoms when, according to church with simple diet control knowledge, develop a method of timing or preventive and urinary bladder training. In addition, pelvic floor exercise can enhance the strength of the pelvic floor muscles, have a strong inhibition of involuntary detrusor contraction can be. In recent years, biofeedback therapy has been used in the treatment of pelvic floor muscles, and it is difficult to achieve the effect of other treatments. Stimulation therapy for the treatment of pelvic OAB biofeedback electrical applications such as Canada Laborie company Li Sha Lin, Luoding and Todd found that its effect is quite [11], but there are still many disputes on the effects of the method. It is reported that corrective action can improve the incidence rate of urinary incontinence by more than 50% [12], and the combination therapy can reduce the urinary incontinence by 84.3%[13].

(two) drug treatment

The goal of drug therapy is to increase bladder capacity and prolong the alarm time, eliminate the urgency without disturbing the emptying of the bladder. At present there are drugs for the treatment of OAB (1) for the parasympathetic nerve, acting on detrusor on cholinergic receptors, including cholinesterase inhibitors. Such as atropine, probanthine, Austria in Bunin, Luoding, Tottenham darifenacin, trospium chloride, Soliferacin etc.. (2) effect on bladder sensory afferent nerve: drug capsaicin and resiniferatoxin (Resiniferatoxin RTX). (3) inhibition of the release of acetylcholine in parasympathetic cholinergic nerve: botulinum toxin A. (4) drugs acting on the central nervous system.

The study found that the body is widely distributed in different subtypes of muscarinic receptor (M receptor). Play different physiological roles in different parts. Such as M1 receptors in the brain and salivary glands are associated with understanding and the production of saliva [14][15]. M2 receptors in the cardiovascular system play an important role in the regulation of heart rate and cardiac output [16]. [17][18] M5 receptor and contraction of the ciliary muscle of the eye. In bladder tissue mainly containing M2 and M3 receptor, M2 receptor density is far greater than the M3 receptor (about 4:1), and on the function of M3 receptor is more important, it directly mediated detrusor contraction, the role of the M2 receptor is not fully understood [19]. Antimuscarinic drugs can bind to these receptors in whole or in part with different affinity for in vivo, not only can improve the symptoms of OAB, but also can cause a lot of adverse effects, such as dry mouth, constipation, cognitive impairment, tachycardia, blurred vision and other [18], thus limiting the long-term use of these drugs. Therefore, several aspects of these drugs have been improved in order to reduce side effects, improve tolerance, access to the maximum efficacy. (1) the modified dosage form is changed from a common drug fast release type to a sustained release dosage form, so that the concentration of the medicine is slowly increased in the body and is stable. (2) changing the route of administration, such as the transdermal penetration of Bunin, the intravesical administration, etc.. (3) to improve the selectivity and affinity of M3 receptor in bladder and bladder, and to decrease the affinity of M receptor in other organs, such as the selective inhibitor of M3 receptor. With the continuous improvement in M receptor blocking agent, its side effects will gradually reduce the patient medication compliance and curative effect will be improved.

The early animal was found after spinal cord transection, usually C bladder afferent fibers induced by spinal micturition reflex inactive to active, intravesical instillation of capsaicin to reverse [20]. This observation and many later studies prompted capsaicin for the treatment of OAB. Capsaicin is the active ingredient extracted from red pepper in it, through the depletion of neuropeptide (such as substance P), specifically to block the unmyelinated afferent nerve fibers in the bladder, C neurons desensitization, reduce bladder sensory function, decreased bladder dilatation induced by micturition reflex. For the treatment of neurogenic bladder with detrusor hyperreflexia, without blocking the normal micturition reflex. But the intravesical capsaicin can cause acute inflammation, even spasm pain, burning sensation and other effects on the use of. In recent years the development of resiniferatoxin (RTX), spicy capsaicin is 1000 times, the concentration of small, mild side effects, patients are willing to accept.

A is a kind of botulinum toxin produced by botulinum neurotoxin, which inhibit the neuromuscular junction of cholinergic nerve endings release of acetylcholine and make the muscle paralysis. The application of botulinum toxin dyssynergia in detrusor urethral sphincter in patients with urethral sphincter relaxation can improve bladder emptying in patients with [21]. Recent studies show that botulinum toxin A can relieve detrusor relaxation, detrusor overactivity in patients with spinal cord injury [22]. Therefore, the application of botulinum toxin A injection can effectively detrusor relaxation, neurogenic detrusor overactivity.

The pathophysiology of OAB is involved in the peripheral and central nervous system, and many central diseases are related to OAB, such as stroke, spinal cord injury, Parkinson's syndrome, multiple sclerosis, etc.. Most drugs in the treatment of OAB are in the peripheral parts, the main effect of the afferent and efferent neurotransmitter or detrusor itself. Because many central transmitters / transmitters are involved in urinary control, new drug targets may be found in the center. Known GABA, glutamate, opioids, 5 serotonin, norepinephrine and dopamine receptors can affect micturition function, such as baclofen, a imipramine, Pelosi D drugs have been identified, play a role in the central nervous system, for the treatment of voiding dysfunction. Drugs that affect these systems are likely to develop drugs to treat OAB. Some studies have shown that [23] is possible.

(three) neuromodulation therapy

If non-invasive behavioral modification and drug treatment fails, consider the need to increase the dose of the drug, to replace the drug, to add other drugs or treatment, or to choose the method of neuromodulation.

Sacral nerve stimulation has made great progress in the treatment of OAB in recent years. The application of electrical stimulation of the sacral nerve root (S3), caused by the pudendal afferent nerve excitement, of course, may also be other excitatory afferent and efferent nerve fibers, regulating sensory and / or motor function, balance and coordination to sacral reflex recovery, so as to improve the symptoms of [24][25] OAB. Sacral neuromodulation therapy is still in its early stages, there is no reliable index to predict the indications and effect, when a patient decides sacral nerve stimulation treatment, we must first choose the location of sacral nerve through the skin, then the individual stimulation test in vitro, after the success of permanently implanted sacral nerve stimulation system. According to available data, this method is more effective in the treatment of urge urinary incontinence ([5]). At present, the stimulation system has become a "double Mimicry", namely the inhibition of detrusor contraction in the "on" state, and in the "off" state is triggered urination. With the continuous improvement of the treatment system and the accumulation of clinical experience, I believe there will be more OAB patients benefit from this.

(four) surgical procedures

No reactivity in patients with OAB and chronic intractable OAB patients may be treated with surgery, including resection of the bladder wall, bladder nerve muscle incision, bladder dilatation, Cystectasy, pelvic nerve transection, sacral nerve rhizotomy and urine flow operation etc..

Bladder denervation is actually to central control, destruction of postganglionic parasympathetic fibers, the requirements of high technology, according to the experience of the current 18~24 months after the recurrence rate is as high as 100%[26]. So it has been rarely used. Angioplasty are in danger of failure due to concurrent bladder emptying less expand the application of bladder, other methods are mainly used in the spinal cord of spastic bladder after injury in surgical treatment of OAB is the last choice, the application scope is limited.

Five, outlook

OAB is a symptom diagnosis basis is urgency, with or without incontinence, usually with frequency and nocturia. The treatment is comprehensive, including behavior, drugs and neuromodulation, surgery, etc.. Future treatments will focus on the improvement of drugs and surgical methods, and the development of effective and well tolerated drugs is the common aspiration of the pharmacist, the Department of Urology physician and the patient.

The non pharmacological treatment of OAB and tissue engineering, that is, the stent on the bladder tissue for bladder angioplasty, can greatly simplify the operation procedures, without anastomosis. In addition there are people interested in gene therapy, is a reversible change reversed some nerve, thereby restoring bladder function, because the OAB seriously affect patient's quality of life, has been more and more people know, the study will also continue to increase investment.



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