16. Possible Etiology of Overactive Bladder Unknown Combination Ouslander J. N Engl J Med . 2004;350(8):786-799 Neurogenic Myogenic
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33. Brief Summary Disclosure for InterStim ® Therapy for Urinary Control InterStim ® Therapy for Urinary Control: Product technical manual must be reviewed prior to use for detailed disclosure. Indications: InterStim Therapy for Urinary Control is indicated for the treatment of urinary retention and the symptoms of overactive bladder, including urinary urge incontinence and significant symptoms of urgency-frequency alone or in combination, in patients who have failed or could not tolerate more conservative treatments. Contraindications: Patients are contraindicated for implant of the InterStim System if they have not demonstrated an appropriate response to test stimulation or are unable to operate the neurostimulator. Also, diathermy (e.g., shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy) is contraindicated because diathermy's energy can be transferred through the implanted system (or any of the separate implanted components), which can cause tissue damage and can result in severe injury or death. Diathermy can damage parts of the neurostimulation system. Precautions/Adverse Events: Warning : This therapy is not intended for patients with mechanical obstruction such as benign prostatic hypertrophy, cancer, or urethral stricture. Safety and effectiveness have not been established for: bilateral stimulation, patients with neurological disease origins such as multiple sclerosis, pregnancy and delivery, or for pediatric use under the age of 16. System may be affected by or adversely affect cardiac pacemakers or therapies, cardioverter defibrillators, electrocautery, external defibrillators, ultrasonic equipment, radiation therapy, magnetic resonance imaging (MRI), theft detectors and screening devices. Adverse events related to the therapy, device, or procedure can include: pain at the implant sites, lead migration, infection or skin irritation, technical or device problems, transient electric shock, adverse change in bowel or voiding function, numbness, nerve injury, seroma at the neurostimulator site, change in menstrual cycle, and undesirable stimulation or sensations. CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician.
Editor's Notes
Pelvic floor muscle exercises, a well-recognized technique, can strengthen the pelvic floor, thereby producing a more powerful inhibition of involuntary detrusor muscle contractions. Biofeedback may be a beneficial measure to enable patients to locate and train their pelvic floor in an effective manner. 1,2 Rovner ES, Gomes CM, Trigo-Rocha FE, Arap S, Wein AJ. Evaluation and treatment of the overactive bladder . Rev Hosp Clin Fac Med Sao Paulo . 2002;57(1):39-48. Wein AJ. Diagnosis and treatment of the overactive bladder. Urology . 2003;62(5 Suppl 2):20-27.
The etiology of OAB is not completely understood. However, evidence suggests that it can be caused by 1 or more factors. Neuronal pathways involved in bladder filling/storage may be damaged by or can malfunction because of neurologic conditions, such as stroke, multiple sclerosis, and Parkinson’s disease. The etiology also may be myogenic in nature, in that denervation or some other factor (eg, aging) can cause increased excitability between myocytes in the detrusor. Because so many components are interconnected and involved in bladder filling and storage, the cause may be a combination of the above, or causative factors may remain to be determined. Ouslander J. Management of overactive bladder. N Engl J Med . 2004;350(8):786-799.
Neurologic control of micturition occurs through the release of neurotransmitters. Numerous receptors for neurotransmitters have been identified in the bladder. The receptors for these transmitters are located in the detrusor muscle. Muscarinic and ß 3 -adrenergic receptors are located in the detrusor muscle. The muscarinic receptor has been the major peripheral target involved in pharmacological manipulation of OAB. Muscarinic receptors are located in various organs throughout the body. There are 5 known muscarinic receptor subtypes: M 1 to M 5 . The human detrusor contains M 2 and M 3 subtypes in a 2:1 ratio. When stimulated, M 3 receptors, although less abundant in the bladder than M 2 subtypes, directly evoke bladder smooth muscle contraction. M 2 receptors indirectly reverse sympathetically mediated smooth muscle relaxation. Recently, evidence has shown that more important functional roles of M 2 receptors emerge in aging and in pathologic states, such as outflow obstruction, neurogenic bladder, and diabetes. Andersson KE. Antimuscarinics for treatment of overactive bladder. L ancet Neurol . 2004;3(1):46-53. Braverman A, Ruggeri MR, Pontari MA. The M 2 muscarinic receptor subtype mediates cholinergic bladder contractions in patients with neurogenic bladder dysfunction. Urology . 2001;165(suppl):36. Braverman AS, Karlovsky M, Pontari MA, Ruggeri MR. Aging and hypertrophy change the muscarinic receptor subtype mediating bladder contraction from M 3 towards M 2 . Urology . 2002;167 (suppl):43. Key Messages: M 2 receptors are the most abundant muscarinic receptor in the detrusor and urothelium M 3 receptors are known to directly evoke bladder smooth muscle contraction New theories behind the etiology of urgency are exploring the role of the M 2 receptor in modulation of afferent signals potentially initiated by the urothelium
Bladder contraction is mediated by the release of acetylcholine (ACh) from parasympathetic nerve endings. ACh then interacts with muscarinic receptors on detrusor smooth muscle of the urinary bladder to initiate contraction. The effect of ACh on the detrusor muscle is modulated by the action of acetylcholinesterase (AChE) and may be blocked by atropine. Sellers DJ, Yamanishi T, Chapple CR, Couldwell C, Yasuda K, Chess-Williams R. M 3 muscarinic receptors but not M 2 mediate contraction of the porcine detrusor muscle in vitro. J Auton Pharmacol . 2000;20:171-176. Sjögren C, Andersson K-E, Husted S, Mattiasson A, Moller-Madsen B. Atropine resistance of transmurally stimulated isolated human bladder muscle. J Urol. 1982;128:1368-1371. Key Message: Contraction of the bladder smooth muscle involves both the M 3 and M 2 muscarinic receptor subtypes