Синдром гиперактивного мочевого пузыря (ГМП) является хроническим состоянием, которое оказывает большое влияние на качество жизни как мужчин, так и женщин. Симптомы ГМП ограничивают повседневную и социальную деятельность больных. Данное состояние не является самостоятельным заболеванием, но входит в клиническую картину ряда нозологическим форм. Наиболее частыми из них принято считать заболевания головного мозга (болезнь Паркинсона, деменция и т.д.), генитоуринарный синдром менопаузы и доброкачественную гиперплазию простаты. Объективно подтвердить гиперактивность мочевого пузыря можно уродинамическим методом (цистометрией): в ходе исследования во время наполнения определяются непроизвольные сокращения детрузора, которые могут быть спонтанными и спровоцированными. В случаях наличия у больного неврологического заболевания детрузорную гиперактивность принято считать нейрогенной, при его отсутствии – идиопатической. В статье рассматриваются вопросы лечения больных как нейрогенным, так и идиопатическим ГМП, особенности подбора лекарственной терапии. При выборе М-холиноблокатора необходимо оценить когнитивный статус пациента и его коморбидность. Применение четвертичных аминов (троспиума хлорида) оправдано при любой форме ГМП. Троспиум хлорид безопасен у пожилых больных вследствие уменьшения риска снижения познавательной функции и изменения фар-макодинамики при полипрагмазии. Быстрый лечебный эффект обеспечивает высокую приверженность пациентов к терапии троспиумом хлоридом.
Overactive bladder syndrome (OAB) is a chronic condition that has a significant influence on the quality of life of both men and women. OAB symptoms limit daily and social activity of patients. This disorder is not a separate disease but is included in clinical presentation of several diseases. The most frequent of them are brain disorders (Parkinson’s disease, dementia and others), genitourinary syndrome of menopause and benign prostate hyperplasia. Bladder overactivity can be confirmed with urodynamic methods (cystometry) where involuntary detrusor contractions that can be spontaneous and provoked are detected at the bladder filling phase. If a neurological disorder is present, detrusor hyperactivity is considered neurogenic, if it is absent – idiopathic. The article discusses treat-ment of patients both with neurogenic and idiopathic OAB as well as special aspects of medical therapy choice. In M-cholinoblockers choice patient cognitive function and comorbid disorders should be evaluated. The use of quaternary amines (trospium chloride) is reasonable in any OAB syndrome form. Trospium chloride is safe for use in older patients as a result of decrease of risk of cognitive function impairment and pharmacodynamics modulation in polypharmacy. Rapid therapeutic effect supports high adherence to treatment with trospium chloride.
1. Stewart WF, Van Rooyen JB, Cundiff GW et al. Prevalence and burden of over-active bladder in the United States. World J Urol 2003; 20: 327–36.
2. Lai HH, Shen B, Rawal A, Vetter J. The relationship between depression and overactive bladder/urinary incontinence symptoms in the clinical OAB population. BMC Urol 2016; 16: 60. DOI: 10.1186/s12894-016-0179-x
3. Haylen BT, de Ridder D, Freeman RM et al. An International Urogynecological Association (IUGA) / International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010; 29: 4–20; International Urogynecology J 2010; 21: 5–26. DOI: 10.1007 / s00192-009-0976-9
4. Abrams P. Describing bladder storage function: overactive bladder syndrome and detrusor overactivity. Urology 2003; 62 (5): 28–37.
5. Irwin DE, Milsom I, Hunskaar S et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 2006; 50 (6): 1306–14.
6. Коршунова Е.С. Диагностика и лечение симптомов нижних мочевых путей у больных болезнью Паркинсона в сочетании и без доброкачественной гиперплазии простаты. Автореф. дис. … канд. мед. наук. М., 2006.
[Korshunova E.S. Diagnostika i lechenie simptomov nizhnikh mochevykh putei u bol'nykh bolezn'iu Parkinsona v sochetanii i bez dobrokachestvennoi giperplazii prostaty. Avtoref. dis. … kand. med. nauk. Moscow, 2006 (in Russian).]
7. Litwiller SE, Frohman EM, Zimmern PE. Multiple sclerosis and the urologist. J Urol 1999; 161 (3): 743–57.
8. Cacabelos R, Rodríguez B, Carrera C et al. APOE-related frequency of cognitive and noncognitive symptoms in dementia. Methods Find Exp Clin Pharmacol 1996; 18 (10): 693–706.
9. Mansfield KJ, Liu L, Mitchelson FJ et al. Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT–PCR: changes in ageing. Br J Pharm 2005; 144: 1089–99.
10. Ikeda K, Kobayashi S, Suzuki M et al. M3 receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder ands alivary gland. Naunyn-Schmiedeberg’s Arch Pharmacol 2002; 366: 97–103.
11. Isik AT, Celik T, Bozoglu E, Doruk H. Trospium and cognition in patients with late onset Alzheimer disease. J Nutr Health Aging 2009; 13 (8): 672–6.
12. Pietzko A, Dimpfel W, Schwantes U, Topfmeier P. Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. Eur J Clin Pharmacol 1994; 47: 337–43.
13. Callegari E, Malhotra B, Bungay PJ et al. A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder. Br J Clin Pharmacol 2011; 72 (2): 235–46. DOI: 10.1111/j.1365-2125.2011.03961.x
14. Rudy D, Cline K, Harris R et al. Time to onset of improvement in symptoms of overactive bladder using antimuscarinic treatment. BJU Int. 2006; 97 (3): 540–6.
15. Position Statement. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013; 20 (9): 888–902.
16. Ковалева Л.А. Гиперактивный мочевой пузырь у женщин, особенности терапии. Лечащий врач. 2016; 3: 34–7.
[Kovaleva L.A. Giperaktivnyi mochevoi puzyr' u zhenshchin, osobennosti terapii. Lechashchii vrach. 2016; 3: 34–7 (in Russian).]
17. Haylen BT, de Ridder D, Freeman RM et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010; 29: 4. DOI: 10.1002 / nau.20798
18. Robinson D, Cardozo L, Milsom I et al. Oestrogens and overactive bladder. Neurourol Urodyn 2014; 33 (7): 1086–91. DOI: 10.1002/nau.22464
19. Thuroff JW, Abrams P, Andersson KE et al. EAU guidelines on urinary incontinence. Eur Urol 2011; 59: 387–400.
20. Rahn DD, Ward RM, Sanses TV. Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines. Int Urogynecol J 2014. DOI: 10.1007/s00192-014-2554-z
21. Ellsworth P, Marschall-Kehrel D, King S et al. Bladder health across the life course. Int J Clin Pract 2013; 67: 397–406. DOI: 10.1111 / ijcp.12127
22. Wróbel A. Overactive bladder syndrome pharmacotherapy: future treatment options. Prz Menopauzalny 2015; 14 (4): 211–7. DOI: 10.5114 / pm.2015.56403
23. Cardoso L, Lose G, McClish D. A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder. Acta Obstet Gynecol Scand 2004; 83: 892–7.
24. Geoffrion, R, Lovatsis, D, Walter J-E et al. Treatments for Overactive Bladder: Focus on Pharmacotherapy. J Obstet Gynaecol Canada 2012; 34 (11): 1092–101. DOI: 10.1016/s1701-2163 (16)35440-8
25. Geller EJ, Crane AK, Wells EC et al. Effect of anticholinergic use for the treatment of overactive bladder on cognitive function in postmenopausal women. Clin Drug Investig 2012; 32 (10): 697–705. DOI: 10.2165 / 11635010-000000000-00000
26. Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc 2008; 56 (12): 2203–10. DOI: 10.1111/j.1532-5415.2008.02009.x
27. Fox C, Richardson K, Maidment ID et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc 2011; 59 (8): 1477–83. DOI: 10.1111/j.1532-5415.2011.03491.x
28. Ancelin ML, Artero S, Portet F et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006; 332 (7539): 455–9.
29. Chung A, Noguchi N, Chan L, Tse V. Voiding dysfunction in older men. Curr Opin Urol 2016; 26 (2): 177–83. DOI: 10.1097/MOU.0000000000000265
30. Athanasopoulols A, Gyftopoulos K, Giannitsas K et al. Combination treatment with an a-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlledstudy. J Urol 2003; 169 (6): 2253–6.
31. Kaplan S A, Walmsley K, Te AE. Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 2005; 174 (6): 2273–5.
32. Yang Y, Zhao SF, Li HZ et al. Efficacy and safety of combined therapy with terazosin and tolterodine for patients with lower urinary tractsymptoms associated with benign prostatic hyperplasia: a prospective study. Chin Med J 2007; 120 (5): 370–4.
33. Kaplan SA, Roehrborn CG, RovnerES et al. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder. JAMA 2006; 296 (19): 2319–28.
34. http://uroweb.org/guideline
35. http://www.auanet.org/guidelines
36. Wiedemann A, Neumann G, Neumeister C et al. Efficacy and Tolerability of Add-On Trospium Chloride in Patients with Benign Prostate Syndrome and Overactive Bladder: A Non-Interventional Trial Showing Use of Flexible Dosing. Uro Today Int J 2009; 2. DOI: 10.3834/uij.1944-5784.2009.04.02
37. MacDiarmid SA, Ellsworth PI, Ginsberg DA et al. Safety and efficacy of once-daily trospium chloride extended-release in male patients with overactive bladder. Urology 2011; 77 (1): 24–9. DOI: 10.1016/j.urology.2010.07.469
38. Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV. Effectiveness of Solifenacin and Trospium for Managing of Severe Symptoms of Overactive Bladder in Patients With Benign Prostatic Hyperplasia. Am J Mens Health 2016; 10 (2): 157–63. DOI: 10.1177/1557988315595692
39. Guay, DRP. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clin Pharmacokinet 2003; 42: 1243–85.
40. Ohtake A, Saitoh C, Yuyama H. Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents. Biol Pharm Bull 2007; 30: 54–8.
41. Chapple, CR, Khullar, V, Gabriel, Z. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 2008; 54: 543–62.
42. De Montellano O, Paul R. Cytochrome P450: structure, mechanism, and biochemistry. 3rd edition. New York: Kluwer Academic/Plenum Publishers, 2005.
43. Crewe HK, Lennard MS, Tucker GT. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992; 34: 262–5.
44. Yaïch M, Popon M, Médard Y. In-vitro cytochrome P450 dependent metabolism of oxybutynin to N-deethyloxybutynin in humans. Pharmacogenetics 1998; 8 (5): 449–51.
45. Коршунова Е.С., Коршунов М.Н. Гиперактивный мочевой пузырь у мультиморбидных больных. Что нужно помнить? Consilium Medicum. 2018; 20 (7): 41–5. DOI: 10.26442/2075-1753_2018.7.41-45
[Korshunova E.S., Korshunov M.N. Hyperactive bladder in multimorbid patients. What should be remembered? Consilium Medicum. 2018; 20 (7): 41–5. DOI: 10.26442/2075-1753_2018.7.41-45 (in Russian).]
46. Zanger, UM, Schwab, M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013; 138: 103–41. DOI: 10.1016 / j.pharmthera.2012.12.007
________________________________________________
1. Stewart WF, Van Rooyen JB, Cundiff GW et al. Prevalence and burden of over-active bladder in the United States. World J Urol 2003; 20: 327–36.
2. Lai HH, Shen B, Rawal A, Vetter J. The relationship between depression and overactive bladder/urinary incontinence symptoms in the clinical OAB population. BMC Urol 2016; 16: 60. DOI: 10.1186/s12894-016-0179-x
3. Haylen BT, de Ridder D, Freeman RM et al. An International Urogynecological Association (IUGA) / International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010; 29: 4–20; International Urogynecology J 2010; 21: 5–26. DOI: 10.1007 / s00192-009-0976-9
4. Abrams P. Describing bladder storage function: overactive bladder syndrome and detrusor overactivity. Urology 2003; 62 (5): 28–37.
5. Irwin DE, Milsom I, Hunskaar S et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 2006; 50 (6): 1306–14.
6. Korshunova E.S. Diagnostika i lechenie simptomov nizhnikh mochevykh putei u bol'nykh bolezn'iu Parkinsona v sochetanii i bez dobrokachestvennoi giperplazii prostaty. Avtoref. dis. … kand. med. nauk. Moscow, 2006 (in Russian).
7. Litwiller SE, Frohman EM, Zimmern PE. Multiple sclerosis and the urologist. J Urol 1999; 161 (3): 743–57.
8. Cacabelos R, Rodríguez B, Carrera C et al. APOE-related frequency of cognitive and noncognitive symptoms in dementia. Methods Find Exp Clin Pharmacol 1996; 18 (10): 693–706.
9. Mansfield KJ, Liu L, Mitchelson FJ et al. Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT–PCR: changes in ageing. Br J Pharm 2005; 144: 1089–99.
10. Ikeda K, Kobayashi S, Suzuki M et al. M3 receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder ands alivary gland. Naunyn-Schmiedeberg’s Arch Pharmacol 2002; 366: 97–103.
11. Isik AT, Celik T, Bozoglu E, Doruk H. Trospium and cognition in patients with late onset Alzheimer disease. J Nutr Health Aging 2009; 13 (8): 672–6.
12. Pietzko A, Dimpfel W, Schwantes U, Topfmeier P. Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. Eur J Clin Pharmacol 1994; 47: 337–43.
13. Callegari E, Malhotra B, Bungay PJ et al. A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder. Br J Clin Pharmacol 2011; 72 (2): 235–46. DOI: 10.1111/j.1365-2125.2011.03961.x
14. Rudy D, Cline K, Harris R et al. Time to onset of improvement in symptoms of overactive bladder using antimuscarinic treatment. BJU Int. 2006; 97 (3): 540–6.
15. Position Statement. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013; 20 (9): 888–902.
16. Kovaleva L.A. Giperaktivnyi mochevoi puzyr' u zhenshchin, osobennosti terapii. Lechashchii vrach. 2016; 3: 34–7 (in Russian).
17. Haylen BT, de Ridder D, Freeman RM et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010; 29: 4. DOI: 10.1002 / nau.20798
18. Robinson D, Cardozo L, Milsom I et al. Oestrogens and overactive bladder. Neurourol Urodyn 2014; 33 (7): 1086–91. DOI: 10.1002/nau.22464
19. Thuroff JW, Abrams P, Andersson KE et al. EAU guidelines on urinary incontinence. Eur Urol 2011; 59: 387–400.
20. Rahn DD, Ward RM, Sanses TV. Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines. Int Urogynecol J 2014. DOI: 10.1007/s00192-014-2554-z
21. Ellsworth P, Marschall-Kehrel D, King S et al. Bladder health across the life course. Int J Clin Pract 2013; 67: 397–406. DOI: 10.1111 / ijcp.12127
22. Wróbel A. Overactive bladder syndrome pharmacotherapy: future treatment options. Prz Menopauzalny 2015; 14 (4): 211–7. DOI: 10.5114 / pm.2015.56403
23. Cardoso L, Lose G, McClish D. A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder. Acta Obstet Gynecol Scand 2004; 83: 892–7.
24. Geoffrion, R, Lovatsis, D, Walter J-E et al. Treatments for Overactive Bladder: Focus on Pharmacotherapy. J Obstet Gynaecol Canada 2012; 34 (11): 1092–101. DOI: 10.1016/s1701-2163 (16)35440-8
25. Geller EJ, Crane AK, Wells EC et al. Effect of anticholinergic use for the treatment of overactive bladder on cognitive function in postmenopausal women. Clin Drug Investig 2012; 32 (10): 697–705. DOI: 10.2165 / 11635010-000000000-00000
26. Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc 2008; 56 (12): 2203–10. DOI: 10.1111/j.1532-5415.2008.02009.x
27. Fox C, Richardson K, Maidment ID et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc 2011; 59 (8): 1477–83. DOI: 10.1111/j.1532-5415.2011.03491.x
28. Ancelin ML, Artero S, Portet F et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006; 332 (7539): 455–9.
29. Chung A, Noguchi N, Chan L, Tse V. Voiding dysfunction in older men. Curr Opin Urol 2016; 26 (2): 177–83. DOI: 10.1097/MOU.0000000000000265
30. Athanasopoulols A, Gyftopoulos K, Giannitsas K et al. Combination treatment with an a-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlledstudy. J Urol 2003; 169 (6): 2253–6.
31. Kaplan S A, Walmsley K, Te AE. Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 2005; 174 (6): 2273–5.
32. Yang Y, Zhao SF, Li HZ et al. Efficacy and safety of combined therapy with terazosin and tolterodine for patients with lower urinary tractsymptoms associated with benign prostatic hyperplasia: a prospective study. Chin Med J 2007; 120 (5): 370–4.
33. Kaplan SA, Roehrborn CG, RovnerES et al. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder. JAMA 2006; 296 (19): 2319–28.
34. http://uroweb.org/guideline
35. http://www.auanet.org/guidelines
36. Wiedemann A, Neumann G, Neumeister C et al. Efficacy and Tolerability of Add-On Trospium Chloride in Patients with Benign Prostate Syndrome and Overactive Bladder: A Non-Interventional Trial Showing Use of Flexible Dosing. Uro Today Int J 2009; 2. DOI: 10.3834/uij.1944-5784.2009.04.02
37. MacDiarmid SA, Ellsworth PI, Ginsberg DA et al. Safety and efficacy of once-daily trospium chloride extended-release in male patients with overactive bladder. Urology 2011; 77 (1): 24–9. DOI: 10.1016/j.urology.2010.07.469
38. Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV. Effectiveness of Solifenacin and Trospium for Managing of Severe Symptoms of Overactive Bladder in Patients With Benign Prostatic Hyperplasia. Am J Mens Health 2016; 10 (2): 157–63. DOI: 10.1177/1557988315595692
39. Guay, DRP. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clin Pharmacokinet 2003; 42: 1243–85.
40. Ohtake A, Saitoh C, Yuyama H. Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents. Biol Pharm Bull 2007; 30: 54–8.
41. Chapple, CR, Khullar, V, Gabriel, Z. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 2008; 54: 543–62.
42. De Montellano O, Paul R. Cytochrome P450: structure, mechanism, and biochemistry. 3rd edition. New York: Kluwer Academic/Plenum Publishers, 2005.
43. Crewe HK, Lennard MS, Tucker GT. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992; 34: 262–5.
44. Yaïch M, Popon M, Médard Y. In-vitro cytochrome P450 dependent metabolism of oxybutynin to N-deethyloxybutynin in humans. Pharmacogenetics 1998; 8 (5): 449–51.
45. Korshunova E.S., Korshunov M.N. Hyperactive bladder in multimorbid patients. What should be remembered? Consilium Medicum. 2018; 20 (7): 41–5. DOI: 10.26442/2075-1753_2018.7.41-45 (in Russian).
46. Zanger, UM, Schwab, M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013; 138: 103–41. DOI: 10.1016 / j.pharmthera.2012.12.007
1 ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Россия;
2 ФГБНУ «Научный центр неврологии», Москва, Россия;
3 ФГБУ ДПО «Центральная государственная медицинская академия» Управления делами Президента РФ, Москва, Россия
*e_korshunova@mail.ru
________________________________________________
Ekaterina S. Korshunova*1–3, Maksim N. Korshunov3, Sergei P. Darenkov3
1 National Medical Radiology Research Center, Moscow, Russia;
2 Scientific Center of Neurology, Moscow, Russia;
3 Central State Medical Academy, Moscow, Russia
*e_korshunova@mail.ru