Mohamed ABDULMAJED, Berkan REŞORLU, Murat Tolga GULPİNAR

Antikolinerjik ilaçların mesane üzerinde ki etki mekanizması nedir – nörojenik mi yoksa non-nörojenik mi?

İnsan mesanesi, kompliansı yüksek, sinirsel desteği ise oldukça kompleks yapıda bir depolama organıdır. Bu bölgeyi innerve eden sinir sisteminin disfonksiyonu nörojen mesane olarak adlandırılmakta ve mesane fonksiyonlarını değişen derecelerde etkileyebilmektedir. Nörojen mesaneye bağlı oluşan semptomlar içerisinde yaşam kalitesini en çok etkileyeni idrar inkontinansı olarak bildirilmektedir. Nörojen mesanede idrar inkontinansı oluşumunun en önemli mekanizmlarından birisi ürodinamik çalışmada detrüsör aşırı aktivitesi ile izah edilmektedir. Oral antikolinerjik ilaçlar nörojen detrüsör aşırı aktivitesinin tedavisinde dönüm noktası olarak kabul edilirler. Bu derlemede nörojen mesane olgularında mesane kompliansını ve kapasitesini arttırmak ve istemsiz detrüsör kontraksiyonlarını azaltmak için kullanılan antikolinerjik tedavinin etki mekanizmasını analiz ettik

Anahtar Kelimeler:

antikolinerjik tedavi, detrüsör aşırı aktivitesi, nörojenik mesane

What is the mechanism of action of anticholinergics in the bladder – is it neurogenic or non-neurogenic?

The human urinary bladder is a highly – compliant storage device and nerve supply to the bladder is relatively complex. Dysfunction of the nervous system could affect the urinary bladder negatively, a condition called ‘neurogenic bladder’. Among neurogenic bladder complications, urinary incontinence is the most significant factor in determining quality of life. Urinary incontinence in neurogenic bladder is explained by detrusor overactivity on urodynamic assessment. Oral anticholinergic medications are largely accepted as the cornerstone in the management of neurogenic detrusor overactivity. In this review article, we closely analyse the mechanism by which anticholinergic treatment help increasing bladder compliance and bladder capacity and reducec involuntary detrusor contraction in neurogenic bladder cases

Keywords:

anticholinergic treatment, detrusor overactivity, neurogenic bladder,

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Werner ME, Knorn AM, Meredith AL, et al. Frequency encoding of cholinergic- and purinergic-mediated signa- ling to mouse urinary bladder smooth muscle: modulation by BK channels. Am J Physiol Regul Integr Comp Physiol 2007;292:616-24.
Andersson KE, Arner A. Urinary bladder contraction and relaxation:physiology and pathophysiology. Physiological Reviews 2004;84:935-86.
Yoshimura N, Kaiho Y, Miyazato M, Yunoki T, Tai C, Chancellor MB, Tyagi P. Therapeutic receptor targets for lower urinary tract dysfunction. Naunyn Schmiedebergs Arch Pharmacol 2008;377:437-48.
Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA. Campbell-Walsh Urology. 10th ed. USA: Saunders. P1909-1978.
Manack A, Motsko SP, Haag-Molkenteller C, Dmchowski RR, Goehring EL Jr, Nguyen-Khoa BA, Jones JK. Epide- miology and Healthcare Utilization of Neurogenic Blad- der Patients in a US Claims Database. Neurourology and Urodyn 2011;30:395-401.
Chancellor MB, Anderson RU, Boone TB. Pharmacothe- rapy for neurogenic detrusor overactivity. American Jour- nal of Physical Medicine and Rehabilitation 2006;85:536- 45.
Nijman RJ. Neurogenic and non-neurogenic bladder dysfunction. Current Opinion in Urology 2001;11:577-83.
Pannek J, Kullik B. Does optimizing bladder management equal optimizing quality of life? Correlation between he- alth-related quality of life and urodynamic parameters in patients with spinal cord lesions. Urology 2009;74:263-6.
Grise P, Ruffion A, Denys P, Egon G, Chartier KE. Efficacy and tolerability of botulinum toxin type A in patients with neurogenic detrusor overactivity and without concomitant anticholinergic therapy: comparison of two doses. Europe- an Urology 2010;58:759-66.
Abrams P, Andersson KE. Muscarinic receptor antagonists for overactive bladder. BJU International 2007;100:987- 1006.
Razdan S, Leboeuf L, Meinbach DS, Weinstein D, Gousse AE. Current practice patterns in the urologic surveillance and management of patients with spinal cord injury. Uro- logy 2003;61: 893-6.
Chapple CR. Muscarinic receptor antagnoists in the treat- ment of overactive bladder. Urology 2000;55:33-46.
Woock JP, Yoo PB, Grill WM. Mechanism of reflex bladder activation by pudendal afferents. Am J Physiol Regul In- tegr Comp Physiol 2011;300:398-400.
Bennett BC, Kruse MN, Roppolo JR, Flood HD, Fra- ser M, de Groat WC. Neural control of urethral outlet activity in vivo: role of nitric oxide. Journal of Urology 1995;153:2004-9.
Mansfield KJ, Liu L, Mitchelson FJ, Moore KH, Millard RJ, Burcher E. Muscarinic receptor subtypes in human blad- der detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing. British Journal of Pharmacology 2005;144:1089-99.
Hegde SS, Choppin A, Bonhaus D, Briaud S, Loeb M, Moy TM, Loury D, Eglen RM. Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. British Journal of Pharmacology 1997;120:1409-18.
Lai FM, Cobuzzi A, Spinelli W. Characterization of mus- carinic receptors mediating the contraction of the urinary detrusor muscle in cynomolgus monkeys and guinea pigs. Life Science 1998;62:1179-86.
Fry CH, Skennerton D, Wood D, Wu C. The cellular ba- sis of contraction in human detrusor smooth muscle from patients with stable and unstable bladders. Urology 2002;59:3-12.
Andersson KE. Antimuscarinics for treatment of overacti- ve bladder. Lancet Neurology 2004;3:46-53.
Ehlert FJ, Griffin MT, Abe DM, Vo TH, Taketo MM, Ma- nabe T, Matsui M. The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse uri- nary bladder. Journal of Pharmacology and Experimental Therapeutics 2005;313:368-78.
Fry CH, Ikeda Y, Harvey R, Wu C, Sui GP. Control of blad- der function by peripheral nerves: avenues for novel drug targets. Urology 2004;63:24-31.
Mukerji G, Yiangou Y, Grogono J, Underwood J, Agarwal SK, Khullar V, Anand P. Localization of M2 and M3 mus- carinic receptors in human bladder disorders and their clinical correlations. Journal of Urology 2006;176:367-73.
Morrison J, Steers WD, Brading A. Neurophysiology and neuropharmacology. In: Abrams P, Khoury S, Wein A. Incontinence: 2nd International Consultation on Inconti- nence. UK: Plymbridge Distributors; 2002. p. 85-161.
Guay DR. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clinical Pharmacokinetics 2003;42:1243–85.
Thüroff JW, Chartier-Kastler E, Corcus J, Humke J, Jonas U, Palmtag H, Tanagho EA. Medical treatment and me- dical side effects in urinary incontinence in the elderly. World Journal of Urology 1998;16:48–61.
Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. European Urology 2008;54:543-62.
Novara G, Galfano A, Secco S, D’Elia C, Cavalleri S, Ficar- ra V, Artibani W. A systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. European Urology 2008;54:740-63.
Roden DM. Drug-induced prolongation of the QT inter- val. New England Journal of Medicine 2004;350:1013-22.
Caulfield MP, Birdsall N. International Union of Pharma- cology: XVI. Classification of muscarinic acetylcholine re- ceptors. Pharmacological Reviews 1998;50:279-90.
Iijima K, De Wachter S, Wyndaele JJ. Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve. European Urology 2007;52:842-7.
Finney SM, Andersson KE, Gillespie JI, Stewart LH. An- timuscarinic drugs in detrusor overactivity and the ove- ractive bladder syndrome: motor or sensory actions? BJU International 2006;98:503–7.
Fader M, Glickman S, Haggar V, Barton R, Brooks R, Ma- lone-Lee J. Intravesical atropine compared to oral oxy- butynin for neurogenic detrusor overactivity: a double- blind, randomized crossover trial. Journal of Urology 2007;177:208.
Ochi M, Inoue R, Yamauchi Y, et al. Development of melo- xicam salts with improved dissolution and pharmacokine- tic behaviors in rats with impaired gastric motility. Pharm Res. 2013;30:377-86.
Madersbacher H, Stöhrer M, Richter R, Burgdörfer H, Hachen HJ, Mürtz G. Trospium chloride versus oxybuty- nin: a randomized double blind, multicentre trial in the treatment of detrusor hyperreflexia. British Journal of Uro- logy 1995;75:452-6.
Menarini M, Del Popolo G, Di Benedetto P, Haselmann J, Bödeker RH, Schwantes U, Madersbacher H; TcP128- Study Group. Trospium chloride in patients with neuroge- nic detrusor overactivity: is dose titration of benefit to the patients? International Journal of Clinical Pharmacology and Therapeutics 2006;44:623-32.
Nilvebrant L, Hallen B, Larsson B. Tolterodine – a new bladder selective muscarinic receptor antagonist: prec- linical pharmacological and clinical data. Life Science 1997;60:1129-36.
Andersson KE. Potential benefits of muscarinic M3 recep- tor selectivity. European Urology 2002;1:23-8.
Kay GG, Ebinger U. Preserving cognitive function for pa- tients with overacıtive bladder: evidence for a differential effect with darifenacin. International Journal of Clinical Practice 2008;62:1792-800.
Olshansky B, Ebinger U, Brum J, Egermark M, Viegas A, Rekeda L. Differential pharmacological effects of anti- muscarinic drugs on heart rate: a randomized, placebo- controlled, double-blind, crossover study with tolterodine and darifenacin in healthy participants ≥50 years. Jour- nal of Cardiovascular Pharmacology and Therapeutics 2008;13:241-51.
Ney P, Pandita RK, Newgreen DT, Breidenbach A, Stöhr T, Andersson KE. Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo. BJU International 2008;101:1036.
Michel MC, Wetterauer U, Vogel M, de la Rosette JJ. Car- diovascular safety and overall tolerability of solifenacin in routine clinical use: a 12-week, open-label, post-marketing surveillance study. Drug Safety 2008;31:505-14.
Stewart DA, Taylor J, Ghosh S, Macphee GJ, Abdullah I, McLenachan JM, Stott DJ. Terodiline causes polymorphic venıtricular tachycardia due to reduced heart rate and prolongation of QT interval. European Journal of Clinical Pharmacology 1992;42:577-82.
Norhona-Blob L, Kachur JF. Enantiomers of oxybutynin: in vitro pharmaıcological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs. Journal of Pharmacology and Experimental Therapeutics 1991;256:562-7.
Kachur JF, Peterson JS, Carter JP, Rzeszotarski WJ, Hanson RC, Noronha-Blob L. R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intesti- ne. Journal of Pharmacology and Experimental Therapeu- tics 1998;247:867-72.
Madersbacher H, Jilg G. Control of detrusor hyperreflexia by the intravesical administration of oxybutynin hydroch- loride. Paraplegia 1991;29:84-90.
Lazzeri M, Spinelli M. The challenge of overactive bladder therapy: alternative to antimuscarinic agents. International Brazilian Journal of Urology 2006;32:620-630.