[Pathophysiology of the overactive bladder and its pharmacological treatment].
This paper reviews the possible mechanisms underlying bladder overactivity and discusses the targets for pharmacological treatment of this disorder. Damage to the brain (cerebrovascular disease, etc.) induces bladder overactivity by reducing suprapontine inhibition. Currently, attention has focused on C-fiber bladder afferents that may concern the mechanisms for bladder overactivity resulting from various etiologies such as spinal cord lesions, bladder outlet obstruction and bladder hypersensitivity disorders. With regard to the pathophysiology of idiopathic overactive bladder, both myogenic and neurogenic mechanisms may be involved in involuntary detrusor contraction. Since an intravesical capsaicin or resiniferatoxin was shown to have favorable therapeutic effects, afferent C-fiber neurons become a new target for pharmacological treatment. C-fiber neurons are known to contain tachykinins and other peptides as neurotransmitters. When released, tachykinins can influence via NK receptors bladder activity. In addition, evidences suggest that ATP receptors (P2X3) and prostaglandin receptors in afferent C-fiber neurons may play a role in mediating bladder overactivity. Thus, NK-antagonist, P2X3-antagonist and PG receptor-antagonist may be potential therapeutic drugs in the near future. beta 3-Adrenoceptor agonist is an another candidate drug for the treatment of the overactive bladder. Finally, it is important to notice that in any etiology including an idiopathic one, antimuscarinic drugs can improve bladder overactivity, although dry mouth and constipation are inevitable side-effects.
Yamaguchi
Osamu
O
Department of Urology, Fukushima Medical University, School of Medicine, Hikarigaoka-1, Fukushima City 960-1295, Japan. yamaosa@fmu.ac.jp
D006801:Humans; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011141:Polyuria / Q000188:drug therapy* / Q000503:physiopathology*; D001743:Urinary Bladder / Q000294:innervation*; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000503:physiopathology*