MacDiarmid Scott A
Clinical Faculty, Department of Urology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
BJU Int. 2007 Jun;99 Suppl 3:8-12. doi: 10.1111/j.1464-410X.2007.06881.x.
Urinary incontinence affects an estimated 20-33% of adults the USA and 55% of the country's elderly [1], having a more substantial impact on the physical and mental dimension of quality of life than other common chronic diseases. Muscarinic receptor antagonists, including oxybutynin, tolterodine, trospium chloride, darifenacin, and solifenacin, are front-line therapies for overactive bladder (OAB), with an efficacy of 65-75% in reducing major symptoms. Strategies to increase the therapeutic index have included behavioural therapy, flexible dosing, and dose escalation, as well as newer formulations that reduce anticholinergic side-effects. Among approved OAB agents, the oxybutynin transdermal-delivery system has been associated with a lower incidence of dry mouth than immediate- and extended-release formulations of traditional agents. With a low propensity for drug interactions and dry mouth, it is a likely candidate for older patients taking multiple medications. The transdermal patch bypasses systemic and first-pass metabolism, avoiding higher plasma concentrations of the active metabolite (N-desethyloxybutynin) thought to be associated with dry mouth symptoms. Anticholinergics have a significant role to play in the management of OAB; newer drugs targeted toward muscarinic receptors, and novel delivery systems, continue to increase the therapeutic index for this condition.
据估计，在美国，20%至33%的成年人以及55%的老年人患有尿失禁[1]，与其他常见慢性病相比，尿失禁对生活质量的身体和心理层面影响更大。毒蕈碱受体拮抗剂，包括奥昔布宁、托特罗定、曲司氯铵、达非那新和索利那新，是治疗膀胱过度活动症（OAB）的一线疗法，在减轻主要症状方面的疗效为65%至75%。提高治疗指数（TI）的策略包括行为疗法、灵活给药和剂量递增，以及减少抗胆碱能副作用的新型制剂。在已获批准的OAB药物中，与传统制剂的速释和缓释剂型相比，奥昔布宁透皮给药系统引发口干的发生率较低。由于药物相互作用的可能性低且不易引发口干，对于服用多种药物的老年患者而言，它是一个合适的选择。透皮贴剂可绕过全身代谢和首过代谢，避免活性代谢物（N-去乙基奥昔布宁）出现较高的血浆浓度，而这种代谢物被认为与口干症状有关。抗胆碱能药物在OAB的治疗中发挥着重要作用；针对毒蕈碱受体的新型药物以及新型给药系统，持续提高了针对这种病症的治疗指数。
