Antimuscarinics

Antimuscarinics

There are five types of muscarinic receptor, M1–5, in various organs in the human body (heart, brain, salivary glands, eye, . smooth muscle). Although the M2 receptor is most abundant in the bladder, it is the M3 receptor that binds acetylcholine to cause detrusor contraction. The most widely used pharma - cological agents to improve bladder function in patients with - neurogenic LUT dysfunction or idiopathic overactive bladder are muscarinic receptor antagonists (antimuscarinics). Mechanism of action Antimuscarinics reduce bladder storage pressures, treat detru - sor overactivity and improve overactive bladder symptoms. Although commonly thought to exert their e ff ect during the voiding phase by antagonising acetylcholine released from parasympathetic nerves and thereby reducing detrusor - contraction, they are now thought to exert their primary e ff ects α α /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF β /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF α /uni25CF /uni25CF in the storage phase of the micturition cycle. During the storage phase they act as antagonists of acetylcholine released from the urothelium, thereby decreasing activity in bladder a ff erent nerves and suppressing involuntary detrusor contractions and the sensation of urgency .

-agonist -receptor 1 (+) G-protein (+) PLC IP PIP 2 3 SR DG (+) 2+ Ca PKC 2+ Contraction Ca Smooth muscle contraction Figure 83.1 Second-messenger systems involved in (a) smooth muscle contraction and phate; cAMP , cyclic AMP; DG, diacylglycerol; IP , inositol 1,4,5-trisphosphate; PIP 3 C; PLC, phospholipase C; SR, sarcoplasmic reticulum. TABLE 83.2 Actions and side effects of commonly used pharmacological agents for the bladder. Class Examples Action Antimuscarinics Solifenacin Reduce bladder storage pressure Oxybutynin Reduce detrusor overactivity Tolterodine Improve functional bladder capacity Fesoterodine Darifenacin Trospium Mirabegron Reduce bladder storage pressure -agonists 3 Vibegron Reduce detrusor overactivity Improve functional bladder capacity Tamsulosin Reduce bladder outlet resistance -antagonists 1 from bladder neck and proximal/ Alfuzosin prostatic urethra Doxazosin