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OAB (over-active bladder) is found in both men and women and is associated with the symptoms of urgency, frequency, nocturia and urge incontinence.

Regulation of bladder storage and voiding involves both sympathetic and parasympathetic control.

Bladder voiding is primarily regulated by the parasympathetic nervous system via the neurotransmitter acetylcholine. Muscarinic receptors (M1-M3-M5) are mediated by acetylcholine in controlling the contraction of the bladder muscle and relaxation of the internal sphincter to facilitate voiding. M2 and M3 are predominate muscarinic receptors found in the bladder. The anti-muscarinic (Ditropan, Ditropan XL, Vesicare, Sanctura, Gelnique, Toviaz and Enablex) all work by blocking the receptor, leading to a reduction in bladder contractions. Because they block the acetylcholine receptor systemically, they can be associated with constipation and dry mouth.

Bladder storage is primarily regulated by the sympathetic nervous system via the neurotransmitter norepinephrine. Norepinephrine released from the sympathetic nerve activates the adrenergic receptors causing the bladder to relax and close the external sphincter. There are three types of beta adrenergic receptors expressed in the bladder. The beta-3 AR makes up 97% of bladder receptors and is predominately responsible for the detrusor muscle relaxation. The drug Myrbetriq has recently been released and is a Beta 3 adrenergic receptor agonist which leads to increased relaxation of the bladder. In contrast to the anti-muscarinics which cause constipation and dry mouth, this is much less common with Myrbetriq which has a small incidence of an increase in blood pressure. Monitoring the patient’s blood pressure is important in patients with a history of hypertension.

A Phase 3 trial in over 400 men and women complaining of OAB symptoms was recently conducted with 3 arms, Tolterodine ER (Detrol LA) Myrbetriq and placebo arm. The incidence of dry mouth was 5 times higher in the Detrol arm than in the Myrbetriq group (10% vs 2%).

It should be noted in all of the clinical trials with both Myrbetriq and the anti-muscarinics, the increase in urinary voided volume was typically in the range of only 1 or 2 ounces. Both approaches do result in a significant decrease in the incidence of urge incontinence.

2017/06/24 04:27 2017/06/24 04:27