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.
A few key points that we have found important in treating OAB patients includes:
1. The treating doctor can use a combination of an anti-muscarinic and Myrbetriq to decrease symptoms of OAB especially in patients with severe symptoms that do not respond to either agent alone.
2. In contrast to prior thinking, there is a very small incidence of urinary retention with the use of either anti-muscarinics or Beta-3 agonists. However, caution should be used in men who really don’t have OAB but have impending urinary retention where they have large residual urine volumes as treatment with anticholinergics or a beta-3 agonist can only exacerbate the situation. Since most primary care physicians don’t have access to a bladder scan, but the PCP can use the tried and true old-fashioned way of simple percussion of the lower abdomen to determine if there is, indeed, significant residual urine.
3. The use of anti-muscarinics in patients with closed angle glaucoma is a contraindication. In patients with a history of glaucoma, we typically give the patients a prescription for their OAB suggest that the patient check with their ophthalmologist prior to initiating treatment.
4. There are a number of tips and coping suggestions in patients with over-active bladder that include: Timed voiding, reduction in caffeine and alcohol, reduction in fluids prior to bedtime and Kegel exercises when patients have strong urges to void. All of these suggestions can help. I provide the patient with a handout on coping suggestions which I have found effective. In fact, numerous studies have shown that behavior modification is as effective as medical therapy.
5. For patients who are unresponsive, an intake and output diary can be of help in determining how big a factor fluid intake can be, as well as, monitoring actual response to treatment.
6. It also is important to realize that many patients complain primarily of nocturia. Nocturia can be a result of numerous urologic as well as non-urologic conditions including CHF, venous insufficiency, and increased fluid intake at night. This is certainly a case where a voiding diary also can be of benefit. For patients whose primary complaint is nocturia, DDAVP .1 to .2 mg. can be used but it is important to monitor the serum sodium for hyponatremia.
7. For patients refractory to either combination or individual drug therapy, there are additional alternatives:
a. Percutaneous posterior tibial nerve stimulation involves a small acupuncture sized needle being placed in the ankle and a minimally perceived current transmitted up to the spinal lumbosacral nerve center where one can “reprogram” the bladder. This is indicated for patients unresponsive to oral medication.
b. For patients with refractory OAB symptoms, Interstim therapy can be utilized. Interstim involves an initial percutaneous trial followed by implanting leads from the spinal cord to the nerves supplying the bladder along with a programmed stimulator, which markedly suppresses and reduces urinary symptoms.