4th Annual Jefferson Urology Symposium: Focus on Urinary Incontinence

© The Canadian Journal of Urology TM : International Supplement, August 2021 blockingM3 receptors in the salivary glands, intestinal smooth muscle, and ciliary and iris sphincter muscles respectively. Other anticholinergic side effects may include headache, drowsiness, and tachycardia. There is a variety of marketed antimuscarinic agents. Although there are different molecular structures, pharmacokinetic profiles, and muscarinic receptor subtype specificities, there does not appear to be a clear superiority of any one agent in managing either clinical symptoms or improving urodynamic parameters in patients with NDO. Intolerance to one antimuscarinic agent does not necessarily portend intolerance to a different agent. Newer antimuscarinic agents may bemore selective for cholinergic detrusor receptors thereforeminimizing systemic side effects. Extended release formulations of antimuscarinic medications avoid high peaks in drug levels and result in less dry mouth and constipation than the immediate release preparations. 11 Transdermal and intravesical formulations of oxybutynin offer the advantage of reducing the severity of the anticholinergic side effects of dry mouth and constipation by avoiding the first pass of oxybutynin through the liver. One pharmacologically active metabolic product resulting from first pass metabolism of oxybutynin is desethyloxybutynin, which appears to be responsible for many of the antimuscarinic side effects of immediate release oxybutynin. Oxybutynin is primarily metabolized in the liver and bowel wall by the cytochrome P450 enzyme systems, particularly CYP3A4 found mostly in the liver and gut wall. Intravesical oxybutynin has been used on an “off-label basis” to minimize the effect of first pass metabolism. 12 Beta-3 agonists, including mirabegron and vibegron, activates detrusor beta-3 receptors to cause relaxation of detrusor muscle. Mirabegron received FDAapproval in 2012 for treatment overactive bladder Although it is clearly effective in increasing bladder capacity as well as decreasing urinary frequency and urge incontinence in patients with idiopathic OAB, it has not been extensively studied as a first line treatment in patients with NDO. 13 In a prospective randomized placebo controlled study of 66 patients with NDO resulting from SCI or multiple sclerosis, the use of mirabegron significantly increased the volume at first detrusor contraction and significantly improved patient reported outcomes. 14 Mirabegron has been shown to result inmeaningful improvements in patient reported outcomes in patients with OAB when used as an add-on treatment to antimuscarinic medications, particularly solifenacin. Although the evidence for use of beta-3 agonists in patients with NDO is still limited, these medications are well-tolerated and have an excellent safety profile. They should be considered as either an alternative to antimuscarinic therapy or as an add-on treatment for patients with persistent symptoms despite treatment with antimuscarinics or botulinum toxin injections. 15 Intra-detrusor botulinum toxins Intra-detrusor injection of botulinum toxin has widespread use in patients with NDO resulting from an array of neurologic conditions including multiple sclerosis, SCI, Parkinson’s disease, CVA, and myelomeningocele. It has clearly been proven to be a safe and effective long term therapy in this patient population. 16 In clinical practice, it is most commonly utilized in patients who exhibit intolerance to, or have symptoms refractory to antimuscarinic therapy. It may be utilizedwith or without intermittent catheterization. Patients who spontaneously void must be willing to perform intermittent catheterization post-treatment due to the risk of urinary retention. OnabotulinumtoxinA (Botox) was approved as a treatment for NDO in 2011. It is generally administered cystoscopically in twenty divided doses of 200 units. This treatment can generally be administered in an office setting with topical anesthesia using 2% lidocaine instilled in the bladder. In rare cases, patients with severe autonomic dysreflexia may require a general anesthetic. In our experience, topical and intravesical lidocaine administration, minimizing bladder distention during treatment, and the use of a flexible cystoscope minimizes the development of autonomic dysreflexia in the vast majority of patients. Botulinumtoxins prevent the release of acetylcholine on the pre-synaptic parasympathetic nerve ending resulting in detrusor relaxation. 17 These agents have been shown to significantly improve bladder capacity, increase volume at first detrusor contraction, reduce maximum detrusor pressure, and reduce episodes of urinary incontinence in comparison to placebo. Due to the local effect of botulinum toxin, systemic side effects are exceedingly rare. The most common adverse events in this population include urinary tract infections, hematuria related to injection, and urinary retention. Urinary retention is of no concern in patients on intermittent catheterization. In patients who void spontaneously, the risk of urinary retention and need for intermittent catheterization should be discussed prior to treatment. The durability of response is variable but typically ranges from 6 to 9 months. Retreatment is generally patient directed and requested when the beneficial effects of treatment begin to subside. In patients 35 Management of neurogenic detrusor overactivity