The article explains that the difference in receptor occupancies between the oral and intravesical routes underpins the difference in efficacies and risks of adverse drug reactions. For example, while the oral route achieves only a minimal difference in receptor occupancy of the bladder’s urothelium and salivary glands, the intravesical route overwhelms urothelial receptors available for binding, concomitantly with minimal attachment to salivary gland receptors.1
With conventional dosing the intravesical administration of antimuscarinics such as oxybutynin and atropine achieve very high mucosal concentrations to saturate the binding sites on bladder sensory nerves to produce beneficial effects as well as local anaesthetic action. This can explain the immediate effect on bladder compliance following their intravesical administration, as seen with urodynamics.
The review suggests the onset and duration of urodynamic effects of intravesical antimuscarinics may be due to alternative sites of action being involved, including retrograde transport of the drug from bladder to nerve cell bodies in spinal dorsal root ganglia for producing neuroplastic changes.4 That possibly could underly a long-lasting therapeutic effect of intravesical antimuscarinics.
While intravesical antimuscarinic treatment can shed light on the complex pathobiology of LUTS in older adults, oral antimuscarinic treatment of LUTS appears only to add to the burden of polypharmacy (as is so common with the elderly), risks drug interactions, and manifests high incidences of adverse drug reactions, including confusion and dementia. Oral administration of these drugs generally is associated with higher risks of adverse drug reactions from actions in the systemic compartment where they have no role to play in treating LUTS. Ganguly et al, state unequivocally, “at clinically used doses, oral antimuscarinics fail to reach the equilibrium dissociation constant for blocking receptors on detrusor muscle even at maximum plasma concentration.” Accordingly, it is unsurprising that the contemporary definition of Overactive Bladder Syndrome in the International Continence Society’s glossary makes no mention of muscle.
Since LUTS, itself, predisposes to nocturnal falls with hip fracture risks, some of which culminate in death, treatment of urgency should not be accompanied by side effects that can cause or exacerbate confusion, especially at such a precarious time, and most especially in the elderly. However, this paper reveals that it is the oral route of administration, rather than the drug, that is the root cause of the problems.
Written by: Laurence Stewart, MD,1 Scott Glickman, MD,2 & Pradeep Tyagi, PhD3
- Consultant Urologist Murrayfield Hospital, Edinburgh
- Medical Director, UroPharma Ltd,
- Department of Urology, University of Pittsburgh
- Ganguly A, Tyagi S, Chermansky C, Kanai A, Beckel J, Hashimoto M, Cho KJ, Chancellor M, Kaufman J, Yoshimura N, Tyagi P. Treating Lower Urinary Tract Symptoms in Older Adults: Intravesical Options. Drugs Aging. 2023 Mar;40(3):241-261. d
- Stoniute A, Madhuvrata P, Still M, Barron-Millar E, Nabi G, Omar MI. Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2023 May 9;5(5):CD003781.
- Zillioux J, Welk B, Suskind AM, Gormley EA, Goldman HB. SUFU white paper on overactive bladder anticholinergic medications and dementia risk. Neurourol Urodyn. 2022;41(8):1928-1933
- Finney SM, Andersson KE, Gillespie JI, Stewart LH. Antimuscarinic drugs in detrusor overactivity and the overactive bladder syndrome: motor or sensory actions? BJU Int. 2006 Sep;98(3):503-7