Systemic, Intrathecal, and Intravesical Pharmacologic Treatment of Neurogenic Lower Urinary Tract Dysfunction
Jacques Corcos, Gilles Karsenty, Thomas Kessler, David Ginsberg in Essentials of the Adult Neurogenic Bladder, 2020
Classically, antimuscarinic medications are the first-line systemic therapy to increase bladder storage capacity and decrease bladder storage pressures in those with NLUTD. The currently available antimuscarinic medications include darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride.3 As a class, antimuscarinics act to block cholinergic stimulation of the detrusor and its neuronal innervation.4 Antimuscarinic medications can be administered via oral routes (tablet), transdermal routes (patch and gel applications), or intravesical routes with the differing routes affecting their metabolism. The varying antimuscarinic medications also have differing molecular sizes (tertiary amine versus quaternary amine), which affect their absorption and their passage through the blood-brain barrier. Both intermediate-release and extended-release versions of certain antimuscarinics are available. Coupled with the varying muscarinic receptor subtype selectivity (M1-M5) (Table 28.1), the differences in molecular size and absorption alter the side-effect profile for one agent versus another (with the common side effects being visual disturbances, dry mouth, and constipation).5,6
Female and Functional Urology
Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed in MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Whilst antimuscarinic agents are the mainstay of pharmacological treatment of overactive bladder syndrome, their use can be limited by side effects. Central nervous system effects are particularly important in the elderly population as the structure of the blood brain barrier may be impaired due to stroke, Alzheimer’s disease or diabetes. Central nervous system side effects include headache, dizziness or tiredness. These may be determined by the ability of the antimuscarinic agent to cross the blood brain barrier, the specificity for muscarinic receptors or actions of metabolites. Antimuscarinics are described as tertiary (e.g., oxybutynin) or quaternary amines (e.g., trospium chloride). Tertiary amines are lipophilic and are more likely to cross the blood brain barrier compared with quaternary amines which are, in theory, associated with fewer central nervous system side effects. All the tertiary amines (darifenacin, tolterodine and solifenacin) may cause cognitive side effects and exacerbating the anticholinergic burden but oxybutynin seems to be the one with the most negative effect on cognitive function. All five muscarinic receptors are found in the brain. M1 and M2 receptors are associated with memory and cognition whereas M3 receptors (which are clinically significant for detrusor contraction) have a low expression in the brain. Antimuscarinics, which have receptor specificity for M3 receptors, in theory, should have a lower risk of cognitive side effects.
The Overactive Bladder
Linda Cardozo, Staskin David in Textbook of Female Urology and Urogynecology - Two-Volume Set, 2017
10% switched from the initiAlly prescribed drug to Another in the sAme clAss, And 52% discontinued Altogether [51]. older people were more likely to persist with the initiAl prescription, but use of AntimuscArinics in older people does cArry some risk of cognitive dysfunction [52]. Another situAtion where cAution is needed for AntimuscArinic prescription is poorly controlled closed-Angle glAucomA. BetA-3 Adrenergic Agonist The mechAnism of Action of mirAbegron is through binding of betA-3 Adrenergic receptors, which cAuse detrusor muscle relAxAtion And which Are not widespreAd on other orgAns. MirAbegron Achieves significAnt reduction in uuI episodes And voiding frequency [54,55], And benefits cAn be Achieved in pAtients with symptoms refrActory to AntimuscArinic drugs [56]. The drug is generAlly well tolerAted, And it does not elicit the common side effects seen with AntimuscArinic drugs. In the elderly populAtion, symptomAtic improvement cAn be Achieved [57], And the concerns regArding potentiAl cognitive impAct for AntimuscArinics do not Apply. Desmopressin Desmopressin, A vAsopressin AnAlogue, hAs An estAblished role in treAting pediAtric nocturnAl enuresis And hAs Also been Approved for nocturiA in multiple sclerosis And nocturnAl polyuriA [58]. It mAy be used off-license to treAt nocturiA
How safe are heartburn medications and who should use them?
Published in Expert Opinion on Drug Safety, 2023
Vincenzo Savarino, Elisa Marabotto, Patrizia Zentilin, Nicola De Bortoli, Pierfrancesco Visaggi, Manuele Furnari, Giorgia Bodini, Edoardo Giannini, Edoardo Savarino
Tricyclic antidepressants have been proposed to treat heartburn in patients with visceral hypersensitivity and then not in cases of evident reflux disease, but imipramine 25 mg/day for 8 weeks has provided a modest success in relieving heartburn of 37,2% against 37,5% of placebo [64]. They are not well tolerated and significant side effects are relatively common. Most of these reactions involve muscarinic effects of these drugs and cerebral intoxication, but cardiac toxicity and orthostatic hypotension also represent serious problems [65]. Clinical consequences of these antimuscarinic effects include dry mouth and a sour or metallic taste, epigastric distress, constipation, dizziness, tachycardia, palpitations, blurred vision, and urinary retention [66]. Special precaution should be taken in men with prostatic hypertrophy. Weakness and fatigue are attributable to the central effects of the drugs.
Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Le Yu Naing, Matthew Heckroth, Prateek Mathur, Thomas L Abell
Antiemetic agents are often used in conjunction with prokinetic agents to treat the symptoms of GpS. Treatment with antiemetics aims to improve nausea and vomiting but does not result in improved gastric emptying or symptoms related to delayed gastric emptying as prokinetics do. In addition to those mentioned previously, other commonly used classes of antiemetic drugs include antihistamines and antimuscarinics. Antihistamines work by blocking histamine (H1) receptors in the CNS, including the area postrema and vomiting center of the vestibular nucleus. Antimuscarinics block the action of acetylcholine at muscarinic receptors (M1) in the same sites. The histamine receptor antagonists also carry central antimuscarinic activity, which further contributes to their antiemetic effects.
Comprehensive overview of the available pharmacotherapy for the treatment of non-neurogenic overactive bladder in children
Published in Expert Opinion on Pharmacotherapy, 2022
Sophie Ramsay, Élisabeth Lapointe, Stéphane Bolduc
When clinicians gain more experience using antimuscarinics and β3-agonists, they should note that children seem to develop or complain less about side effects. Therefore, we need to take advantage of this window of opportunity and offer dose-escalation to achieve continence as soon as possible. Urinary incontinence in children is bothersome to them and to their family dynamics. If side effects are significant, clinicians must be proactive and offer a better tolerated alternative. One could switch to another molecule if the efficacy of the first one was negligible, or reduce the dosage to a well-tolerated level and offer dual treatment (for example, add-on mirabegron). Once continence is achieved and the %EBC is close to 75%, we usually initiate a progressive dose reduction. We work in stages, each step being one to two months, to avoid significant clinical deterioration and allow detection of recurrent symptoms. If continence remains satisfactory and %EBC fairly stable, we progress toward complete medication cessation. When the child becomes medication-free, we like to obtain a new voiding diary 6 months later to monitor %EBC and make sure that patients and their family stay alert to returning symptoms. We often tell them to remember where they came from and that they should not tolerate going back down that road. Refractory OAB cases might need medication beyond 24 months, and significant growth in early teenage years is often the breakaway point where we gain the most on %EBC and finally achieve continence. Patience is the rule.
Related Knowledge Centers
- Anticholinergic
- Asthma
- Bradycardia
- Bronchoconstriction
- Central Nervous System
- Overactive Bladder
- Peripheral Nervous System
- Chronic Obstructive Pulmonary Disease
- Parasympathetic Nervous System
- Muscarinic Acetylcholine Receptor