Antimuscarinic Effects Research Articles

Urinary retention induced by psychotropics: A case report

IntroductionNeurological bladder is considered a functional disability that has a significant impact on the quality of life and psychological state of patients. Psychotropic drugs, in turn, can worsen the urinary dysfunction caused by this disease.ObjectivesOur objective is to illustrate, through the case of a patient suffering from a neurological bladder decompensated by the treatment of a characterized depressive episode, the link between these two pathologies.MethodsWe report the case of Ms. M.W., aged 51, with a history of high blood pressure stabilized under nebivolol and a neurological bladder diagnosed 10 years ago with episodic pollakiuria, admitted to the psychiatric department for repeated suicide attempts. She had never used psychoactive substances and had no family psychiatric history. The patient presented depressive symptoms evolving for 5 months. The diagnosis of a characterized depressive episode with melancholic features was made and the patient was treated with sertraline. From the first intake of the drug, the patient presented acute urinary retention (UR) requiring the placement of a permanent bladder catheter. The urinary symptoms improved upon stopping the treatment. Sertraline was changed to olanzapine and escitalopram. The patient stopped the treatment after one month because of the worsening of urinary symptoms requiring the installation of a suprapubic catheter. The urinary problem, together with the cessation of treatment, were responsible for a worsening of psychiatric symptoms leading to multiple suicide attempts. Given the advanced stage of the neurological bladder demonstrated by the urodynamic tests, our patient was treated with paroxetine, quetiapine and oxazepam along with psychotherapeutic education. The evolution was characterized by improvement in psychiatric symptoms and the urinary symptoms were stable.ResultsThe lack of improvement after treatment discontinuation could be explained by an underlying neurological bladder manifesting with pollakiuria. The current literature on UR induced by psychotropic treatments is quite rare limited in case reports. This effect occurs especially when selective serotonin reuptake inhibitors (SSRIs) are prescribed in combination with other antipsychotics. Unlike first generation antipsychotics, atypical antipsychotics have muscarinic receptor antagonist properties which can induce UR. Among atypical antipsychotics, olanzapine has been shown to have the greatest antimuscarinic effects. Regarding SSRIs, they are associated with a lower risk of UR than other antidepressants and sertraline had the highest risk of UR.ConclusionsSSRIs can induce UR particularly in combination with atypical antipsychotics. Coordination of care across multiple specialties and understanding the side effects of psychotropic medications can enable faster diagnoses and adequate management.Disclosure of InterestNone Declared

Pharmacoencephalographic Assessment of Antiphyschotic Agents’ Effect Dose-Dependency in Rats

Pharmacoencephalography (pharmaco-EEG) is a prominent instrument for the pharmacological screening new psychoactive molecules. This experimental approach has not remained a vestige of neurobiological studies, and can be used successfully to complete today’s research objectives. The development and rise to universal use of machine learning techniques opens up novel prospects for the use of pharmaco-EEG data to solve the problems of classification and prognosis. We have previously shown that naïve Bayes classifier (NBC) combined with the principal component analysis (PCA) can be used to differentiate between antipsychotic and sedative drug effects as well as to distinguish among the antipsychotics’ effects. In the present study, we evaluated the possibility to employ this method to assess the dose-dependency of antipsychotic effects. The experiments were carried out in white outbred male rats with chronically implanted electrocorticographic electrodes. As the agents of interest, we chose two drugs with antipsychotic activity, chlorpromazine and promethazine, in three doses each (0.1, 1, 10 mg/kg and 0.5, 5 and 20 mg/kg, respectively). The training set, used as a reference to determine the pharmacological effects of the agents of interest, included the D2-dopamine receptor blocker haloperidol, M-cholinergic receptor blocker tropicamide, H1-histamine receptor blocker chloropyramine, the sedative dexmedetomidine, and the anxiolytic phenazepam. We have shown that the lowest chlorpromazine dose (0.1 mg/kg) can be characterized as antipsychotic with a marked histaminolytic effect, while the highest one (10 mg/kg) exhibits predominantly antipsychotic activity with a cataleptogenic effect. All the doses demonstrated anticholinergic activity, which increased with the dose. For promethazine, we observed a clear dose-dependent transition from antipsychotic action to cataleptogenic, alongside a notable antimuscarinic effect of all doses. None of promethazine doses showed any resemblance to chloropyramine, which probably indicates its anti-dopaminergic and antimuscarinic effects being able to mask its H1-antihistamine effect in the used dose range. In summary, our results demonstrate that NBC coupled with PCA can be used to determine the dose-dependency of antipsychotic agents’ effects based on their impact on electrocorticogram parameters. Further development of this method as well as expansion of psychotropic agent electropharmacogram library would allow for more precise prognosis of pharmacological activity of the agents of interest.

Sugammadex: A Milestone that Brings Changes in Anesthesia Practice

Sugammadex is a modified form of gamma-cyclodextrin that reverses the effects of rocuronium and vecuronium, which are aminosteroid non-depolarizing muscle relaxants (NDMR). It is the first and only reversal agent in the class of selective relaxant binding agents (SRBA) that reverses any depth of neuromuscular blockade without the unwanted muscarinic side effects of neostigmine (bronchospasm, nausea, vomiting, bradycardia, diarrhea, etc.) and anti-muscarinic side effects of glycopyrrolate (dry mouth, palpitations, urinary retention, constipation, etc.). It is an Food and Drug Administration (FDA)-approved agent that is safe for the reversal of neuromuscular block (NMB) caused by rocuronium and is available worldwide. Sugammadex practical use is predicted to alleviate many of the faults in present anesthetic practice regarding the antagonistic effects of rocuronium and other aminosteroid muscle relaxants. Despite being a novel agent in the reversal of NMB, the cost of sugammadex may limit its use as a regular antagonist of neuromuscular-blocking drugs.

Cyclizine-induced proinflammatory responses through Akt-NFκB pathway in macrophages.

Cyclizine exhibits sedation and treatment of nausea, vomiting, and motion sickness due to antihistaminic and antimuscarinic effects. Cyclizine has the potential for abuse due to the hallucinogenic and euphoric effect. The response of overdose and illegal abuse of cyclizine includes confusion, tremors, chest pain, ataxia, seizures, and lead to suicide. Macrophage plays the important role in the innate immunity. However, over activation of macrophages results in pro-inflammatory responses in peripheral tissues. In the present study, cyclizine was found to enhanced the generation of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. We further found that secretion of nitrogen oxide (NO) induced by cyclizine via expression of inducible nitric oxide synthases (iNOS). Cyclizine exhibited parallel stimulation of phosphorylation of nuclear factor-κB (NFκB) p65, and its up-stream factor Akt. These results indicated that the expression of pro-inflammatory cytokines, pro-inflammatory mediators, and adhesion molecules would be induced by cyclizine via activation of Akt-NFκB pathway in macrophages.

EFFECT OF CUSCUTA REFLEXA EXTRACT ON GASTROINTESTINAL MOTILITY

Background: Motility disorders of the gut are one of the major challenges to the medical profession. The stem of Cuscuta reflexa had been used by traditional practitioners for the treatment of gastrointestinal and bilious disorders. The objective of the current study was to determine the effects of an extract of C. reflexa on carbachol-induced contractions of isolated rabbit ileum. Methods: The study was conducted from January to July 2020 at Department of Pharmacology, Muhammad College of Medicine, Peshawar after approval from the Ethical Committee of the College. The sample size was calculated using the ‘Degree of Freedom in Anova’ formula. The rabbit’s ileum tissues were dissected and divided into two main groups, and each was further divided into three subgroups. Each subgroup consisted of six isolated rabbit’s ileum tissues. After equilibration and stabilization of tissues in an organ bath containing Tyrode’s solution, the effect of atropine and C. reflexa extract on carbachol-induced contractions in isolated rabbit’s ileum was recorded. Results were analysed statistically, and p?0.05 was considered significant. Results: Ethanolic extract of C. reflexa of different concentrations significantly decreased the amplitude of carbachol-induced contractions of rabbit ileum (p<0.05). The most powerful response of ethanolic extract of C. reflexa was observed at a concentration of 0.4 mg/ml. Conclusion: The ethanol extract of C. reflexa produces antimuscarinic effects on smooth muscles of the rabbit ileum. Pak J Physiol 2023;19(2):10–4

Are antimuscarinic effects common in hydroxyzine overdose? A cohort analysis of antimuscarinic effects in hydroxyzine and diphenhydramine-poisoned patients

Introduction Exposures to hydroxyzine, a first-generation H1 antihistamine, have increased rapidly over the last two decades. Many assumptions about hydroxyzine poisoning are based on other antihistamines, like diphenhydramine. However, the receptor affinities of hydroxazine suggest that there should be fewer antimuscarinic findings than diphenhydramine. Methods This was a cohort study that compared hydroxyzine and diphenhydramine exposures reported to the National Poison Data System between January 1, 2000, and December 31, 2020, and the Toxicologic Investigators Consortium Core Registry between January 1, 2010, and December 31, 2020. The primary outcome was to assess for antimuscarinic findings in hydroxyzine-poisoned patients, using diphenhydramine-poisoned patients as a comparison group. The secondary outcomes were to assess for markers of overall toxicity. Inclusion criteria were single-substance exposures with known outcomes. Exclusion criteria for National Poison Data System exposures were chronic exposures, unintentional exposures, and patients younger than 12 years old. There were no exclusion criteria for exposures reported to the Toxicologic Investigators Consortium Core Registry. Results There were 17,265 hydroxyzine and 102,354 diphenhydramine exposures reported to the National Poison Data System and 134 hydroxyzine and 1,484 diphenhydramine exposures reported to the Toxicologic Investigators Consortium Core Registry that met inclusion criteria. In both datasets, hydroxyzine-poisoned patients had lower rates and relative risk of developing antimuscarinic findings or receiving physostigmine, with the exception of hyperthermia in the Toxicologic Investigators Consortium Core Registry dataset. Coma/central nervous system depression (major), respiratory depression, seizures, ventricular dysrhythmias, intubation, and benzodiazepine administration were less likely in hydroxyzine-poisoned patients, but central nervous system depression (mild) was more likely in exposures reported to the National Poison Data System. The mortality in hydroxyzine-poisoned patients was rare: 0.02% and 0.8% of exposures reported to the National Poison Data System and Toxicologic Investigators Consortium Core Registry, respectively. Discussion The clinical manifestations of hydroxyzine exposures are consistent with the pharmacology of hydroxazine. The clinical effects were consistent across two United States national datasets. Clinicians should not generalize the illness script of diphenhydramine exposures to hydroxyzine exposures. Conclusions Hydroxyzine-poisoned patients were less likely to develop antimuscarinic findings than diphenhydramine-poisoned patients. Hydroxyzine-poisoned patients were more likely to have mild central nervous system depression than an antimuscarinic toxidrome.

Otilonium Bromide Prevents Cholinergic Changes in the Distal Colon Induced by Chronic Water Avoidance Stress, a Rat Model of Irritable Bowel Syndrome.

Irritable Bowel syndrome (IBS) is a highly widespread gastrointestinal disorder whose symptomatology mainly affect the large intestine. Among the risk factors, psychosocial stress is the most acknowledged. The repeated water avoidance stress (rWAS) is considered an animal model of psychosocial stress that is capable of mimicking IBS. Otilonium bromide (OB), which is orally administered, concentrates in the large bowel and controls most of the IBS symptoms in humans. Several reports have shown that OB has multiple mechanisms of action and cellular targets. We investigated whether the application of rWAS to rats induced morphological and functional alterations of the cholinergic neurotransmission in the distal colon and whether OB prevented them. The results demonstrated that rWAS affects cholinergic neurotransmission by causing an increase in acid mucin secretion, in the amplitude of electrically evoked contractile responses, abolished by atropine, and in the number of myenteric neurons expressing choline acetyltransferase. OB counteracted these changes and also showed an intrinsic antimuscarinic effect on the post-synaptic muscular receptors. We assume that the rWAS consequences on the cholinergic system are linked to corticotrophin-releasing factor-1 (CRF1) receptor activation by the CRF hypothalamic hormone. OB, by interfering with the CFR/CRFr activation, interrupted the cascade events responsible for the changes affecting the rWAS rat colon.

Combination therapy of solifenacin and mirabegron vs monotherapy in overactive bladder

Introduction and Objectives: Overactive bladder (OAB) with symptoms of frequency, urgency with or without urgency incontinence and nocturia is one of the most bothersome symptom affecting the quality of life of both men and women. Antimuscarinics and Beta 3 agonists both play an important role in reducing the bothersome symptoms. In this study we find the efficacy of low dose combination therapy of solifenacin 5 mg with mirabegron 25 mg vs the monotherapy solifenacin 10 mg or Mirabegron 50 mg.Materials and Methods: It is a prospective study conducted on 150 patients at Madras medical college and were divided into 3 groups. Group A received solifenacin 10 mg/day, Group B received solifenacin 5 mg/day + Mirabegron 25 mg/day and Group C received Mirabegron 50 mg/day. Patients were evaluated for improvement in frequency, urgency, leak episodes, voided volume and improvement in quality of life after a period of 4 weeks and 12 weeks. The three groups were compared using anova test and chi square test and p value was calculated.Results and Observations: Majority of patients of OAB belong to age group > 50 years and majority were females showing female predilection towards OAB. The mean duration of symptoms was 36.01± 7.91 months. Compared with monotherapy, the combination therapy resulted in a significant improvement in reducing the mean number of micturition/24hr from baseline to End of Treatment (EoT). The frequency of urgency episodes and mean number of nocturia episodes/24hr was significantly reduced in patients taking combination therapy as compared to monotherapy. In all the groups a decrease in mean number of incontinence episodes/24hr was observed from baseline to EoT but was not statistically significant. The frequency of antimuscarinic side effects (dry mouth, constipation, urinary retention) had lower incidence in combination therapy compared with solifenacin group. Conclusions: Combination therapy of solifenacin and mirabegron demonstrated significant improvement over monotherapy (solifenacin 10 mg & mirabegron 50 mg) in frequency of micturition, urgency and nocturia episodes without increasing bothersome adverse effects associated with antimuscarinic therapy.

Investigation into the Antihypertensive Effects of Diosmetin and Its Underlying Vascular Mechanisms Using Rat Model.

Objective: Diosmetin is a flavonoid that is found in many important medicinal plants that have antihypertensive therapeutic potential. Diosmetin has been shown to have antiplatelet, anti-inflammatory and antioxidant properties, which suggests that it could be a potential candidate for use in antihypertensive therapy. Methods: In vivo and in vitro methods were used for our investigation into the antihypertensive effects of diosmetin. Results: Diosmetin significantly decreased the mean arterial pressure (MAP). The effects of diosmetin on the MAP and heart rate were more pronounced in hypertensive rats. To explore the involvement of the muscarinic receptors-linked NO pathway, Nω-nitro-L-arginine methyl ester (L-NAME) and atropine were pre-administered in vivo. The pretreatment with L-NAME did not significantly change the effects of diosmetin on the MAP by excluding the involvement of NO. Unlike L-NAME, the atropine pretreatment reduced the effects of diosmetin on the MAP, which demonstrated the role of the muscarinic receptors. In the in vitro study, diosmetin at lower concentrations produced endothelium-dependent and -independent (at higher concentrations) vasorelaxation, which was attenuated significantly by the presence of atropine and indomethacin but not L-NAME. Diosmetin was also tested for high K+-induced contractions. Diosmetin induced significant relaxation (similar to verapamil), which indicated its Ca2+ antagonistic effects. This was further confirmed by diosmetin shifting the CaCl2 CRCs toward the right due to its suppression of the maximum response. Diosmetin also suppressed phenylephrine peak formation, which indicated its antagonist effects on the release of Ca2+. Moreover, BaCl2 significantly inhibited the effects of diosmetin, followed by 4-AP and TEA, which suggested that the K+ channels had a role as well. Conclusions: The obtained data showed the Ca2+ channel antagonism, potassium channel activation and antimuscarinic receptor-linked vasodilatory effects of diosmetin, which demonstrated its antihypertensive potential.

Acute Kidney Injury in a Patient with Darifenacine Overdose

Introduction:Darifenacin is a medication that has anticholinergic and antimuscarinic effects and is used in the treatment of overactive bladder.Adverse and overdose effects of the medication such as dry mouth and eyes,headache,nausea, constipation, urinary retention, and dyspepsia have been reported .An overdose effect on AKI has not been reported in the literature, and no dose adjustment is recommended in patients with renal impairment
 Case:A 24-year-old male patient applied to the emergency department with a declaration of taking 25 drugs containing darifenacin active ingredient for suicidal purposes.The patient had complaints of nausea and difficulty urinating.The patient's physical examination was normal.In laboratory, creatinine was 2.09mg/dL, and hemoglobi (+++) and protein(++) were found in urine test.Renal USG revealed a grade 1-2 increase in echogenicity of both kidneys.The patient was followed up with intravenous fluid replacement therapy, and the patient whose creatinine levels regressed was discharged with the recommendation of nephrology outpatient control.
 Conclusion:Any molecule taken in overdose can cause AKI via ATN should not be ignored by emergency physicians.The fact that such a side effect or undesirable situation has not been reported with Darifenacin so far doesn’t mean that the molecule is safe for this situation.An overdose of Darifenacin may cause AKI in patients.

Anticholinergic syndrome in a patient with schizophrenia

IntroductionAnticholinergic syndrome (AS) is a complication that can appear due to different drugs with antimuscarinic effects, such as antihistamines, alkaloids, antipsychotics, tricyclic antidepressives or anesthetics, and it is characterized by urinary retention, dry mouth and skin, mydriasis, low-grade fever, and confusion or coma.ObjectivesTo describe a clinical case of AS admitted to our hospital.MethodsWe present a case report of a patient with schizophrenia who presented an anticholinergic syndrome. We also searched for previous studies of AS using a pubmed query.ResultsA 53-year-old male was admitted for a psychotic decompensation to another hospital in Barcelona. The usual treatment at home was amisulpride 1200mg/d, olanzapine 30mg/d and lormetazepam, and haloperidol 6mg/d and clotiapine 40mg/d were added to treat the decompensation. Then, the patient started to present mydriasis, mucocutaneous dryness, low-grade fever, slight hypertension and tachycardia, repeated retentions of urine, confusion, unintelligible speech and agitation, so he was referred to our hospital. Once he was admitted, haloperidol was withdrawn and support measures (bladder catheterization, fluid therapy, etc.) were applied. After a few days, most of the mentioned alterations were stabilized, but the psychotic symptoms, such as thought and behavioural disorganization, persisted and required electroconvulsive therapy, with subsequent improvement.ConclusionsAS is a relatively frequent side effect of psychiatric medication, which diagnosis is clinical, so, we must be capable to identify it and initiate early treatment to prevent possible complications. The first step, as reflected in the case described, is to stop the causative drugs, and apply support measures. Additionally, physostigmine can be used, as it is an effective antidote.DisclosureNo significant relationships.

PD38-08 EFFICACY OF LOW-INTENSITY SHOCK WAVE THERAPY ON PERSISTENT STORAGE SYMPTOMS AFTER TRANSURETHRAL SURGERY FOR BENIGN PROSTATIC OBSTRUCTION: PRELIMINARY RESULTS OF A RANDOMIZED CONTROLLED TRIAL

You have accessJournal of UrologyCME1 May 2022PD38-08 EFFICACY OF LOW-INTENSITY SHOCK WAVE THERAPY ON PERSISTENT STORAGE SYMPTOMS AFTER TRANSURETHRAL SURGERY FOR BENIGN PROSTATIC OBSTRUCTION: PRELIMINARY RESULTS OF A RANDOMIZED CONTROLLED TRIAL Mohammed Hegazy, Khaled Zaky Sheir, Mohamed Ahmed Gaballah, and Ahmed Mohamed Elshal Mohammed HegazyMohammed Hegazy More articles by this author , Khaled Zaky SheirKhaled Zaky Sheir More articles by this author , Mohamed Ahmed GaballahMohamed Ahmed Gaballah More articles by this author , and Ahmed Mohamed ElshalAhmed Mohamed Elshal More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002596.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aimed to evaluate the efficacy of low-intensity shock wave therapy (Li-SWT) on persistent storage symptoms after transurethral surgery (TUS) for benign prostatic obstruction (BPO) in a randomized controlled study. METHODS: Patients with persistent storage symptoms for at least 3 months after TUS for BPO were eligible once they have urgency episodes/24 hrs ≥1 and daytime frequency ≥8. Patients were allocated to Li-SWT versus sham versus standard of care (solifenacin 10 mg once daily) in 3:1:1 ratio. Li-SWT was applied to suprapubic and perineal regions once-weekly for 8 weeks. The treatment efficacy was assessed by overactive bladder symptoms score (OABSS) at baseline, 4, 8 and 12 weeks as well as international index of prostate symptom score (IPSS), quality of life (QoL), uroflowmetry and post-void residual urine volume (PVR) at baseline and 8 weeks. Moreover, patient compliance and treatment-related adverse effects were evaluated. Visual analogue scale (VAS) ranging from 0-10 was used for pain evaluation during Li-SWT sessions. RESULTS: A total of 115 patients were enrolled (72, 18 and 25 patients in Li-SWT, sham and solifenacin group respectively). Baseline data were comparable between groups. OABSS at 4, 8 and 12 weeks as well as IPSS and QoL at 8 weeks showed significant improvement from the baseline level in Li-SWT and solifenacin groups compared to sham group (P=0.001). Solifenacin was associated with bothersome antimuscarinic adverse effects in 84% of the patients and it was intolerable in 9.5% of them. However, no adverse effects related to Li-SWT were noted apart from local pain during the procedure (mean VAS = 4.18±1.31). CONCLUSIONS: Li-SWT ameliorates persistent storage symptoms and promotes the QoL after TUS for BPO. It can be used as an alternative treatment to muscarinic receptor blockers with similar efficacy and without bothersome adverse effects. Source of Funding: No source of funding © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e648 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammed Hegazy More articles by this author Khaled Zaky Sheir More articles by this author Mohamed Ahmed Gaballah More articles by this author Ahmed Mohamed Elshal More articles by this author Expand All Advertisement PDF DownloadLoading ...

Outcome reporting in randomized controlled trials (RCTs) on the pharmacological management of idiopathic overactive bladder (OAB) in women; a systematic review for the development of core outcome sets (COS)

Introduction and hypothesisEvidence on OAB management remains suboptimal and methodological limitations in randomized control trials (RCTs) affect their comparability. High quality meta-analyses are lacking. This study aimed to compare selection and reporting of outcomes and outcome measures across RCTs as well as evaluate methodological quality and outcome reporting quality as a first stage in the process of developing core outcome sets (COS).MethodsRCTs were searched using Pubmed, EMBASE, Medline, Cochrane, ICTRP and Clinicaltrials.gov from inception to January 2020, in English language, on adult women. Pharmacological management, interventions, sample size, journal type and commercial funding were documented. Methodological and outcome reporting quality were evaluated using JADAD and MOMENT scores.ResultsThirty-eight trials (18,316 women) were included. Sixty-nine outcomes were reported, using 62 outcome measures. The most commonly reported outcome domains were efficacy (86.8%), safety (73.7%) and QoL (60.5%). The most commonly reported outcomes in each domain were urgency urinary incontinence episodes (UUI) (52.6%), antimuscarinic side effects (76.3%) and change in validated questionnaire scores (36.8%).A statistically significant correlation was found between JADAD and MOMENT (Spearman’s rho = 0.548, p < 0.05) scores. This indicates that higher methodological quality is associated with higher outcome reporting quality.ConclusionsDevelopment of COS and core outcome measure sets will address variations and lead to higher quality evidence. We recommend the most commonly reported outcomes in each domain, as interim COS. For efficacy we recommend: UUI episodes, urgency and nocturia episodes; for safety: antimuscarinic adverse events, other adverse events and discontinuation rates; for QoL: OAB-q, PPBC and IIQ scores.

Development of Phenothiazine Hybrids with Potential Medicinal Interest: A Review.

The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.

Effects of chlorpheniramine on emergence agitation after general anesthesia for ureteroscopic stone surgery: a retrospective cohort study.

BackgroundThe presence of a urinary catheter, postoperative pain, and postoperative nausea and vomiting are risk factors for emergence agitation (EA). Antimuscarinic agents are primary agents used in the prevention and treatment of urinary catheter-related bladder discomfort. Chlorpheniramine has antimuscarinic, antinociceptive, and antiemetic effects. This retrospective study investigated the role of chlorpheniramine in EA prevention following ureteroscopic stone surgery.MethodsOf 110 adult patients who underwent ureteroscopic stone surgery under general anesthesia between January and December 2019, the medical records of 93 patients were analyzed retrospectively. The patients were divided into control (n = 52) and chlorpheniramine (n = 41) groups according to the receipt of intravenous chlorpheniramine before the induction of anesthesia. The incidence and severity of EA were compared between the groups as primary and secondary endpoints, respectively. The effects of chlorpheniramine on the requirement for inhalation anesthetic (desflurane) during surgery, changes in mean blood pressure and heart rate during emergence, and adverse events were also compared.ResultsThe incidence (21.2% in the control group, 24.4% in the chlorpheniramine group) and severity of EA did not differ between groups. The intraoperative requirement for desflurane, changes in mean blood pressure and heart rate during emergence, and adverse events were also similar between groups.ConclusionsChlorpheniramine was not associated with a decrease in EA incidence or severity in patients who underwent ureteroscopic stone surgery.

PD27-11 PRELIMINARY PHARMACOKINETIC DATA OF AN IN VITRO AND ANIMAL STUDY OF A NOVEL INTRAVESICAL SUSTAINED DELIVERY SYSTEM OF LIDOCAINE AND OXYBUTYNIN (TRG-042)

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-11 PRELIMINARY PHARMACOKINETIC DATA OF AN IN VITRO AND ANIMAL STUDY OF A NOVEL INTRAVESICAL SUSTAINED DELIVERY SYSTEM OF LIDOCAINE AND OXYBUTYNIN (TRG-042) Boris Chertin, David Dothan, Nadav Malchi, Avi Gordon, and Dan Touitou Boris ChertinBoris Chertin More articles by this author , David DothanDavid Dothan More articles by this author , Nadav MalchiNadav Malchi More articles by this author , Avi GordonAvi Gordon More articles by this author , and Dan TouitouDan Touitou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial Cystitis / Bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine administration has demonstrated pain relief in patients with IC/BPS. Intravesical administration of Oxybutynin has a well-documented therapeutic effect in patients with urinary bladder disorders due to a direct local anesthetic, antimuscarinic and spasmolytic effect within the bladder wall. However, intravesical use of the both drugs in the clinical practice did not stand the test of time due to rapid dilution and loss of drug with urination requiring multiple administrations. The ability to prolong drug retention in the urinary bladder enhances the bladder wall tissue exposure to adequate therapeutic level of drugs. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of Lidocaine and Oxybutynin novel polymeric composition forming instantly in the urine a sustained delivery system named TRG-042. METHODS: We have In-Vitro tested release of Lidocaine and Oxybutynin from TRG-042 in artificial urine (AUF) and have quantitatively determined Oxybutynin and Lidocaine concertation utilizing high-pressure liquid chromatography(HPLC). Following the successful In-Vitro study weekly formulation of TRG-042 was instilled into urinary bladder of 6 pigs. All pigs were followed with cystoscopy and US in order to assess the gradual degradation of the intravesical delivery system and to evaluate the response of the bladder over the seven days. Daily blood samples were tested for drug quantitation. Three pigs, who received TRG-042 without Oxybutynin and Lidocaine served as a control. RESULTS: In-Vitro studies have demonstrated Oxybutynin and Lidocaine sustained release over the one-week period coupled with the full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of the TRG-042 over one-week period with no adverse reaction of the bladder mucosa. Plasma concentrations of Oxybutynin and Lidocaine were uniformly high and stable over the one-week study period 1.46+/-0.176 ng/ml and 4.29+/-2.48 ng/ml respectively (mean+/-SEM) with almost undetectable concentration of active metabolite N-desethyloxybutynin (NDO) 0.032+/-0.068 ng/ml. CONCLUSIONS: The In-Vitro and animal data suggest that TRG-042 can safely be used for possible intravesical sustain release of Lidocaine and Oxybutynin in the treatment of BPS/IC. Our preliminary results should be further confirmed in clinical studies. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e448-e448 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Boris Chertin More articles by this author David Dothan More articles by this author Nadav Malchi More articles by this author Avi Gordon More articles by this author Dan Touitou More articles by this author Expand All Advertisement Loading ...

Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity

Background Diphenhydramine is frequently misused and ingested recreationally for its antihistaminergic and antimuscarinic effects and is often involved in both serious and fatal poisonings, either in isolation or in combination with other xenobiotics. Objective This analysis sought to determine which patient and encounter characteristics were associated with severe outcome after diphenhydramine overdose. Methods This is an analysis of the multi-center ToxIC registry (2010–2016). Descriptive analysis of all cases with diphenhydramine listed as the “primary agent” contributing to toxicity were included. Analysis sought to determine which patient and encounter characteristics were associated with severe outcome, defined as occurrence of seizure, ventricular dysrhythmia, or intubation. To determine which patient and encounter characteristics were individually associated with severe outcome, we performed chi-square tests. Fisher’s exact tests were used in the case of sparse data. We also performed multivariable logistic regression to further determine independent risk factors for severe outcome in diphenhydramine overdose. Results Eight hundred and sixty-three cases remained after exclusion with 15.6% (n = 135) of all patients having one or more severe outcome. The most common severe outcome was seizures which occurred in 98 (11.6%) of all ingestions. Females comprised 59.1% (n = 510) of all ingestions. Most ingestions were intentional (86.0%, n = 742) with the most common known reason for an intentional ingestion being self-harm, accounting for 37.5% (n = 324) of all ingestions. Self-harm ingestions and ingestions in males were more commonly associated with intubation. When examining outcomes by age, there were no significant differences overall or in any individual outcome except intubation in which children 0–12 were less likely to be intubated as compared to teens and adults. Signs and symptoms most strongly associated with a severe outcome included acidemia (pH < 7.2), QRS prolongation (QRS > 120 ms), and elevated anion gap (AG > 20). Discussion Acidemia, QRS prolongation, and elevated anion gap are associated with severe outcomes in diphenhydramine toxicity. Further research is warranted to determine their predictive characteristics.

A Review of a Hallucinogenic Plant (Brugmensia) Used as Criminal Tools and Exercises

Scopolamine, named also hyoscine, is a tropane alkaloid drug with antimuscarinic effects. It is also a tertiary ammonium compound, so it can be easily absorbed by the gut and the most important thing is that it crosses the hematoencephalic barrier (blood-brain barrier). This substance has many effects on the human body and it is produces effects on a range of micrograms. Scopolamine itself is used as a treatment for some diseases in low doses (like kinetosis), but when it comes to use it as a weapon, it’s mixed up with some other substances to produce the compost called burundanga. Burundanga is the cocktail and scopolamine is the main active principle. Regarding to its physical appearance, burundanga is a white thin dust similar to cocaine, tasteless and odourless. Scopolamine can be find almost in all the species of the Solenaceae family. The drug is stored in the plant’s flowers, leaves, and stems. Scopolamine is obtained principally from Datura stramonium, Brugmansia candida, and Hyoscyamus albus. There are many ways to commit a crime, but the perfect crime is not a concept easily achieved. Scopolamine is the ideal example. This substance has been utilised for a long time by humans and has been considered a gate to extra sensorial experiences with spirits. Nowadays though, it has turned into a majestic crime weapon or tool.

Literature Review: Efektivitas, Keamanan, dan Biaya Terapi Imidafenacin untuk Pasien Overactive Bladder

Imidafenacin is a new antimuscarinic agent in Indonesia that was recently approved in 2019 to treat overactive bladder (OAB) symptoms, including urinary incontinence, urinary frequency, and urinary urgency. As a new OAB medication in the Indonesian commercial market, a comprehensive review on the efficacy, safety, and cost of imidafenacin are essentially needed to optimize the responsible use of this drug, particularly in the era of universal coverage implementation in Indonesia. This review aimed to describe the profile of imidafenacin and to compare the efficacy, safety, and cost of imidafenacin with the other antimuscarinic drugs in Indonesia, and the guideline recommendations towards when to use imidafenacin for OAB treatment. Only results from systematic reviews and meta-analyses were used in the efficacy and safety comparison. Our review found that the efficacy of imidafenacin was relatively comparable to the other antimuscarinic drugs in Indonesia, including solifenacin, tolterodine, dan propiverine. Also, a better safety profile was found in the imidafenacin group, in particular, imidafenacin caused less dry mouth and constipation. This could be attributable to the higher affinity of imidafenacin to the M3 receptor resulting in less antimuscarinic effect at the other receptors. From the cost perspective, the cost of medication by using imidafenacin was relatively lower compared to the other antimuscarinic drugs in Indonesia. It, therefore, could be suggested to use imidafenacin as a potential agent for OAB.

Suppression of voltage-gated K+ channels by darifenacin in coronary arterial smooth muscle cells

Darifenacin, an anticholinergic agent, has been used to treat overactive bladder syndrome. Despite its extensive clinical use, there is little information about the effect of darifenacin on vascular ion channels, specifically K+ channels. This study aimed to investigate the effect of the anti-muscarinic drug darifenacin on voltage-gated K+ (Kv) channels, vascular contractility, and coronary blood flow in rabbit coronary arteries. We used the whole-cell patch-clamp technique to evaluate the effect of darifenacin on Kv channels. Darifenacin inhibited the Kv current in a concentration-dependent manner. Applying 1 μM darifenacin shifted the activation and inactivation curves toward a more positive and negative potential, respectively. Darifenacin slowed the time constants of recovery from inactivation. Furthermore, blockade of the Kv current with darifenacin was increased gradually by applying a train of pulses, indicating that darifenacin inhibited Kv currents in a use- (state)-dependent manner. The darifenacin-mediated inhibition of Kv currents was associated with the Kv1.5 subtype, not the Kv2.1 or Kv7 subtype. Applying another anti-muscarinic drug atropine or ipratropium did not affect the Kv current or change the inhibitory effect of darifenacin. Isometric organ bath experiments using isolated coronary arteries were applied to evaluate whether darifenacin-induced inhibition of the Kv channel causes vasocontraction. Darifenacin substantially induced vasocontraction. Furthermore, darifenacin caused membrane depolarization and decreased coronary blood flow. From these results, we concluded that darifenacin inhibits the Kv currents in concentration- and use- (state)-dependent manners. Inhibition of the Kv current with darifenacin occurred by shifting the steady-state activation and inactivation curves regardless of its anti-muscarinic effect.