Search Results (12)

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies. Full article

This single-center retrospective exploratory analysis evaluated the effects of sugammadex compared with neostigmine on postoperative recovery in patients with myasthenia gravis (MG) who underwent video-assisted thoracoscopic surgery (VATS)–thymectomy. This retrospective study included 180 patients with MG, aged >18 years, who received sugammadex (sugammadex group, n = 83) or neostigmine–glycopyrrolate (neostigmine group, n = 88) after VATS–thymectomy between November 2007 and December 2020. Inverse probability of treatment weighting (IPTW) adjustment was performed to balance the baseline characteristics between the two groups. The primary outcome was the length of postoperative hospital stay, and the secondary outcomes were the incidence of postoperative mortality and complications, as well as the postoperative extubation and reintubation rates, in the operating room after VATS–thymectomy; the outcomes were compared between the two groups. After IPTW adjustment, the sugammadex group showed a significantly shorter median postoperative hospital stay than the neostigmine group (4 (2, 4) vs. 5 (3, 6) days, respectively; p = 0.003). There were no significant differences between the two groups in the incidences of postoperative complications (including postoperative myasthenic crisis, nerve palsy, atelectasis, and pleural effusion). Patients with MG following VATS–thymectomy who received sugammadex showed a significantly shorter postoperative hospital stay than those who received neostigmine. Full article

Sialorrhea is common in children with neurodevelopmental disabilities (NDD) and is reported in >40% of children with cerebral palsy (CP). It causes a range of complications, including significant respiratory morbidity. This single-center retrospective chart review aims to document sublingual atropine (SLA) utilization to guide further study in establishing its role in secretion management for children with NDD. A chart review was completed for patients with NDD ≤ 22 years of age treated with SLA at a free-standing children’s hospital between 1 January 2016 and 1 June 2021. Descriptive statistics were generated to summarize findings. In total, 190 patients were identified, of which 178 met inclusion criteria. The average starting dose for SLA was 1.5 mg/day, or 0.09 mg/kg/day when adjusted for patient weight. Eighty-nine (50%) patients were prescribed SLA first line for secretion management while 85 (48%) patients tried glycopyrrolate prior to SLA. SLA was used after salivary Botox, ablation, and/or surgery in 16 (9%) patients. This study investigates SLA as a potential pharmacologic agent to treat sialorrhea in children with NDD. We identify a range of prescribing patterns regarding dosing, schedule, and place in therapy, highlighting the need for further evidence to support and guide its safe and efficacious use. Full article

We aimed to determine if not using residual neuromuscular blockade (RNB) analysis to guide neuromuscular blockade reversal administration in the postsurgical ICU resulted in consequences related to residual weakness. This single-center, prospective study evaluated 104 patients arriving in a postcardiac surgical ICU. After demonstrating spontaneous movement and T > 35.5 °C, all patients underwent RNB evaluation, and neostigmine/glycopyrrolate was then administered. When patients later demonstrated an adequate Rapid Shallow Breathing Index, negative inspiratory force generation, and arterial blood gas values with minimal mechanical ventilatory support, RNB evaluation was repeated in 94 of the 104 patients, and all patients were extubated. Though RNB evaluation was performed, patients were extubated without considering these results. Eleven of one hundred four patients had not achieved a Train-of-Four (TOF) count of four prior to receiving neostigmine. Twenty of ninety-four patients demonstrated a TOF ratio ≤ 90% prior to extubation. Three patients received unplanned postextubation adjunct respiratory support—one for obvious respiratory weakness, one for pain-related splinting compounding baseline disordered breathing but without obvious benefit from BiPAP, and one for a new issue requiring surgery. Residual neuromuscular weakness may have been unrecognized before extubation in 1 of 104 patients administered neostigmine without RNB analysis. ICU-level care may mitigate consequences in such cases. Full article

Background: Triple fixed-dose combination (FDC) therapy is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations and/or symptoms not controlled by dual FDCs. Since no randomized controlled trials (RCTs) have directly compared the different inhaled corticosteroid/long-acting β₂-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) FDCs, we performed a meta-analysis to compare the impact of the current available ICS/LABA/LAMA FDCs in COPD. Methods: A meta-analysis was performed by connecting beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide or glycopyrrolate (BDP/FOR/GLY), budesonide (BUD)/GLY/FOR, and fluticasone furoate/umeclidinium bromide/vilanterol (FF/UMEC/VI) FDCs via ICS/LABA or LABA/LAMA FDCs arms. The safety and efficacy profiles were investigated, and the Implemented Bidimensional Surface under the cumulative ranking curve analysis (IBiS) was carried out. Protocol registration: CRD42022301189. Results: Data from 21,809 COPD patients were extracted from the ETHOS, IMPACT, KRONOS, and TRILOGY studies. No significant (p > 0.05) differences were detected across the triple FDCs with respect to the risk of exacerbation, trough forced expiratory volume in the first second (FEV₁), transition dyspnea index (TDI), St. George’s Respiratory Questionnaire (SGRQ), risk of serious adverse events (SAEs), cardiovascular (CV) SAEs, pneumonia, and all-cause mortality. According to IBiS score, BDP/FOR/GLY 200/12/25 µg twice daily (BID) was the FDC reporting the best combined efficacy/safety profile (area 41.41%), although FF/UMEC/VI 100/62.5/25 µg once daily (QD) showed the greatest efficacy profile (50.54%). The protection against mortality related to the dose of ICS. Conclusions: All triple FDCs are effective and safe in COPD regardless of the regimen of administration (twice daily vs. once daily), with no relevant difference in the risk of CV SAEs and pneumonia. Full article

Postoperative bowel dysfunction poses difficulty to patients during their recovery from surgery, and reversal agents may affect bowel function. This study aimed to investigate and compare the effects of sugammadex and a neostigmine/glycopyrrolate combination on postoperative bowel movement in patients undergoing robotic thyroidectomy. The electronic medical records of 122 patients, who underwent robotic thyroidectomy between March 2018 and December 2020, were retrospectively reviewed. Demographic, clinical, and laboratory findings and the first gas-passing time after surgery were assessed. The number of patients with a first gas emission time over 24 h was significantly higher in the neostigmine group than in the sugammadex group (p = 0.008). Multivariate logistic regression analysis indicated that sugammadex was a prognostic factor for the first gas-passing time within 24 h (odds ratio = 4.60, 95% confidence interval 1.47–14.36, p = 0.005). Although postoperative bowel motility, based on the first gas emission time, was comparable, the number of patients with a first gas emission time within 24 h was significantly higher in the sugammadex group than in the neostigmine group. This shows that the use of sugammadex did not affect the delayed recovery of postoperative bowel motility after robotic thyroidectomy. Full article

Background and Objectives: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to cholinesterase inhibitors. Here, we compare the incidence of postoperative catheter-related bladder discomfort (CRBD) between sugammadex and pyridostigmine/glycopyrrolate treatments for reversing neuromuscular blockade. Materials and Methods: We retrospectively analyzed patients aged ≥ 18 years who underwent surgery under general anesthesia, received sugammadex or pyridostigmine with glycopyrrolate to reverse neuromuscular blockade, and had a urinary catheter in the post-anesthesia care unit between March 2019 and February 2021. After applying the exclusion criteria, 1179 patients were included in the final analysis. The incidence and severity of CRBD were collected from post-anesthesia recovery records. Results: The incidence was 13.7% in the sugammadex group (n = 211) and 24.7% in the pyridostigmine group (n = 968). Following propensity score matching, 211 patients each were included in the pyridostigmine and sugammadex matched group (absolute standardized difference (ASD), 0.01–0.05). Compared to the pyridostigmine group, the odds ratio for CRBD occurring in the sugammadex group was 0.568 (95% confidential interval, 0.316–1.021, p = 0.059). Conclusions: Sugammadex has a similar effect on the occurrence of postoperative CRBD compared with pyridostigmine. Full article

Corneal confocal microscopy (CCM) is emerging as a tool for identifying small fiber neuropathy in both peripheral neuropathies and neurodegenerative disease of the central nervous system (CNS). The value of corneal nerves as biomarkers for efficacy of clinical interventions against small fiber neuropathy and neurodegenerative disease is less clear but may be supported by preclinical studies of investigational agents. We, therefore, used diverse investigational agents to assess concordance of efficacy against corneal nerve loss and peripheral neuropathy in a mouse model of diabetes. Ocular delivery of the peptides ciliary neurotrophic factor (CNTF) or the glucagon-like peptide (GLP) analog exendin-4, both of which prevent diabetic neuropathy when given systemically, restored corneal nerve density within 2 weeks. Similarly, ocular delivery of the muscarinic receptor antagonist cyclopentolate protected corneal nerve density while concurrently reversing indices of systemic peripheral neuropathy. Conversely, systemic delivery of the muscarinic antagonist glycopyrrolate, but not gallamine, prevented multiple indices of systemic peripheral neuropathy and concurrently protected against corneal nerve loss. These data highlight the potential for use of corneal nerve quantification by confocal microscopy as a bridging assay between in vitro and whole animal assays in drug development programs for neuroprotectants and support its use as a biomarker of efficacy against peripheral neuropathy. Full article

Expression of bronchodilatory β₂-adrenoceptors and bronchoconstrictive muscarinic M₃-receptors alter with airway size. In COPD, (a combination of) β₂-agonists and muscarinic M₃-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β₂-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β₂-agonist) and glycopyrrolate (anticholinergic) against methacholine- and EFS-induced constrictions of large and small airways was measured in guinea pig and human lung slices using video-assisted microscopy. In guinea pig lung slices, glycopyrrolate (1, 3 and 10 nM) concentration-dependently protected against methacholine- and EFS-induced constrictions, with no differences between large and small intrapulmonary airways. Indacaterol (0.01, 0.1, 1 and 10 μM) also provided concentration-dependent protection, which was greater in large airways against methacholine and in small airways against EFS. Indacaterol (10 μM) and glycopyrrolate (10 nM) normalized small airway hyperresponsiveness in COPD lung slices. Synergy of low indacaterol (10 nM) and glycopyrrolate (1 nM) concentrations was greater in LPS-challenged guinea pigs (COPD model) compared to saline-challenged controls. In conclusion, glycopyrrolate similarly protects large and small airways, whereas the protective effect of indacaterol in the small, but not the large, airways depends on the contractile stimulus used. Moreover, findings in a guinea pig model indicate that the synergistic bronchoprotective effect of indacaterol and glycopyrrolate is enhanced in COPD. Full article

Persons with spinal cord injury (SCI) have neurogenic bowel disorders characterized by difficulty with evacuation (DWE), fecal incontinence, and discoordination of defecation. Six medically stable in-patients with SCI with a mean age of 57 ± 10 years (range: 39–66 years) and time since injury of 18 ± 17 years (range: 3–47 years) were investigated. Standard of care (SOC) for bowel care was followed by two weeks of SOC plus neostigmine (0.07 mg/kg) and glycopyrrolate (0.014 mg/kg) administered transcutaneously by iontophoresis thrice weekly for two weeks while patients continued to receive SOC. The primary endpoint was time to bowel evacuation. Body weights and abdominal radiographs were obtained. Ten questions related to bowel function and the Treatment Satisfaction Questionnaire for Medication were acquired after each arm. Bowel evacuation time decreased after the dual drug intervention arm (106.9 ± 68.4 vs. 40.8 ± 19.6 min; p < 0.0001). Body weight decreased (2.78 ± 0.98 kg; p < 0.0001), a finding confirmed on abdominal radiograph. Both questionnaires demonstrated improvement after the dual drug intervention arm. No major adverse events occurred. The addition of neostigmine and glycopyrrolate by transcutaneous administration to SOC for bowel care in persons with SCI and DWE resulted in the safe, effective, and predictable bowel evacuation with subjective improvement in bowel care. Full article

Purpose: The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate. Methods: In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm²) was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line) of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI). The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant. Results: A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm² at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm². Both iontophoresis (158.53 ± 17.50 µg/cm²) and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm²) significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%. Conclusion: Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin. Full article

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent. Full article