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Skeletal muscle relaxants have previously not been examined in multimodal anesthesia regimens following joint arthroplasty. We sought to evaluate cyclobenzaprine's effect on postoperative opioid consumption as well as surgical recovery following joint arthroplasty. In this retrospective cohort study, 471 patients undergoing 554 joint arthroplasty procedures were evaluated. Patients were divided into cohorts who did and did not receive cyclobenzaprine postoperatively, and postoperative opioid consumption and functional recovery measures were recorded in each cohort. In the unadjusted model, the cyclobenzaprine cohort experienced a 1.11 increase in pain scores on postoperative day zero (95% CI (0.60, 1.62), p < 0.0001). After adjusting for age, sex, BMI, CCI, perioperative MME, laterality, procedure, anesthesia, pre-op opioid use, pre-operative other controlled substance uses and pre-op benzodiazepine use, the cyclobenzaprine cohort's pain scores were 1.08 units higher at rest (95% CI (0.59, 1.56), p < 0.0001) and 1.25 units higher with activity on postoperative-day-zero (95% CI (0.78, 1.72), p < 0.0001). Both cohorts experienced statistically insignificantly different changes in mobility scores between postoperative day zero and postoperative day one, range of motion at 6 and 12 weeks, and readmission in <90 days. Postoperative morphine milliequivalents were insignificantly different between cohorts after controlling for pain in all models (base model mean ratio: 1.06, 95% CI (0.87,1.29), p = 0.5599) (Full model mean ratio: 1.09, 95% CI (0.91,1.30), p = 0.3608). Cyclobenzaprine shows utility in a multimodal anesthetic approach after joint arthroplasty in patients with higher baseline pain. [ABSTRACT FROM AUTHOR]

BACKGROUND: In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. OBJECTIVE: The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. METHODS: This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution’s implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. RESULTS: The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group (P < 0.001; P = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose (P < 0.001). CONCLUSION: Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines. [ABSTRACT FROM AUTHOR]

A nanocomposite of Ce-doped ZnO/r-GO was synthesized using a conventional hydrothermal method. The synthesized nanocomposites were utilized for the purpose of sensitive and selective detection of cyclobenzaprine hydrochloride (CBP). The properties of the composite were extensively analyzed, including its morphology, structure, and electrochemical behavior. This study investigates the application of a modified glassy carbon electrode for the detection of CBP, a muscle relaxant used to treat musculoskeletal diseases that cause muscle spasms. The electrode is modified with Ce-doped ZnO/r-GO. Various detection methods, such as cyclic voltammetric and square wave techniques (SWV), were utilized. The composite material showed high effectiveness as an electron transfer mediator in the oxidation of CBP. The electrode showed a good response for SWV evaluations in CBP identification, with a minimum detection limit of 1.6 × 10−8 M and a wide linear range from 10 × 10−6 M to 0.6 × 10−7 M, under ideal conditions. The rate constant for charge transfer (ks) and the estimation of the electrochemical active surface area were obtained. A developed sensor exhibited desirable selectivity, long-lasting stability, and remarkable reproducibility. A sensor was used to analyze water, human serum, and urine samples, resulting in positive recovery results. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this case series is to describe the clinical signs and outcome of cyclobenzaprine ingestion in two dogs treated with intralipid emulsion (ILE) and supportive care. Case or series summary: Two dogs presented for evaluation of cyclobenzaprine ingestion. A 4-year-old female spayed Rat Terrier (dog 1) presented within 4 h of ingestion of cyclobenzaprine (between 9.7 and 25.9 mg/kg). The dog experienced abnormal behavior, agitation, tremors, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. The dog was treated with ILE, cyproheptadine, and activated charcoal. All clinical signs resolved after treatment. A 5-month-old female intact mixed-breed dog (dog 2) presented after ingestion of an unknown amount of cyclobenzaprine 2--3 h prior to presentation. The dog experienced dull mentation, tremors, loss of gag reflex, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. Orogastric decontamination was performed via gastric lavage, and activated charcoal was given via orogastric tube, followed by ILE. All clinical signs resolved after therapeutic intervention. Discussion: This is the first report documenting clinical signs of cyclobenzaprine toxicity in two dogs followed by successful treatment with gastric emptying, ILE, and supportive care. [ABSTRACT FROM AUTHOR]

The use of physiologically based biopharmaceutics modeling (PBBM) and bioequivalence safe space is increasingly common for immediate-release drug products. However, for extended-release (ER) formulations there are only a few examples of this application. In this study, we developed ER formulations containing cyclobenzaprine 15 mg, supported by PBBM and bioequivalence safe space. Four formulations were prepared, F1, F2, F3 (ER mini-tablet formulations) and F4 (ER tablet formulation), and the dissolution profiles were evaluated. The dissolution profile of the reference drug product was also evaluated and used to set a bioequivalence safe space. A PBBM was set up, evaluated, and used to predict the in vivo behavior of the formulations. The bioequivalence safe space was calculated to be between – 25% and + 75% of the k1 and Tlag values of the dissolution profile of the reference drug product when applying the first-order dissolution kinetic model. All time points of the dissolution profile of the ER mini-tablet formulation F2, were within the safe space, and was approved in 10 of 10 trials of crossover virtual bioequivalence studies. Based on the PBBM strategy and bioequivalence safe space, it was possible to develop an ER mini-tablet formulation virtually bioequivalent to the reference drug product, even though this formulation failed the f2 test. [Display omitted] • Formulation development based on PBBM and bioequivalence safe space. • Failing similarity factor f2 but approved on virtual bioequivalence study. • Higher surface area from ER mini-tablets driving drug dissolution. [ABSTRACT FROM AUTHOR]

IntroductionThe objective of this case series is to describe the clinical signs and outcome of cyclobenzaprine ingestion in two dogs treated with intralipid emulsion (ILE) and supportive care.Case or series summaryTwo dogs presented for evaluation of cyclobenzaprine ingestion. A 4-year-old female spayed Rat Terrier (dog 1) presented within 4 h of ingestion of cyclobenzaprine (between 9.7 and 25.9 mg/kg). The dog experienced abnormal behavior, agitation, tremors, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. The dog was treated with ILE, cyproheptadine, and activated charcoal. All clinical signs resolved after treatment. A 5-month-old female intact mixed-breed dog (dog 2) presented after ingestion of an unknown amount of cyclobenzaprine 2–3 h prior to presentation. The dog experienced dull mentation, tremors, loss of gag reflex, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. Orogastric decontamination was performed via gastric lavage, and activated charcoal was given via orogastric tube, followed by ILE. All clinical signs resolved after therapeutic intervention.DiscussionThis is the first report documenting clinical signs of cyclobenzaprine toxicity in two dogs followed by successful treatment with gastric emptying, ILE, and supportive care.

Purpose: Cyclobenzaprine is a muscle relaxant indicated for acute pain. Little is known about cyclobenzaprine's safety during pregnancy. We explored the association between maternal cyclobenzaprine exposure and risk of birth defects among offspring. Methods: We combined data from two large, multi‐site, population‐based case–control studies in the United States. Cases were identified from birth defects registries across 10 states; controls were liveborn infants without birth defects randomly selected from the same catchment areas. Participants reported cyclobenzaprine use during the month before conception through the third month of pregnancy ("periconception") via computer‐assisted telephone interview. We used logistic regression to assess associations between periconceptional cyclobenzaprine exposure and selected structural birth defects. We calculated crude odds ratios (OR) with corresponding 95% confidence intervals (CI). Results: Our study included 33 615 cases and 13 110 controls. Overall, 51 case (0.15%) and 9 control (0.07%) participants reported periconceptional cyclobenzaprine use. We observed increased risk for all seven defects with ≥3 exposed cases: cleft palate (OR = 4.79, 95% CI 1.71–13.44), cleft lip (OR = 2.50, 95% CI 0.89–7.02), anorectal atresia/stenosis (OR = 6.91, 95% CI 1.67, 28.65), d‐transposition of the great arteries (OR = 6.97, 95% CI 2.17–22.36), coarctation of the aorta (OR = 5.58, 95% CI 1.88–16.58), pulmonary valve stenosis (OR = 4.55, 95% CI 1.10–18.87), and secundum atrial septal defect (OR = 3.08, 95% CI 0.83–11.45). Conclusions: Even in our large sample, cyclobenzaprine use was rare. Our estimates are unadjusted and imprecise so should be interpreted cautiously. These hypothesis‐generating results warrant confirmation and further research to explore possible mechanisms. [ABSTRACT FROM AUTHOR]

With musculoskeletal back pain being one of the most common presentations in the emergency department, evidence-based management strategies are needed to address such complaints. Along with other medications, cyclobenzaprine is a muscle relaxant commonly prescribed for patients complaining of musculoskeletal pain, in particular, pain associated with muscle spasms. However, with recent literature questioning its efficacy, the role of cyclobenzaprine use in patients with musculoskeletal back pain remains unclear. The objective of the study is to investigate trends of cyclobenzaprine utilization among patients presenting to the emergency department (ED) in the United States. This is a retrospective cohort review of data obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) between 2007 and 2019. We analyzed ED visits of patients 18 years and older. Visits during which cyclobenzaprine was administered in the ED or prescribed at discharge were identified. Trends were described using a time series analysis of patients' visits who received administration and prescriptions of cyclobenzaprine. Between 2007 and 2019, we identified an estimated 1.35 billion ED visits, 57.2% (772.6 million) were female. From that sample, 2.4% (32.7 million) of all visits received cyclobenzaprine prescription in the ED only, and 0.5% (6.6 million) of total visits were both given the drug in the ED and were prescribed the drug at discharge). Overall trend analysis shows a slight decrease in annual percentages of cyclobenzaprine administration and prescriptions during the study period. Visits of certain subgroups: 26–44 years, white showed relatively higher percentages of administration and prescription of cyclobenzaprine. Although there was a slight decrease, our study still shows significant cyclobenzaprine utilization in the ED, despite conflicting evidence demonstrating efficacy for patients with musculoskeletal complaints and the concern for adverse effects. Additional studies are needed to examine its overall effectiveness and risk-benefit analysis in treating patients with such conditions. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) causes 2.6 million visits to U.S. emergency departments (EDs) annually. These patients are often treated with skeletal muscle relaxants (SMRs).Objectives: The goal of this study was to determine whether efficacy of SMRs is associated with age, sex, or baseline LBP severity.Methods: This was a planned analysis of data from 4 randomized studies of patients with acute nonradicular LBP. Patients were enrolled during an ED visit and followed-up 1 week later. The primary outcome was improvement in the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and the 1-week follow-up. We compared the change in RMDQ among 8 groups: placebo, baclofen, metaxalone, tizanidine, diazepam, orphenadrine, methocarbamol, and cyclobenzaprine. All patients also received a nonsteroidal anti-inflammatory drug. We performed analysis of variance to determine statistically significant differences between medications and linear regression to determine the association of age, sex, and baseline severity with the primary outcome.Results: The mean improvement in RMDQ per group was placebo 10.5 (95% confidence interval [CI] 9.5-11.5), baclofen 10.6 (95% CI 8.6-12.7), metaxalone 10.3 (95% CI 8.1-12.4), tizanidine 11.5 (95% CI 9.5-13.4), diazepam 11.1 (95% CI 9-13.2), orphenadrine 9.5 (95% CI 7.4-11.5), methocarbamol 8.1 (95% CI 6.1-10.1), and cyclobenzaprine 10.1 (95% CI 8.3-12). The between-group differences were not statistically significantly different. Results were similar regardless of age, sex, and baseline severity. Higher baseline RMDQ was associated with greater clinical improvement (B coefficient 5.7, p < 0.01). Adverse medication effects were more common with cyclobenzaprine than with placebo (p < 0.01).Conclusions: Among patients in the ED with acute LBP treated with a nonsteroidal anti-inflammatory drug, SMRs do not improve outcomes more than placebo. Neither age, sex, nor baseline impairment impacts these results. [ABSTRACT FROM AUTHOR]

• Intestinal Ischemia /Reperfusion(I/R) injury causes inflammatory response. • Inflammatory response from (I/R) injury activates toll-like receptor4(TLR4). • Activated TLR4 is leading to activation of TRIF-MYD88 pathway. • TRIF-MYD88 pathway is responsible for induction inflammatory-immune response. • TLR4 inhibitors are involved in decreasing activated TRIF-MYD88 pathway. Intestinal ischemia/reperfusion (I/R) injury is a serious condition that causes intestinal dysfunction and can be fatal. Previous research has shown that toll-like receptor 4 (TLR4) inhibitors have a protective effect against this injury. This study aimed to investigate the protective effects of TLR4 inhibitors, specifically cyclobenzaprine, ketotifen, amitriptyline, and naltrexone, in rats with intestinal (I/R) injury. Albino rats were divided into seven groups: vehicle control, sham-operated, I/R injury, I/R-cyclobenzaprine (10 mg/kg body weight), I/R-ketotifen (1 mg/kg body weight), I/R-amitriptyline (10 mg/kg body weight), and I/R-naltrexone (4 mg/kg body weight) groups. Anesthetized rats (urethane 1.8 g/kg) underwent 30 min of intestinal ischemia by occluding the superior mesenteric artery (SMA), followed by 2 h of reperfusion. Intestinal tissue samples were collected to measure various parameters, including malondialdehyde (MDA), nitric oxide synthase (NO), myeloperoxidase (MPO), superoxide dismutase (SOD), TLR4, intercellular adhesion molecule-1 (ICAM-1), nuclear factor kappa bp65 (NF-ĸBP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), macrophages CD68, myeloid differentiation factor 88 (MYD88), and toll interleukin receptor-domain-containing adaptor-inducing interferon β (TRIF). The use of TLR4 inhibitors significantly reduced MDA, MPO, and NO levels, while increasing SOD activity. Furthermore, it significantly decreased TLR4, ICAM-1, TNF-α, MCP-1, MYD88, and TRIF levels. These drugs also showed partial restoration of normal cellular structure with reduced inflammation. Additionally, there was a decrease in NF-ĸBP65 and macrophages CD68 staining compared to rats in the I/R groups. This study focuses on how TLR4 inhibitors enhance intestinal function and protect against intestinal (I/R) injury by influencing macrophages CD86 through (MYD88-TRIF) pathway, as well as their effects on oxidation and inflammation. [ABSTRACT FROM AUTHOR]

We present a case of a 15‐year‐old female who was admitted in a comatose state with no spontaneous respiratory effort and absence of brainstem reflexes after cyclobenzaprine ingestion. Due to severe presentation and recent ingestion of high plasma protein binding medication with long half‐life, therapeutic plasma exchange (TPE) was performed and resulted in full neurological recovery. This case explores the role of TPE as an effective treatment option for life‐threatening cyclobenzaprine overdose. TPE is generally beneficial for drugs that have a low volume of distribution and high plasma protein binding. Cyclobenzaprine is known to have a relatively high volume of distribution. However, in the case of drug intoxication with relatively high‐volume distribution, high protein binding, and long half‐life, TPE could be effective if it is conducted promptly. [ABSTRACT FROM AUTHOR]

Although the team appropriately initiated supportive treatment for coma with mechanical ventilation, patients with coma related to cyclobenzaprine overdose are expected to improve with time regardless of extracorporeal removal. Keywords: cyclobenzaprine; intoxication; overdose; plasmapheresis; poisoning; therapeutic plasma exchange EN cyclobenzaprine intoxication overdose plasmapheresis poisoning therapeutic plasma exchange 415 416 2 08/10/22 20220801 NES 220801 We read with interest the recent case report by Buyukgoz and colleagues on the use of therapeutic plasma exchange (TPE) in a case of cyclobenzaprine overdose. Cyclobenzaprine, intoxication, overdose, plasmapheresis, poisoning, therapeutic plasma exchange. [Extracted from the article]

Aim: Serotonin syndrome (SS) is a life-threatening syndrome that occurs with the use of serotonergic drugs, most commonly due to two or more agents. Cerebral palsy is associated with mood disorders, and more commonly pain, with a prevalence of up to 50-80%. Case presentation: A 58-year-old female with cerebral palsy, metastatic malignancy and mood disorder who presented to the emergency department with acute-on-chronic pain, and signs of SS. She was initiated on iv. dilaudid, titrated off oral medications and scheduled for a left-sided sacroiliac joint injection. Results: It was suspected that due to additional doses of hydrocodone and cyclobenzaprine, she developed moderate-SS. Conclusion: Physicians need to be cognizant of comorbidities and uncommon pain medications that can predispose patients to SS.

[Display omitted] • Cyclobenzaprine caused a decrease of ATP in L. infantum promastigotes. • The drug induced an irreversible depolarization of plasma membrane. • The drug collapsed the mitochondrial electrochemical potential. • It also induced Ca2+ imbalance and DNA fragmentation. • Cyclobenzaprine can be considered a promising drug candidate. Leishmaniases have a broad spectrum of clinical manifestations, ranging from a cutaneous to a progressive and fatal visceral disease. Chemotherapy is nowadays the almost exclusive way to fight the disease but limited by its scarce therapeutic arsenal, on its own compromised by adverse side effects and clinical resistance. Cyclobenzaprine (CBP), an FDA-approved oral muscle relaxant drug has previously demonstrated in vitro and in vivo activity against Leishmania sp., but its targets were not fully unveiled. This study aimed to define the role of energy metabolism as a target for the leishmanicidal mechanisms of CBP. Methodology to assess CBP leishmanicidal mechanism variation of intracellular ATP levels using living Leishmania transfected with a cytoplasmic luciferase. Induction of plasma membrane permeability by assessing depolarization with DiSBAC(2)3 and entrance of the vital dye SYTOX® Green. Mitochondrial depolarization by rhodamine 123 accumulation. Mapping target site within the respiratory chain by oxygen consumption rate. Reactive oxygen species (ROS) production using MitoSOX. Morphological changes by transmission electron microscopy. CBP caused on L. infantum promastigotes a decrease of intracellular ATP levels, with irreversible depolarization of plasma membrane, the collapse of the mitochondrial electrochemical potential, mild uncoupling of the respiratory chain, and ROS production, with ensuing intracellular Ca2+ imbalance and DNA fragmentation. Electron microscopy supported autophagic features but not a massive plasma membrane disruption. The severe and irreversible mitochondrial damage induced by CBP endorsed the bioenergetics metabolism as a relevant target within the lethal programme induced by CBP in Leishmania. This, together with the mild-side effects of this oral drug, endorses CBP as an appealing novel candidate as a leishmanicidal drug under a drug repurposing strategy. [ABSTRACT FROM AUTHOR]