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The paper considers modern strategies for pharmacological treatment of non-specific back pain. It has been shown that despite some controversial approaches to the treatment according to the latest clinical guidelines, central muscle relaxants still play an important role in the treatment of back pain is significantly increased. At the same time, non-narcotic analgesics (paracetamol) are no longer considered as first line drugs for the treatment of acute back pain, as recommended several years ago. The analysis was carried out of the group of centrally acting muscle relaxants. Significant heterogeneity of the group and individual differences between various drugs are shown. As for some preparations of the group, their manufacturers received instructions from the regulatory authorities due to the unfavorable benefit/risk ratio. Cyclobenzaprine, one of the central muscle relaxants, which is new on the pharmaceutical market of Ukraine, is considered with more details. It is noted that one of major advantages is the dosage form of this drug with a slow release of the active substance. This allows cyclobenzaprine to be used once a day and contributes to improving the safety profile and patient’s compliance.

Objective To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults in the United States. Methods We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥2-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method. Analyses were stratified by age group, sex, geographic region, individual SMR agent, and musculoskeletal disorder. Results 48.7 million individuals were included. Treatment prevalence ranged from 61.5 to 68.3 per 1,000. About one-third of users did not have a preceding musculoskeletal disorder diagnosis. Cyclobenzaprine was the dominant agent accounting for >50% of prescriptions. The considerable growth in the use of baclofen, tizanidine, and methocarbamol paralleled with a decline in carisoprodol and metaxalone use. The prevalence was highest in the South while lowest in the Northeast. The median treatment duration was 14 days with 4.0%, 1.9%, and 1.0% of individuals using SMRs for more than 90, 180, and 365 days, respectively. Compared with cyclobenzaprine, patients initiating baclofen, tizanidine, and carisoprodol had longer treatment duration. Conclusions SMRs are widely used in the United States. Their use slightly increased in recent years, but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use.

The aim of this study is to use new drugs capable of crossing the blood-brain barrier (BBB) to develop new radiopharmaceuticals for non-invasive brain imaging. Quetiapine (QTP) and cyclobenzaprine (CBP), as two 5-HT2A receptor antagonists, were successfully labeled with radioactive iodine (125I) using Chloramine-T (CAT) as an oxidizing agent via electrophilic substitution reactions. After studying the parameters affecting the labeling yield (substrate amount, CAT amount, pH of the reaction mix., reaction time and temperature), the highest radiochemical yields of125I-QTP and 125I-CBP were found to be 94.5 % ± 1.0 and 91.7 % ± 0.6, respectively, at pH 2. The biodistribution and the SPECT/CT image showed that the maximum uptake of radioiodinated-QTP by the mouse brain was 10.2% and 10.9% at 120 minutes post-injection, while the radioiodinated-CBP was 7.7% and 12.4% at 240 minutes post-injection. The results have shown that radioiodinated-QTP and radioiodinated-CBP are novel radiopharmaceuticals and may be used for brain imaging.

Aim: The aim of present study was to develop and validate a dissolution test method for Cyclobenzaprine HCL in its formulation using RP-HPLC method. Design: Optimization of chromatographic parameters, development of the dissolution test method using RP-HPLC and to validate the developed methods as per ICH guidelines. Materials and Methods: The optimized dissolution parameters includes USP apparatus II at a paddle rotation rate of 50 rpm and 900 ml of 1.2 pH 0.1N HCL buffer at 37?C0.5?C. Under these conditions, the in vitro release profiles of cyclobenzaprine HCL showed good results. The drug release was estimated by RP-HPLC using column Shodex C18-4E (250×4.6mm×5mm), detection wavelength 289.4 nm having the flow rate 1.0 mL/min using Acetonitrile : phosphate buffer (3.0 pH) in the proportion of 65:35%v/v. Results: The percent drug amount released estimated by proposed method was found to be 99.04%, The method was found to be linear with correlation coefficient was found to be 0.9991 in the concentration range was 2-10 mg/mL. The mean % recovery of Cyclobenzaprine was found to be 100.04.Precision values observed less than 2.All the validation parameters were within the acceptance range. Conclusion: The results obtained by proposed dissolution method for tablet formulation containing Cyclobenzaprine HCL are reliable, precise and accurate. Hence it was routinely adopted for dissolution analysis of the said drugs in the formulation. Keywords: Cyclobenzaprine HCL, Dissolution test, RPHPLC, Validation.

BACKGROUND: The opioid epidemic is at epic proportions currently in the United States. Exposure to opioids for surgery and subsequent postoperative pain management is a known risk factor for opioid dependence. In addition, opioids can have a negative impact on multiple aspects including clinical outcomes, length of hospital stay, and overall cost of care. Thus, the greatest effort to reduce perioperative opioid use is necessary and a multimodal pain control (MMPC) has been gaining popularity. However, its efficacy in spine surgery is not well known. We aimed to evaluate the efficacy of a MMPC protocol in patients undergoing lumbar single-level anterior lumbar interbody fusion (ALIF). METHODS: This is a retrospective comparative study. From a prospective, single-surgeon, surgical database, consecutive patients undergoing single-level ALIF with or without subsequent posterior fusion for degenerative lumbar conditions were identified before and after initiation of the MMPC protocol. The MMPC protocol consisted of a preoperative oral regimen of cyclobenzaprine (10 mg), gabapentin (600 mg), acetaminophen (1 g), and methadone (10 mg). Postoperatively they received a bilateral transverse abdominis plane block with 0.5% Ropivacaine prior to extubation. We compared in-hospital opioid consumption between the MMPC and non-MMPC cohorts as well as baseline demographic, the length of hospital stay, cost, and rate of postoperative ileus. Opioid consumption was calculated and normalized to the morphine milligram equivalents (MMEs). RESULTS: In total, 68 patients in the MMPC cohort and 39 in the non-MMPC cohort were identified. There was no difference in baseline demographics including sex, body mass index, smoking status, or preoperative opioid use between the two groups. Although there was no difference in the MMEs on the day of surgery (58.5 vs. 66.9, P=0.387), cumulative MMEs each day after surgery was significantly lower in the MMPC cohort, with final cumulative MMEs being reduced by 62% (120.2 vs. 314.8, P

What is known and objective Tolperisone is a centrally acting muscle relaxant under development in the United States as a treatment for acute and painful symptoms of muscle spasms. The objective of this three‐way, randomized, blinded, three‐period crossover study was to assess the safety and cognitive effects of tolperisone compared to placebo and the widely used muscle relaxant cyclobenzaprine in healthy volunteers. Methods Subjects were randomized to 1 of 3 treatment arms to receive tolperisone (150 mg), cyclobenzaprine (10 mg) or placebo 3 times per day (TID) in 3 separate study periods. Subjects completed a driving test on the Cognitive Research Corporation's Driving Simulator (CRCDS Mini‐Sim), a validated driving simulator, on day 1 at time to maximum plasma concentration, on day 2 before the morning dose of study drug and on day 3 at steady state following the morning dose. Subjects were assessed on various driving parameters and on a computer‐administered digit‐symbol substitution test (CogScreen symbol digit coding test). The driving scenario is a monotonous 100 km highway route on which subjects are instructed to maintain speed and lane position. Results and discussion The performance of subjects who had received tolperisone was not significantly different from those who had received placebo in terms of the primary end point: standard deviation of lateral position, a measure of weaving. Subjects who had received tolperisone also performed comparably to those who had received placebo on a range of secondary measures assessing driving ability, cognition and psychomotor performance. In contrast, subjects who had received cyclobenzaprine showed significant impairment compared to placebo (P, Tolperisone is a centrally acting muscle relaxant under development for the treatment of acute and painful symptoms of muscle spasm. In this study of driving ability and cognitive effects, subjects who received tolperisone experienced no impact on measures of driving, self‐reported sleepiness, or cognition compared to placebo, in contrast to those who received the widely used muscle relaxant cyclobenzaprine.

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., This work was supported by grants of Sao Paulo State Research Foundation (FAPESP 2019/10434-4 to S.E.T.B. and 2021/04464-8 and 2017/50333-7 to A.G.T.); Subdirección General de Redes y Centros de Investigación Cooperativa - FEDER (RICET RD16/0027/0010, and Ministerio de Ciencia e Innovación España. Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020-FEDER PID2019- 108166GB-100 /AEI/10.13039/501100011033 to L. R.), EADS-CASA/Brazilian Air Force (FAB) mobility program to M.L.L., and Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) to M. L.L.

In this work, a resonance Rayleigh scattering technique and a spectrofluorimetric technique were applied to the quantification of cyclobenzaprine through two validated methods. The suggested methods are based on a facile association complex formation between cyclobenzaprine and eosin Y reagent in the acidic medium. The resonance Rayleigh scattering method relied on the enhancement in the resonance Rayleigh scattering spectrum of eosin Y at 370 nm after the addition of cyclobenzaprine. On the other hand, the spectrofluorimetric quantification relied on the quenching effect of cyclobenzaprine on the fluorescence strength of the eosin Y reagent at 545 nm (excitation wavelength at 300 nm). The suggested methods were linear over the ranges of 0.07–1.75 μg/mL and 0.15–2.0 μg/mL with detection limit values of 0.023 μg/mL and 0.048 μg/mL for the resonance Rayleigh scattering method and the spectrofluorimetric method, respectively. All reaction conditions for cyclobenzaprine–eosin Y formation were experimentally evaluated and optimized. In addition, both methods were validated based on ICH rules. Furthermore, the developed methods were practically applied to the analysis of cyclobenzaprine in its commercial tablet dosage form with acceptable recoveries. Moreover, the content uniformity test of the commercial cyclobenzaprine tablets was successfully applied using the proposed spectroscopic methods based on USP rules.

Background Many clinical toxicology laboratories receive urine specimens in urine cups that contain point of care (POC) drug testing strips. We conducted this study to evaluate the effect on the stability of commonly measured drugs in the clinical toxicology laboratory when urine is exposed to POC urine drug testing cups. Methods Drug free urine was spiked with 85 drugs that were measured by a validated liquid chromatography mass spectrometry (LCMS) method after exposure to POC urine drug testing cups at ambient and 2–6 °C temperatures. Alterations ≥20% were defined as significant changes in the drugs concentration. Results Concentrations of amitriptyline, cyclobenzaprine, fentanyl, fluoxetine, flunitrazepam, nortriptyline, paroxetine, and sertraline were significantly reduced when urine specimens were stored inside POC urine drug testing cups for 24 h at ambient temperature. Storage of urine in urine chemistry dipsticks reduced the concentration of several drugs. When spiked urine was exposed to an increasing number of POC urine drug testing strips, the concentrations of some drugs were reduced in a dose-dependent manner. The drugs that were absorbed by POC urine drug testing strips were partially back extracted from the strips. Conclusion Exposure of urine specimens to POC urine drug testing strips reduces the concentration of several drugs measured by LCMS method.

The Beers Criteria for Potentially Inappropriate Medication (PIM) use is a list of medications with multiple risks in older patients. Approximately 24 per cent use rate is reported in prior studies. Our objective was to determine the local PIM use and subsequent fall risk in geriatric trauma patients. We conducted a retrospective analysis of PIM use in all geriatric patients evaluated at our Level 1 trauma center between 2014 and 2017. Patients were identified from our trauma database. Pre-admission medication use was determined through medication reconciliation from our electronic medical record (EMR). Patients not undergoing medication reconciliation were excluded. After initial analysis, patients were stratified by age into three groups: 65 to 74, 75 to 84, and ≥85 years. Multivariate logistic regression analyses were used to calculate odds ratios of falls for specific PIMs. In all, 2181 patients met the inclusion criteria. Overall, 71.2 per cent of geriatric trauma patients were prescribed at least one PIM—73.1 per cent of falls compared with 68.6 per cent for other mechanisms. Specific PIM use varied by age group. PIMs associated with fall risk in all patients included antipsychotics, benzodiazepines, and diclofenac. For those aged 65 to 74 years, antihistamines, diclofenac, proton pump inhibitors, and promethazine were associated. In those aged 75 to 84 years, alprazolam, antipsychotics, benzodiazepines, cyclobenzaprine, diclofenac, and muscle relaxants were implicated. No significant associations were found for patients aged ≥85 years. PIM use at our trauma center seems to be rampant and well above the national average. Geriatric falls were associated with using ≥1 PIM and multiple specific PIMs implicated. We are designing a targeted educational program for local primary care physicians (PCPs) that will attempt to decrease geriatric PIM use.

Introduction: Cyclobenzaprine is a skeletal muscle relaxant primarily used in the treatment of pain. Its use during lactation is a matter of concern as its level of exposure to infants through human milk is still unknown. Main issue: The aim of this study was to determine cyclobenzaprine concentrations in the milk samples collected from two lactating mothers. Management: The present study describes the analysis of cyclobenzaprine in human milk using liquid chromatography mass spectrometry, which determined the drug concentration-time profiles in human milk. Conclusion: This study shows low levels of concentrations of cyclobenzaprine in human milk with calculated relative infant dose of 0.5%. However, due to the sedative properties of cyclobenzaprine, regular clinical assessment of the infant is recommended to evaluate for long-term effects.

Background and Purpose Neck pain in the United States is pervasive and contributes to disability. While the majority of neck pain in young and healthy individuals is neuromusculoskeletal in nature, screening for red flags is necessary for ruling-out serious medical pathologies. The purpose of this case report is to describe a young and healthy male subject with a primary complaint of acute neck pain with multiple underlying upper extremity superficial vein thromboses (UESVTs). Case Description The subject was a 27-year-old male active-duty Soldier referred to physical therapy by his primary care provider (PCP) for acute left-sided neck pain. Prior to physical therapy, the subject had been treated with cyclobenzaprine, oxycodone-acetaminophen, trigger point injection and had undergone a D-dimer to rule out a potential thrombus due to air travel and lower extremity immobilization. Outcomes The subject underwent a D-dimer, Doppler ultrasound, pharmacological treatment of Rivaroxaban, and was referred to hematology/oncology to rule out systemic causes of SVTs. Evidence of subtle increases in blood pressure over the course of three months, a positive D-dimer, and symptoms incongruent with clinical presentation contributed to referral to a hematology/oncology specialist and a diagnosis of multiple UESVTs. The subject was able to return to his previous level of activity by six months and remained free of SVTs at two-year follow-up. Discussion UESVT events are rare and can be challenging to identify. This case report describes a unique presentation of acute neck pain caused by underlying UESVTs in an otherwise healthy and active young male. Level of Evidence Level 4

We present a case of a 64-year-old woman who developed severe non-exertional hyperthermia (NEHT) due to excessive anticholinergic effects from her psychiatric medications. The patient was found unresponsive in a non-air-conditioned room where the outside temperature was over 33°C. She presented with altered mental status, hypotension and an oral temperature of 42°C. Drug–drug interactions from her home medications for depression, bipolar disorder and seizures (amitriptyline, cyclobenzaprine, benztropine, topiramate, clonazepam, trazodone) were suspected. Blood cultures grew Staphylococcus hominis. The patient quickly returned to baseline with supportive care in the intensive care unit. She was treated for the Staph hominis bacteraemia with a 7-day course of vancomycin. Due to her quick recovery and lack of neurological findings, severe NEHT with associated bacteraemia was determined to have caused her presenting symptoms. This patient’s multiple anticholinergic medications increased her susceptibility to develop NEHT by inhibited sweating, this patient’s natural cooling mechanism.

Background Opioids are a mainstay of pain management. To limit the use of opioids, enhanced recovery after surgery (ERAS) protocols implement multimodal approaches to treat postoperative pain. Objectives The aim of this paper was to be the first to assess the efficacy of an ERAS protocol for plastic surgery outpatients that includes ultrasound-guided, surgeon-led regional blocks. Methods A retrospective review of patients undergoing outpatient plastic surgery on an ERAS protocol was performed. These patients were compared to a well-matched group not on an ERAS protocol (pre-ERAS). Endpoints included the amounts of opioid, antinausea, and antispasmodic medication prescribed. ERAS patients were given a postoperative questionnaire to assess both pain levels (0-10) and opioid consumption. ERAS patients anticipated to have higher levels of pain received ultrasound-guided anesthetic blocks. Results There were 157 patients in the pre-ERAS group and 202 patients in the ERAS group. Patients in the pre-ERAS group were prescribed more opioid (332.3 vs 100.3 morphine milligram equivalents (MME)/patient; P < 0.001), antinausea (664 vs 16.3 mg of promethazine/patient; P < 0.001), and antispasmodic (401.3 vs 31.2 mg of cyclobenzaprine/patient; P < 0.001) medication. Patients on the ERAS protocol consumed an average total of 22.7 MME/patient postoperatively. Average pain scores in this group peaked at 5.32 on postoperative day 1 and then decreased significantly daily. Conclusions Implementation of an ERAS protocol for plastic surgery outpatients with utilization of ultrasound-guided regional anesthetic blocks is feasible and efficacious. The ability to significantly decrease prescribed opioids in this unique patient population is noteworthy. Level of Evidence: 4

Context Low back pain is one of the most frequent diagnoses in primary care, and prescription pain medication is commonly used for management. Osteopathic physicians may use osteopathic manipulative treatment (OMT) as an additional tool to help alleviate pain. Objective To determine if nonpharmacological options can improve back pain with the use of OMT. Methods Two groups were studied: patients receiving OMT but not using prescribed pain medications (OMT-only group) and patients who received prescribed pain medication and began receiving OMT after three months of pharmacologic therapy (OMT + medication group). All patients were enrolled in the study for one year. The amount of time between treatments was determined by the physician performing the OMT and the patient’s pain improvement. The Keele STarT survey and Oswestry Disability Index tool were used at each appointment to assess the patient’s functionality and pain. Results Thirty-six patients enrolled in the study: 26 in the OMT-only group and 10 in the OMT + medication group. Each group reported improvement in low back pain (LBP) according to both scales used. The OMT-only group reported improvement according to the Keele STarT survey (30% relative decrease in the mean score) and the Oswestry Disability Index tool (18% relative decrease in disability index), while patients in the OMT + medication group also reported improvement according to the Keele STarT survey (29.5% relative decrease in the mean score) and the Oswestry Disability Index tool (18% relative decrease in disability index). A decrease in Cyclobenzaprine usage was also observed in the OMT + medication group. Conclusion Both groups showed significant decreases in overall pain, and this similar effect in each group may indicate a lack of need for medications when OMT is used. Additional research on efficacy of OMT in this patient population is needed with larger, multicenter, randomized trials.

The purpose of this chapter is to review the adverse effects associated with neuromuscular blocking agents and skeletal muscle relaxants. A literature search using PubMed, Medline, and Cochrane (January 2020–December 2020) was performed utilizing keywords: succinylcholine, suxamethonium, atracurium, cisatracurium, mivacurium, pancuronium, rocuronium, vecuronium, gantacurium, CW002, CW011, adamgammadex, sugammadex, neostigmine, calabadion, L-cysteine, baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine, neuromuscular blocking agents, skeletal muscle relaxants, adverse effects, and side effects. All English-language reports during the specified year were included for this review. Adverse effects were reported for the following medications between January 2020 and December 2020: succinylcholine (suxamethonium), cisatracurium, rocuronium, neostigmine, adamgammadex, sugammadex, baclofen, metaxalone, and tolperisone. This chapter outlines the findings from the identified articles including adverse effects, suspected mechanisms underlying these effects, and implications to clinical practice and patient care.

Introduction: Nearly 80% of children with epilepsy have one or more chronic comorbidities that require specific drug treatments in several cases. Drug-drug interactions (DDIs) between antiseizure medications (ASMs) and all other drugs (NON-ASMs) used to treat comorbid diseases may have serious consequences. Areas covered: All potential DDIs between 27 ASMs and all NON-ASMs used for oral chronic treatment of those disorders most often comorbid with epilepsy in children were searched for drug compendia. Clinical evidence of the identified DDIs was also searched in the literature. Forty-eight drugs have been identified as potential DDIs with at least one ASM. Most important DDIs are between some ASMs and omeprazole and pantoprazole (drugs for gastrointestinal disorders), ibuprofen and cyclobenzaprine (drugs for musculoskeletal disorders), loratidine, lumacaftor/ivacaftor, montelukast, and theophylline (drugs for respiratory system), levothyroxine, liothyronine and several corticosteroids (systemic hormonal preparations), almotriptan, dihydroergotamine, ergotamine, and several antipsychotics, antidepressants and anxiolytics (drugs for nervous diseases). Clinical evidence of the predicted DDIs was found in a minority of cases. Expert opinion: Treatment of children with epilepsy should be decided considering treatment of both seizures and comorbid diseases and aimed at minimizing the risk of DDIs between ASMs and NON-ASMs.

Almost totality of fibromyalgia patients complain of disturbed sleep, but to date, this topic is at the centre of many controversies. First of all, subjective sleep complaints can be found in all patients, but not all studies observed altered objective parameters when investigating sleep using polysomnography; therefore, currently, no disease-specific sleep alterations have been found. Secondly, sleep disturbances correlate with many fibromyalgia symptoms, and it is now known that the relationship between sleep and pain is bidirectional, but it is still not clear why the sleep of fibromyalgia patients is so disrupted. Putative mechanisms include alterations in the hormonal, neurotransmitter and immune systems, and in the autonomic nervous system. There are also no interventions that are both safe and effective for improving sleep in fibromyalgia patients; hence, treatment must be multidimensional and take into account the multiple causative factors and the frequent fibromyalgia comorbidities. First, it is necessary to adopt behavioural changes, including sleep hygiene practices and regular exercise; secondly, some pharmacological treatments can be tried, such as pregabalin, amitriptyline and very low dose cyclobenzaprine, which are frequently used to treat pain and sleep disturbances in fibromyalgia patients, whilst duloxetine and milnacipran are less effective on sleep. New promising drugs are sodium oxybate, cannabis and cannabinoids. The high frequency of sleep alterations and their complex relationship with other manifestations in fibromyalgia mean that physicians should specifically address them, in order to have a positive effect on patients’ quality of life.

Effective posttraumatic stress disorder (PTSD) pharmacotherapy is needed. This 12-week randomized multicenter trial evaluated efficacy and safety of TNX-102 SL, a bedtime sublingual formulation of cyclobenzaprine, in patients with military-related PTSD randomized to TNX-102 SL 2.8 mg or 5.6 mg, or placebo. Primary analysis comparing change from baseline in Clinician-Administered PTSD Scale-5 score between 2.8 mg (n=90) and placebo (n=92) was not significant. Secondary analysis of 5.6 mg (n=49) vs placebo demonstrated a mean difference of -4.5 units, p=.05, or, accounting for missing data by multiple imputation, -5.0 units, p=.03. Clinician Global Impression - Improvement responder rate was greater in 5.6 mg than placebo (p=0.04), as was mean functional improvement in Sheehan Disability Scale social domain (p=.03) and trended in work domain (p=.05). Post-hoc analyses showed early sleep improvement predicted improvement in PTSD after 12 weeks for TNX-102 SL (p

Pyridoxine is an important co-factor for many biochemical reactions in cellular metabolism related to the synthesis and catabolism of amino acids, fatty acids, neurotransmitters. Deficiency of pyridoxine results in impaired transcellular signaling between neurons and presents with muscular convulsions, hyperirritability, and peripheral neuropathy. Deficiency of pyridoxine is usually found in association with other vitamin B deficiencies such as folate (vitamin B9) and cobalamin (vitamin B12). Isolated pyridoxine deficiency is extremely rare. We present the case of a 59-year old female with type 2 diabetes who complained of painful muscle spasms. Her muscle spasms involved in both feet, which have spread proximally to her legs. She also experienced intermittent muscle spasms in her left arm, which is not alleviated by baclofen, cyclobenzaprine. Her plasma pyridoxal 5-phosphate confirmed pyridoxine deficiency. Vitamins B1, B3, B12, and folate were within normal limits. The patient received standard-dose intramuscular pyridoxine injections for three weeks followed by oral supplements for 3 months and her symptoms resolved. This case illustrates the rare instance of isolated pyridoxine deficiency in type 2 diabetes patient manifesting as myoclonic muscle spasms involving the legs and arms in the absence of objective polyneuropathy. Pyridoxine level should, therefore, be assessed in patients with type 2 diabetes, including newly diagnosed patients.

Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure (SBP) ≤ 70 mmHg during periods of drug co-exposure. Severe hypotension occurred more often in the tizanidine group (2.03%; n = 33) than the cyclobenzaprine group (1.28%; n = 64); odds ratio (OR) = 1.60; P = 0.029. This difference remained statistically significant after adjustment for a log-transformed propensity score that included age, sex, race, Charlson's comorbidity index, and concurrent use of antihypertensive medications (OR = 1.57; P = 0.049). A sensitivity analysis that defined hypotension as SBP < 90 mmHg also yielded higher rates of hypotension among patients prescribed tizanidine. In conclusion, CYP1A2 inhibition increases the risk of hypotensive episodes associated with the use of tizanidine in routine clinical practice.

The purpose of this study was to test the hypothesis that skeletal muscle relaxants could inhibit the in vitro metabolism of common comedications opioids buprenorphine, methadone and oxycodone. The compounds [solubility-limited concentration (μM) studied] were as follows: baclofen (1000), carisoprodol (200), its metabolite meprobamate (1000), chlorzoxazone (200), cyclobenzaprine (1000), metaxalone (50), methocarbamol (1000), orphenadrine (1000) and tizanidine (1000). Compounds were first incubated with human liver microsomes ± pre-incubation, screened with pathway-specific cDNA-expressed cytochrome P450s (rCYP), and then IC50 values determined using either 8-concentration tests for those where the rCYP screen suggested an IC50 was achievable, or a 3-concentration test with downward extrapolation if screen suggested 50% inhibition was not achievable. These results were then extrapolated to determine an inhibitory potential. Six pathway inhibitor combinations were identified with a moderate inhibitory potential (≥2.0 < 5.0): five with chlorzoxazone, R-EDDP, S-EDDP and noroxycodone production by CYP3A4, and R- and S-EDDP production by CYP2B6; and one for the meprobamate effect on noroxycodone production by CYP3A4. An additional eleven combinations were found with a weak inhibitory potential (≥1.25 < 2.0): five with carisoprodol, two each with methocarbamol and meprobamate, and one each with metaxalone and orphenadrine. This represents the first comprehensive study of the inhibitory effect of this class of drugs and suggests that some of them may produce significant drug-drug interactions with opioids that are frequent comedications with skeletal muscle relaxants.

Objective Difficulty swallowing pills can compromise pain control in painful musculoskeletal disorders. This open-label, 2-period crossover study assessed pharmacokinetics and safety of cyclobenzaprine extended-release (CER) 30-mg capsule contents sprinkled over applesauce compared with intact capsules in healthy subjects. Materials and methods 32 subjects were randomized to treatment sequences AB or BA (A = single CER intact capsule; B = single CER capsule contents sprinkled over applesauce (15 mL)). Treatments were separated by a ≥ 14-day washout. Pharmacokinetic assessments included maximum observed plasma drug concentration (Cmax), time to Cmax (tmax), time to first quantifiable plasma drug concentration (tlag), and area under the plasma drug concentration-vs.-time curve from time 0 to the last measurable drug concentration (AUC0-t) and extrapolated to infinity (AUC0-∞). Bioequivalence was established if the 90% confidence intervals (CIs) of the geometric least squares (LS) means ratios of B:A of Cmax, AUC0-t, and AUC0-∞ were 80 - 125%. Safety was also assessed. Results Mean plasma drug concentration-vs.-time profiles were similar for CER intact and sprinkled over applesauce. The 90% CIs of LS means ratios indicated bioequivalence: Cmax 91.96 - 100.76%, AUC0-t 96.18 - 103.50%, and AUC0-∞ 95.70 - 103.07%. Median tmax was not significantly different (p > 0.05), and median tlag was the same (1 hour). All adverse effects were mild and resolved during the study. No clinically meaningful changes were noted for clinical laboratory values. Conclusion CER capsules intact and sprinkled over applesauce are bioequivalent. Sprinkling CER capsule contents is not expected to affect efficacy or safety and can, therefore, be an option for patients with musculoskeletal pain and difficulty swallowing capsules. .

Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1/β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule.

Cyclobenzaprine hydrochloride, a skeletal muscle relaxant has been determined using an ecofriendly micellar HPLC method in its pure form and tablets. The chromatographic determination was performed using C8 monolithic column (100mm×4.6mm i.d., 5μm particle size) and micellar eluent which was composed of sodium dodecyl sulfate (0.15M), n-propanol (15%), 0.02M orthophosphoric acid (pH 4.5) and 0.3% triethylamine using UV detection of effluent was set at 225nm. The calibration plot showed good linearity over concentration range from 2-40μg/mL. The assay results were statistically validated for linearity, accuracy, precision and specificity according to ICH guidelines. Additionally, regarding USP guidelines, the uniformity of tablets content and in-vitro dissolution test of the tablets was tested using the proposed method. Simple and rapid applicability of the developed method allowed determination of the drug in its pure and tablet dosage forms. Moreover, the major advantage of micellar HPLC technique is to determine the drug in biological fluids without prior extraction steps. Depending on this, the estimation of cyclobenzaprine in spiked human urine was so simple without traditional tedious procedures. The proposed method offers the advantages of sensitivity and simplicity in addition to short analysis time which didn't exceed 6 minutes.

As part of early drug development, preformulation studies are used to comprehensively explore the properties of new drugs. In particular, this includes the biopharmaceutical characterization and evaluation of impacting factors (e.g. excipients, microenvironmental conditions etc.) by permeation studies. To overcome the limitations of current studies, a novel standardized ex vivo procedure using esophageal mucosa as surrogate has been established successfully and applied to preformulation studies for oromucosal delivery of cyclobenzaprine hydrochloride, a tricyclic muscle relaxant with potential for psychopharmacotherapeutic use. By using the standardized ex vivo permeation process, a twofold enhancement of permeability (0.98 ± 0.16 to 1.96 ± 0.10 * 10-5 cm/s) was observed by adjustment and controlling of microenvironmental pH, empowering a targeted and effective development of sublingual formulations. Predictivity and suitability were superior compared to in vitro experiments using artificial biomimetic membranes, revealing a determination coefficient (R2) of 0.995 vs. 0.322 concerning pH-dependent permeability of cyclobenzaprine. In addition, diffusion properties were extensively examined (e.g. influence of mucosal thicknesses, tissue freezing etc.). The alignment of the study design regarding physiologically/clinically relevant conditions resulted in ex vivo data that allowed for the estimation of plasma AUC levels in the extend of reported in vivo ranges.

Made available in DSpace on 2022-04-28T19:30:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-20 The present work describes the performance of a new voltammetric sensor based on the modification of glassy carbon electrodes (GCE) with carbon black (CB) and botryosphaeran (BOT) (CB-BOT/GCE) for the electroanalytical determination of cyclobenzaprine. BOT is a fungal exocellular (1→3)(1→6)-β-ᴅ-glucan, which was used to improve the adherence of CB onto the surface of GCE. The electrochemical characterisation was performed by electrochemical impedance spectroscopy which showed an improvement in the transfer of electrons on the surface of the sensor developed in relation to the unmodified (bare) GCE. The voltammetric behaviour of cyclobenzaprine was studied using bare GCE, BOT/GCE, CB/GCE, and CB-BOT/GCE. All electrodes presented an oxidation peak (+ 1.0 V) for cyclobenzaprine, while the cyclobenzaprine peak intensity on CB-BOT/GCE was found to be 480% higher than the bare GCE. Through employing square-wave voltammetry, the analytical curve was found to be linear over the concentration range of 2.0 to 20.6 μmol L−1 (in 0.1 mol L−1 NaCl solution) with a detection limit (based on 3-sigma) of 0.63 μmol L−1. The developed electrochemical sensor exhibited excellent sensitivity and selectivity and was successfully applied for the voltammetric determination of cyclobenzaprine in pharmaceutical, biological, and environmental samples for the first time using the CB-BOT/GCE electrochemical sensing platform. Departamento de Química Centro de Ciências Exatas Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, 445 Km 380 Faculty of Science and Engineering Manchester Metropolitan University, Chester Street Departamento de Química e Bioquímica Escola de Ciência e Tecnologia Universidade do Estado de São Paulo Programa de Pós-Graduação em Ciências Fisiológicas Departamento de Ciências Fisiológicas Centro de Ciências Biológicas Universidade Estadual de Londrina Beta-Glucan Produtos Farmoquímicos EIRELI UTFPR Câmpus Londrina, Lote 24A, Bloco Zircônia, Avenida João Miguel Caram 731

Tissue-based ex-vivo studies on the oromucosal permeability of drugs are often insufficiently adapted to physiological and clinical conditions, which limits their predictivity. Moreover, the scientific community demands for the standardization of ex-vivo studies, since conceptual limitations (e.g. low sensitivity of analytical methods, insufficient monitoring, different designs) restrict the wide implementation in preclinical drug development. Therefore, an innovative ex-vivo permeation process consisting of novel Kerski diffusion cell coupled to fully automated sampling and sample preparation with LC-MS/MS quantification was developed and standardized. Novel assays for routine examination of tissue integrity and viability were developed and embedded in a comprehensive analytical control system. The high level of standardization and automation reduced the differences of between-run to within-run precision to ≤ 0.27 % CV. Successful validation proved a broad calibration range of 0.93-952.38 ng/mL of the model drug cyclobenzaprine with guideline-compliant relative errors from -7.9-12.6 % (between-run accuracy). Consequently, the method allowed the physiological-clinical alignment of the study conditions to therapeutic doses and the short residence time of intraoral drugs (sampling times 1-60 min). Applicability was demonstrated by assessing the oromucosal permeability for different sublingual cyclobenzaprine hydrochloride formulations representing the excipient selection as a common aspect during galenic development. Thereby, expressive evaluation of the dosage forms was achieved resulting in an improved permeation by replacing croscarmellose into polyvinylpyrrolidone (cumulative amount of 42.6 vs. 112.6 μg/cm²). Thus, the automated permeation process ensured lean, standardized and reproducible assessment of oromucosal permeability within quality-controlled academic and regulatory environments. Simultaneously, the improved ex-vivo predictivity through physiological-clinical adjustments facilitates the reduction of costly in-vivo studies.

The aim of this study was to investigate the effect of backing films on transdermal delivery of cyclobenzaprine patch. Different backing films were chosen to prepare the cyclobenzaprine transdermal patch. The cumulative amount of cyclobenzaprine released from different patches was evaluated in vitro. To investigate the interaction between cyclobenzaprine and backing films, the partitioning experiments and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were performed. The cumulative amount of cyclobenzaprine released from the patch with Cotran™ 9700 as backing film was less than that of other patches with different backing films. Furthermore, the cumulative amount of cyclobenzaprine released from the patch with Cotran™ 9700 as backing film decreased significantly after 7 d storage at room condition. The partitioning experiments indicated a strong adsorption of cyclobenzaprine onto the Cotran™ 9700, which could explain the decrease of cumulative amount of cyclobenzaprine released from the patch with Cotran™ 9700 as backing film. According to the ATR-FTIR results, there was no interaction between Cotran™ 9700 and cyclobenzaprine. The effect of backing films on the release behavior of cyclobenzaprine transdermal patch was attributed to the adsorption of cyclobenzaprine onto the Cotran™ 9700.

The aim of this study was to improve the transdermal delivery of cyclobenzaprine (CBZ) from drug-in-adhesive patch which showed less side effects and better compliance. CBZ base was prepared and then characterized using differential scanning calorimetry (DSC). The interaction between CBZ and pressure-sensitive adhesive (PSA) was determined by Fourier Transform Infrared Spectroscopy (FT-IR). The influences of PSAs, penetration enhancers, patch thickness and drug content on the transdermal delivery of CBZ were studied thoroughly in vitro. Both CBZ releasing from patch and penetrating through the skin showed very great effect on the transdermal delivery of CBZ. The percentage of drug released from patch was increased with the decreasing of patch thickness, and so did the permeation percentage. The stratum corneum (SC) contributed approximately 57% resistance of total skin permeation resistance, and Span 20 increased the transdermal permeation by approximately 1.59-fold. The pharmacokinetic parameters were obtained through in vivo experiments of the optimized formulation using rabbit. Furthermore, the in vitro skin permeation results of CBZ patch correlated well with the in vivo absorption results in rabbit.

Objetivo: Revisar a literatura acerca da eficácia de fármacos antidepressivos no tratamento de pacientes com disfunções musculares faciais crônicas em termos de redução da dor e efeitos adversos. Métodos: Pesquisaram-se os descritores “Antidepressive Agents”, “Facial Pain”, “Drug Therapy,”, conectados pelo operador booleano “AND”, na base de dados Pubmed dos últimos 10 anos. Obtiveram-se 40 artigos, dos quais foram selecionados 10 com base na leitura de títulos e resumos. Foram incluídos estudos e ensaios clínicos que relataram tratamentos de disfunções musculares faciais crônicas com fármacos antidepressivos. Resultados: 3 estudos concluíram que houve redução da dor em pacientes tratados com Amitriptilina e naqueles que receberam Amitriptilina com Pindolol. 2 estudos perceberam efeitos positivos nos pacientes tratados com Milnacipran. 2 estudos inferiram que, após o início da administração de Duloxetina, houve redução significativa da dor. 2 estudos sugeriram eficácia em pacientes com disfunções musculares faciais crônicas e que utilizaram Amitriptilina e Nortriptilina. 1 estudo observou o uso de Tizanidina ou Ciclobenzaprina, e concluiu sua ineficácia comparado ao placebo. Considerações finais: Os fármacos antidepressivos possuem a capacidade de tratar com eficácia as dores miofasciais, principalmente dores crônicas, devido a capacidade de possuir efeitos analgésicos, sendo a Amitriptilina considerada padrão-ouro para esses tratamentos.

BACKGROUND CONTEXT Recent studies suggest as much as 25% of patients undergoing spine surgery are still on opioids two years later. In response, we developed protocols to minimize opioid consumption following elective spine surgery. Our goal was to evaluate patients undergoing single-level Anterior Lumbar Interbody Fusions (ALIF ± posterior fixation) on MMPC compared to patients who were not (nonMMPC). PURPOSE To determine if the combination of an oral preoperative pain cocktail with transverse abdominis plane (TAP) block (multi-modal pain control: MMPC) will reduce length of stay (LOS), ileus, and in-hospital opioid consumption. STUDY DESIGN/SETTING Retrospective chart review. PATIENT SAMPLE Consecutive patients undergoing single-level ALIF for degenerative lumbar conditions by a single-surgeon. OUTCOME MEASURES Length of stay (LOS), incidence of ileus and in-hospital opioid consumption. METHODS A retrospective review of a prospective, single-surgeon, surgical database was utilized for consistency in technique. Consecutive patients undergoing single-level ALIF for degenerative lumbar conditions were identified before and after initiation of the MMPC. The MMPC consisted of a preop oral regimen of cyclobenzaprine (10mg), gabapentin (600mg), acetaminophen (1g) and methadone (10mg). Postoperatively they received a bilateral transverse abdominis plane (TAP) block with 0.5% Ropivicaine. Our primary outcome was total, in-hospital opioid consumption (morphine milligram equivalents: MME). RESULTS There were 68 patients in the MMPC cohort and 39 in the nonMMPC cohort. There was no difference in baseline demographics such as sex, BMI, smoking, or preoperative opioid use between the two groups. The MMPC cohort was older (56.7 vs 51.1 years, p=0.026). Similar rates of ileus (4 vs 6, p=0.102), no difference in LOS (3.8 vs 4.5, p=0.246) and no difference in index hospital costs was found. Although there was no difference in day of surgery MMEs (58.5 vs 68.9, p=0.387), cumulative MMEs each day after surgery was significantly lower in the MMPC cohort, with final cumulative MMEs being reduced by 62% (120.2 vs 314.8, p CONCLUSIONS The use of a MMPC regimen in patients undergoing single-level ALIF for degenerative conditions reduced opioid consumption starting on POD 1, resulting in a cumulative reduction of 62%. Further research should strive to minimize opioid use and the downstream effects. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Skeletal muscle relaxants are frequently prescribed for low back pain and other musculoskeletal pain with or after failure of first-line treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs). While there can be benefits of using skeletal muscle relaxants in the short term, the long-term effects are unclear. These medications are heterogeneous and not chemically related and have several important adverse effects that should be considered given their widespread utilization. In the United States, carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine are FDA approved for acute musculoskeletal conditions. Baclofen, tizanidine, and dantrolene are approved for spasticity. There is no clear evidence to show superiority of one muscle relaxant over another in managing acute low back pain, and most studies only evaluate results at 12 weeks or less. Most guidelines and current evidence support short-term use for all medications discussed in this chapter.

Rationale & Objective Muscle relaxants are often used to treat musculoskeletal pain or cramping, which are commonly experienced by hemodialysis patients. However, the extent to which muscle relaxants are prescribed in this population and the risks associated with their use have not been characterized. Study Design Observational cohort study. Setting & Participants 140,899 Medicare-covered adults receiving hemodialysis in 2011, identified in the US Renal Data System. Exposure Time-varying muscle relaxant exposure. Outcomes Primary outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, or fracture. Secondary outcomes were death and composites of death with each of the primary outcomes. Analytical Approach Multivariable Cox regression analysis. Results 10% of patients received muscle relaxants in 2011. 11%, 6%, 3%, and 13% had an episode of altered mental status, fall, fracture, and death, respectively. Muscle relaxant use was associated with higher risk for altered mental status (HR, 1.39; 95% CI, 1.29-1.51) and fall (HR, 1.18; 95% CI, 1.05-1.33) compared to no use. Muscle relaxant use was not statistically significantly associated with higher risk for fracture (HR, 1.17; 95% CI, 0.98-1.39). Muscle relaxant use was associated with lower hazard of death (HR, 0.85; 95% CI, 0.76-0.94). However, hazards were higher for altered mental status or death (HR, 1.17; 95% CI, 1.10-1.25), fall or death (HR, 1.14; 95% CI, 1.06-1.22), and fracture or death (HR, 1.10; 95% CI, 1.01-1.20). Limitations A causal association between muscle relaxant use and outcomes cannot be inferred, and residual confounding cannot be excluded. Exposure and outcomes were ascertained using administrative claims. Conclusions Muscle relaxant use was common in hemodialysis patients and associated with altered mental status and falls. We could not rule out a clinically meaningful association between muscle relaxant use and fracture. The lower risk for death with muscle relaxants may have been the result of residual confounding. Future research to define the appropriate use of muscle relaxants in this population is warranted.

Purpose Systematic studies of the diversion of nonscheduled drugs, except for gabapentin, are not apparent. We searched diversion case reports of all other nonscheduled psychoactive prescription drugs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System. Methods Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies. Rates of diversion per 100 000 population were calculated for each year from 2002 to 2017 for prescription medications with greater than 400 reported cases during the period. Results Cyclobenzaprine, quetiapine, and trazodone met criteria for analysis. We found a significant and steady increase in the diversion of each drug over the period. The 2017 annual rates of diversion per 100 000 population for the three medications range from 0.0428 to 0.0726. Although these rates of diversion are much lower than the rate for total opioid analgesics, they are all more than five times higher in 2017 compared with 2002. While diversion rates for opioids have decreased in recent years, rates for cyclobenzaprine, quetiapine, and trazodone have continued to increase. Conclusions A common attribute of the three nonscheduled drugs studied here is that all are used for the treatment and/or self-treatment of opioid withdrawal symptoms, and the increasing diversion of these drugs may be related to the ongoing opioid epidemic and to increasing levels of control over pharmaceutical opioid availability in the United States. Prescribers need to be aware of illicit markets for these medications and prescribe to their patients with appropriate caution.

Objective: The influence of cyclobenzaprine hydrochloride (Miosan®,10mg/orally/single dose), taken prior to the extraction of impacted mandibular third molars on the electrical activity of superficial masseter and anterior temporal muscles was evaluated through electromyographic recordings aiming at contributing to the discussion of the diagnosis of stomatognathic dysfunctions in relation to long lasting operative procedures. Material and Methods: Twenty patients referred for the extraction of impacted and embedded mandibular third molars at the Discipline of Oral and maxillofacial Surgery and Traumatology (Institute of Science and Technology of São José dos Campos/Unesp), without systemic disease and allergic reactions to the drugs used, both sexes were selected. An electromyographer model EMG-800C (EMG System do Brasil Ltd.), with four input channels, previously calibrated with active electrodes and 20-fold amplification gain was used together with a channel linked to the system to record the mouth opening (mandibular goniometer). The following conditions were assessed: rest, maximum voluntary isometric contraction, and maximum mouth opening, at the following periods: pre-surgical, surgical, and post-surgical (7, 15, and 30 days). Results: The electrical activity of the studied muscles was reduced at the beginning of the surgical procedure, but it did not significantly alter by the administration of the drug at all evaluated periods. The masseter muscle, after the drug administration, reestablished its activity just after the post-operative period, unlikely the control group, which reestablished the activity after 7 days. A significant mouth opening was seen for the comparison between control and experimental groups (p < 0.001). Conclusion: Thus, based on these results, we suggest that the single-dose myorelaxant taken prior to the surgical procedure interfere on the motor activity of the studied muscles. This approach can be useful as adjuvant therapy in patients exhibiting stomatognathic system dysfunctions causing damage to the masticatory system due to the presence of embedded mandibular third molar. Keywords: Myorelaxants; Third Molars; Electromyography; Cyclobenzaprine; Surgery.

Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of this study was to evaluate the efficacy of 2 compounded topical creams, "Cream I" and "Cream II," in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic topical pain conditions and compare their efficacy with Voltaren gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. The Cream I contained Flurbiprofen (20%), Tramadol (5%), Clonidine (0.2%), Cyclobenzaprine (4%), and Bupivacaine (3%). The Cream II contained Flurbiprofen (20%), Baclofen (2%), Clonidine (0.2%), Gabapentin (10%), and Lidocaine (5%). The Voltaren gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren gel. After treatment, the pain intensity score decreased by 3.11 ± 1.65 (37%) with Cream I (from 8.44 ± 1.19 to 5.33 ± 2.0, P < 0.001), by 2.93 ± 1.58 (35%) with Cream II (from 8.42 ± 1.27 to 5.50 ± 1.96, P < 0.001), and by 1.49 ± 0.73 (19%) with Voltaren gel (from 7.93 ± 0.81 to 6.44 ± 1.14, P < 0.001). Cream I and Cream II did not differ significantly in efficacy, and both were significantly more effective than Voltaren gel (P < 0.001). It is concluded that Voltaren gel had less efficacy than the compounded creams, which were effective and provided pain relief in the majority of the patients studied.

In this case report, a 22-year-old male developed severe hypothermia after an accidental overdose of cyclobenzaprine. During transport, the patient developed cardiac arrest. He received active rewarming measures, including pleural lavage, gastric lavage, an intravascular heat exchange catheter, and cardiopulmonary bypass. Intravenous lipid emulsion (ILE) was also administered. A discussion of cyclobenzaprine toxicity, hypothermia, ILE, and accidental hypothermic cardiac arrest follows.

Fibromyalgia is a syndrome characterized by chronic generalized pain in addition to different symptoms such as fatigue, sleep disturbances, stiffness, cognitive impairment, and psychological distress. Multidisciplinary treatment combining pharmacological and nonpharmacological therapies is advised.Publications describing randomized controlled trials and long-term extension studies evaluating drug treatment for fibromyalgia were searched in PubMed and Scopus and included in this review.Different drugs are recommended for the treatment of fibromyalgia by different published guidelines, although only three of them have been approved for this indication by the US FDA, and none have been approved by the European Medicines Agency. According to the available evidence, pregabalin, duloxetine and milnacipran should be the drugs of choice for the treatment of this disease, followed by amitriptyline and cyclobenzaprine. Other drugs with at least one positive clinical trial include some selective serotonin reuptake inhibitors, moclobemide, pirlindole, gabapentin, tramadol, tropisetron, sodium oxybate and nabilone. None of the currently available drugs are fully effective against the whole spectrum of fibromyalgia symptoms, namely pain, fatigue, sleep disturbances and depression, among the most relevant symptoms. Combination therapy is an option that needs to be more thoroughly investigated in clinical trials.

Aim The aim of this study was to characterize urethral neuromuscular function before and 2 weeks after medication therapy. Methods Premenopausal women without lower urinary tract symptoms were randomly allocated to 1 of the 6 medications for 2 weeks (pseudoephedrine ER of 120 mg, imipramine of 25 mg, cyclobenzaprine of 10 mg, tamsulosin of 0.4 mg, solifenacin of 5 mg, or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle electromyography (CNE) of the urethral sphincter using automated multimotor unit action potential software, current perception threshold (CPT) testing to measure periurethral sensation, and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Results Fifty-six women had baseline testing, 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean, 34.3; SD, 10.1), body mass index (mean, 31.8; SD, 7.5), parity (median, 1; range, 0-7), or race (14% Caucasian, 80% African American). The PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5-Hz stimulation level was observed after treatment with pseudoephedrine (0.15-0.09 mA at 5 Hz, P = 0.03). Conclusions In women without lower urinary tract symptoms, pseudoephedrine improved urethral sensation but not urethral neuromuscular function on CNE or PFS. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function.

A 35-year-old female patient was brought into the emergency department by EMS one weekend morning after being found down by her parents, with a chief complaint of altered mental status, confusion, and somnolence. Upon arrival the patient was drowsy but arousable and able to converse. She admitted to taking a handful of her muscle relaxant medicine (cyclobenzaprine) with some alcohol that prior evening when she had an argument with her boyfriend. Her past medical history included depression, for which she took escitalopram 10 mg daily. The muscle relaxant was given to her recently for an acute muscle spasm of her lower back. She denied any other drugs or medications.

This health technology assessment evaluated the efficacy of pharmacological treatment in patients with oro-facial pain. Randomised controlled trials were included if they reported pharmacological treatment in patients ≥18 years with chronic (≥3 months) oro-facial pain. Patients were divided into subgroups: TMD-muscle [temporomandibular disorders (TMD) mainly associated with myalgia]; TMD-joint (TMD mainly associated with temporomandibular joint pain); and burning mouth syndrome (BMS). The primary outcome was pain intensity reduction after pharmacological treatment. The scientific quality of the evidence was rated according to GRADE. An electronic search in PubMed, Cochrane Library, and EMBASE from database inception to 1 March 2017 combined with a handsearch identified 1552 articles. After screening of abstracts, 178 articles were reviewed in full text and 57 studies met the inclusion criteria. After risk of bias assessment, 41 articles remained: 15 studies on 790 patients classified as TMD-joint, nine on 375 patients classified as TMD-muscle and 17 on 868 patients with BMS. Of these, eight studies on TMD-muscle, and five on BMS were included in separate network meta-analysis. The narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain. The network meta-analysis showed that clonazepam and capsaicin reduced pain intensity in BMS, and the muscle relaxant cyclobenzaprine, for the TMD-muscle group. In conclusion, based on a limited number of studies, evidence provided with network meta-analysis showed that clonazepam and capsaicin are effective in treatment of BMS and that the muscle relaxant cyclobenzaprine has a positive treatment effect for TMD-muscle pain.

Some forms of tinnitus are believed to arise from abnormal central nervous system activity following a single or repeated noise exposure, for which there are no widely accepted pharmacological treatments. One central site that could be related to tinnitus awareness or modulation is the locus coeruleus, a brainstem structure associated with stress, arousal, and attention. In the present study, we evaluated the effects of cyclobenzaprine, a drug known to act on the rat locus coeruleus, on noise-induced tinnitus using Gap Prepulse Inhibition of the Acoustic Startle (GPIAS). In untreated rats, brief silent gaps presented prior to a 5-10-kHz bandpass startling stimulus produced robust GPIAS. Treatment with cyclobenzaprine alone had no effect on the ability of gaps to suppress the startle response. When animals were exposed to intense narrow-band (126 dB SPL, 16 kHz, 100 Hz BW) unilateral noise, GPIAS was significantly reduced, suggesting the presence of tinnitus. Following the noise exposure, a subset of rats that maintained a robust startle response continued to show GPIAS impairment at 6-20 kHz, 40 days post-noise, suggesting chronic tinnitus. When this subset of animals was treated with cyclobenzaprine, at a dose that had no significant effects on the startle response (0.5 mg/kg), GPIAS recovered partially or to near baseline levels at the affected frequencies. These results were consistent with the absence of tinnitus. By 48 h post-treatment, evidence of tinnitus re-emerged. Our results suggest that cyclobenzaprine was effective in transiently suppressing noise-induced tinnitus in rats.

A rapid and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma. After extracted with organic solvent, post-treatment samples were separated on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode. Multiple reaction monitoring was performed using the transitions of m / z 276.2 → 216.1 and m / z 325.1 → 109.0 to quantify cyclobenzaprine and escitalopram (internal standard), respectively. The mobile phase consisted of acetonitrile: 5 mM ammonium acetate: formic acid (90:10:0.01, v/v/v) at a flow rate of 0.3 ml/min. The total analysis time was 2.4 min. The method was linear over the concentration range of 0.0200–10.0 ng/ml. The intra- and inter-day precision was within 12.8% in terms of relative standard deviation (RSD%) and the accuracy within 5.6% in terms of relative error. This method was successfully applied in a pharmacokinetic study of extended-release cyclobenzaprine in dogs.