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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.

Background It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs. Methods Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs. Results MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding. Conclusions An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.

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.

Interstitial Cystitis and Painful Bladder Syndrome are chronic conditions that are associated with urinary frequency, urgency, pain, and nocturia. The etiology of IC/PBS is not clearly understood, therefore diagnosis and treatment can be challenging. IC/PBS greatly affects the quality of life in several ways. In this report, we present the case of a patient with longstanding interstitial cystitis symptoms who was successfully treated with a novel approach after failing treatment established by the current guidelines in the management of IC/PBS. This case illustrates the complex nature of this syndrome and offers a new treatment approach that can potentially change the way IC/PBS are medically managed.

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.

Background EpiFibro (Brazilian Epidemiological Study of Fibromyalgia) was created to study patients with fibromyalgia (FM). Patients were included since 2011 according to the classification criteria for FM of the American College of Rheumatology of 1990 (ACR1990). Objective To analyze the therapeutic measures prescribed by Brazilian physicians. Materials and methods Cross-sectional study of a multicenter cohort. The therapeutic measures were described using descriptive statistics. Results We analyzed 456 patients who had complete data in the registry. The mean age was 54.0 ± 11.9 years; 448 were women (98.2%). Almost all patients (98.4%) used medications, 62.7% received health education, and less than half reported practicing physical exercise; these modalities were often used in combination. Most patients who practiced exercises practiced aerobic exercise only, and a significant portion of patients combined it with flexibility exercises. The most commonly used medication was amitriptyline, followed by cyclobenzaprine, and a minority used medication specifically approved for FM, such as duloxetine and pregabalin, either alone or in combination. Combinations of two or three medications were observed, with the combination of fluoxetine and amitriptyline being the most frequent (18.8%). Conclusion In this evaluation of the care of patients with FM in Brazil, it was found that the majority of patients are treated with a combination of pharmacological measures. Non-pharmacological methods are underused, with aerobic exercise being the most commonly practiced exercise type. The most commonly prescribed single drug was amitriptyline, and the most commonly prescribed combination was fluoxetine and amitriptyline. Drugs specifically approved for FM are seldom prescribed.

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.

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. .

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.

Made available in DSpace on 2019-10-06T17:11:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Purpose: The aim of this study was to evaluate the influence of cyclobenzaprine and dexamethasone on ​the electrical activity of the masticatory muscles in patients who had undergone lower third molar surgery. Methods: Thirty bilateral impacted lower third molars with indication of extraction were randomised into three groups: the control group, the dexamethasone, and the cyclobenzaprine group. To obtain muscular electrical activity and mouth opening, an electromyographic device was used at mandibular rest and maximum voluntary contraction and compared pre- and post-operatively. Results: During muscle contraction, no significant difference was observed in the electromyographic records on the non-operated side. On the operated side, there was a reduction in electrical activity for both drugs pre-operatively and immediately post-operatively compared to the control group. All pharmacological agents promoted a higher mouth opening compared to control group. Conclusion: The results suggest that dexamethasone and cyclobenzaprine may be useful as an adjuvant in the prevention of motor dysfunctions in third molar surgery. Department of Surgery and Oral Diagnoses College of Dentistry State University of São Paulo – UNESP Department of Oral and Maxillofacial Surgery College of Dentistry State University of São Paulo – UNESP, Av. Eng. Francisco José Longo, 777 Department of Bioscience and Oral Diagnoses College of Dentistry State University of São Paulo – UNESP Department of Surgery and Oral Diagnoses College of Dentistry State University of São Paulo – UNESP Department of Oral and Maxillofacial Surgery College of Dentistry State University of São Paulo – UNESP, Av. Eng. Francisco José Longo, 777 Department of Bioscience and Oral Diagnoses College of Dentistry State University of São Paulo – UNESP

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.

Back pain affects people across any socio-economic category and is a leading cause of absenteeism and decreased productivity in the workplace. This symptomatic condition is caused by multiple factors, making it difficult to manage. With a small proportion of people experiencing back pain due to pathological reasons, in the larger majority, back pain is due to a mechanical cause. Taking a complete history that includes identifying risk factors such as depression, poor posture, lack of exercise, older age and a physically demanding job is crucial to the effective management of the condition. Behavioural, psychological and social factors of the patient should form the backbone for treatment of back pain. Non-pharmacological management such as exercise, spinal manipulation and acupuncture should be the first-line treatment; however, if this provides poor results then pharmacological measures such as the use of non-steroidal anti-inflammatory drugs (NSAIDS) like ibuprofen or muscle relaxants such as cyclobenzaprine should be considered. Keywords: back pain, narcotics, non-narcotics, NSAIDs

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.

Objetivo: Avaliar as evidências sobre eficácia e efeitos adversos dos relaxantes musculares de uso oral disponíveis no Brasil para espasticidade, condições musculoesqueléticas, fibromialgia e cefaleia tensional. Métodos: Realizou-se uma revisão da literatura a partir de revisões sistemáticas publicadas no Medline, BVS, biblioteca Cochrane e National Institute for Health and Care Excellence (NICE) até dezembro de 2016, que avaliaram os fármacos considerados relaxantes musculares pela Anatomical Therapeutic Chemical (ATC) e disponíveis no Brasil na forma oral: ciclobenzaprina, tizanidina, carisoprodol, orfenadrina e baclofeno. Resultados: Foram identificados 20 estudos, sendo 17 revisões sistemáticas e três meta-análises. As evidências de eficácia dos relaxantes musculares consistem principalmente em estudos com concepção metodológica ruim. Estudos de comparação não mostraram que um relaxante muscular esquelético seja superior a outro. Ciclobenzaprina demonstrou eficácia em condições musculoesqueléticas, como dor miofascial mandibular, fibromialgia e dor lombar. Na fibromialgia, demonstrou benefício na melhora geral e no sono. No manejo da dor lombar, a ciclobenzaprina mostrou efeito modesto, mais presente nos quatro primeiros dias. Carisoprodol na dor lombar baixa não parece ter diferença de ciclobenzaprina, mas esse medicamento pode causar dependência. Baclofeno e tizanidina parecem ser eficazes em comparação com placebo e equivalentes em doentes com espasticidade. Conclusões: Os relaxantes musculares em geral, comparados a placebo ou entre si, apresentaram poucas evidências com estatística significante. Portanto, a seleção do medicamento deve ser baseada no perfil de efeitos adversos, preferência do paciente, potencial de abuso, potencial de interação com outros medicamentos, custo e outras características dos fármacos.

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.