Efficacy of Methocarbamol for Acute Pain Management in Young Adults With Traumatic Rib Fractures.

BACKGROUND: Rib fractures account for more than one-third of blunt thoracic injuries and are associated with serious complications. Use of nonopioid adjunctive agents such as methocarbamol for pain control has increased considerably. OBJECTIVE: This study aimed to assess the impact of methocarbamol addition to the pain control regimen on daily opioid requirements for young adults with rib fractures. METHODS: This observational, retrospective study included patients aged 18 to 39 years with 3 or more rib fractures who were admitted to a level 1 trauma center between July 2014 and July 2018. Patients were dichotomized based on admission before and after methocarbamol addition to the institutional rib fracture protocol. The primary outcome was to determine the impact of methocarbamol on daily opioid requirements. Secondary outcomes included hospital length of stay (LOS) and diagnosis of pneumonia. RESULTS: A total of 50 patients were included, with 22 and 28 patients in the preprotocol and postprotocol groups, respectively. All patients in the latter group received methocarbamol, whereas no patient in the preprotocol group received methocarbamol. Cumulative opioid exposure was significantly less for patients admitted after methocarbamol addition to the protocol (219 vs 337 mg oral morphine equivalents; P = 0.01), and hospital LOS was also decreased (4 vs 3 days; P = 0.03). No significant differences in the incidence of pneumonia or adverse effects were observed. CONCLUSION AND RELEVANCE: This is the first study to evaluate the impact of methocarbamol on reducing opioid requirements. Given the risks associated with opioids, use of methocarbamol as an analgesia-optimizing, opioid-sparing multimodal agent may be reasonable.

Utilization Patterns of Skeletal Muscle Relaxants Among Commercially Insured Adults in the United States from 2006 to 2018.

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.

Daniel Bovet, Nobelist: muscle relaxants in anaesthesia : The role played by two neglected protagonists.

In 1957, Professor Daniel Bovet received the Nobel Prize in Physiology or Medicine for his studies on various compounds including the muscle relaxants gallamine and succinylcholine that became very useful in anaesthesia. Textbooks credit Professor Bovet for the discovery of these drugs. However, although he indeed did discover their pharmacological character, the actual syntheses were made by Ernest Fourneau and Reid Hunt, respectively; sadly, these two scientists have largely been ignored. In this paper, a brief biography of Bovet is presented along with some of his more notable accomplishments. Particular emphasis has been placed on gallamine and succinylcholine along with their history. In an attempt to undo the "injustice" dealt to both Fourneau and Hunt, brief accounts of their history, story and character are provided.

Impact of using thiocolchicoside during endoscopic ureteral calculi removal: A preliminary study.

OBJECTIVE: To evaluate the effects of thiocolchicoside during endoscopic treatment of ureteral calculus. MATERIAL AND METHODS: Between May 2014 and December 2014, 498 consecutive patients were enrolled. Exclusion criteria were operations under general anaesthesia, chancing laser lithotripter settings, and urinary tract infection. All patients were divided into three groups: Group 1 consisted of patients who were not administered thiocolchicoside, group 2 consisted of patients who were administered 5 mg thiocolchicoside, and group 3 consisted of patients who were administered 10 mg thiocolchicoside. Demographic, perioperative, and postoperative data were recorded. Complications were noted according to Clavien-Dindo classifications. A p value of p ≤ 0.05 was considered statistically significant. RESULTS: A total of 427 patients (319 male and 108 female) with full data were investigated. Mean age was 43.3 ± 13.3 years. There were 157 patients in group 1, 141 patients in group 2, and 129 patients in group 3. Stone migration and operation time were significantly lower in groups 2 and 3 than in group 1 (respectively; p < 0.001, p = 0.03). However, usage of jj stents was significantly lower in group 3 than in the other groups (p < 0.001). CONCLUSION: Stone migration can be decreased by using locally administered thiocolchicoside in irrigation solution during endoscopic treatment of ureteral calculus. Additional doses may decrease usage of jj stents and operation time.

Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain.

For patients with low back pain, skeletal muscle relaxants are often initiated after failure of first-line analgesics. However, these medications (reviewed in this article) are controversial alternatives that carry risks of adverse effects and increased cost.

Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations.

Background: Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria® for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration. Methods: Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase. Results: Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel. Conclusion: Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.

Utilizing experimental design and desirability function in optimizing RP-HPLC method for simultaneous determination of some skeletal muscle relaxants and analgesics.

An experimental design and response surface methodologies using Plackett-Burman and Box-Behnken designs were applied for selecting and optimizing the most appropriate parameters which significantly affect the separation and quantitative estimation of five skeletal muscle relaxants and four analgesic drugs (baclofen, methocarbamol, dantrolene sodium, orphenadrine citrate, cyclobenzaprine hydrochloride, ketoprofen, etoricoxib, ibuprofen, and mefenamic acid) with a relatively short duration of analysis in a single run. For the separation of the nine drugs, an INERTSIL ODS-V3-5 µm C18 column (250 × 4.6 mm I.D.) was used with the optimum mobile phase conditions (45.15 mM ammonium acetate buffer pH 5.56 adjusted with acetic acid, acetonitrile, and methanol in a ratio of 30.5:29.5:40, v/v/v with a flow rate of 1.5 mL/min) and UV-detection at 220 nm. The optimized method was successfully subjected to the validation steps as described in ICH guidelines for linearity, precision, accuracy, robustness, and sensitivity. The optimized and validated method was effectively applied to determine the content of the studied drugs in their pharmaceutical preparations and to expand its applicability to the counterfeit estimation of etoricoxib in different brands of tablet dosage forms.

Prescription medication use of United States military service members by therapeutic classification.

Background: This cross-sectional study investigated the prevalence of, and factors associated with, filled prescription medications (FPMs) among United States (US) service members (SMs). Methods: A stratified random sample of active duty SMs from the Air Force, Army, Marine Corps, and Navy was obtained from military workforce records. Participants (n = 26,680) completed a questionnaire on demographics, physical characteristics, and lifestyle factors and approved access to their FPM for the previous 6 months. FPMs were obtained from the military Pharmacy Data Transaction Service that included all prescription medications dispensed at military medical treatment facilities, abroad, at retail pharmacies in the US, and/or through mail-order programs. Results: About two-thirds (65%) of SMs had ≥1 FPM in the 6 months surveillance period. Central nervous system (CNS) agents had the highest prevalence (41%), followed by anti-infective agents (20%), eye/ear/nose/throat preparations (20%), gastrointestinal drugs (18%), autonomic drugs (17%), skin and mucous membrane agents (13%), antihistamine drugs (12%), respiratory tract agents (12%) and cardiovascular drugs (9%). Among CNS agents, overall prevalence of dispensed non-steroidal anti-inflammatory drug (NSAIDs) was 30%. The odds of any FPM was independently associated with female gender, older age, higher body mass index, former tobacco use (smoking and smokeless tobacco), lower alcohol consumption, and was highest among Army, lowest among Marine Corps personnel. Conclusion: In this sample of SMs, dispensing of prescription medication was high, especially NSAIDs, but dispensing of cardiovascular drugs was much lower compared to the general US population, likely because of the younger age and higher level of physical activity of SMs.

Impact of Schedule IV controlled substance classification on carisoprodol utilization in the United States: An interrupted time series analysis.

BACKGROUND: In January 2012, the Drug Enforcement Agency (DEA) classified carisoprodol as a Schedule IV controlled substance at the US federal level. We aimed to examine the effect of this policy on the use of carisoprodol in a commercially-insured population. METHODS: This interrupted time series study included individuals with musculoskeletal disorders in the IBM MarketScan Commercial Database between December 2009 and February 2014. We used comparative segmented linear regression to assess changes in the proportions of patients who filled/newly filled carisoprodol each month. RESULTS: A total of 13.3 million patients were included. 29 states with no scheduling prior to the DEA classification had lower baseline prevalence of carisoprodol use compared to 17 states that had scheduled carisoprodol individually before 2010 (11.0 vs. 21.1 patients with fills per 1000 patients). The federal scheduling was associated with an immediate decline (-1.12 per 1000 patients, p < 0.01) and decreasing trend in prevalence (-0.07 per 1000 patients per month, p = 0.02). This effect was not modified by existing state-level scheduling status. During the first, second, third, and fourth 6-month periods after federal scheduling, the relative difference between observed and predicted prevalence was 7.8%, 10.5%, 13.4%, and 19.8%. Similar patterns were observed for carisoprodol initiation. Overall, declining use was more pronounced among younger age groups and patients with injury. CONCLUSIONS: Schedule IV controlled substance classification at the federal level was associated with a moderate reduction in the dispensing of carisoprodol regardless of whether scheduling was already present at the state level.