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CNS Drugs Apr 2022Use of muscle relaxants is rapidly increasing in the USA. Little is understood about the role of drug interactions in the known association between muscle relaxants and...
BACKGROUND
Use of muscle relaxants is rapidly increasing in the USA. Little is understood about the role of drug interactions in the known association between muscle relaxants and unintentional traumatic injury, a clinically important endpoint causing substantial morbidity, disability, and death.
OBJECTIVE
We examined potential associations between concomitant drugs (i.e., precipitants) taken with muscle relaxants (affected drugs, i.e., objects) and hospital presentation for unintentional traumatic injury.
METHODS
In a series of self-controlled case series studies, we screened to identify drug interaction signals for muscle relaxant + precipitant pairs and unintentional traumatic injury. We used Optum's de-identified Clinformatics Data Mart Database, 2000-2019. We included new users of a muscle relaxant, aged 16-90 years, who were dispensed at least one precipitant drug and experienced an unintentional traumatic injury during the observation period. We classified each observation day as precipitant exposed or precipitant unexposed. The outcome was an emergency department or inpatient discharge diagnosis for unintentional traumatic injury. We used conditional Poisson regression to estimate rate ratios adjusting for time-varying confounders and then accounted for multiple estimation via semi-Bayes shrinkage.
RESULTS
We identified 74,657 people who initiated muscle relaxants and experienced an unintentional traumatic injury, in whom we studied concomitant use of 2543 muscle relaxant + precipitant pairs. After adjusting for time-varying confounders, 16 (0.6%) pairs were statistically significantly and positively associated with injury, and therefore deemed signals of a potential drug interaction. Among signals, semi-Bayes shrunk, confounder-adjusted rate ratios ranged from 1.29 (95% confidence interval 1.04-1.62) for baclofen + sertraline to 2.28 (95% confidence interval 1.14-4.55) for methocarbamol + lamotrigine.
CONCLUSIONS
Using real-world data, we identified several new signals of potential muscle relaxant drug interactions associated with unintentional traumatic injury. Only one among 16 signals is currently reported in a major drug interaction knowledge base. Future studies should seek to confirm or refute these signals.
Topics: Bayes Theorem; Databases, Factual; Drug Interactions; Emergency Service, Hospital; Humans; Muscles
PubMed: 35249204
DOI: 10.1007/s40263-022-00909-1 -
PloS One 2023In an investigation of pharmaceutical contamination in the Lac du Flambeau Chain of Lakes (hereafter referred to as "the Chain"), few contaminants were detected; only...
In an investigation of pharmaceutical contamination in the Lac du Flambeau Chain of Lakes (hereafter referred to as "the Chain"), few contaminants were detected; only eight pharmaceuticals and one pesticide were identified among the 110 pharmaceuticals and other organic contaminants monitored in surface water samples. This study, conducted in cooperation with the Lac du Flambeau Tribe's Water Resource Program, investigated these organic contaminants and potential biological effects in channels connecting lakes throughout the Chain, including the Moss Lake Outlet site, adjacent to the wastewater treatment plant lagoon. Of the 6 sites monitored and 24 samples analyzed, sample concentrations and contaminant detection frequencies were greatest at the Moss Lake Outlet site; however, the concentrations and detection frequencies of this study were comparable to other pharmaceutical investigations in basins with similar characteristics. Because established water-quality benchmarks do not exist for the pharmaceuticals detected in this study, alternative screening-level water-quality benchmarks, developed using two U.S. Environmental Protection Agency toxicological resources (ToxCast database and ECOTOX knowledgebase), were used to estimate potential biological effects associated with the observed contaminant concentrations. Two contaminants (caffeine and thiabendazole) exceeded the prioritization threshold according to ToxCast alternative benchmarks, and four contaminants (acetaminophen, atrazine, caffeine, and carbamazepine) exceeded the prioritization threshold according to ECOTOX alternative benchmarks. Atrazine, an herbicide, was the most frequently detected contaminant (79% of samples), and it exhibited the strongest potential for biological effects due to its high estimated potency. Insufficient toxicological information within ToxCast and ECOTOX for gabapentin and methocarbamol (which had the two greatest concentrations in this study) precluded alternative benchmark development. This data gap presents unknown potential environmental impacts. Future research examining the biological effects elicited by these two contaminants as well as the others detected in this study would further elucidate the ecological relevance of the water chemistry results generated though this investigation.
Topics: Environmental Monitoring; Lakes; Atrazine; Caffeine; Water Pollutants, Chemical; Water; Pharmaceutical Preparations
PubMed: 37267346
DOI: 10.1371/journal.pone.0286571 -
Frontiers in Veterinary Science 2023A 10-month-old, 3 kg, female spayed Domestic Shorthair cat was presented with a chronic, infected wound at the level of the proximo-lateral left pelvic limb. General...
A 10-month-old, 3 kg, female spayed Domestic Shorthair cat was presented with a chronic, infected wound at the level of the proximo-lateral left pelvic limb. General physical examination revealed a weight-bearing lameness of the left pelvic limb, which was moderately and circumferentially swollen and edematous proximal to the tarsal joint. On the lateral aspect of the proximal thigh, there was a chronic wound of 1 cm in diameter and an additional exudative skin lesion was present throughout the whole length of the caudo-lateral thigh. Complete blood count and serum biochemistry profile revealed mild anemia, increased serum amyloid A, hyponatraemia, hypochloraemia, hypocalcaemia, hyperkalaemia, hypermagnesaemia, hyperglycaemia, increased creatine kinase, and increased liver parameters. Surgical exploration of the wound was performed, and necrotizing fasciitis was suspected. The affected limb was amputated and swabs for bacterial culture were taken from both the skin lesions and surgical site before wound closure. One day after surgery, mild muscular contractions on the forehead and an increased muscle tone of the right pelvic limb were evident. One day later, the cat developed a generalized increase in extensor tone, with intermittent opisthotonos, resulting in lateral recumbency. Based on these clinical signs, a diagnosis of generalized tetanus was made and treatment with midazolam, methocarbamol, and metronidazole was started. Despite an improvement of all blood parameters, the cat progressively deteriorated and 4 days after surgery, it developed episodes of tetanic convulsions, associated with hyperthermia and ventricular arrhythmias. Despite intensive care and medical management, the cat died following a cardio-respiratory arrest 3 days later. This case report describes a rare case of severe generalized tetanus in a young cat.
PubMed: 38130435
DOI: 10.3389/fvets.2023.1328331 -
Toxicology Reports Dec 2023Methocarbamol is a muscle relaxant medication that is commonly used to treat muscle spasms and musculoskeletal pain. Methocarbamol intramuscular injection can cause...
BACKGROUND
Methocarbamol is a muscle relaxant medication that is commonly used to treat muscle spasms and musculoskeletal pain. Methocarbamol intramuscular injection can cause necrosis of the soft tissue. This rare condition can create severe adverse event with permanent disability.
CASE PRESENTATION
A 32-year-old woman with no significant past medical history presented to the emergency department with severe pain, redness, and swelling involving her left buttock and the surrounding back area.
CLINICAL DISCUSSION
The necrotic changes due to methocarbamol intramuscular injection can progress rapidly, leading to the formation of deep ulcers, cellulitis, and even abscesses. Prompt recognition and intervention are crucial to prevent further tissue damage and complications.
CONCLUSION
Comprehending the fundamental mechanisms and identifying risk factors related to this complication is imperative in enabling healthcare professionals to proficiently manage and avert its manifestation.
PubMed: 37859670
DOI: 10.1016/j.toxrep.2023.10.002 -
Clinical Pharmacology and Therapeutics Nov 2022Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs). We performed high-throughput screening...
Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs). We performed high-throughput screening for clinically relevant DDIs with methadone or buprenorphine by combining pharmacoepidemiologic and pharmacokinetic approaches. We conducted pharmacoepidemiologic screening via a series of self-controlled case series studies (SCCS) in Optum claims data from 2000 to 2019. We included persons 18 years or older who experienced an outcome of interest during target drug treatment. Exposures were all overlapping medications (i.e., the candidate precipitants) during target drug treatment. Outcomes were opioid overdose, non-overdose adverse effects, and cardiac arrest. We used conditional Poisson regression to calculate rate ratios, accounting for multiple comparisons with semi-Bayes shrinkage. We explored the impact of key study design choices in analyses that varied the exposure definitions of the target drugs and the candidate precipitant drugs. Pharmacokinetic screening was conducted by incorporating published data on CYP enzyme metabolism into an equation-based static model. In SCCS analysis, 1,432 events were included from 248,069 new users of methadone or buprenorphine. In the primary analysis, statistically significant DDIs included gabapentinoids with either methadone or buprenorphine; baclofen with methadone; and benzodiazepines with methadone. In sensitivity analysis, additional statistically significant DDIs included methocarbamol, quetiapine, or simvastatin with methadone. Pharmacokinetic screening identified two moderate-to-strong potential DDIs (clonidine and fluconazole with buprenorphine). The combination of clonidine and buprenorphine was also associated with a significantly increased risk of opioid overdose in pharmacoepidemiologic screening. These DDI signals may be the most important targets for future confirmation studies.
Topics: Humans; Buprenorphine; Methadone; Clonidine; Baclofen; Opiate Overdose; Quetiapine Fumarate; Methocarbamol; Fluconazole; Bayes Theorem; Opioid-Related Disorders; Benzodiazepines; Drug Interactions; Simvastatin; Opiate Substitution Treatment
PubMed: 35881659
DOI: 10.1002/cpt.2717 -
Cureus Feb 2024This case report highlights the complexities of tizanidine withdrawal in a 68-year-old woman with chronic pain. Tizanidine, a widely used imidazole-derived muscle...
This case report highlights the complexities of tizanidine withdrawal in a 68-year-old woman with chronic pain. Tizanidine, a widely used imidazole-derived muscle relaxant, poses challenges due to the absence of standardized withdrawal protocols. The patient's presentation included hypertension and tachycardia following a gradual reduction in her outpatient tizanidine dose. During the de-escalation of tizanidine, the patient experienced withdrawal symptoms, including severe body aches, hypertension, and tachycardia. Management during withdrawal involved a unique approach using a one-time dose of phenobarbital, a measure that allowed the resolution of hemodynamic instability and pain with complete discontinuation of tizanidine. The ultimate decision to transition the patient to methocarbamol and stop taking tizanidine for pain control highlights the importance of individualized care. The patient has responded to this therapy upon follow-up.
PubMed: 38435197
DOI: 10.7759/cureus.53444 -
Frontiers in Veterinary Science 2023Tetanus is a severe neurologic disease caused by , resulting in spastic paralysis. Canine tetanus is associated with serious complications such as aspiration and a high...
OBJECTIVE
Tetanus is a severe neurologic disease caused by , resulting in spastic paralysis. Canine tetanus is associated with serious complications such as aspiration and a high mortality rate of up to 50%.
MATERIALS AND METHODS
Medical records of all dogs diagnosed with tetanus over 8 years (2014-2022) were analyzed for severity grade, treatment protocols, nutritional management, and complications, as well as outcome, vaccination, and antibody production in some dogs. No medical records were excluded. Normality was analyzed by the D'Agostino-Pearson test. Parametric, normally distributed data were presented as mean ± standard deviation. Non-parametric, non-normally distributed data were presented as median (m) and range (minimum-maximum). The association between tetanus grade, progression of diseases, and duration of hospitalization was analyzed using the -test, Mann-Whitney U test, and Kruskal-Wallis test. A ≤ 0.05 was considered significant.
RESULTS
Eighteen dogs were identified. Most affected dogs were classified into severity grade II (66.7%, 12 of 18). Clinical signs deteriorated in 55.6% of dogs (10 of 18). A source was identified in 88.9% of dogs (16 of 18). Nine dogs required surgical wound revision. A percutaneous endoscopic gastropexy tube was placed in 83.3% of dogs (15 of 18) for nutritional support. Medical treatment included metronidazole, methocarbamol, and combinations of different sedatives adapted to the patient's requirements. Tetanus antitoxin was used in 72.2% of dogs (13 of 18) without reported adverse events. The survival rate was 88.9% (16 of 18). Complications, such as hypertension, aspiration pneumonia, and laryngeal spasm occurred in 12 of 18 dogs. Median hospitalization time (8 days; range 0-16 days) was associated with the maximum tetanus severity grade (p = 0.022). Rapid eye movement behavior disorder was observed in 72.2% of dogs (13 of 18). In 5 dogs, antibodies were measured after recovery, and in 4 of 5 dogs, no antibodies were detectable despite generalized tetanus disease. Vaccination with tetanus toxoid was performed in five dogs following the disease.
CONCLUSION
In the present study, the mortality rate was lower than previously reported. Tetanus is still a life-threatening disease, but the prognosis may be good if adequate management and monitoring can be ensured.
PubMed: 38026664
DOI: 10.3389/fvets.2023.1249833 -
British Journal of Pharmacology Nov 19681. Mephenesin, methocarbamol and diazepam abolished polysynaptic reflex contractions of the cat tibialis anterior muscle elicited by stimulation of the homolateral...
1. Mephenesin, methocarbamol and diazepam abolished polysynaptic reflex contractions of the cat tibialis anterior muscle elicited by stimulation of the homolateral femoral nerve.2. Mephenesin and methocarbamol caused a prolongation of the mean refractory period of directly or indirectly stimulated skeletal muscle. These effects were due to a direct action on the muscle fibres. There was no effect on responses to single stimuli.3. The increase in refractory period produced by mephenesin was greater in indirectly than in directly stimulated rat diaphragms. Experiments using the isolated phrenic nerve suggest that this difference is due to the local anaesthetic action of mephenesin.4. In the indirectly stimulated cat tibialis anterior muscle high frequency stimulation resulted in a non-maintained tetanus in the presence of mephenesin and methocarbamol.5. Diazepam was without peripheral effects on the responses of skeletal muscle.6. The results with mephenesin and methocarbamol are discussed in relation to their mode of action in reducing muscle spasm.
Topics: Action Potentials; Anesthesia; Animals; Cats; Diaphragm; Diazepam; Mephenesin; Methocarbamol; Muscle Contraction; Neural Conduction; Phrenic Nerve; Rats
PubMed: 5726787
DOI: 10.1111/j.1476-5381.1968.tb08486.x -
Psychosomatics 2020
Topics: Adult; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; COVID-19; Catatonia; Coronavirus Infections; Delusions; Hallucinations; Humans; Hypnotics and Sedatives; Lorazepam; Male; Methocarbamol; Muscle Relaxants, Central; Pandemics; Pneumonia, Viral; SARS-CoV-2; Spasm
PubMed: 32605766
DOI: 10.1016/j.psym.2020.05.021 -
Annals of Emergency Medicine Mar 2018In US emergency departments (EDs), patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and muscle relaxants. We compare functional... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
In US emergency departments (EDs), patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and muscle relaxants. We compare functional outcomes among patients randomized to a 1-week course of naproxen+placebo versus naproxen+orphenadrine or naproxen+methocarbamol.
METHODS
This was a randomized, double-blind, comparative effectiveness trial conducted in 2 urban EDs. Patients presenting with acute, nontraumatic, nonradicular low back pain were enrolled. The primary outcome was improvement on the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and 1 week later. All patients were given 14 tablets of naproxen 500 mg, to be used twice a day, as needed for low back pain. Additionally, patients were randomized to receive a 1-week supply of orphenadrine 100 mg, to be used twice a day as needed, methocarbamol 750 mg, to be used as 1 or 2 tablets 3 times per day as needed, or placebo. All patients received a standardized 10-minute low back pain educational session before discharge.
RESULTS
Two hundred forty patients were randomized. Baseline demographic characteristics were comparable. The mean RMDQ score of patients randomized to naproxen+placebo improved by 10.9 points (95% confidence interval [CI] 8.9 to 12.9). The mean RMDQ score of patients randomized to naproxen+orphenadrine improved by 9.4 points (95% CI 7.4 to 11.5). The mean RMDQ score of patients randomized to naproxen+methocarbamol improved by 8.1 points (95% CI 6.1 to 10.1). None of the between-group differences surpassed our threshold for clinical significance. Adverse events were reported by 17% (95% CI 10% to 28%) of placebo patients, 9% (95% CI 4% to 19%) of orphenadrine patients, and 19% (95% CI 11% to 29%) of methocarbamol patients.
CONCLUSION
Among ED patients with acute, nontraumatic, nonradicular low back pain, combining naproxen with either orphenadrine or methocarbamol did not improve functional outcomes compared with naproxen+placebo.
Topics: Acute Pain; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Low Back Pain; Male; Methocarbamol; Muscle Relaxants, Central; Naproxen; Orphenadrine; Pain Measurement; Time Factors; Treatment Outcome
PubMed: 29089169
DOI: 10.1016/j.annemergmed.2017.09.031