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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 -
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 -
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 -
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 -
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 -
MethodsX 2020In this study, a novel method was developed to measure acidic and basic drugs in biological and wastewater samples. The method used magnetic nanoparticles based on...
In this study, a novel method was developed to measure acidic and basic drugs in biological and wastewater samples. The method used magnetic nanoparticles based on Vortex-Assisted Dispersive Micro-Solid Phase Extraction (SPE) and then identifying with HPLC-UV. The magnetic nanoparticle (FeO@SiO@Kit-6@NH) has been used as an efficient adsorbent for the extraction of acidic and basic drugs ibuprofen (IFB), fenoprofen calcium (FPC), methocarbamol (MTC), and clonazepam (CZP). The magnetic nanoparticle was characterized by techniques including SEM, XRD, EDX, and FT-IR. The effect of various parameters in the V-D-μ-SPE method was studied completely through the design of the response surface methodology (RSM) of the Box-Behnken design (BBD) based response method and the utility function. The parameters affecting the extraction efficiency were optimized including sample pH, adsorbent amount, absorption time, the salt concentration in the sample solution, CTAB of concentration, desorption time, and the volume of an eluent. After optimization, the limit of detection and calibration curve in the linear range were obtained 0.062-0.32 μg L and 0.1-800 μg L, respectively. Its linear correlation was > 0.9951. The relative standard deviation ( = 5) was between 2.4% and 5.1%. Finally, this method was used to determine target analytes in human serum, urine, and wastewater.•In this study, for the first time, a novel method for the determination of some drugs from human serum, urine, and wastewater samples.•The Synthesized FeO@SiO@Kit-6@NH NPs based V-D-μ-SPE was characterized by techniques including SEM, XRD, EDX, and FT-IR.•The effects of various parameters in the V-D-μ-SPE methods were studied through the design of the RSM of BBD.
PubMed: 32596135
DOI: 10.1016/j.mex.2020.100952 -
Journal of the American Veterinary... May 20214 dogs, 7.5 to 10 years of age, were presented for evaluation of signs of chronic cervical pain and forelimb lameness secondary to cervical foraminal intervertebral disk...
Ultrasound-guided paravertebral perineural glucocorticoid injection for signs of refractory cervical pain associated with foraminal intervertebral disk protrusion in four dogs.
CASE DESCRIPTION
4 dogs, 7.5 to 10 years of age, were presented for evaluation of signs of chronic cervical pain and forelimb lameness secondary to cervical foraminal intervertebral disk protrusion (IVDP). All dogs were refractory to ≥ 2 weeks of conservative management including strict rest and pain management with anti-inflammatory drugs, methocarbamol, and gabapentin.
CLINICAL FINDINGS
The MRI findings included left foraminal IVDP at C2-3 causing mild C3 nerve root compression (dog 1), multifocal degenerative disk disease with mild focal left-sided disk protrusion at C6-7 without associated spinal cord or nerve root compression (dog 2), left foraminal C6-7 IVDP with suspected focal spinal cord atrophy or mild compression (dog 3), and right foraminal C6-7 IVDP and multifocal cervical intervertebral disk degeneration with annulus fibrosus protrusion (dog 4).
TREATMENT AND OUTCOME
Ultrasound-guided paravertebral perineural injections with methylprednisolone acetate (1 mg/kg [0.45 mg/lb]) at the C3 nerve root in dog 1 and at the C7 nerve root in the other 3 dogs were performed. Injections were repeated at intervals of 4 weeks to 3 months on the basis of clinical response. None of the dogs had any complications from the procedures. For dogs 1 and 4, there was complete resolution of lameness and signs of cervical pain following perineural injections, and for dog 3, there was complete resolution of lameness and only minimal residual cervical pain. Dog 2 did not have long-lasting improvement.
CLINICAL RELEVANCE
Findings indicated that ultrasound-guided paravertebral perineural injection can be an effective treatment of cervical foraminal IVDP for some dogs. Additional studies to determine appropriate case selection and better assess the overall success rate and risks associated with this technique are warranted.
Topics: Animals; Cervical Vertebrae; Dog Diseases; Dogs; Glucocorticoids; Intervertebral Disc; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Neck Pain; Ultrasonography, Interventional
PubMed: 33856871
DOI: 10.2460/javma.258.9.999 -
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