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Journal of Advanced Pharmaceutical... 2017Fasciculation is a minor adverse effect of succinylcholine and may be an unpleasant experience for patient. The aim of this study was to compare the use of atracurium...
Fasciculation is a minor adverse effect of succinylcholine and may be an unpleasant experience for patient. The aim of this study was to compare the use of atracurium and methocarbamol to decrease the occurrence and severity of succinylcholine-induced muscle fasciculation. Fifty-nine adults with American Society of Anesthesiologists I or II hospitalized for elective surgery were randomly assigned to two groups: Group A ( = 29) who received succinylcholine 1 mg/kg body weight (BW) intravenously followed by 0.2-0.5 mg/kg BW atracurium and patients in Group B (= 29) who received succinylcholine 1 mg/kg BW intravenously followed by methocarbamol 0.2-0.5 mg/kg BW. Anesthesia was induced in all patients with thiopental sodium 3-5 mg/kg. Fasciculation was scored on a four-point (0-4) Likert scale. There were no statistically significant differences in demographic variables between two groups, whereas in Group A, 27 patients (93.1%) suffered from mild fasciculation and two (6.9%) from moderate fasciculation. In Group B, twenty patients (68.9%) suffered from mild fasciculation, five (17.2%) from moderate fasciculation, and four (13.9%) from severe fasciculation. The difference between the groups was statistically significant ( < 0.05). Atracurium is more effective than methocarbamol in decreasing the occurrence and severity of succinylcholine-induced fasciculations. In addition, the use of methocarbamol before succinylcholine administration can decrease the incidence of severe fasciculation.
PubMed: 28516057
DOI: 10.4103/japtr.JAPTR_172_16 -
Journal of Research in Pharmacy Practice 2021Acute low back pain is a common ailment and causes pain and disability. Physicians often prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) to treat acute low back...
Efficacy of the Combination of Indomethacin and Methocarbamol versus Indomethacin Alone in Patients with Acute Low Back Pain: A Double-Blind, Randomized Placebo-Controlled Clinical Trial.
OBJECTIVE
Acute low back pain is a common ailment and causes pain and disability. Physicians often prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) to treat acute low back pain; however, due attention has recently been drawn to muscle relaxants to reduce the severity of patients' daily physical dysfunction. Therefore, this study aimed to evaluate the therapeutic effect of the administration of indomethacin alone compared with methocarbamolas a muscle relaxant and indomethacin as an NSAID on the treatment of acute low back pain.
METHODS
The present double-blind clinical trial was performed on 64 patients with acute low back pain. The patients were categorized into two groups and received the treatments as follows. Indomethacin capsules of 25 mg every 8 h and placebo tablets every 8 h were administered in the first group (Group I). Indomethacin capsules of 25 mg every 8 h and methocarbamol tablets of 500 mg every 8 h were administered in the second group (Group I + M). Patient pain intensity and physical function based on Back Pain Function Scale (BPFS) were recorded before and 1 week after the intervention.
FINDINGS
The present study results revealed that the mean pain reduction of patients in Group I + M was significantly higher than that of Group I (3.66 ± 3.17 vs. 1.84 ± 1.53; < 0.001). Moreover, the mean BPFS increase in Group I + M was significantly higher than that of Group I (19.44 ± 8.66 vs. 4.75 ± 4.35; < 0.001).
CONCLUSION
According to the results of the present study, concomitant administration of indomethacin and methocarbamol can be more effective in reducing pain intensity and improving the patient's physical function (or performance).
PubMed: 34527615
DOI: 10.4103/jrpp.JRPP_21_31 -
Scientific Reports Jan 2023Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play...
Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play major roles in skin wound healing such as in wound contraction and release of growth factors which are of importance in angiogenesis and tissue remodeling. Abnormal fibroblast phenotypes have been identified in patients with chronic wounds. In this work, we analyzed scRNA-seq datasets of normal and wounded skin from mice at day 4 post-wound to investigate fibroblast heterogeneity during the proliferative phase of wound healing. Compositional analysis revealed a specific subset of fibroblast (cluster 3) that primarily increased in wounded skin (14%) compared to normal skin (3.9%). This subset was characterized by a gene signature marked by the plasma membrane proteins Sfrp2 + Sfrp4 + Sfrp1 + and the transcription factors Ebf1 + Prrx1 + Maged1 + . Differential gene expression and enrichment analysis identified epithelial to mesenchymal transition (EMT) and angiogenesis to be upregulated in the emerging subset of fibroblasts of the wounded skin. Using two other datasets for murine wounded skin confirmed the increase in cluster 3-like fibroblasts at days 2, 7 and 14 post-wounding with a peak at day 7. By performing a similarity check between the differential gene expression profile between wounded and normal skin for this emerging fibroblast subset with drug signature from the ConnectivityMap database, we identified drugs capable of mimicking the observed gene expression change in fibroblasts during wound healing. TTNPB, verteprofin and nicotinic acid were identified as candidate drugs capable of inducing fibroblast gene expression profile necessary for wound healing. On the other hand, methocarbamol, ifosfamide and penbutolol were recognized to antagonize the identified fibroblast differential expression profile during wound healing which might cause delay in wound healing. Taken together, analysis of murine transcriptomic skin wound healing datasets suggested a subset of fibroblasts capable of inducing EMT and further inferred drugs that might be tested as potential candidates to induce wound closure.
Topics: Mice; Animals; Skin; Epithelial-Mesenchymal Transition; Wound Healing; Transcription Factors; Fibroblasts; Neoplasm Proteins
PubMed: 36650180
DOI: 10.1038/s41598-022-27152-4 -
Frontiers in Veterinary Science 2022To define factors associated with survival in dogs with tetanus and to evaluate the prognostic significance of an established severity classification scheme.
OBJECTIVE
To define factors associated with survival in dogs with tetanus and to evaluate the prognostic significance of an established severity classification scheme.
METHODS
Medical records of dogs with the clinical diagnosis of tetanus were retrospectively reviewed with regard to signalment, clinical signs, clinicopathological findings on admission, wound characteristics, complications, therapeutic measures, and survival to discharge. Based on the extracted data, dogs were graded according to a previously published 4-class severity scheme. Non-parametric tests were applied for comparisons between survival categories.
RESULTS
Forty-two dogs fulfilled inclusion criteria, of which 32 survived. Of 10 non-survivors, 4 died and 6 were euthanised. Non-survivors were more often younger than 2 years of age (6/10 vs. 7/32 dogs, = 0.023), had shorter duration of specific signs of tetanus (time from onset of typical signs to presentation) (2 vs. 4 days, = 0.016), were prescribed less often antibiotics prior to presentation ( = 0.006), had higher tetanus severity grade (10/12 dogs in Class III or IV died, < 0.001), more often received acepromazine ( = 0.009) and atropine ( = 0.012), and more often had hyperthermia ( = 0.005) and respiratory complications (pneumonia, laryngeal spasm; = 0.008). Wound characteristics, the use of tube feeding, metronidazole, methocarbamol, magnesium and antitoxin were not significantly different between non-survivors and survivors.
CLINICAL SIGNIFICANCE AND CONCLUSION
Young dogs with a rapid course of severe generalized tetanus have a guarded prognosis. The previously described severity classification scheme proved valuable in predicting survival. Prospective multi-center studies are needed to clarify the prognostic significance of age, sedative usage and modified versions of an established classification scheme, including the presence of respiratory complications.
PubMed: 36590798
DOI: 10.3389/fvets.2022.1015569 -
Veterinary Medicine and Science Mar 2022The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major...
INTRODUCTION/BACKGROUND
The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major racetracks in Louisiana between 2016 and 2020.
METHODS
During this 5-year period, 27,237 blood samples and 25,672 urine samples collected during the course of normal race meeting activities were analysed by initial screening procedure utilizing Liquid Chromatography Mass Spectrometry (LC-MS/MS). Following initial screening, suspect samples were subject to quantitative or semi- quantitative confirmation analysis by LC-MS/MS.
RESULTS
The total number of violations reported was 534 (1.01% of the total number of specimens analysed). The total number of violations reported in Thoroughbred horses was 210 while the total number of violations reported in Quarter Horses was 324. The percentage of total violations was %0.59 for all the specimens analysed in Thoroughbred horses while this percentage was %1.9 for all the specimens analysed in Quarter Horses during this 5-year period. The most frequent violations included the overages (concentrations of permitted medications equal to or exceeding the set threshold) of clenbuterol (165 violations), non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylbutazone (73 violations), combination of phenylbutazone with flunixin (45 violations) and muscle relaxant methocarbamol (40 violations).
DISCUSSION/CONCLUSIONS
The total number of violations were relatively low during 5-year period, but wide varieties of medications with different pharmacological actions were confirmed in performance horses in Louisiana. The most frequently reported violations in Louisiana were for permitted therapeutic medications (clenbuterol, phenylbutazone, flunixin methocarbamol) with established threshold and/or withdrawal guidelines in racehorses.
Topics: Animals; Chromatography, Liquid; Clenbuterol; Horses; Methocarbamol; Phenylbutazone; Tandem Mass Spectrometry
PubMed: 34989156
DOI: 10.1002/vms3.724 -
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 Oct 2023Background Patients staying in acute rehabilitation often use large amounts of opioids during their stay. There are a number of reasons for this increased opioid...
Background Patients staying in acute rehabilitation often use large amounts of opioids during their stay. There are a number of reasons for this increased opioid exposure, including but not limited to daily exercises with physical and occupational therapists, increased demand on a healing body, and use of previously atrophying musculature. Some physiatrists have noticed that patients who concurrently are prescribed medications such as Robaxin seem to require fewer opioids during their stay in acute rehabilitation. This study aimed to determine the association between non-opioid analgesic use and total opioid load, as measured using morphine milligram equivalents (MMEs), during inpatient rehabilitation for traumatic brain injury. Methodology A retrospective study of individuals with a diagnosis of traumatic brain injury admitted to an acute inpatient rehabilitation program was performed. Non-opioid medications that were reviewed in the study included acetaminophen, amitriptyline, baclofen, diclofenac, gabapentin, ibuprofen, lidocaine, methocarbamol, nortriptyline, and pregabalin. Five of the most-used non-opioid medications (acetaminophen, diclofenac, gabapentin, lidocaine, and methocarbamol) were statistically analyzed using regression and analysis of variance to evaluate for any significant variables. Results Results showed that the average daily dose of acetaminophen has a significant effect on the average daily MME and that the average daily dose of gabapentin and methocarbamol each have a significant effect on the change of daily MME usage from admission to discharge from acute rehab (ΔMME). Results also showed that the mere presence of methocarbamol (regardless of daily or total dosage) had a significant effect on the ΔMME. Conclusions Based on these findings, physicians may want to consider prescribing acetaminophen, gabapentin, or methocarbamol for patients admitted for inpatient rehabilitation following traumatic brain injury who require high amounts of opioids.
PubMed: 37954704
DOI: 10.7759/cureus.46872 -
Veterinary Medicine (Auckland, N.Z.) 2017The objective of this study was to describe a case of severe lamotrigine toxicosis in a dog, which was successfully treated using minimal medical interventions.
OBJECTIVE
The objective of this study was to describe a case of severe lamotrigine toxicosis in a dog, which was successfully treated using minimal medical interventions.
CASE SUMMARY
A 7-month-old male, intact, Labrador mix was evaluated because of acute onset of vomiting, rigidity, and dull mentation after ingesting lamotrigine tablets. The estimated oral dose that had been ingested was 278 mg/kg (611.6 mg/lb). Physical examination was unremarkable other than abnormalities noted in the cardiovascular and neurological systems. Neurological examination revealed dull mentation, vertical nystagmus, four-legged extensor limb rigidity, and alligator rolling. Cardiovascular examination revealed pale pink mucous membranes and multifocal ventricular tachycardia. Intravenous (IV) fluids were started at three times maintenance (180 mL/kg/day). Methocarbamol (100 mg/kg [220 mg/lb], rectally) and lidocaine (2 mg/kg [4.4 mg/lb, IV]) were administered. Twenty-four and seventy-two hours after presentation, the dog was clinically normal with no ventricular tachycardia being noted.
CONCLUSION
Lamotrigine (6-[2,3-dichlorophenyl]-1,2,4-triazine-3,5-diamine) is an anticonvulsant medication used in humans, which inhibits voltage-gated sodium channels. The clinical success of this case suggests that administration of only methocarbamol for the neurologic effects and lidocaine for the arrhythmias, as well as supportive IV fluid therapy, could be a successful treatment strategy for dogs, even with severe lamotrigine toxicosis.
PubMed: 30050852
DOI: 10.2147/VMRR.S131583 -
Basic & Clinical Pharmacology &... Sep 2018The purpose of this study was to test the hypothesis that skeletal muscle relaxants could inhibit the in vitro metabolism of common comedications opioids buprenorphine,...
The purpose of this study was to test the hypothesis that skeletal muscle relaxants could inhibit the in vitro metabolism of common comedications opioids buprenorphine, methadone and oxycodone. The compounds [solubility-limited concentration (μM) studied] were as follows: baclofen (1000), carisoprodol (200), its metabolite meprobamate (1000), chlorzoxazone (200), cyclobenzaprine (1000), metaxalone (50), methocarbamol (1000), orphenadrine (1000) and tizanidine (1000). Compounds were first incubated with human liver microsomes ± pre-incubation, screened with pathway-specific cDNA-expressed cytochrome P450s (rCYP), and then IC values determined using either 8-concentration tests for those where the rCYP screen suggested an IC was achievable, or a 3-concentration test with downward extrapolation if screen suggested 50% inhibition was not achievable. These results were then extrapolated to determine an inhibitory potential. Six pathway inhibitor combinations were identified with a moderate inhibitory potential (≥2.0 < 5.0): five with chlorzoxazone, R-EDDP, S-EDDP and noroxycodone production by CYP3A4, and R- and S-EDDP production by CYP2B6; and one for the meprobamate effect on noroxycodone production by CYP3A4. An additional eleven combinations were found with a weak inhibitory potential (≥1.25 < 2.0): five with carisoprodol, two each with methocarbamol and meprobamate, and one each with metaxalone and orphenadrine. This represents the first comprehensive study of the inhibitory effect of this class of drugs and suggests that some of them may produce significant drug-drug interactions with opioids that are frequent comedications with skeletal muscle relaxants.
Topics: Analgesics, Opioid; Animals; Buprenorphine; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Humans; In Vitro Techniques; Inhibitory Concentration 50; Insecta; Male; Methadone; Microsomes, Liver; Neuromuscular Agents; Oxycodone
PubMed: 29504673
DOI: 10.1111/bcpt.12999 -
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