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Biomedicines Feb 2022(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules.... (Review)
Review
(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP ( = 25), and benztropine ( = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.
PubMed: 35203563
DOI: 10.3390/biomedicines10020355 -
Computational and Structural... 2023Stroke is the leading cause of death and disability worldwide, with a growing number of incidences in developing countries. However, there are currently few medical...
Stroke is the leading cause of death and disability worldwide, with a growing number of incidences in developing countries. However, there are currently few medical therapies for this disease. Emerged as an effective drug discovery strategy, drug repurposing which owns lower cost and shorter time, is able to identify new indications from existing drugs. In this study, we aimed at identifying potential drug candidates for stroke computationally repurposing approved drugs from Drugbank database. We first developed a drug-target network of approved drugs, employed network-based approach to repurpose these drugs, and altogether identified 185 drug candidates for stroke. To validate the prediction accuracy of our network-based approach, we next systematically searched for previous literature, and found 68 out of 185 drug candidates (36.8 %) exerted therapeutic effects on stroke. We further selected several potential drug candidates with confirmed neuroprotective effects for testing their anti-stroke activity. Six drugs, including cinnarizine, orphenadrine, phenelzine, ketotifen, diclofenac and omeprazole, have exhibited good activity on oxygen-glucose deprivation/reoxygenation (OGD/R) induced BV2 cells. Finally, we showcased the anti-stroke mechanism of actions of cinnarizine and phenelzine western blot and Olink inflammation panel. Experimental results revealed that they both played anti-stroke effects in the OGD/R induced BV2 cells inhibiting the expressions of IL-6 and COX-2. In summary, this study provides efficient network-based methodologies for identification of drug candidates toward stroke.
PubMed: 37206617
DOI: 10.1016/j.csbj.2023.04.018 -
Scientific Reports Aug 2023Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of...
Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of DMN in 0.1 M hydrochloric acid (HCl) and 1.0% sodium dodecyl sulphate (SDS) at 286 nm after λ 222 nm, while for determination of ORP in 1.0% w/v SDS involves measuring the fluorescence at 285 nm after λ 220 nm. For DMN and ORP, the detection and quantitation limits were 2.99 and 4.71 and 9.08 and 14.29 ng/mL, respectively. The ranges of DMN and ORP were 0.10-1.0 and 0.04-0.5 µg/mL, respectively, in micellar aqueous solution. Method II, the derivative intensities of DMN and CNN were measured at a fixed of different wavelength between the excitation and the emission wavelengths (Δλ) = 60 nm at 282 and 322 nm, at the zero crossing of each other, respectively. The detection and quantitation limits for DMN and CNN were 1.77 and 0.88 ng/mL and 5.36 and 2.65 ng/mL, correspondingly, through the entire range of 0.1-1.0 µg/mL for DMN and CNN. The linearity was perfectly determined through the higher values of the correlation coefficient ranging from 0.9997 to 0.9999 for both direct and synchronous methods. The precision of the proposed methods was also confirmed via the lower values of the standard deviation which ranged from 0.39 to 1.11. The technique was expanded to analyze this mixture in combined tablets and laboratory-prepared mixtures. The method validation was done depending on the international conference on harmonization (ICH) recommendations. An analysis of the statistical data revealed a high agreement between the proposed data and the comparison methodology. Three different assessment methods demonstrated the greenness of the technique.
Topics: Cinnarizine; Dimenhydrinate; Hydrochloric Acid; Laboratories; Orphenadrine; Spectrometry, Fluorescence
PubMed: 37599333
DOI: 10.1038/s41598-023-40559-x -
Journal of Clinical and Experimental... 2022Muscle cramps are witnessed in 22-88% of patients with cirrhosis of liver and frequently lead to sleep disturbance with an appalling impact on quality of life. Despite... (Review)
Review
BACKGROUND
Muscle cramps are witnessed in 22-88% of patients with cirrhosis of liver and frequently lead to sleep disturbance with an appalling impact on quality of life. Despite such a high prevalence, there is lack of evidence-based management protocol due to scarcity of trials on treatment options in the literature. This study aimed to review systematically the available therapeutic options for muscle cramps in patients with cirrhosis of liver.
METHODS
A systematic review of the relevant databases (PubMed, Scopus, Embase, and Web of Science) to identify treatments for muscle cramps in patients with hepatic cirrhosis was performed. Studies meeting the selection criteria were reviewed and assessed for risk of bias and analyzed.
RESULTS
Twenty-four publications were identified as eligible for inclusion in this systematic review. Seven randomized controlled trials (RCTs) and 17 prospective studies were included. Taurine, methocarbamol, baclofen, and orphenadrine are relatively safer and effective treatment option for muscle cramps in cirrhosis on the basis of recently conducted RCTs. Moreover, l-carnitine, branched-chain amino acids (BCAAs), pregabalin, zinc, and vitamin D are also safe and showed beneficial effects on muscle cramps. However, studies on vitamin E revealed contradictory results.
CONCLUSION
Taurine, BCAAs, orphenadrine, and baclofen are safe and well-tolerated treatment options for muscle cramps in cirrhosis. However, well-designed randomized controlled clinical trials are the need of the hour to determine the most suitable treatment options for skeletal muscle cramps in patients with cirrhosis of liver.
PubMed: 35677500
DOI: 10.1016/j.jceh.2021.10.147 -
The Cochrane Database of Systematic... Jan 2018Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders. Because of this, many people treated with antipsychotic medication also receive anticholinergic drugs in order to reduce some of the associated movement side-effects. However, there is also a suggestion from animal experiments that the chronic administration of anticholinergics could cause tardive dyskinesia.
OBJECTIVES
To determine whether the use or the withdrawal of anticholinergic drugs (benzhexol, benztropine, biperiden, orphenadrine, procyclidine, scopolamine, or trihexylphenidyl) are clinically effective for the treatment of people with both antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illnesses.
SEARCH METHODS
We retrieved 712 references from searching the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (16 July 2015 and 26 April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports identified in the search if they were controlled trials dealing with people with antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illness who had been randomly allocated to (a) anticholinergic medication versus placebo (or no intervention), (b) anticholinergic medication versus any other intervention for the treatment of tardive dyskinesia, or (c) withdrawal of anticholinergic medication versus continuation of anticholinergic medication.
DATA COLLECTION AND ANALYSIS
We independently extracted data from included trials and we estimated risk ratios (RR) with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The previous version of this review included no trials. We identified two trials that could be included from the 2015 and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in the USA and Germany. Overall, the risk of bias was unclear, mainly due to poor reporting: allocation concealment was not described; generation of the sequence was not explicit; studies were not clearly blinded; and outcome data were not fully reported.Findings were sparse. One study reported on the primary outcomes and found that significantly more participants allocated to procyclidine (anticholinergic) had not improved to a clinically important extent compared with those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1 RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that there was no evidence of a difference in the incidence of any adverse effects (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other trial compared anticholinergic withdrawal with anticholinergic continuation and found no evidence of a difference in the incidence of acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95% CI 0.11 to 42.52; very low quality evidence).No trials reported on social confidence, social inclusion, social networks, or personalised quality of life - outcomes designated important to patients. No studies comparing either i. anticholinergics with placebo or no treatment, or ii. studies of anticholinergic withdrawal, were found that reported on the primary outcome 'no clinically important improvement in TD symptoms and adverse events'.
AUTHORS' CONCLUSIONS
Based on currently available evidence, no confident statement can be made about the effectiveness of anticholinergics to treat people with antipsychotic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with antipsychotic-induced TD should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow-up.
Topics: Antipsychotic Agents; Biperiden; Cholinergic Antagonists; Dyskinesia, Drug-Induced; Humans; Isocarboxazid; Procyclidine; Randomized Controlled Trials as Topic; Schizophrenia; Withholding Treatment
PubMed: 29341071
DOI: 10.1002/14651858.CD000204.pub2 -
Wiener Klinische Wochenschrift Feb 2023Postoperative intravenous diclofenac reduces patient opioid demand and is commonly used in surgical units. Orphenadrine is mainly used in combination with diclofenac for... (Randomized Controlled Trial)
Randomized Controlled Trial
Intravenous diclofenac and orphenadrine for the treatment of postoperative pain after remifentanil-based anesthesia : A double-blinded, randomized, placebo-controlled study.
BACKGROUND
Postoperative intravenous diclofenac reduces patient opioid demand and is commonly used in surgical units. Orphenadrine is mainly used in combination with diclofenac for musculoskeletal injuries and postoperative pain control. The objective of this study was to compare the analgesic efficacy of diclofenac-orphenadrine, diclofenac alone and saline.
METHODS
We performed a double-blind, randomized, placebo-controlled, parallel-group, single-center clinical study investigating the opioid-sparing effect of a combination of diclofenac and orphenadrine versus diclofenac alone versus isotonic saline solution. Initially 72 patients were included and received total intravenous anesthesia during cruciate ligament surgery. All patients were postoperatively treated with a patient-controlled analgesia (PCA) device containing hydromorphone. Pharmacological safety was assessed by laboratory parameters, vital signs, and delirium detection scores.
RESULTS
There was no significant difference between the groups in cumulative dose of PCA analgesics required after 24 h postsurgery, with 5.90 mg (SD ± 2.90 mg) in the placebo group, 5.73 mg (SD ± 4.75 mg) in the diclofenac group, and 4.13 mg (SD ± 2.57 mg) in the diclofenac-orphenadrine group. Furthermore, there was no significant difference between the groups in cumulative dose of PCA analgesics required 2 h postsurgery (n = 65). Mean dose of hydromorphone required after 2 h was 1.54 mg (SD ± 0.57 mg) in the placebo group, 1.56 mg (SD ± 1.19 mg) in the diclofenac-only group, and 1.37 mg (SD ± 0.78 mg) in the diclofenac-orphenadrine group. However, when comparing the diclofenac-orphenadrine group and the diclofenac group combined to placebo there was a significant reduction in PCA usage in the first 24 h postsurgery. In total, there were 25 adverse events reported, none of which were rated as severe.
CONCLUSION
Orphenadrine-diclofenac failed to significantly reduce postoperative opioid requirements. However, in an exploratory post hoc analysis the diclofenac-orphenadrine and the diclofenac group combined versus placebo showed a tendency to reduce opioid demand in postoperative pain control. Further research is required to determine the value of orphenadrine as an adjuvant in a multimodal approach for postoperative pain management.
Topics: Humans; Diclofenac; Orphenadrine; Remifentanil; Analgesics, Opioid; Hydromorphone; Pain, Postoperative; Analgesics; Anesthesia; Double-Blind Method; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 36576555
DOI: 10.1007/s00508-022-02131-x