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Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Oct 2023Objective To explore the inhibitory effects and mechanisms of benzodiazepines on (Hp).Methods The Hp international standard strain ATCC43504 was treated with...
Objective To explore the inhibitory effects and mechanisms of benzodiazepines on (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T)and 1(T),2(T),3(T),4(T),5(T),6(T),and 7 h(T)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K in the diazepam,midazolam,and control groups increased during T-T compared with those at T(all <0.01).The concentration of K in diazepam and midazolam groups during T-T was higher than that in the control group(all <0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all <0.01)and had no significance differences from that in the water for injection group(all >0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
Topics: Midazolam; Helicobacter pylori; Urease; Clarithromycin; Benzodiazepines; Diazepam; Amoxicillin; Water; Anti-Bacterial Agents
PubMed: 37927020
DOI: 10.3881/j.issn.1000-503X.15651 -
Biosensors Jul 2023The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and... (Review)
Review
The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, µPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma-hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors.
Topics: Microfluidics; Ketamine; Forensic Toxicology; Cocaine; Lab-On-A-Chip Devices
PubMed: 37504142
DOI: 10.3390/bios13070743 -
Evaluating the Quality of Systematic Reviews on Pediatric Sedation in Dentistry: An Umbrella Review.Journal of Clinical Medicine Jun 2024Sedation is a depression of a patient's state of consciousness, induced by medications, that can reach different levels of intensity during a medical procedure.... (Review)
Review
Sedation is a depression of a patient's state of consciousness, induced by medications, that can reach different levels of intensity during a medical procedure. Conscious sedation produces a minimally depressed level of consciousness without impairment of the ability to maintain an open airway, of protective reflexes or of responses to verbal and physical stimulation. This umbrella review is aimed at critically assessing the available systematic reviews (SRs) and meta-analyses (MA) on sedation in children/adolescents. An electronic database search was conducted that included Pubmed-Medline, Web of Science, Cochrane, Scopus, Scielo, Embase, LILACS and TRIP and the scope of which extended until January 2023. The risk of bias (RoB) of SRs was analyzed using the Measurement Tool to Assess SRs criteria 2 (AMSTAR2). Of 998 entries, 37 SRs were included. In terms of methodological quality, eight studies were assessed as having critically low quality, four studies had low quality, nine studies had moderate quality, and sixteen were considered to be of high quality. Based on the current guidelines, the most employed drugs in pediatric dentistry for sedation are nitrous oxide and midazolam; however, the available evidence supporting their use is insufficient and of low/critically low quality. The combined technique is recommended (nitrous oxide (30-50%) + midazolam). The optimal dose of oral midazolam is 0.75 mg/kg. The level of methodological quality of SRs is expected to increase according to the results and future directions of this umbrella review.
PubMed: 38930074
DOI: 10.3390/jcm13123544 -
Frontiers in Veterinary Science 2023Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively...
BACKGROUND
Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date.
HYPOTHESIS OR OBJECTIVES
To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home.
METHOD
Observational study based on online surveys of owners of dogs with emergency seizure disorders.
RESULTS
The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively.
CONCLUSIONS AND CLINICAL IMPORTANCE
Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.
PubMed: 37850066
DOI: 10.3389/fvets.2023.1278618 -
Drugs in R&D Mar 2024Daridorexant, a dual orexin receptor antagonist was recently approved for the treatment of insomnia at doses up to 50 mg once per night. This study investigated the...
BACKGROUND AND OBJECTIVES
Daridorexant, a dual orexin receptor antagonist was recently approved for the treatment of insomnia at doses up to 50 mg once per night. This study investigated the effect of single-dose and multiple-dose daridorexant 50 mg at steady state on the pharmacokinetics (PK) of the cytochrome P450 (CYP) 3A4-sensitive substrate midazolam, and the effect of single-dose daridorexant 50 mg on the PK and pharmacodynamics (PD) of the CYP2C9-sensitive substrate warfarin.
METHODS
In this prospective, single-center, open-label, fixed-sequence, phase I, drug-drug interaction study, 18 healthy male subjects sequentially received Treatment A, B, and C in three periods. Treatment A consisted of a single oral concomitant administration of midazolam 2 mg and warfarin 25 mg on day 1 of the first period. Treatment B consisted of one oral administration of daridorexant 50 mg followed 1 h later by a single oral dose of midazolam 2 mg concomitantly with a single oral dose of warfarin 25 mg on day 1 and a once-daily oral administration of daridorexant 50 mg for 6 days of the second period. Treatment C consisted of a single oral administration of daridorexant 50 mg at steady state followed 1 h later by a single oral administration of midazolam 2 mg on day 1 of the third period. Blood samples were assessed for midazolam and S-warfarin PK, and PD (international normalized ratio and factor VII). Noncompartmental PK parameters and PD variables were evaluated with geometric mean ratios and 90% confidence intervals of Treatment B/A versus C/A for midazolam, and treatment B/A for warfarin. Safety and tolerability of each treatment were also assessed.
RESULTS
Midazolam maximum plasma concentration (C) and area under the plasma concentration-time curve from 0 to 24 h (AUC) were 1.13- and 1.42-fold higher, respectively, after single-dose administration of daridorexant 50 mg compared to administration of midazolam alone, while C and AUC were 1.12- and 1.35-fold higher, respectively, after administration of daridorexant 50 mg once daily at steady state. Terminal half-life and time to maximum plasma concentration were comparable between treatments. Daridorexant had no influence on the PK and PD of warfarin. All treatments were safe and well tolerated.
CONCLUSIONS
Daridorexant at 50 mg is classified as a weak CYP3A4 inhibitor after single- and multiple-dose administration once daily at steady state. Daridorexant 50 mg did not induce CYP3A4 activity or inhibit CYP2C9 activity.
CLINICAL TRIAL REGISTRATION
This trial (NCT05480488) was registered on 29 July, 2022.
Topics: Humans; Male; Drug Interactions; Midazolam; Adult; Warfarin; Young Adult; Healthy Volunteers; Triazoles; Prospective Studies; Orexin Receptor Antagonists; Area Under Curve; Imidazoles; Pyrrolidines
PubMed: 38472696
DOI: 10.1007/s40268-024-00456-8 -
Frontiers in Bioengineering and... 2023The role of ocular rigidity and biomechanics remains incompletely understood in glaucoma, including assessing an individual's sensitivity to intraocular pressure (IOP)....
The role of ocular rigidity and biomechanics remains incompletely understood in glaucoma, including assessing an individual's sensitivity to intraocular pressure (IOP). In this regard, the clinical assessment of ocular biomechanics represents an important need. The purpose of this study was to determine a possible relationship between the G661R missense mutation in the gene and the ocular pulse amplitude (OPA), the difference between diastolic and systolic intraocular pressure (IOP), in a well-established canine model of open-angle glaucoma (OAG). Animals studied included 39 -mutant dogs with different stages of OAG and 14 unaffected control male and female dogs between 6 months and 12 years (median: 3.2 years). Dogs were sedated intravenously with butorphanol tartrate and midazolam HCl, and their IOPs were measured with the Icare Tonovet rebound tonometer. The Reichert Model 30™ Pneumotonometer was used to measure OPA. Central corneal thickness (CCT) was measured via Accutome PachPen, and A-scan biometry was assessed with DGH Technology Scanmate. All outcome measures of left and right eyes were averaged for each dog. Data analysis was conducted with ANOVA, ANCOVA, and regression models. -OAG-affected dogs displayed a greater IOP of 23.0 ± 7.0 mmHg (mean ± SD) compared to 15.3 ± 3.6 mmHg in normal dogs ( < 0.0001). Mutant dogs had a significantly lower OPA of 4.1 ± 2.0 mmHg compared to 6.5 ± 2.8 mmHg of normal dogs ( < 0.01). There was no significant age effect, but OPA was correlated with IOP in -mutant dogs. The lower OPA in -mutant dogs corresponds to the previously documented weaker and biochemically distinct posterior sclera, but a direct relationship remains to be confirmed. The OPA may be a valuable clinical tool to assess ocular stiffness and an individual's susceptibility to IOP elevation.
PubMed: 38130820
DOI: 10.3389/fbioe.2023.1242166 -
The Journal of Pharmacology and... Jan 2024Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine...
Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine pharmacoresistance is thought in part to result from internalization of synaptic GABA receptors, which are the main target of the drug. The naturally occurring neurosteroid allopregnanolone is a therapy of interest against SE for its ability to modulate all isoforms of GABA receptors. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been partially effective in combination with benzodiazepines in mitigating SE-associated neurotoxicity. In this study, allopregnanolone as an adjunct to midazolam or midazolam-ketamine combination therapy was evaluated for efficacy against cholinergic-induced SE. Adult male rats implanted with electroencephalographic (EEG) telemetry devices were exposed to the organophosphorus chemical (OP) soman (GD) and treated with an admix of atropine sulfate and HI-6 at 1 minute after exposure followed by midazolam, midazolam-allopregnanolone, or midazolam-ketamine-allopregnanolone 40 minutes after seizure onset. Neurodegeneration, neuronal loss, and neuroinflammation were assessed 2 weeks after GD exposure. Seizure activity, EEG power integral, and epileptogenesis were also compared among groups. Overall, midazolam-ketamine-allopregnanolone combination therapy was effective in reducing cholinergic-induced toxic signs and neuropathology, particularly in the thalamus and hippocampus. Higher dosage of allopregnanolone administered in combination with midazolam and ketamine was also effective in reducing EEG power integral and epileptogenesis. The current study reports that there is a promising potential of neurosteroids in combination with benzodiazepine and ketamine treatments in a GD model of SE. SIGNIFICANCE STATEMENT: Allopregnanolone, a naturally occurring neurosteroid, reduced pathologies associated with soman (GD) exposure such as epileptogenesis, neurodegeneration, and neuroinflammation, and suppressed GD-induced toxic signs when used as an adjunct to midazolam and ketamine in a delayed treatment model of soman-induced status epilepticus (SE) in rats. However, protection was incomplete, suggesting that further studies are needed to identify optimal combinations of antiseizure medications and routes of administration for maximal efficacy against cholinergic-induced SE.
Topics: Rats; Male; Animals; Midazolam; Ketamine; Pregnanolone; Soman; Anticonvulsants; Neuroinflammatory Diseases; Neurosteroids; Status Epilepticus; Seizures; Benzodiazepines; Cholinergic Agents; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 37770198
DOI: 10.1124/jpet.123.001784 -
BMC Oral Health Oct 2023Dental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for...
BACKGROUND
Dental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for sedation. However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents. This study aimed to investigate the efficacy and safety of remimazolam besilate (hereinafter called "remimazolam") and to determine the optimal dosages for sedation in outpatients undergoing dental procedures.
METHODS
Thirty-one outpatients aged 18-65 years scheduled for impacted third molar extraction were included in the study. Remimazolam was administered as a single dose of 0.05 mg/kg followed by a continuous infusion at a rate of 0.35 mg/kg/h, with the infusion rate adjusted to maintain a sedation level at a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of 2-4. The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events.
RESULTS
The sedation success rate with remimazolam monotherapy was 100%. The remimazolam induction dose was 0.08 (0.07-0.09) mg/kg, and the anesthesia induction time was 3.2 (2.6-3.9) min. The mean infusion rate of remimazolam during the procedure was 0.40 (0.38-0.42) mg/kg/h. The time from the end of remimazolam administration to awakening was 8.0 (6.7-9.3) min, and the time from the end of remimazolam administration to discharge was 14.0 (12.5-15.5) min. There were no significant respiratory or circulatory effects requiring intervention during sedation.
CONCLUSIONS
Continuous intravenous administration of remimazolam can achieve optimal sedation levels without significantly affecting respiratory or circulatory dynamics. The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures. Additionally, the study findings suggest that electroencephalogram monitoring can be a reliable indicator of the level of sedation during dental procedural sedation with remimazolam.
TRIAL REGISTRATION
The study was registered in the Japan Registry of Clinical Trials (No. jRCTs061220052) on 30/08/2022.
Topics: Humans; Midazolam; Outpatients; Prospective Studies; Molar, Third; Benzodiazepines; Anesthesia; Tooth, Impacted
PubMed: 37865761
DOI: 10.1186/s12903-023-03538-2 -
BMC Gastroenterology Apr 2024Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic...
BACKGROUND
Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients.
METHODS
The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study. Patients were categorized into three groups: middle-aged (50-64 years, n = 202), elderly (65-79 years, n = 216), and very elderly (≥ 80 years, n = 192). Intraoperative vital signs and complications were compared among these groups.
RESULTS
The three groups showed no significant difference in terms of intraoperative variation of systolic blood pressure (P = 0.291), diastolic blood pressure (P = 0.737), heart rate (P = 0.107), peripheral oxygen saturation (P = 0.188), bispectral index (P = 0.158), and the occurrence of sedation-related adverse events including hypotension (P = 0.170) and hypoxemia (P = 0.423).
CONCLUSION
The results suggest that a low-dose three-drug regimen consisting of midazolam, alfentanil, and propofol seems safe and effective for deep sedation of elderly and very elderly patients undergoing ERCP procedures. However, further studies are required to verify these findings and clarify the benefits and risks of this method.
Topics: Aged; Middle Aged; Humans; Propofol; Midazolam; Alfentanil; Cholangiopancreatography, Endoscopic Retrograde; Hypnotics and Sedatives; Deep Sedation; Retrospective Studies; Conscious Sedation
PubMed: 38566038
DOI: 10.1186/s12876-024-03197-9 -
Cureus Apr 2024Magnetic resonance imaging (MRI) is a critical diagnostic tool that often requires patient sedation to ensure optimal image quality and patient comfort, particularly in... (Review)
Review
Evaluating Sedation Strategies for Magnetic Resonance Imaging: A Comprehensive Review of Intravenous Fentanyl, Butorphanol, and Midazolam in Adult and Pediatric Populations.
Magnetic resonance imaging (MRI) is a critical diagnostic tool that often requires patient sedation to ensure optimal image quality and patient comfort, particularly in those with anxiety or an inability to remain still. This comprehensive review examines the efficacy, safety, and practical considerations of three commonly used intravenous sedatives, namely, fentanyl, butorphanol, and midazolam, in adult populations undergoing MRI procedures. This review highlights the pharmacological profiles, advantages, and limitations associated with each sedative agent through a detailed analysis of current literature, clinical guidelines, and practice-based evidence. Fentanyl is noted for its potent analgesic properties and rapid onset of action, making it suitable for painful procedures. Butorphanol, with its unique opioid agonist-antagonist activity, presents an alternative with a balance between analgesia and sedation, potentially offering a safer profile for certain patient populations. Midazolam, widely recognized for its anxiolytic and amnestic effects, remains a staple in managing procedure-related anxiety. The review further discusses patient selection criteria, dosing strategies, and the importance of individualized sedation planning to enhance patient experience and procedural outcomes. Future directions highlight the potential of emerging sedation agents and non-pharmacological approaches to improve patient comfort and compliance. The findings underscore the necessity for healthcare providers to adapt sedation practices to the specific needs of each patient, considering both the clinical context and the inherent characteristics of the sedative agents. This review aims to guide clinicians in selecting the most appropriate sedation strategy for adult patients undergoing MRI, optimizing patient care and diagnostic efficacy.
PubMed: 38770500
DOI: 10.7759/cureus.58593