Sedative Effects Research Articles

Central Nervous System Medications: Pharmacokinetic and Pharmacodynamic Considerations for Older Adults.

Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10-40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge.

Effect of esketamine on the ED50 of propofol for successful insertion of ureteroscope in elderly male patients: a randomized controlled trial

BackgroundPropofol is effective and used as a kind of routine anesthetics in procedure sedative anesthesia (PSA) for ureteroscopy. However, respiratory depression and unconscious physical activity always occur during propofol-based PSA, especially in elderly patients. Esketamine has sedative and analgesic effects but without risk of cardiorespiratory depression. The purpose of this study is to investigate whether esketamine can reduce the propofol median effective dose (ED50) for successful ureteroscope insertion in elderly male patients.Materials and methods49 elderly male patients undergoing elective rigid ureteroscopy were randomly divided into two groups: SK Group (0.25 mg/kg esketamine+propofol) and SF Group (0.1 µg/kg sufentanil+propofol). Patients in both two groups received propofol with initial bolus dose of 1.5 mg/kg after sufentanil or esketamine was administered intravenously. The effective dose of propofol was assessed by a modified Dixon’s up-and-down method and then was adjusted with 0.1 mg/kg according to the previous patient response. Patients’ response to ureteroscope insertion was classified as “movement” or “no movement”. The primary outcome was the ED50 of propofol for successful ureteroscope insertion with esketamine or sufentanil. The secondary outcomes were the induction time, adverse events such as hemodynamic changes, hypoxemia and body movement were also measured.Result49 patients were enrolled and completed this study. The ED50 of propofol for successful ureteroscope insertion in SK Group was 1.356 ± 0.11 mg/kg, which was decreased compared with that in SF Group, 1.442 ± 0.08 mg/kg (P = 0.003). The induction time in SK Group was significantly shorter than in SF Group (P = 0.001). In SK Group, more stable hemodynamic variables were observed than in SF Group. The incidence of AEs between the two groups was not significantly different.ConclusionThe ED50 of propofol with esketamine administration for ureteroscope insertion in elderly male patients is 1.356 ± 0.11 mg/kg, significantly decreased in comparsion with sufentanil.Trial registrationChinese Clinical Trial Registry, No: ChiCTR2300077170. Registered on 1 November 2023. Prospective registration. http://www.chictr.org.cn.

Local and global effects of sedation in resting-state fMRI: a randomized, placebo-controlled comparison between etifoxine and alprazolam

TSPO ligands are promising alternatives to benzodiazepines in the treatment of anxiety, as they display less pronounced side effects such as sedation, cognitive impairment, tolerance development and abuse potential. In a randomized double-blind repeated-measures study we compare a benzodiazepine (alprazolam) to a TSPO ligand (etifoxine) by assessing side effects and acquiring resting-state fMRI data from 34 healthy participants after 5 days of taking alprazolam, etifoxine or a placebo. To study the effects of the pharmacological interventions in fMRI in detail and across different scales, we combine in our study complementary analysis strategies related to whole-brain functional network connectivity, local connectivity analysis expressed in regional homogeneity, fluctuations in low-frequency BOLD amplitudes and coherency of independent resting-state networks. Participants reported considerable adverse effects such as fatigue, sleepiness and concentration impairments, related to the administration of alprazolam compared to placebo. In resting-state fMRI we found a significant decrease in functional connection density, network efficiency and a decrease in the networks rich-club coefficient related to alprazolam. While observing a general decrease in regional homogeneity in high-level brain networks in the alprazolam condition, we simultaneously could detect an increase in regional homogeneity and resting-state network coherence in low-level sensory regions. Further we found a general increase in the low-frequency compartment of the BOLD signal. In the etifoxine condition, participants did not report any significant side effects compared to the placebo, and we did not observe any corresponding modulations in our fMRI metrics. Our results are consistent with the idea that sedation globally disconnects low-level functional networks, but simultaneously increases their within-connectivity. Further, our results point towards the potential of TSPO ligands in the treatment of anxiety and depression.

Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.

Despite the availability of numerous pain medications, the current array of Food and Drug Administration-approved options falls short in adequately addressing pain states for numerous patients and consequently worsens the opioid crisis. Thus, it is imperative for basic research to develop novel and nonaddictive pain medications. Toward addressing this clinical goal, nalfurafine (NLF) was chosen as a lead and its structure-activity relationship (SAR) systematically studied through design, syntheses, and in vivo characterization of 24 analogues. Two analogues, 21 and 23, showed longer durations of action than NLF in a warm-water tail immersion assay, produced in vivo effects primarily mediated by KOR and DOR, penetrated the blood-brain barrier, and did not function as reinforcers. Additionally, 21 produced fewer sedative effects than NLF. Taken together, these results aid the understanding of NLF SAR and provide insights for future endeavors in developing novel nonaddictive therapeutics to treat pain.

The Prevalence of Benzodiazepine Use among Italian Drivers in 15,988 Cases of Driving License Regranting from 2015 to 2023: Risks and Implications for Driving Fitness

The use of benzodiazepines is strongly associated with an increased risk of traffic accidents due to their side effects of sedation and drowsiness, which can significantly impair driving performance. The main aim of our study was to investigate the trend of benzodiazepine use over nine years (2015–2023) in a population of 15,988 subjects who had their license suspended for driving under the influence (DUI) of alcohol or drugs. Among the 15,988 users accessed to our laboratory, 924 tested positive for at least one benzodiazepine. An increase in the number of positive-testing users was observed in the period 2015–2018, followed by a slight decrease in 2019. Overall, the trend of benzodiazepine use was stable over the next four years (2020–2023), with the highest incidence in 2022. The most common benzodiazepines, and/or metabolites, found in urine samples were α-OH-alprazolam (28.66%; n = 366) and oxazepam (27.25%; n = 348). Several cases of mixed positivity were observed in the study population. The main substances taken with benzodiazepines were cocaine and Δ9-tetrahydrocannabinol. Our findings suggest that people taking benzodiazepines should be monitored, as these have a relevant impact on driving ability in addition to significant interindividual differences in the behavioral effects of benzodiazepines on driving performance.

A prospective, randomized, single-blinded study comparing the efficacy and safety of dexmedetomidine and propofol for sedation during endoscopic retrograde cholangiopancreatography

BackgroundBalanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In various clinical settings, the combination of dexmedetomidine with opioids and benzodiazepines has provided effective sedation with increased safety. The aim of this investigation was to compare the efficacy and safety of dexmedetomidine and propofol for sedation during ERCP.MethodsForty-one patients were randomly divided into two groups: the dexmedetomidine (DEX) group and the propofol (PRO) group. Patients in the DEX group received an additional bolus of 0.6 μg kg−1 dexmedetomidine followed by a dexmedetomidine infusion at 1.2 μg kg−1 h−1, whereas the PRO group received 1–2 mg kg−1 of propofol bolus followed by a propofol infusion at 2–3 mg kg−1 h−1. During ERCP, the primary outcome was the incidence of hypoxemia (SpO2 < 90% for > 10 s). Other intraoperative adverse events were also recorded as secondary outcomes, including respiratory depression (respiratory rate of < 10 bpm min−1), hypotension (MAP < 65 mmHg), and bradycardia (HR < 45 beats min−1).ResultsThe incidence of hypoxemia was significantly reduced in the DEX group compared to the PRO group (0% versus 28.6%, respectively; P = 0.032). Patients in the PRO group exhibited respiratory depression more frequently than patients in the DEX group (35% versus 81%, respectively; P = 0.003). There were no significant differences in terms of hypotension and bradycardia episodes between groups. During the procedures, the satisfaction scores of endoscopists and patients, as well as the pain and procedure memory scores of patients were comparable between groups.ConclusionIn comparison with propofol, dexmedetomidine provided adequate sedation safety with no adverse effects on sedation efficacy during ERCP.Trial registrationChinese Clinical Trial Registry, ChiCTR2200061468, 25/06/2022.

Comparative observation of the effectiveness and safety of remimazolam besylate versus dexmedetomidine in gastrointestinal surgery in obese patients.

Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients. Thus, a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety. To compared the effectiveness and safety of remimazolam besylate versus dexmedetomidine (DEX) in gastrointestinal surgery in obese patients. The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023, comprising 30 patients who received DEX intervention (control group) and 30 patients who received remimazolam besylate intervention (research group). Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), safety (nausea and vomiting, bradycardia, hypotension, and apnea), anesthesia and examination indices [induction time, anesthesia recovery time, and postanesthesia care unit (PACU) discharge time], sedation effect (Ramsay Sedation Scale), and postoperative pain visual analog scale were comparatively analyzed before anesthesia (T0), during anesthesia (T1), and after anesthesia (T2). At T1, the research group showed significantly smaller changes in HR, RR, MAP, and SpO2 than the control group, with a significantly lower adverse reaction rate and shorter induction, anesthesia recovery, and PACU discharge times. Additionally, the intra- and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group. Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.

Application of superior iliac fascia block of inguinal ligament combined with patient controlled intravenous analgesia in elderly patients after hip arthroplasty

To compare the effect of patient-controlled intravenous analgesia(PCIA) and superior inguinal ligament iliac fascia block combined with PCIA after hip replacement in the elderly. Total of 82 elderly patients were treated with hip arthroplasty from June 2019 to June 2021 and randomly divided into observation group and control group. There were 42 patients in control group, including 18 males and 24 females, aged from 60 to 78 years old with an average of (70.43±3.67) years old, 28 femoral neck fractures and 14 femoral head necrosis, who received PCIA. The study group consisted of 42 cases, including 20 males and 22 females, aged from 61 to 76 years old with an average of (69.68±3.74) years old, 25 femoral neck fractures and 17 femoral head necrosis, who received superior inguinal ligament iliac fascia block combined with PCIA. Pain visual analogue scale (VAS) and Ramesay sedation scores at 2 h, 6 h, 12 h, 24 h and 48 h after operation were evaluated. In addition, the follow-up results of the total consumption of sufentanil and the total number of PCIA compressions at 48 hours after operation, the first time of landing after surgery, the time of hospital stay, the incidence of adverse reactions, the satisfaction with analgesia of two groups were observed. All patients were followed up for 9 to 24 months with an average of(13.85±2.67) months. There was no significant difference in operation time and intraoperative bleeding between two groups (P>0.05). There was no difference in VAS between two groups at 2 hours after operation (P>0.05), and the VAS of the study group at 6 h, 12 h, 24 h and 48 h after operation were lower than those of the control group(P<0.05). The Ramesay sedation scores of the study group at 2 h, 6 h and 12 h after operation were higher than those of the control group(P<0.05), and there were no differences in Ramesay score between two groups at 24 h and 48 h after operation (P>0.05). The consumption of sufentanil in the study group within 48 hours after operation was lower than that in the control group (P<0.05), and PCIA compression times were lower than those in the control group(P<0.05), and the time of first landing was earlier than that in the control group(P<0.05). There was no significant difference in hospital stay, adverse reaction rate, complications between two groups (P>0.05). The satisfaction of analgesia in the study group was higher than that in the control group (P<0.05). Superior iliac fascia block of inguinal ligament combined with PCIA has significant analgesic and sedative effects after hip arthroplasty in the elderly. It can reduce the amount of sufentanil used and the total number of PCIA compressions, which is conducive to the early activity of patients out of bed, improve the satisfaction of analgesia.

Effects of propofol, ketamine-propofol mixture in pediatric dental patients undergoing intravenous sedation: a clinical study

This study aimed to evaluate the clinical effects, complications (peri- and postoperative), depth of sedation, recovery times, and changes in anxiety levels in paediatric dental patients receiving intravenous sedation with propofol and ketamine–propofol mixtures. This prospective clinical study included 69 healthy children (ASA 1) aged 3–7 years. The patients were assigned randomly to propofol group (n = 23), which received propofol; 1:3 ketofol group (n = 23), which received 1:3 ketofol; or 1:4 ketofol group (n = 23), which received 1:4 ketofol. The bispectral index (BIS) and Ramsay Sedation Scale (RSS) score were recorded at intervals of 5 min to measure the depth of sedation, and vital signs were evaluated. Peri- and postoperative complications and recovery times were recorded. Anxiety levels were also evaluated using the Facial Image Scale (FIS) and changes in saliva cortisol levels (SCLs) before and after the intravenous sedation procedure. The Kruskal‒Wallis test and Wilcoxon signed-rank test were used to determine pre- and posttreatment parameters. Dunn’s test for post hoc analysis was used to determine the differences among groups. Children’s pre- and posttreatment anxiety levels did not differ significantly according to FIS scores, and increases in SCLs were detected in 1:3 ketofol and 1:4 ketofol groups after dental treatment was completed. Compared with those in the other groups, the BIS values of the patients in 1:4 ketofol indicated a slightly lower depth of sedation. The recovery time of the patients in 1:3 ketofol was longer than that of patients in propofol and 1:4 ketofol. The incidence of postoperative complications (agitation, hypersalivation, nausea/vomiting, and diplopia) did not differ among the groups. Ketamine–propofol combinations provided effective sedation similar to that of propofol infusion without any serious complications during dental treatment performed under intravenous sedation. The ketofol infusion increased the anxiety level of paediatric dental patients to a greater extent than the propofol infusion.

Electro-tranquilization in the relief of pre-nosological forms of psychosomatic disorders

Tranquilizers, widely used in the treatment of distress, neuroses, and psychosomatic disorders, have excessive sedative effect and narcogenicity. Transcranial pulsed current stimulation (tPCS) (electrotranquilization — ET, transcranial electrical stimulation) as non-pharmacological impact with a tranquilizing effect is devoid of these disadvantages. The purpose of the study was to determine the effectiveness of using ET in relation to distress, somatization, depression, and anxiety as the initial manifestations of psychosomatic disorders. Methods. Eighty patients who consulted a psychotherapist for somato-vegetative disorders were randomly divided into a group that received weekly ET treatment and a group that received placebo treatment. The severity of disorders and their dynamics were assessed using the Four-Dimensional Symptom Questionnaire (4DSQ). Results. After a week of ET treatment, rates of anxiety, depression, somatization, and distress decreased. Conclusions. The use of ET in patients with psychosomatic disorders at a pre-nosology stage leads to a significant reduction in the severit y of these disorders.

Агонисты альфа-2адренорецепторов. Дексмедетомидин

Dexmedetomidine is a selective alpha2-adrenoreceptor agonist with a powerful sedative effect and analgesic properties. High selectivity of dexmedetomidine (1620:1) makes it the optimal drug among all representatives of the alpha-2adrenoreceptor agonist class for use in relatively small animals. Dexmedetomidine is currently the most popular sedative used for premedication and sedation, as well as in multimodal analgesia in a constant-rate infusion mode in intensive care. In 2024, a domestic drug with the trade name «Dexody» of the pharmaceutical company «Apicenna» with the active substance dexmedetomidine was registered. The drug is a complete analogue of the original drug and is approved for use in veterinary medicine.

Effect of remifentanil in clinical anesthesia and postoperative analgesia

Purpose: To investigate the effect of remifentanil in clinical anesthesia and postoperative intravenous analgesia. Methods: A retrospective analysis was conducted on the medical records of 100 patients who received remifentanil for anesthesia and postoperative intravenous analgesia at Zibo Center Hospital, Zibo, China from February 2020 to February 2023. The patients were divided into study and control groups comprising 50 patients in each group. The study group received remifentanil intravenously (8 g/kg) while the control group received fentanyl (3 - 4 μg/kg). Heart rate (HR), mean arterial pressure (MAP), and Bispectral Index (BIS) were monitored 5 min before anesthesia (T1), 10 min after (T2), 40 min after (T3), and 5 min before the end of surgery (T4). The levels of blood glucose (Glu), angiotensin II (Ang II), and cortisol (Cor) were measured at T1, T2, T3, and T4. Analgesic and sedative effects were evaluated 3, 12 and 24 h after surgery using the visual analog scale (VAS) and Ramsay sedation score. Results: At T1, T2, T3, and T4, there were no significant differences in HR, MAP, and BIS between the two groups (p &gt; 0.05), while the levels of Glu, Ang II, and Cor in study group were significantly lower (p &lt; 0.05). At 3, 12 and 24 h after surgery, VAS score in the study group was significantly lower, while Ramsay's analgesia score was significantly higher (p &lt; 0.05). Total effectiveness was significantly higher in the study group (p &lt; 0.05). Recovery time for orientation, spontaneous breathing, awakening, stay in the recovery room, and incidence of adverse reactions were significantly lower in study group (p &lt; 0.05). Conclusion: The use of remifentanil for postoperative intravenous analgesia significantly lowers stress response, sedation and improves recovery time. It is, therefore, effective, and produces lower adverse effects than fentanyl. Large-scale investigation to determine the impact of confounding factors on the outcome of fentanyl/remifentanil combination is required.

Awake VA-ECMO in cardiogenic shock, single centre experiences

Abstract Funding Acknowledgements None. Background/Introduction "Awake" V-A ECMO when the patient is fully awake, breathing spontaneously, without deep sedation. Advantages of awake VA-ECMO include reduced sedative side effects, early active movements, reduced muscle mass loss, increased interaction with the family and medical staff, description of their symptoms, and more exact information than sedative patients so that early detection of complications. Purpose and Methods Present a series of 15 patients with cardiac support by awake VA-ECMO, techniques, parameters, complications, and treatment results. Results Enrolled in this study, including 15 patients: 04 NSTEMI (very high-risk PCI), 09 Myocarditis, 02 electrical storm; Age 53,2 ± 19,5. The local anesthesia, mild sedation when the patient is anxious; performed vascular access with DSA system. The duration from the patient's admission to ECMO was 3,8 ± 2,9 (day) and awake VA-ECMO 3,1 ± 2,5 (day) (min to max: 1 – 6). The CO of ECMO: 1,6 ± 1,2 (l/ph); 03 patients with continuous renal replacement therapy. A patient with acute thrombosis of the lower extremity had successful percutaneous thrombectomy; fifteen patients were successfully weaned from ECMO (100%), no patient death in 7 days, and 02 patient deaths in 30 days. Conclusion Awake VA-ECMO can be performed safety on the cardiac patient when waiting for recovery or management.

Benefits of dexmedetomidine during noninvasive mechanical ventilation in major abdominal surgery patients with postoperative respiratory failure.

The efficacy of non-invasive mechanical ventilation (NIMV) on the postoperative ARF is conflicting and the failure rate of NIMV in this patient population is high. In our study, we hypothesized that the use of dexmedetomidine during NIMV in major abdominal surgical patients can reduce NIMV failure without significant side affect. Medical records of patients who underwent major abdominal surgery, admitted to our general surgery intensive care unit (ICU), developed postoperative ARF, received NIMV (with oro-nasal mask) and dexmedetomidine infusion were enrolled in this study. The infusion rate was adjusted to maintain a target sedation level of a Richmond Agitation-Sedation Scale (RASS) (-2)-(-3). The sedation was stopped when NIMV was discontinued. A total of 60 patients, 42 (70.0%) male, and 18 (30.0%) female, with a mean age of 68 ± 11 years were included in the study. The mean APACHE II score was 20 ± 6. Dexmedetomidine was infused for a median of 25 h (loading dose of 0.2 mcg/kg for 10 min, maintained at 0.2-0.7 mcg/kg/h, titrated every 30 min). RASS score of all study group significantly improved at the 2 h of dexmedetomidine initiation (+3 vs. -2, p = 0.01). A targeted sedation level was achieved in 92.5% of patients. Six (10.0%) patients developed bradycardia and 5 (8.3%) patients had hypotension. The mean NIMV application time was 23.4 ± 6.1 h. Seven (11.6%) patients experienced NIMV failure, all due to worsening pulmonary conditions, and required intubation and invasive ventilation. Fifty-three (88.3%) patients were successfully weaned from NIMV with dexmedetomidine sedation and discharged from ICU. The duration of NIMV application and ICU stay was shorter in NIMV succeded group (21.4 ± 3.2 vs. 29.9 ± 6.4; p = 0.012). Our study suggests that dexmedetomidine demonstrates effective sedation in patients with postoperative ARF during NIMV application after abdominal surgery. Dexmedetomidine can be considered safe and capable of improving NIMV success.

Synthesis, evaluation of biological activity and SAR of new thioalkyl derivatives of pyridine

BackgroundPyridine and its derivatives play a vital role in medicinal chemistry, serving as key scaffolds for drugs. The ability to bind to biological targets makes pyridine compounds significant, sparking interest in creating new pyridine-based drugs. Thus, the purpose of the research is to synthesize new thioalkyl derivatives of pyridine, predict their biological spectrum, study their psychotropic properties, and based on these findings, perform structure–activity relationships to assess pharmacophore functional groups. MethodsClassical organic methods were employed for synthesizing new thioalkyl derivatives of pyridine, with a multifaceted pharmacological profiles. Various software packages and methods were employed to evaluate the biological spectrum of the newly synthesized compounds. For the evaluation of neurotropic activity of new synthesized compounds, some biological methods were used according to indicators characterizing anticonvulsant, sedative and antianxiety activity as well as side effects. ResultsEffective synthetic methods for 6-amino-4-phenyl-2-thio-2H-thiopyran-5-carboxylic acid ethyl ester, 2-amino substituted thiopyridine derivatives and 6-cycloamino-2-thioalkyl-4-phenylnicotinate derivatives were obtained in high yield. Predicted biological spectra and pharmacokinetic data indicated high gastrointestinal absorption and low blood–brain barrier passage for most compounds and demonstrated potential various biological effects, particularly psychotropic properties. Studied compounds demonstrated high anticonvulsant activity through antagonism with pentylenetetrazole. They exhibited low toxicity without inducing muscle relaxation in the studied doses. In psychotropic studies, the compounds displayed activating, sedative, and anxiolytic effects. Notably, the 6-amino-2-thioalkyl-4-phenylnicotinate derivatives demonstrated significant anxiolytic activity (about four times more compared to diazepam). They also exhibited pronounced sedative effects. Ethyl 2-({2-[(diphenylmethyl)amino]-2-oxoethyl}thio)-4-phenyl-6-pyrrolidin-1-ylnicotinate exhibited anxiolytic activity even two times greater than diazepam. Moreover, all studied compounds showed statistically significant antidepressant effects. Noteworthy ethyl 2-({2-oxo-2-[(tetrahydrofuran-2-ylmethyl)amino]ethyl}thio)-4-phenyl-6-pyrrolidin-1-ylnicotinate showcasing its unique psychotropic effect. ConclusionsThe selected compounds demonstrate anticonvulsant properties, activating behavior, and anxiolytic effects, while simultaneously exhibiting antidepressant effects and these compounds as promising candidates for further exploration in the development of therapeutics with a broad spectrum of neuropsychiatric applications.

Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar surgeries: a triple-blind randomized clinical trial.

To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO2)], and sedation assessed by the Ramsay scale. A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO2 between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects. Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect. The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries. Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.

Ethnomedicinal Study and Evaluation of the Anxiolytic-like and Diuretic Effects of the Orchid Stanhopea tigrina Bateman ex Lindl-(Orchidaceae).

Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.

Effective treatment of stress and anxiety symptoms in patients with chronic diseases

Acute or chronic stress, as well as high anxiety condition constitute risk factors leading to the development and progression of many common chronic diseases, including cardiovascular, endocrinological, pulmonary, oncological diseases, etc. A particular feature of these conditions co-occurring with chronic diseases is their significant impact on the motivational aspect of medication compliance, including non-pharmaceutical treatments and a healthy lifestyle, which can increase manyfold the risk for complicated course of chronic somatic disease. On the one hand, the urgent need to identify and manage anxiety and stress disorders in the outpatient practice is caused by high incidence rates of these disorders in patients with chronic pathologies, deteriorated quality of life and increased adverse outcomes, and on the other hand, by inadequate awareness of the options available for safe and efficient correction of these disorders. Therapeutic approaches to the management of high anxiety conditions, in particular those under chronic stress, include both pharmaceutical and non-pharmaceutical treatments, but their efficiency, availability and safety are often not interchangeable. This review article presents the most common variants of anxiety disorders combined with chronic somatic diseases in outpatient practice. A safe and effective option to combat symptoms of stress and high anxiety using modern herbal medicines with anti-anxiety, sedative and antispasmodic effects that can be regarded as alternatives to conventional anxiolytics is considered.

Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans

Gelsemium elegans Benth. (G. elegans) is a traditional medicinal herb that has anti-inflammatory, analgesic, sedative, and detumescence effects. However, it can also cause intestinal side effects such as abdominal pain and diarrhea. The toxicological mechanisms of gelsenicine are still unclear. The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans (C. elegans). The nematodes were treated with gelsenicine, and subsequently their growth, development, and locomotion behavior were evaluated. The targets of gelsenicine were predicted using PharmMapper. mRNA-seq was performed to verify the predicted targets. Intestinal permeability, ROS generation, and lipofuscin accumulation were measured. Additionally, the fluorescence intensities of GFP-labeled proteins involved in oxidative stress and unfolded protein response in endoplasmic reticulum (UPRER) were quantified. As a result, the treatment of gelsenicine resulted in the inhibition of nematode lifespan, as well as reductions in body length, width, and locomotion behavior. A total of 221 targets were predicted by PharmMapper, and 731 differentially expressed genes were screened out by mRNA-seq. GO and KEGG enrichment analysis revealed involvement in redox process and transmembrane transport. The permeability assay showed leakage of blue dye from the intestinal lumen into the body cavity. Abnormal mRNAs expression of gem-4, hmp-1, fil-2, and pho-1, which regulated intestinal development, absorption and catabolism, transmembrane transport, and apical junctions, was observed. Intestinal lipofuscin and ROS were increased, while sod-2 and isp-1 expressions were decreased. Multiple proteins in SKN-1/DAF-16 pathway were found to bind stably with gelsenicine in a predictive model. There was an up-regulation in the expression of SKN-1:GFP, while the nuclear translocation of DAF-16:GFP exhibited abnormality. The UPRER biomarker HSP-4:GFP was down-regulated. In conclusion, the treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction.

WALANT surgery of the hand: state of the art.

Wide-awake local anesthesia no tourniquet is named the WALANT technique. WALANT has had a major positive impact on cost, convenience, ecology, patient satisfaction, access to surgical care, and outcomes in hand surgery in the last 20 years. Safe and efficient application of the technique is based on two principles. The first principle is the tumescent injection of a large volume low concentration 0.25-1% lidocaine, with 1:100 000-1:400 000 epinephrine. The second principle of WALANT is that the proper injection should be almost painless, with the patient only feeling the first needle poke of a tiny 30G needle. This wide awake patient approach reduces pain, neuropraxia, and systemic side effects of sedation with preservation of motor control, thereby aiding balanced reconstruction in hand surgery.