Selective Alpha 2-adrenoceptor Agonist Research Articles

The Limited Use Of Dexmedetomidine For Subarachnoid Blocks In Pakistan.

Respected Madam, Dexmedetomidine is a selective alpha-2 adrenoceptor agonist. It acts by binding to the presynaptic alpha-2 adrenoceptors and inhibits the release of norepinephrine. Thereafter, it causes a decrease in the sympathetic tone and terminates the propagation of pain signals. As a result, the haemodynamic and the endocrine stress responses of the body to surgery and anesthesia are attenuated, the blood pressure and heart rate are decreased, and the requirement for other anaesthetic agents is reduced. These effects have meant that dexmedetomidine has been widely used prior to endotracheal intubation to optimize the patients and prevent the likelihood of hemodynamic adverse effects (1). In addition to its use in general anesthesia, peri-operative physicians worldwide are now becoming increasingly aware of the dexmedetomidine’s potential usefor subarachnoid blocks. A few studies have documented the efficacy of intravenous (IV) dexmedetomidine in prolonging the duration of sensory and motor blockade induced by agents such as bupivacaine, prilocaine, and ropivacaine up to 4 hours (2), (3). Recent studies have found that intrathecal administration of dexmedetomidine in combination with the local anesthetic agent yields similar benefits (4). This has been attributed to the activation of presynaptic alpha2-A receptors at locus ceruleus and the termination of pain signal propagation via the medullospinal noradrenergic pathway (4). Therefore, it is no surprise that the use of dexmedetomidine in conjunction with local anesthetics for the subarachnoid block is common practice in peri-operative physicians throughout the globe. While Pakistani peri-operative physicians are aware of the benefits of dexmedetomidine prior to endotracheal intubation (5), the same cannot be said for subarachnoid blocks induced in Pakistan. Peri-operative physicians in Pakistan are either yet to realize the potential benefits the use of dexmedetomidine can provide for subarachnoid blocks or still adhere to conventional spinal anesthesia practices. Since the effects of a conventional subarachnoid block last from 2 to 3 hours, in any case of a surgical adverse event that prolongs the surgery, severe pain, nausea, vomiting, and derangement of the hemodynamic status have been noted in patients. Often times, this results in a shift towards general anesthesia midway through the procedure. Ultimately, the postoperative stay is prolonged which directly impacts the clinical outcome and the quality of life for these patients. ---Continue

Intranasal Dexmedetomidine as Sedative for Non-Invasive Pediatric Diagnostic Procedures Outside Operating Room

Background: Children often require sedation for long non-invasive diagnostic procedures. Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with sedative, anxiolytic and analgesic properties. It mimics natural sleep and allows patients to easily arouse with minimal effects on respiration and airway patency. Objective: To assess the successful completion of pediatric non-invasive diagnostic procedures with intranasal dexmedetomidine as a sedative agent. Methods: Seventy-nine subjects of age six months to twelve years scheduled for non-invasive diagnostic procedures were included. Dexmedetomidine (4 mcg/kg) was administered intranasally 25 minutes before the scheduled time of procedure. A sedation score of two or above as per the MICHIGAN sedation scale was considered satisfactory for starting the procedure. Results: Seventy-four (95%) out of the seventy-nine subjects were successfully sedated with Intranasal dexmedetomidine (p

Dexmedetomidine versus propofol sedation in flexible bronchoscopy: a randomized controlled trial

BackgroundDexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes.MethodsWe conducted an RCT to evaluate the efficacy and safety of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was the number of desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction.ResultsOverall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0–1) and 1 (0–2) in the DEX and control groups, respectively (P = 0.29). Median desaturation time was 1 (0–2) and 1 (0–3) minutes in the DEX and control groups, respectively (P = 0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P = 0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P = 0.009).ConclusionDexmedetomidine sedation during bronchoscopy did not show differences in oxygen saturation and transcutaneous CO2 level in comparison to propofol. Moreover, DEX sedation required a significantly higher number of rescue boluses, due to inadequate sedation and was associated with a higher rate of adverse events.Trial registration NCT04211298, registration date: 26.12.2019.

Comparing the effects of dexmedetomidine and dexamethasone as perineural adjuvants on peripheral nerve block: A PRISMA-compliant systematic review and meta-analysis.

Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB). We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796. After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05). This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.

Early extubation after liver transplantation: Is dexmedetomidine a good option?: A retrospective cohort study.

Dexmedetomidine is a potent and highly selective alpha-2 adrenoceptor agonist with sympatholytic, sedative, anxiolytic and analgesic properties. The aim of this study is to determine the effect of a dexmedetomidine infusion in liver transplant recipients in the early postoperative period on early and smooth extubation. We performed a retrospective chart review of 21 patients undergoing liver transplantation between December 1, 2018 and February 31, 2020. Patients were divided into the dexmedetomidine and midazolam groups. The primary outcome was the extubation time. Secondary outcomes were mean arterial pressure and heart rate before and after extubation. The collected data included the patients' age, gender, surgery time, Model for End-stage Liver Disease score, cold ischemia time, blood transfusion amount and extubation visual analogue scale (VAS) scores. Extubation time was significantly shorter in the dexmedetomidine group than in the midazolam group (median [minimum-maximum], 4 [0-6], 8 [4-13] hours, respectively, P = .000). Extubation VAS scores were statistically significantly lower in dexmedetomidine group (P = .000). Mean arterial pressure values before and after extubation were significantly higher in patients' midazolam group than the dexmedetomidine group (P = .003, P = .005, respectively). Dexmedetomidine infusions provided early and smooth extubation with stable haemodynamics in our patients.

Dexmedetomidine attenuates H2O2-induced apoptosis of rat cardiomyocytes independently of antioxidant enzyme expression

Introduction and ObjectivesDexmedetomidine is a highly selective alpha-2 adrenoceptor agonist that has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effect of dexmedetomidine on cardiomyocytes remains unknown. This study mainly aimed to investigate the effects of dexmedetomidine on the generation of reactive oxygen species (ROS) in cardiomyocytes and whether it inhibits the apoptosis of cardiomyocytes by affecting antioxidant enzyme expression. MethodsNeonatal rat cardiomyocytes were pretreated with dexmedetomidine (100 nM) for 24 h. The cardiomyocytes were then incubated with 200 μM hydrogen peroxide solution (H2O2) for 4 h. PCR assay was used to determine the mRNA expression of antioxidant enzymes. Western blot assay was used to determine the protein expression of antioxidant enzymes. Fluorescence microscopy with the MitoSOX probe was used to detect the formation of ROS in cardiomyocytes, and fluorescence-activated cell sorting with annexin V/PI was used to determine the number of apoptotic cardiomyocytes. ResultsDexmedetomidine reduced ROS generation and antioxidant enzymes levels in cardiomyocytes before H2O2 stimulation (p<0.05). However, ROS generation and apoptosis in cardiomyocytes were significantly increased after H2O2 treatment, and dexmedetomidine pretreatment markedly inhibited the changes (p<0.05). ConclusionFor the first time, to the best of our knowledge, our study shows that dexmedetomidine has a protective effect on cardiomyocytes through inhibition of ROS-induced apoptosis, and more importantly, this effect is independent of antioxidant enzyme mRNA and protein expression.

A clinical comparative study of dexmedetomidine as an adjuvant to 2% plain lignocaine and 2% lignocaine with 1:200,000 adrenaline as local anesthetic agents for surgical removal of impacted mandibular third molars.

Introduction:Dexmedetomidine is a selective alpha-2 adrenoceptor agonist. It is conventionally used as a sedative in the intensive care unit. However, recently, the application of dexmedetomidine as an adjuvant to a local anesthetic agent has been studied. The present study intends to evaluate the effectiveness of dexmedetomidine as an adjuvant to 2% plain lignocaine for surgical removal of impacted mandibular third molar and to compare the efficacy of dexmedetomidine with 2% plain lignocaine with 2% lignocaine and 1:200000 adrenaline.Materials and Methods:A total of 80 patients who required surgical removal of impacted mandibular third molar extraction were included in the study. Patients were randomly divided into two groups using a computer-generated table. Patients in the study group received 2% plain lignocaine with 1 mcg/ml dexmedetomidine. Patients in the control group received 2% lignocaine with 1:200000 adrenaline. The parameters evaluated were onset and duration of action, pulse rate, blood pressure, oxygen saturation, and blood loss.Results:Onset of action was faster and the duration of action was longer when dexmedetomidine was used with lignocaine as a local anesthetic agent. The vital parameters in both the groups were stable. Bleeding at the surgical site was less in the dexmedetomidine group.Conclusion:The study concluded that the combination of dexmedetomidine with lignocaine enhances the local anesthetic potency of lignocaine when injected for nerve blocks.

Dexmedetomidine alleviated neuropathic pain in dorsal root ganglion neurons by inhibition of anaerobic glycolysis activity and enhancement of ROS tolerance.

Neuropathic pain is a kind of chronic pain that is triggered or caused primarily by damage to the nervous system and neurological dysfunction. It’s known that dexmedetomidine is a new type of highly selective alpha2-adrenoceptor agonist with sedation, anti-anxiety, analgesic and other effects. However, the function and mechanism of dexmedetomidine on neuropathic pain are not clear. Rat DRG neurons were isolated and identified using immunofluorescence assay. Following treatment with H2O2, dexmedetomidine or ROS inhibitor (NAC), the apoptosis and ROS levels were examined by flow cytometery; apoptosis- and anaerobic glycolysis-related proteins were determined by Western blot assay; glucose consumption, pyruvic acid, lactic acid and ATP/ADP ratios were also measured. The results revealed that dexmedetomidine inhibited H2O2-induced apoptosis and reactive oxygen species (ROS) in rat DRG neurons and in addition, dexmedetomidine down-regulated the expression levels of anaerobic glycolysis-related proteins, significantly reduced glucose, pyruvic acid and lactic acid levels. It also increased the ATP/ADP ratio in H2O2-treated rat dorsal root ganglion (DRG) neurons. Moreover, we also demonstrated that ROS inhibitor (NAC) also inhibited H2O2-induced apoptosis and anaerobic glycolysis in rat DRG neurons. In conclusion, dexmedetomidine suppressed H2O2-induced apoptosis and anaerobic glycolysis activity by inhibiting ROS, in rat DRG neurons. Therefore, dexmedetomidine might play a pivotal role in neuropathic pain by the inhibition of ROS.

Dexmedetomidine for the management of postictal agitation after electroconvulsive therapy with S-ketamine anesthesia.

ObjectivesPostictal agitation (PIA) represents one of the most common complications during a modified electroconvulsive therapy (ECT) course. Its clinical management can be challenging especially in cases with poor response to benzodiazepines. Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist acting predominantly in the locus coeruleus, exerts sedative effects without causing relevant respiratory depression. To the best of our knowledge, this is the first study that aimed to assess the impact of dexmedetomidine use with S-ketamine anesthesia on PIA reduction in ECT.Patients and methodsWe retrospectively analyzed 7 patients who underwent 178 ECT sessions with S-ketamine anesthesia between June 2011 and July 2015 at the Central Institute of Mental Health Mannheim. In 101 sessions, the patients received dexmedetomidine in combination with S-ketamine anesthesia. The decision for dexmedetomidine use was based on individual clinical presentation (patients with positive PIA history). A multivariate repeated measurement logistic regression analysis was conducted to investigate the effect of dexmedetomidine use on the occurrence of PIA. We hypothesized that the use of dexmedetomidine reduced the incidence of PIA also in combination with S-ketamine anesthesia.ResultsThe prevalence of PIA in ECT sessions with dexmedetomidine administration was lower (mean per patient, 34% vs 62%). In the multivariate logistic regression analysis, the use of dexmedetomidine predicted the non-occurrence of PIA in a highly significant manner (P=0.001, z=−3.83, odds ratio =0.011–0.303).ConclusionAdjunctive use of dexmedetomidine to S-ketamine anesthesia in ECT seems to be a promising tool for the management of intractable PIA syndrome.

Abstract PR439

Background & Objectives: Dexmedetomidine (DEX) is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in paediatric anesthesia. Although the pharmacokinetics of DEX has been studied in paediatric patients (1), there are no data for Chinese children available. The aim of this study was to characterize the pharmacokinetics of DEX in a Chinese paediatric population. Materials & Methods: After approval by the local clinical ethics committee and written informed consent from the parents, 39 Chinese children aged 1 to 9 yrs. undergoing surgery were enrolled in the study. DEX was administered as short infusion of 1 - 2 µg/kg in 10 min. Venous blood samples were drawn until 480 min after stop of infusion. DEX plasma concentrations were measured with HPLC and mass-spectrometry. Pharmacokinetic modelling was performed by population analysis using linear compartment models. Results: Data of 36 patients (age: 1-9 yrs, weight: 10-27 kg) were analyzed. The pharmacokinetics of DEX was best described by a two-compartment model with an allometric power model for body weight scaling: CL1,2=CL1,2 TV*(BW/70)0.75 and V1,2=V1,2 TV*(BW/70). The population estimates (95% CI) per 70 kg bodyweight were: elimination clearance CL1TV=36.2 (33.3 – 41.1) L/h, central volume of distribution V1TV=84.3 (70.3 – 91.4) L, intercompartmental clearance CL2TV=82.8 (63.6 – 136.6) L/h, peripheral volume of distribution V2TV=114 (95 - 149) L, and terminal half-life T1/2el=4.4 (3.6 – 5.3) h. Age did not show any influence on weight adjusted parameters. Conclusion: Chinese children showed a similar clearance but larger volumes of distribution and a longer terminal half-life when compared to previous studies of DEX in Caucasian children (1).

Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion in Chinese Children.

Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been studied in pediatric patients, there are no data for Chinese children available. As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was the aim of this study to characterize the pharmacokinetics of dexmedetomidine in Chinese pediatric patients. Thirty-nine children aged 1-9years undergoing surgery were enrolled in the study. Dexmedetomidine was administered as short intravenous infusion of 1-2µg/kg in 10min. Venous blood samples were drawn until 480 min after stopping of infusion. Dexmedetomidine plasma concentrations were measured with high-performance liquid chromatography and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models. Data of 36 patients (age 1-9years, weight 10-27kg) were analyzed. The pharmacokinetics of dexmedetomidine were best described by a two-compartment model with an allometric power model and estimates standardized to 70kg body weight. The population estimates (95% CI) per 70kg bodyweight were: clearance 36.2 (33.3-41.1) l/h, central volume of distribution 84.3 (70.3-91.4) l, intercompartmental clearance 82.8 (63.6-136.6) l/h, peripheral volume of distribution 114 (95-149) l, and terminal half-life 4.4 (3.6-5.3) h. Age did not show any influence on weight-adjusted parameters. Chinese children showed a similar clearance, but larger volumes of distribution and longer terminal half-life when compared to studies in Caucasians. ChiCTR-OPC-14005659.

Optimal Dose of Intrathecal Dexmedetomidine in Lower Abdominal Surgeries in Average Indian Adult.

Dexmedetomidine, a selective alpha2 adrenoceptor agonist, has been used as adjuvant to spinal anaesthesia. To find out the optimum dose of dexmedetomidine to be used in lower abdomen surgery intrathecally. This was a randomized, controlled, double blinded study which included adult ASA I and II patients. They were allocated into five groups (n=20). Patients allergic to drugs to be used in the study and those with co-existing neurological disorders, coagulopathies, cardiac diseases, obesity and hypertension were excluded. Groups were designed as 2.5ml hyperbaric bupivacaine with 0.5ml saline (Control) or 0.5ml dexmedetomidine: 5mcg (D1), 10mcg (D2), 15 mcg (D3) and 20mcg (D4). Data were collected for 10 point VRS for pain, Bromage motor block, Ramsay sedation score, haemodynamics, time of first rescue analgesia (TRA) and any adverse effects and groups were analysed using one way analysis of variance (ANOVA) by SPSS16.0 (p-value <0.05 significant). The mean duration of analgesia and need of first rescue analgesics are 201.5±29.1 mins in control group but in D1 group 259.1±15.2 mins, D2 310.7±48.1mins, D3 540.3±51.6 mins and D4 702.4±52 mins. p=0.003. The mean highest VRS score along with analgesic requirements were significantly reduced in dexemeditomidine groups, but D3 and D4 had hypotension which needed correction. Weighing the prolongation of anesthesia and analgesia and side effects we conclude that 10 mcg of dexmedetomidine is optimum intrathecal dose.

Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation.

Vasoconstriction mediated by the highly selective alpha-2 adrenoceptor agonist dexmedetomidine leads to transiently increased blood pressure and severe hypertension. The dexmedetomidine-induced contraction involves the protein kinase C (PKC)-mediated pathway. However, the main PKC isoform involved in the dexmedetomidine-induced contraction remains unknown. The goal of this in vitro study was to examine the specific PKC isoform that contributes to the dexmedetomidine-induced contraction in the isolated rat aorta. The endothelium-denuded rat aorta was suspended for isometric tension recording. Dexmedetomidine dose-response curves were generated in the presence or absence of the following inhibitors: the pan-PKC inhibitor, chelerythrine; the PKC-α and -β inhibitor, Go6976; the PKC-α inhibitor, safingol; the PKC-β inhibitor, ruboxistaurin; the PKC-δ inhibitor, rottlerin; the c-Jun NH2-terminal kinase (JNK) inhibitor, SP600125; and the myosin light chain kinase inhibitor, ML-7 hydrochloride. Western blot analysis was used to examine the effect of rottlerin on dexmedetomidine-induced PKC-δ expression and JNK phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) and to investigate the effect of dexmedetomidine on PKC-δ expression in VSMCs transfected with PKC-δ small interfering RNA (siRNA) or control siRNA. Chelerythrine as well as SP600125 and ML-7 hydrochloride attenuated the dexmedetomidine-induced contraction. Go6976, safingol, and ruboxistaurin had no effect on the dexmedetomidine-induced contraction, whereas rottlerin inhibited the dexmedetomidine-induced contraction. Dexmedetomidine induced PKC-δ expression, whereas rottlerin and PKC-δ siRNA transfection inhibited dexmedetomidine-induced PKC-δ expression. Dexmedetomidine also induced JNK phosphorylation, which was inhibited by rottlerin. Taken together, these results suggest that the dexmedetomidine-induced contraction involves PKC-δ-dependent JNK phosphorylation in the isolated rat aorta.

Dexmedetomidine-induced contraction involves c-Jun NH2 -terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta.

Vasoconstriction induced by dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist, mainly involves c-Jun NH2 -terminal kinase (JNK) phosphorylation in the isolated endothelium-denuded aorta. We carried out an in vitro study to determine the main arachidonic acid metabolic pathway that is involved in dexmedetomidine-induced JNK activation. Cumulative dexmedetomidine concentration-contractile response curves were generated in the endothelium-denuded rat aorta in the presence or absence of the following inhibitors: the JNK inhibitor SP600125, the phospholipase A2 inhibitor quinacrine dihydrochloride, the non-specific lipoxygenase (LOX) inhibitor nordihydroguaiaretic acid, the 5-LOX inhibitor AA-861, the dual 5-LOX and cyclooxygenase (COX) inhibitor phenidone, the non-specific COX inhibitor indomethacin, the cytochrome p450 epoxygenase inhibitor fluconazole, the COX-1 inhibitor SC-560, and the COX-2 inhibitor NS-398. The effect of the alpha-2 adrenoceptor inhibitor rauwolscine and other inhibitors, such as quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, indomethacin and the protein kinase C inhibitor GF 109203X, on dexmedetomidine-induced JNK phosphorylation was investigated in rat aortic vascular smooth muscle cells with western blotting. The effect of dexmedetomidine on 5-LOX and COX-2 expression was investigated in vascular smooth muscle cells. SP600125, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, rauwolscine and chelerythrine attenuated dexmedetomidine-induced contraction. Indomethacin slightly attenuated dexmedetomidine-induced contraction. Fluconazole and SC-560 had no effect on dexmedetomidine-induced contraction, whereas NS-398 attenuated contraction. SP600125, rauwolscine, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone and GF 109203X attenuated dexmedetomidine-induced JNK phosphorylation. 5-LOX and COX-2 were upregulated by dexmedetomidine. Thus, dexmedetomidine-induced alpha-2 adrenoceptor-mediated contraction is mediated mainly by 5-LOX and partially by COX-2, which leads to JNK phosphorylation.

To evaluate the effects of dexmedetomidine on intraocular pressure and haemodynamic changes in response to laryngoscopy and tracheal intubation

Abstract Background: The most important prerequisites for neurosurgeries are brain relaxation, need of stable haemodynamics with less fluctuation in intracranial pressure and speedy recovery from anaesthesia. Endotracheal intubation is the major stressful stimuli that can elicit a marked pressor response. Various drugs have been used to attenuate these reflexes. Dexmedetomidine, a highly selective alpha 2-adrenoceptor agonist, have neuroprotective, cardioprotective, and sedative effects so it is potentially useful during neuroanaesthesia. This is a prospective randomised control trial carried out to see whether administration of Dexmedetomidine prior to intubation can attenuate the various haemodynamic responses, intraocular pressure (IOP) and the requirement of induction dose of propofol in control and study group. Materials and Methods: Fifty patients (ASA grade 1, 2) scheduled for intracranial tumour surgeries were divided into two groups (25 each). Group D received Dexmedetomidine 0.8 μg/kg i.v. over 10 mins and group C received 20 ml saline. Anaesthesia induced with Propofol, dose adjusted using bispectral index monitor. The groups were compared with IOP, Heart rate (HR), Mean arterial pressure (MAP), and dose of Propofol required for induction. Results: Groups were well matched for their demographic data and pre-operative. IOP in both the eyes decreases significantly after premedication and remained below baseline even after 10th min of intubation in group D while in Group C; it increased significantly after intubation and remained above baseline. The difference between groups was also statistically significant. HR and MAP decreased significantly in patients of group D compared to group C ( P&lt; 0.05). Patients were more haemodynamicaly stable at all time points after premedication in group D ( P&lt; 0.05). Propofol requirements for induction was lesser in group D (P &lt; 0.05). Bradycardia and hypotension incidences were higher in group D. Conclusion: Dexmedetomidine premedication decreases the sympathoadrenal effect on IOP and haemodynamic parameters during laryngoscopy/intubation and decreases the requirement of propofol for induction of general anaesthesia.

Involvement of spinal microglia and interleukin-18 in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI

Dexmedetomidine, a selective alpha 2-adrenoceptor (α2AR) agonist, has provided significant analgesia in neuropathic pain. However, its underlying molecular mechanism has not been fully elucidated. In the present study, we found that intrathecal administration of dexmedetomidine alleviated mechanical allodynia induced by chronic constriction injury (CCI), and pretreatment with BRL44408 significantly reversed the dexmedetomidine-induced anti-nociceptive effect. Western blotting revealed that dexmedetomidine reduced the activation of microglia and the upregulation of interleukin-18 (IL-18) protein expression in the ipsilateral lumbar spinal dorsal horn, while BRL44408 pretreatment significantly blocked these effects of dexmedetomidine. Immunocytochemistry/immunohistochemistry indicated that the α2A-adrenoceptor was localised to microglia in primary culture, and IL-18 predominantly colocalised with the microglial marker Iba-1 in the dorsal horn of the spinal cord. These results suggest that the IL-18 signalling pathway in microglia may be involved in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.

Involvement of Protein Kinase B/Akt in Analgesic Effect of Dexmedetomidine on Neuropathic Pain

Involvement of Protein Kinase B/Akt in Analgesic Effect of Dexmedetomidine on Neuropathic Pain

A Prospective Study to Analyse the efficacy of Apraclonidine in Preventing Intraocular Pressure Rise After Neodymium: YAG (Nd-YAG) Laser Posterior Capsulotomy

Objective: To analyse the efficacy of (0.5%) apraclonidine in preventing the acute rise of intraocular pressure following Nd-YAG Laser posterior capsulotomy. Material and method: A prospective case controlled randomised study was performed in the department of ophthalmology of SIMS in collaboration of department of pharmacology. Result: A total 52 patients were divided in two groups. Half of the patients were given 0.5% topical apraclonidine 15 minutes before the procedure and immediately after the procedure and after 1 hr, 2hr, and 4hrs respectively. The other half were not given any IOP lowering drug.IOP was measured by tonometry. There was significant fall in IOP in test group patients. IOP in two groups 1hr after procedure was 13.08% rise in control and 6.40% fall in test group. Conclusion: Apraclonidine, a highly selective alpha2 adrenoceptor agonist effectively and safely lowers IOP spikes after laser treatment without causing significant side effects like bradycardia or hypotension.

Pre- and Post-junctional α-Adrenoceptor-mediated Responses in the Rat Gastric Fundus In-vitro

The effects of alpha 1- and alpha 2-adrenoceptor agonists on smooth muscle tone and on cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory responses to field stimulation have been investigated in the rat gastric fundus in-vitro. None of the alpha-adrenoceptor agonists tested, noradrenaline, phenylephrine, cirazoline, guanoxabenz or UK-14,304 showed any contractile effects at concentrations up to 30 microM. In preparations where tone was raised by barium (0.5-2 mM), the mixed alpha 1- and alpha 2-adrenoceptor agonist noradrenaline (0.01-10 microM), and the selective alpha 1-adrenoceptor agonists cirazoline (0.01-10 microM) and phenylephrine (0.01-10 microM) produced concentration-dependent relaxations which were antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.01-1.0 microM). The selective alpha 2-adrenoceptor agonists UK-14,304 (0.03-30 microM) and guanoxabenz (0.03-30 microM), had no relaxant effects in raised tone. UK-14,304 (0.03-1.0 microM) produced a concentration-dependent inhibition of cholinergic nerve-induced responses which was antagonized by the alpha 2-adrenoceptor antagonist idazoxan (0.03-1.0 microM) but not by prazosin (0.03-1.0 microM). Noradrenaline (0.03-1.0 microM) also produced an inhibition of cholinergic nerve-induced responses which was antagonized by idazoxan (0.03-1.0 microM). A small component of the noradrenaline inhibitory effects was antagonized by prazosin (10%). Cirazoline (0.03-1.0 microM) produced a small inhibition of cholinergic nerve-induced responses which was antagonized by prazosin (0.03-1.0 microM). The prazosin-sensitive components of the inhibitory effects of noradrenaline and cirazoline occurred at concentrations which also produced post-junctional relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-adrenoceptor subtypes and Ca2+ mobilization in the rabbit ear artery.

The mobilization of cellular and extracellular Ca2+ pools by selective alpha 1-adrenoceptor (phenylephrine) and alpha 2-adrenoceptor (xylazine) agonists as well as noradrenaline was evaluated in rabbit ear artery. Noradrenaline and phenylephrine possess full intrinsic activity for both types of Ca2+ mobilization whereas xylazine up to 1 mM had only a limited contractile effect, being more effective in inducing extracellular Ca2+-dependent response. However, extracellular Ca2+ was mobilized by xylazine in a concentration 20 times higher than that required to stimulate pre-junctional alpha 2-adrenoceptors. Noradrenaline (5 microM) and xylazine (1 mM) induced cellular and extracellular Ca2+-dependent contractions which were prazosin-sensitive and yohimbine-resistant. Xylazine-induced contractile activity, particularly that dependent upon the extracellular Ca2+ pool, was markedly reduced by selective adrenergic denervation with 6-hydroxydopamine, but the actions of noradrenaline were unaffected. These results suggest that: (1) rabbit ear artery contain post-junctional alpha 1-adrenoceptor but not alpha 2-adrenoceptors; (2) stimulation of these alpha 1-adrenoceptors can account for the overall contractile activity of exogenously added noradrenaline and (3) stimulation of alpha 1-adrenoceptors results in mobilization of cellular as well as extracellular Ca2+ pools.