Alpha 2-receptor Agonist Research Articles

Opioid free multimodal analgesia versus opioid based analgesia in bariatric surgery outcome

Background: Combined Opioid-free analgesia (OFA) and thoracic epidural (TE) by ultrasound is the technique that may have an enhanced recovery after surgery (ERAS), decrease perioperative opioid consumption and more improved positive outcomes than balanced general anesthesia with use of opioid after bariatric surgery. The Opioid free analgesia includes local anesthetics (Na channel blocker), alpha-2 receptor agonists (dexmetedomidine), NMDA antagonists (ketamine, lidocaine, magnesium sulfate), anti-inflammatory drugs (NSAID) and dexamethasone. Aim: evaluation the effect of opioid free analgesia with thoracic epidural as a multimodal analgesia versus balanced general analgesia on outcome of bariatric surgery on total opioid requirements, pain scores, and complications. Patients and Methods: The current study recruited sixty patients aged 20-50 years, ASA I, II, under bariatric surgery. 30 patients received OFA with Ultrasonic guided thoracic epidural with pre-induction by precedex, ketamine, xylocaine, esmolol, dexamethasone, paracetamol and magnesium. Then propofol, and atracurium to insert (ETT), 30 patients received balanced general anesthesia (BGA), patients received fentanyl, propofol, atracurium. Results: There was significant decrease in pain scores within 24-hour postoperative p- value < 0.05 and there was a clinically significant reduction in time for outcome from the recovery room for OFA & TE group. The number of satisfied was higher in the OFA& TE group (60%) than BGA group (30%) (p=0.037). Conclusions: Ultrasonic-guided TE block combined with Opioid free analgesia (OFA) is an option with a better ERAS pathway for pariatric surgery to decrease consumption of opioid perioperativly with no effect on recovery or pain control, better efficiency and patient satisfaction.

The Effectiveness of Dexmedetomidine as a Prophylactic Treatment for Emergence Delirium Among Combat Veterans With High Anxiety: A Randomized Placebo-Controlled Trial.

Emergence delirium (ED) is characterized by agitation, confusion, and violent physical and verbal behavior associated with awakening from general anesthesia. Combat exposure among U.S. military veterans has been identified as a risk factor for ED. Preoperative baseline anxiety was shown to be a predictor of ED, and combat veterans are known to be at high risk for anxiety as well as depression and PTSD. Dexmedetomidine is an alpha-2 receptor agonist proven to mitigate ED in several patient populations. Perioperative use of dexmedetomidine demonstrated promising benefits in pediatric ED but has not been evaluated in combat veterans. This study was a multi-site, prospective, randomized controlled investigation of 369 patients with a history of military combat exposure who were scheduled for elective surgery with a general anesthetic as the primary means of anesthesia. The trial was funded by the Tri-Service Nursing Research Program Grant HU0001-14-TS05 (N14-PO3) and approved by the Institutional Review Boards at the Naval Medical Center San Diego, Womack Army Medical Center, Walter Reed National Military Medical Center, and the Uniformed Services University of the Health Sciences, Bethesda, MD. All subjects were administered the State-Trait Anxiety Inventory (STAI) to evaluate baseline anxiety. Those enrolled subjects with a low anxiety level (STAI < 39) (n = 215) were placed in the observational arm of the study. Those with a high anxiety level (STAI ≥ 39) were placed in the experimental arm (n = 153) and were further randomized to treatment with intraoperative dexmedetomidine infusion (1 μg/kg bolus at induction, followed by a 0.6 μg/kg/h infusion continued until emergence) (n = 75) or a placebo intraoperative infusion (n = 75). Following the delivery of the prescribed anesthetic, all subjects were observed for signs of ED using the Pediatric Anesthesia Emergence Delirium (PAED) Scale. The patient and data recorder remained blinded to the randomization results. The central tendencies of demographics and clinical characteristics are reported. PAED among those randomized to dexmedetomidine (median 7, interquartile interval (IQI) 5.2-9.2) tended to be less (P < .0001) than that of those randomized to control (median 12, IQI 10-13). Dexmedetomidine was found to be the most important predictor of PAED (35% relative importance), followed by Patient Health Questionnaire (14%), STAI-Trait (9%), and PTSD Checklist-Military Version (8%); the overall rankings are featured. Randomization to receipt of dexmedetomidine was associated with a 3.7-unit reduction (95% CI 2.5-4.9) in PAED (P < .001) in a linear model controlling for several variables, and the directionality of the effect persisted upon regularization in a penalized linear model. Dexmedetomidine was effective at reducing PAED among combat veterans who were experiencing symptoms of pre-operative anxiety (i.e., STAI-State ≥39). Although psychological morbidity is not unique to the military population, combat veterans carry some of the highest rates of anxiety, PTSD and depression compared to the general population. Dexmedetomidine can be safety employed by anesthesia providers to reduce symptoms of ED in the perioperative period. The double-blind randomized, controlled study design strengthens our analyses; however, this study did not control for the type of surgical procedure or the duration of anesthetic. Furthermore, we only enrolled patients with combat exposure experiencing symptoms of anxiety and did not investigate the role of dexmedetomidine in combat veterans with less anxiety. Further study of the relationship between psychological comorbidities, ED, and dexmedetomidine is warranted.

Comparison of pulmonary function in isoflurane anaesthetized ventilated sheep (Ovis aries) following administration of intravenous xylazine versus medetomidine.

Alpha2 receptor agonists (alpha2-agonists) are useful sedative and analgesic agents in sheep, but have adverse pulmonary effects, which are reportedly similar between different alpha2-agonists. This randomized crossover study compared pulmonary function after intravenous administration of an alpha2-agonist, either xylazine or an equipotent dose of medetomidine in 34 female sheep anaesthetized twice. Pulmonary function was assessed using spirometry, volumetric capnography, arterial blood gas analysis 1 min prior to, and 5 and 10 min after administration of the allocated alpha 2 agonist drug. Pulmonary structural changes were subsequently assessed using computed tomography (CT). Tachypnoea or hypoxaemia prompted reversal with atipamezole and exclusion of data. Data were analysed for a fixed effect of drug using a mixed effect linear model with significance set at p < 0.05. Ten sheep administered xylazine required atipamezole while none of sheep receiving medetomidine did. Xylazine produced significantly higher respiratory frequency, airway pressures, airway resistance and arterial carbon dioxide (CO2), and lower dynamic compliance, tidal volume, CO2 elimination and end tidal CO2 tension and arterial oxygen tension than medetomidine. This was associated with a significantly lower % of aerated tissue and higher % poorly and non-aerated tissue in CT images of sheep receiving xylazine versus medetomidine. In conclusion, xylazine administration produced marked decreases in pulmonary function, in ventilated isoflurane anaesthetized sheep, when compared to an equipotent dose of medetomidine when administered as an intravenous bolus supporting the use of medetomidine when alpha2-agonists are required.

Effects of Dexmedetomidine and Fentanyl Premedication on Quality of Extubation in Children undergoing Tonsillectomy: A Prospective Cohort Study

Introduction: Smooth extubation in children is a challenging task, especially those undergoing tonsillectomy. Dexmedetomidine, an alpha-2 receptor agonist has been found to be beneficial in paediatric anaesthesia due to its anxiolytic, sedative and analgesic properties. It also attenuates haemodynamic stress response and airway reflexes to intubation and extubation. Fentanyl, a synthetic opioid is also extensively used in paediatric anaesthesia. Aim: To compare the effects of dexmedetomidine and fentanyl premedication on quality of extubation and extubation haemodynamics. Materials and Methods: The prospective cohort study was conducted in 120 children divided into two groups of 60 each, aged 5-12 years, belonging to American Society of Anaesthesiologists’ (ASA) physical status I and II, posted for elective tonsillectomy under general anaesthesia. Group F received fentanyl 2 μg/kg intravenously and group D, dexmedetomidine 0.5 μg/kg as intravenous infusion over 10 minutes as premedication. The time from discontinuation of anaesthetics to extubation and to opening the eyes in response to verbal stimuli were noted. The quality of extubation was evaluated according to the 5 point extubation score and postoperative sedation assessed using Ramsay sedation score. The haemodynamic parameters were monitored immediately after discontinuation of anaesthetics and at 1, 3, 5 and 10 minutes postextubation. Any complications like airway obstruction, bradycardia, and hypotension were noted and treated appropriately. Statistical Package for Social Sciences (SPSS) software version 22 was used for statistical analysis and categorical outcomes compared with Chi-square test/Fisher’s-Exact test. Results: Extubation was smoother in group receiving dexmedetomidine. The median time from discontinuation of anaesthetics to extubation and eye opening was significantly shorter in dexmedetomidine group compared to fentanyl group (p&lt;0.001). Postoperative sedation score was comparable between the two groups. Heart Rate (HR) and Mean Arterial Pressure (MAP) monitored showed significantly stable values in the dexmedetomidine group (p&lt;0.001) when compared to fentanyl soon after discontinuation of anaesthetics and 1, 3, 5 and 10 minutes postextubation. Conclusion: Premedication with dexmedetomidine 0.5 μg/kg intravenously provides better quality and haemodynamics of extubation compared to fentanyl 2 μg/kg in children undergoing tonsillectomy, without causing significant sedation.

Dexmedetomidine Versus Clonidine as Adjuvants in Epidural Analgesia in Gynecological Laparotomy

Abstract Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. If the management of acute postoperative pain is not done properly, it can lead to the complication such as chronic pain. Epidural anesthesia reduces perioperative stress response in surgery, increasing the surgery outcome. Epidural analgesia is one of the potential acute postoperative pain treatments. The administration of α-2 agonists has analgesic and sedative effect when used as adjuvant in epidural analgesia. The administration of α-2 adrenergic agonists' adjuvant can increase the potential duration of analgesia and reduce the local anesthetic dose needed 30%–40% and can reduce the occurrence of the side effects. Dexmedetomidine is one of the most potent and high selective alpha-2 adrenergic receptor agonists. The use of dexmedetomidine during epidural anesthesia has faster onset and longer motor sensory blockade duration with hemodynamic stability that can be accepted. While clonidine acts as selective partial alpha-2 receptor agonists that cause the analgesic action of alpha-2 receptor in the dorsal of spinal cord. Clonidine has been shown its ability to reduce the local anesthesia needed and improve the pain scores when is combined with bupivacaine 0.125% with or without fentanyl opioid 1–2 μg/mL.

Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions.

No AccessJournal of UrologyUrological Survey1 Dec 2020Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001285.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions." The Journal of Urology, 204(6), p. 1385 Suggested Reading : Systemic and topical drug administration in the pig ureter: effect of phosphodiesterase inhibitors alpha1, beta and beta2-adrenergic receptor agonists and antagonists on the frequency and amplitude of ureteral contractions. J Urol 2001; 166: 714. Link, Google Scholar © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 204Issue 6December 2020Page: 1385-1385 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF DownloadLoading ...

Using clonidine in the treatment of tizanidine abuse and withdrawal: a case report of a patient with somatoform pain disorder

ABSTRACT Tizanidine is a noradrenergic alpha-2 receptor agonist approved in the treatment of muscle spasticity. Limited data on abuse and withdrawal of Tizanidine are available. We present a case of severe withdrawal and symptoms of psychological and physiological dependence: A 52-year-old woman who was transferred to the psychosomatic unit because of pain and anxiety. She presented with a long history of inpatient treatment due to symptoms of pain. After multiple treatment options had been tried without much efficacy, the patient was prescribed Tizanidine for her symptoms of pain. As symptoms were diminished, treatment was upheld. Soon, abuse, and later, dependence of Tizanidine had established. At time of admission, the patient had been on a self-escalated daily administration scheme of 40 mg of Tizanidine. As dose tapering proved unsuccessful, dose reduction with Lorazepam to reduce withdrawal symptoms was attempted. As also the additive treatment with Lorazepam showed no satisfying results, another treatment option was needed. After establishing Clonidine, the off tapering of Tizanidine was much better tolerated by the patient and finally proved successful. This case report draws attention to possible severe abuse of Tizanidine and the major clinical aspects and challenges in the treatment of Tizanidine withdrawal.

To compare the efficacy of postoperative analgesia between clonidine and dexmedetomidine as adjuvants with 0.5% ropivacaine by ultrasound-guided supraclavicular brachial plexus block for upper limb surgeries: A prospective, double-blind, randomized study

Context:The supraclavicular brachial plexus block is a very safe, useful and effective method for upper limb surgeries. Among local anesthetics, ropivacaine has special applications in neuraxial and peripheral nerve blocks due to its low cardiotoxicity and less toxicity to central nervous systems compared to bupivacaine and lignocaine. Dexmedetomidine is a newer and potent alpha-2 receptor agonist which has 10 times higher selectivity for alpha-2 receptors as compared to clonidine, So far, very few studies have been undertaken to compare the efficacy of clonidine and dexmedetomidine to provide and prolong postoperative analgesia, especially with the use of ultrasound for nerve localization.Aims:To compare the efficacy of postoperative analgesia between clonidine and dexmedetomidine as adjuvants with 0.5% ropivacaine by ultrasound-guided supraclavicular brachial plexus block for upper limb surgeries.Settings and Design:Prospective, randomised, double-blind interventional study.Subjects and Methods:Eighty patients of ASA grade I or II undergoing elective upper limb surgery were randomly divided into two groups:- Group RC (n = 40) received 35 ml of 0.5% ropivacine with 1 μg.kg−1 of clonidine. Group RD (n = 40) received 35 ml of 0.5% ropivacaine with 1 μg.kg−1 of dexmedetomidine.Statistical analysis used:The statistical software SPSS version 20 has been used for the analysis. By using Pearson's Chi-Square test for Independence of Attributes/Fisher's Exact. Continuous variables were expressed as Mean, Median, and Standard Deviation and compared across the groups using unpaired t-test.Results:In our comparative study, dexmedetomidine 1 μg.kg−1 with 35 ml of 0.5% ropivacaine provided significantly longer duration of postoperative analgesia and earlier sensory block as compared to clonidine 1 μg.kg−1 with same dose of ropivacaine in ultrasound-guided supraclavicular brachial plexus block.Conclusions:The ropivacaine-dexmedetomidine group in our study provided earlier sensory block and more prolonged postoperative analgesia as compared to ropivacaine-clonidine group. Thus ropivacaine-dexmedetomidine combination may be effectively used in all painful upper limb surgeries specially orthopaedic procedures.

The alpha-2 receptor agonist dexmedetomidine attenuates vancomycin‑induced acute kidney injury.

This study was conducted to evaluate the protective effect of dexmedetomidine on nephrotoxicity and the mechanism of renoprotection following vancomycin-induced nephrotoxicity in rats. Thirty-two albino Wistar rats were divided into four groups. The control group received intraperitoneal (IP) physiological saline solution, the vancomycin (VMC) group received IP 200 mg/kg vancomycin, the dexmedetomidine (DEX) group received IP 5 µg/kg dexmedetomidine, and the vancomycin and dexmedetomidine (VMC+DEX) group received IP 200 mg/kg vancomycin followed by IP 5 µg/kg dexmedetomidine 20 min after the vancomycin injection. On the 8th day of the experiment, histopathological and biochemical parameters were assessed. Creatinine levels were significantly higher in VMC and VMC+DEX groups. The endothelin-1 level was significantly higher in VMC group. Nitric oxide levels were statistically lower in VMC and VMC+DEX groups. Histopathologic assessments revealed that the extent of renal damage was significantly higher in group VMC (n = 4 with damage of Grade 3) compared to group VMC+DEX (n = 0 with damage of Grade 3). It was determined that dexmedetomidine can reduce the extent of renal damage by preventing the elevation of vasoconstrictor agents (Tab. 2, Fig. 1, Ref. 36).

Comparison of the Analgesic Efficacy of a Single Dose of Epidural Dexmedetomidine versus Fentanyl as an Adjuvant to Bupivacaine in Abdominal Surgery.

Background:Fentanyl as an epidural additive act on spinal opioid receptors, while dexmedetomidine has selective alpha-2 receptor agonist action enhancing analgesic effects.Aims:We aimed to compare the postoperative analgesic efficacy of single doses of dexmedetomidine against fentanyl as epidural adjuvant to 0.125% bupivacaine.Settings and Design:A prospective, randomized, controlled, double-blind trial was conducted in a tertiary care teaching institute.Patients and Methods:Forty-six patients undergoing abdominal surgery under general anesthesia with epidural analgesia were allocated into two groups to receive postoperative analgesia with single doses of 10 mL 0.125% bupivacaine with the addition of dexmedetomidine 0.5 μg.kg-1 (Group D) or fentanyl 0.5 μg.kg-1 (Group F). The primary outcome was the duration of postoperative analgesia between the two groups. The secondary outcomes were hemodynamic variations, vasopressor need, and motor blockade.Statistical Analysis:Chi-square test for static parameters and Student's t-test or Mann–Whitney test for continuous variables were used for analysis.Results:The duration of analgesia was longer in Group D (5.0 ± 2.0 h) versus Group F (2.9 ± 1.4 h), Sixteen patients in Group D versus seven patients in Group F needed vasopressors after the bolus to maintain the blood pressure (BP) within 20% of prebolus value (P = 0.018). Heart rate and mean and systolic BP were lower in Group D at various time points following bolus administration.Conclusion:A single dose of dexmedetomidine as an additive to epidural local anesthetic postoperatively prolongs the duration of analgesia in comparison to fentanyl but is associated with changes in hemodynamics, including the need for the administration of vasoactive drugs.

The effects of loading dose administration rate of dexmedetomidine on sedation and dexmedetomidine requirement in elderly patients undergoing spinal anesthesia

Background: This study evaluated the effect of decrease in loading dose administration rate of dexmedetomidine (DMT) on sedation and DMT requirement in elderly patients. Methods: Fifty-eight patients over 65 years old with ASA I-II who were planned to receive DMT sedation during spinal anesthesia were randomly assigned to two groups. Group S (n = 29) received a 0.5 μg/kg DMT loading dose over 20 minutes, while group C (n = 29) received the DMT loading dose over 10 minutes. Then, both groups received a continuous infusion of 0.4 μg/kg/h. The sedative status was recorded before and at 5, 10, 15, 20, 25, and 30 minutes after administration of DMT and at the end of the anesthesia according to the Ramsay sedation scale (RSS). Also, the time to reach RSS-3 (patients asleep, responsive to commands) and the dose of DMT until reaching RSS-3 were recorded. Results: The time to reach RSS-3 was similar between the two groups (group S = 16.0 ± 4.3 minutes vs. group C = 15.5 ± 4.2 minutes, P = 0.673). However, the DMT required to reach RSS-3 in group S was significantly lower than that in group C (23.3 ± 7.1 vs. 32.5 ± 6.0 g, P < 0.001). There was no difference in RSS between the two groups from the administration of DMT to the end of the anesthesia (P = 0.927). Conclusions: Decreasing the administration rate of the DMT loading dose did not delay the onset of RSS-3 sedation and reduced the DMT requirement in elderly patients. Keywords: Adrenergic alpha-2 receptor agonists; Aged; Dexmedetomidine; Hypnotics and sedatives; Spinal anesthesia

ПОСТТРАВМАТИЧНИЙ СТРЕСОВИЙ РОЗЛАД: НЕЙРОНАУКОВІ ОСНОВИ ДОКАЗОВОГО ЛІКУВАННЯ

Posttraumatic stress disorder (PTSD) is a relatively common anxiety spectrum syndrome, in which memory of a triggering trauma becomes aberrantly linked to autonomic and emotional arousal. The recurrent, internally generated stress response can produce enduring behavioral and brain changes. Mechanistically, this may involve both dysregulation of the hypothalamo-pituitaryadrenal axis as well as degradation of the capacity of supramodal cortical areas to process and manage trauma-related emotional content. The optimal balance of information processing and hence behavioral reactivity shifts from the refl ective prefrontal cortex in favor of the more emotionally reactive amygdala. Trauma-focused therapies exploit adaptive neuroplasticity to decouple the memory of the trauma from the aberrant emotional and behavioral responses, in effect reconfi guring brain networks. The effect-size of such psychological therapies is generally larger than that for pharmacological treatments which are currently limited to drugs repurposed for PTSD. Nonetheless, in a signifi cant number of patients, some symptoms can be at least partially attenuated by selective serotonin reuptake inhibitors. In addition, the frequency and intensity of trauma-related nightmares can usually be lowered by adrenergic alpha-1 receptor agonists. Even as novel modalities continue to be developed, the judicious implementation of currently available evidence-based treatments for PTSD can target the underlying neurobiology, provide symptomatic relief, and promote psychosocial recovery.

Dexmedetomidine: A Potential Cause of Circulatory Collapse in Patient With Severe Pulmonary Arterial Hypertension

SESSION TITLE: Cardiothoracic Surgery SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Dexmedetomidine is an alpha2 receptor agonist with unique mechanism of action for sedation and sympatholysis via receptors in the locus ceruleus, analgesia via receptors in the spinal cord without significant effect on respiration. Due to these properties, it has been increasingly used in the ICU and more recently in patient requiring non-invasive ventilation (NIV) who cannot tolerate this modality. A prostective randomized study compared dexmedetomidine vs midazolam in patients requiring NIV and sedation if they cannot tolerate the positive pressure ventilation.1 Dexmedetomidine was found to more desirable than midazolam in terms of level of awake sedation, shortened duration of mechanical ventilation and length of the ICU stay. However, patients treated with DM had statistical significant increase in bradycardia without needing intervention or stopping the medication. Although the study included patients with cardiogenic pulmonary edema they had normal EF. A retrospective multicenter international study found that about 80% of hospitalized patients with PAH who had circulatory collapse and cardiopulmonary rescusitation (CPR) did not survive the resuscitation effort despite minimal delay between collapse and initiation of CPR. ECG at the time of the CPR showed bradycardia in 45% of the patients. CASE PRESENTATION: We report the case of 75-year-old female with long-standing pulmonary fibrosis with secondary moderate to severe pulmonary arterial hypertension (PAH) who developed bradycardia requiring cardiovascular resuscitation believed secondary to dexmedetomidine (DM) infusion. Patient was on high oxygen for 4 weeks on acute-care floor before she had altered level of consciousness and worsening oxygenation requiring non- invasive ventilation (NIV) and transfer to the ICU. She was started on DM drip at 0.3 mcg/kg/min due to agitation, in part due to not being able to tolerate the NIV. Without developing hypoxemia, patient had a sudden onset of severe bradycadia with loss of blood pressure requiring advanced cardiopulmonary resuscitation. She responded to 1 mg epinephrine and brief chest compression with return of pulse and blood pressure. Dexmedetomidine was immediately stopped. After intubation, patient developed severe hypotension requiring multiple pressors. Bedside echo showed severe RV dilation and global hypokinesis. DISCUSSION: There is limited published studies on the use of DM in patients with PAH. Successful elective procedural sedations with DM were anecdotally reported in few adults and pediatric patients with severe PAH. Based on the above case, we caution against the use of DM in patients with severe PAH in the ICU due to risk of bradycardia that jeopardize the patient cardiac output that is highly dependent on heart rate. There are limited studies and inconclusive results on the effect of DM on pulmonary arterial pressure and pulmonary vascular resistance both in humans and animal models. CONCLUSIONS: Patients with severe PAH requiring NIV have significant comorbid condition, tenuous cardiac output and are at increased risk of acute de-compensation . DM should be avoided due to inceased risk of bradycardia and circulatory collapse. Any deterioration requiring acute resuscitation and emergency intubation are likely to be detrimental in this patient population. Reference #1: Dexmedetomidine versus Midazolam for sedation of Patients with Non-invasive Ventilation Failure. Huang, Z. Internal Medicine 2012; 51:2299-2305. Reference #2: Outcome after Cardiopulmonary Resuscitation in Patients with Pulmonary Arterial Hypertension. AM J Respir Crit Care Med 2002;165:341-344 Reference #3: Dexemedetomidine and Pulmonary Hypertension: A Case Report and Review of the Literature J Med Cases 2013; 4(7):481-484. DISCLOSURE: The following authors have nothing to disclose: Khaled Saleh, Fadi Hamed No Product/Research Disclosure Information

From the Editor’s desk...: July 2017

From the Editor’s desk...: July 2017

671 Characterization of the in vivo pharmacology of Oxymetazoline and Brimonidine using a mouse model of UV-induced erythema

Introduction: Brimonidine topical gel, 0.33%, an alpha2-selective agonist, received US Food and Drug Administration approval in 2013 for treatment of persistent facial erythema of rosacea. Oxymetazoline, a full alpha1-receptor agonist, has completed phase 3 clinical development for this dermatologic condition. We compared the in vivo pharmacology of oxymetazoline and brimonidine in a mouse model of skin erythema. Methods: To induce erythema, right sides of male SKH1 hairless mice were irradiated with 120 mJ/cm2 of ultraviolet B (UVB) light. Inhibition of alpha-adrenergic receptors was achieved by injecting mice with 0.3 mg/kg of the alpha1 antagonist prazosin or the alpha2 antagonist rauwolscine 1.75 hours after UVB exposure. Fifteen minutes later, antagonist-treated mice received oxymetazoline cream 1%, brimonidine gel 0.33%, or no additional treatment. Other mice received oxymetazoline, brimonidine, or respective vehicles without alpha antagonist pretreatment. Erythema, expressed as mean hemoglobin index scores (mean Hb), was measured at baseline and up to 4 hours after UVB exposure using a chromameter(normal Hb index values: 1.1–1.3). Treatment groups were n=5. Analysis of variance with Bonferroni t-tests compared differences between treatment groups (statistical significance: PPP1 antagonist prazosin impaired oxymetazoline reduction of erythema (mean Hb: 1.51 vs 1.30 without prazosin; P2 antagonist rauwolscine had little effect on erythema following oxymetazoline application (mean Hb: 1.44 vs 1.39 without rauwolscine), but impaired brimonidine function in improving erythema (mean Hb: 1.52 vs 1.34 without rauwolscine; P < 0.05). No changes were observed with prazosin (mean Hb: 1.61, 1.66) or rauwolscine alone (mean Hb: 1.72, 1.67). Conclusion: In this study, oxymetazoline reduced erythema through alpha1 receptors, and brimonidine reduced erythema through alpha2 receptors.

The Cardioprotective Effect of Dexmedetomidine in Rats Is Dose-Dependent and Mediated by BKCa Channels.

The alpha-2 receptor agonist Dexmedetomidine (Dex) protects the heart against ischemia-reperfusion injury. We investigated the signaling cascade underlying Dex-induced acute cardioprotection, with special emphasis on large-conductance Ca2+-sensitive potassium (BKCa) channels. Rats were anesthetized with pentobarbital. Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer. Hearts underwent 33 minutes of ischemia followed by 60 minutes of reperfusion. Before the beginning of ischemia, Dex was administered at different doses (0.1-30 nM) for characterization of a dose-effect relationship. In another set of experiments, Dex (3 nM) was administered together with the BKCa channel inhibitor paxilline and the connexin-43 inhibitor peptide Gap27. Also, the BKCa channel opener NS1619 was administered. In control animals, infarct size was 49% ± 5%. Dex at 3-30 nM reduced infarct size to ∼22%, whereas lower (0.1-1 nM) doses reduced infarct size to ∼38%. Paxilline (1 μM) and GAP27 (6 μM) blocked the Dex-induced cardioprotection. NS1619 (10 μM) reduced infarct size to about the same magnitude as did the higher doses of Dex. Functional heart parameters and coronary flow were not different between the study groups. In male rats, the Dex-induced protection against ischemia-reperfusion injury involves connexin-43 and activation of BKCa channels.

Apraclonidine in the treatment of ptosis

Transient ptosis is a known complication of botulinum toxin (BoNT) injection due to inadvertent migration of toxin into the levator palpebrae superioris muscle. Currently there is no treatment available for BoNT induced ptosis. Apraclonidine hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak alpha-1 receptor agonist activity that has the ability to elevate the eye lid. Apraclonidine has been used as a diagnostic test in Horner's syndrome. We evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a patient with Horner syndrome. Each patient was administered 2 drops of apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20–30min later. All 6 patients showed improvement in ptosis. There was also improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not only useful as a diagnostic test in Horner's syndrome, but may be an effective and safe treatment for BoNT-induced ptosis.

Prolonged Use of Dexmedetomidine Infusion in an Infant for Sedation as Adjuvant Therapy

Dexmedetomidine, a central and peripheral alpha-2 receptor agonist approved by the FDA for the use in patients 18 years old and older, it has been increasingly used in the pediatric population for sedation and analgesia due to its advantage of minimal respiratory depression and lack of abuse/dependence. This is a case report of a successful use of dexmedetomidine in an infant for 15 weeks achieving; symptom control, reduction in the dose of opioids and benzodiazepines by 50% and a safe transition to oral equivalents.

Effects of a PPAR-gamma receptor agonist and an angiotensin receptor antagonist on aortic contractile responses to alpha receptor agonists in diabetic and/or hypertensive rats.

SummaryAimThe aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats.MethodsMale Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hypertensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose–response curves to phenylephrine (Phe) (10-9–10-5 M) and clonidine (Clo) (10-9–10-5 M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 μM) and/or losartan (10 μM).ResultsPioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups.ConclusionThe sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidinediones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension.

EPINEPHRINE

The most common complication of spinal anesthesia for cesarean section ishypotension. Ephedrine is the most commonly used vasopressor that increases blood pressurewith minimal impact on uteroplacental blood flow. An alpha-1 adrenergic receptor agonist mayneed to be administrated when ephedrine is ineffective. Unavailability of alpha-1 receptoragonists in a period of time in our center leads to administration of epinephrine as the seconddrug. In the present study, the data of 14 patients with ephedrine resistant hypotension duringspinal anesthesia for cesarean section were reviewed. Increase in maternal blood pressurewas recorded one minute after epinephrine administration in all patients. Surprisingly, thismedication also causes uterine relaxation after one to five minutes. Ease of fetal extractionwas noticed in 13 patients. All patients achieved adequate uterine contraction after delivery.Epinephrine helped regulate blood pressure and surprisingly facilitate uterine relaxation inpatients with emergency cesarean section with spinal anesthesia.