DOCSLIB.ORG

Comparison of the Β-Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacoc

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparison of the Β-Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacoc 1521-0103/359/1/73–81$25.00 http://dx.doi.org/10.1124/jpet.116.232884 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 359:73–81, October 2016 Copyright ª 2016 by The American Society for Pharmacology and Experimental Therapeutics Comparison of the b-Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacochaperoning Actions Shahrooz Nasrollahi-Shirazi, Sonja Sucic, Qiong Yang, Michael Freissmuth, and Christian Nanoff Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria Received February 15, 2016; accepted July 18, 2016 Downloaded from ABSTRACT Blockage of b1-adrenergic receptors is one of the most effective was very low. Both landiolol and esmolol caused a very modest treatments in cardiovascular medicine. Esmolol was introduced rise in cAMP levels but a robust increase in the phosphorylation some three decades ago as a short-acting b1-selective antag- of extracellular signal regulated kinases 1 and 2, indicating that the onist. Landiolol is a more recent addition. Here we compared the two drugs exerted partial agonist activity with a signaling bias. If two compounds for their selectivity for b1-adrenergic receptors cells were incubated for $24 hours in the presence of $1 mM jpet.aspetjournals.org over b2-adrenergic receptors, partial agonistic activity, signaling esmolol, the levels of b1-adrenergic—but not of b2-adrenergic— bias, and pharmacochaperoning action by using human embry- receptors increased. This effect was contingent on export of onic kidney (HEK)293 cell lines, which heterologously express the b1-receptor from endoplasmic reticulum and was not seen each human receptor subtype. The affinity of landiolol for b1- in the presence of landiolol. On the basis of these observa- adrenergic receptors and b2-adrenergic receptors was higher tions, we conclude that landiolol offers the advantage of: 1) and lower than that of esmolol, respectively, resulting in an improved selectivity and 2) the absence of pharmacochaperon- improved selectivity (216-fold versus 30-fold). The principal ing activity, which sensitizes cells to rebound effects upon drug metabolite of landiolol (M1) was also b -selective, but its affinity discontinuation. 1 at ASPET Journals on October 2, 2021 Introduction which the affinity is quoted in reviews, (e.g., Plosker, 2013), but for which the original data are inaccessible. b Landiolol is a short-acting -adrenergic receptor antagonist G protein-coupled receptor antagonists have been catego- – that has a half-life (3 4 minutes) shorter than the reference rized traditionally according to receptor selectivity, binding compound esmolol (9 minutes) (Plosker, 2013). Cleavage of an affinity, and the pharmacokinetic properties of the com- ester bond generates the major landiolol metabolite, M1, pounds. Additional possible discriminators that have been which has a half-life (1.8 hours) substantially longer than appreciated more recently are their intrinsic activity and the parent compound (Murakami et al., 2005). During short- signaling bias (Kenakin, 2005) and their ability to act as term infusion, M1 reaches peak concentrations in the range of pharmacochaperones (Tao and Conn, 2014): m 3.24 M (Murakami et al., 2005). Because of its long half-life, 1) G protein-coupled receptors elicit signals not only the concentrations of M1 are predicted to increase further by recruiting their cognate G protein. They can activate upon prolonged infusion and to reach their steady state, with additional signaling pathways in a manner independent of continuous intravenous infusion, after about 7 hours. In fact, heterotrimeric G proteins. Among all receptors known, the b2- the ratio of half-lives predicts that under steady-state condi- adrenergic receptor has been most extensively investigated tions, the concentration of M1 may exceed that of landiolol by with respect to its ability to generate a second wave of several fold. It was therefore of interest to document the intracellular signals: Agonist occupancy triggers phosphor- b b affinity and selectivity of M1 for human 1- and 2-adrenergic ylation of several serine and threonine residues in the receptors and to compare it to that of the parent compound, for C-terminus of the b2-adrenergic receptor by G protein- coupled receptor kinases (Lefkowitz and Shenoy, 2005). This supports binding of b-arrestins, which serve as versatile This work was supported by a grant from AOP Orphan Pharmaceuticals AG, adapters: They recruit the endocytotic machinery and thus Vienna, Austria, which markets esmolol and has a commercial interest in landiolol. support the clathrin-dependent endocytosis of receptors. dx.doi.org/10.1124/jpet.116.232884. In addition, b-arrestins scaffold via their C-terminus the ABBREVIATIONS: ANOVA, analysis of variance; BSA, bovine serum albumin; COPII, coatomer protein II; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase (MAP kinase); FCS, fetal calf serum; GFP, green fluorescent protein; HEK, human embryonic kidney cells; M1, principal landiolol metabolite (3-{4-[(S)-2-hydroxy-3-(2-morpholinocarbonylamino) ethylamino]propoxy}phenylpropionic acid); MAP, mitogen- activated protein; PBS, phosphate-buffered saline; PMA, phorbol-12-myristat-13-acetate; PMSF, phenylmethylsulfonyl fluoride; siRNA, small- interfering RNA. 73 74 Nasrollahi-Shirazi et al. assembly of kinase cascades, most prominently the mitogen- 100, 31, and 33 mM, respectively. Isoproterenol (33 mM) was dissolved activated protein (MAP) kinase cascade (Lefkowitz and She- in 0.1 M HCl. noy, 2005; Shenoy and Lefkowitz, 2011). Receptor ligands Cell Transfections, Cell Cultures, and Cell Membrane b b differ in their ability to stabilize the active conformations of Preparations. Plasmids encoding human 1-and 2-adrenergic the receptor. Full agonists are thought to stabilize all active receptors,whichweretaggedontheirN-terminiwithaFLAG- epitope, were a generous gift of Dr. Mark von Zastrow (University conformations, pure antagonists are thought to trap the of California at San Francisco). Human embryonic kidney receptor in the inactive conformation. However, there is a (HEK)293 cells (a fibroblast cell line) were transfected using the continuum with respect to agonistic or antagonistic activity polycationic TurboFect reagent (Fermentas/Thermo Fisher Scien- and with respect to the conformations, which are achieved tific) as follows: The plasmid encoding the human b1-orthehuman upon binding of individual ligands (Kenakin, 2005). Accord- b2-adrenergic receptor plasmids (3 mg) were diluted with empty m m ingly, in the case of the b2-adrenergic receptor, antagonists carrier plasmid pcDNA3 (7 g) and 20 l of the TurboFect reagent have been found to act as b-arrestin-biased ligands, i.e., they in 1 ml Dulbecco’s modified Eagle’s medium (DMEM; Sigma- Aldrich). This mixture was incubated for 20 minutes at room block the canonical signaling pathway (i.e., Gs-dependent stimulation of adenylyl cyclase), but they support the re- temperature (22°C) to allow for complex formation between the cruitment of b-arrestin and the resulting MAP kinase stimu- DNA and the polycationic TurboFect reagent. Thereafter, it was pipetted dropwise onto the layer of HEK293 cells (80% confluent in lation (Azzi et al., 2003; Whalen et al., 2011). a 10-cm dish). After 24 hours the medium was exchanged and the 2) Continuous exposure to cell-permeable ligands can in- cells propagated in a humidified atmosphere (95% air/5% CO2)at crease the surface levels of a receptor and result in exagger- 37°C in DMEM containing 10% fetal calf serum (FCS) and Downloaded from ated responses to endogenous agonists, if the treatment with 0.7 mg/ml geneticin (G418) for selection of stable transfectants. an antagonist is suddenly stopped. In fact, this was first In some instances, a plasmid (3 mg/2 Â 106 cells) encoding a green observed with the b-adrenergic antagonist propranolol (“pro- fluorescent protein (GFP)-tagged bovine b-arrestin-2 (arrestin-3) pranolol withdrawal rebound”; Alderman et al., 1974; Miller or an empty control plasmid was subsequently introduced into et al., 1975) and linked to an increase in surface receptor levels stably transfected HEK293 cells. (Aarons et al., 1980). This effect is currently thought to reflect For membrane preparation, stably transfected cells were har- – jpet.aspetjournals.org pharmacochaperoning by cell-permeable antagonists, i.e., vested from 15-cm dishes (80 90% confluent) as follows: The dishes were first rinsed with phosphate buffered saline (PBS) and then specific ligands can assist receptor folding in the ER (endo- mechanically detached from the dish with a plastic scraper in 5 ml of plasmic reticulum) by binding to and stabilizing conforma- ice-cold PBS containing 0.1 mM phenylmethylsulfonyl fluoride tional intermediates on the trajectory to the stable low-energy (PMSF). Cells were recovered by centrifugation (400g for 10 minutes state of the mature receptor (Morello et al., 2000; Nanoff and at 4°C). The cell pellet was resuspended in 1 ml hypotonic HME Freissmuth, 2012). buffer (20 mM HEPES NaOH, pH 7.5, 1 mM EDTA, 2 mM MgCl2) The underlying chemistry behind the development of the containing 0.1 mM PMSF and the Complete Protease Inhibitor short-acting b-blocker landiolol resulted in a large molecular Cocktail (Roche Biochemical Reagents/Sigma-Aldrich) and subse- at ASPET Journals on October 2, 2021 structure. Given the chemical difference with conventional
Load more

Recommended publications
  • Use of Intravenous Esmolol to Predict Efficacy of Oral Beta-Adrenergic Blocker Therapy in Patients with Neurocardiogenic Syncope
    402 JACC Vol. 19, No. 2 February 1992:402-8 REPORTS ON THERAPY Use of Intravenous Esmolol to Predict Efficacy of Oral Beta­ Adrenergic Blocker Therapy in Patients With Neurocardiogenic Syncope JASBIR S. SRA, MD, VISHNUBHAKTA S. MURTHY, MD, PHD, MOHAMMAD R. JAZAYERI, MD, FACC, YUE-HUA SHEN, MD, PAUL J. TROUP, MD, FACC, BOAZ AVITALL, MD, PHD, MASOOD AKHTAR, MD, FACC Milwaukee, Wisconsin The usefulness of esmolol in predicting the efficacy of treatment Irrespective of their response to esmolol infusion, all patients with an oral beta-adrenergic blocking agent was evaluated in 27 had a follow-up tilt test with oral metoprolol after an interval of consecutive patients with neurocardiogenic syncope. Seventeen ~5 half-lives of the drug. All 16 patients (100%) with a negative patients had a positive head-up tilt test response at baseline and 10 tilt test response during esmolol infusion had a negative tilt test patients required intravenous isoproterenol for provocation of response with oral metoprolol. Of the 11 patients with a positive hypotension. All patients were then given a continuous esmolol tilt test response during esmolol infusion, 10 (90%) continued to infusion (500 JLg/kg per min loading dose for 3 min followed by have a positive response with oral metoprolol. 300 Jlg/kg per min maintenance dose) and rechallenged with a It is concluded that in the electrophysiology laboratory, es­ head-up tilt test at baseline or with isoproterenol. molol can accurately predict the outcome of a head-up tilt Of the 17 patients with a positive baseline tilt test response, 11 response to oral metoprolol.
    [Show full text]
  • Esmolol Hydrochloride 10 Mg/Ml Solution for Injection Esmolol Hydrochloride
    Package leaflet: Information for the patient Esmolol hydrochloride 10 mg/ml solution for injection Esmolol hydrochloride Read all of this leaflet carefully before you start using this medicine because it contains important information for you. – Keep this leaflet. You may need to read it again. – If you have any further questions, ask your doctor or nurse. – This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. – If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet: 1. What Esmolol hydrochloride 10 mg/ml solution for injection is and what it is used for 2. What you need to know before you use Esmolol hydrochloride 10 mg/ml solution for injection 3. How to use Esmolol hydrochloride 10 mg/ml solution for injection 4. Possible side effects 5. How to store Esmolol hydrochloride 10 mg/ml solution for injection 6. Contents of the pack and other information 1. What Esmolol hydrochloride 10 mg/ml chlor promazine, used to treat mental dis - solution for injection is and what it is orders) used for – Clozapine which is used to treat mental Esmolol hydrochloride 10 mg/ml belongs to the disorders group of beta-blockers. These medicines slow – Epinephrine, which is used to treat allergic down the heartbeat and reduce blood pressure. reactions – Medicines used to treat asthma Esmolol hydrochloride 10 mg/ml is used for – Medicines used to treat colds or a blocked short-term treatment if your heart beats too nose, called nasal “decongestants” fast.
    [Show full text]
  • Keeping up with the Pace of Antiarrhythmic Drugs ANNMARIE PALATNIK, APN,BC, MSN Coordinator of Continuing Education • Virtua Health • Marlton, N.J
    D rug File Keeping up with the pace of antiarrhythmic drugs ANNMARIE PALATNIK, APN,BC, MSN Coordinator of Continuing Education • Virtua Health • Marlton, N.J. HAVE YOU NOTICED how challenging it is to Conducting impulses keep pace with the The conduction system of the heart, shown below, begins with the heart’s natural pacemaker, the changing beat of phar- sinoatrial (SA) node. When an impulse leaves the SA node, it travels through the atria along macology? Just as you Bachmann’s bundle and the internodal pathways on its way to the atrioventricular (AV) node. After learn the latest drugs the impulse passes through the AV node, it travels to the ventricles, first down the bundle of His, and classifications, new then along the bundle branches and, finally, down the Purkinje fibers. classes are developed and new drugs added to Bachmann’s bundle classes. Even drugs that have been on the mar- ket a long time can have dosing and indica- SA node tion changes. Antiarrhythmic Internodal tracts drugs, which restore Posterior (Thorel’s) normal rhythm and Middle (Wenckebach’s) conduction to the heart, Anterior are no exception. In this AV node article, I’ll bring you up-to-date on the Bundle of His antiarrhythmics now Right bundle branch available. Left bundle branch Class assignments Most antiarrhythmic drugs used to slow a rapid heart rate are classified according to the Vaughn Williams classification system Purkinje fibers (see Classifying Anti- arrhythmics the Vaughn Williams way). These drugs fall Class I into four general groups in this classification system Sodium channel blockers stop the flow of sodium into with each group having several subgroups.
    [Show full text]
  • Comparative Study of IV Esmolol, IV Diltiazem, and IV Lignocaine Hydrochloride in Attenuating Pressure Response to Laryngoscopy and Intubation
    Jemds.com Original Research Article Comparative Study of IV Esmolol, IV Diltiazem, and IV Lignocaine Hydrochloride in Attenuating Pressure Response to Laryngoscopy and Intubation Sathya Narayanan Karunanithi1, Geeta Bhandari2, Kedar Singh Shahi3, Aditya Kumar Chauhan4, Pooja Gautam5 1Department of Anaesthesiology, Critical Care, Pain and Palliative Medicine Government Medical College, Haldwani, Uttarakhand, India. 2 Department of Anaesthesiology, Critical Care, Pain and Palliative Medicine Government Medical College, Haldwani, Uttarakhand, India. 3Department of Surgery, Government Medical College, Haldwani, Uttarakhand, India. 4Department of Anaesthesiology, Critical Care, Pain and Palliative Medicine Government Medical College, Haldwani, Uttarakhand, India. 5Department of Anaesthesiology, Critical Care, Pain and Palliative Medicine Government Medical College, Haldwani, Uttarakhand, India. ABSTRACT BACKGROUND Not many studies have compared more than two drugs in attenuating pressor Corresponding Author: responses to laryngoscopy and intubation. This study compares four groups of Dr. Geeta Bhandari, considerable size. The present study compared intravenous esmolol, diltiazem, and Professor and HOD, Department of Anaesthesiology, lignocaine, for their efficacy to abate pressure response to laryngoscopy and Critical Care, Pain and Palliative Medicine, intubation. Government Medical College, Haldwani-263139, Uttarakhand, India. METHODS E-mail: [email protected] This is a prospective, randomized, double-blinded, controlled clinical study conducted among 220 patients of ASA grade I/II (age 18–60 years), undergoing DOI: 10.14260/jemds/2020/447 elective surgical procedure requiring general anaesthesia with endotracheal intubation over a period of 15 months at a tertiary hospital setup. Study subjects How to Cite This Article: were categorised as Groups D, E, L, and N that received diltiazem (0.2 mg/Kg IV), Karunanithi SN, Bhandari G, Shahi KS, et esmolol (2 mg/Kg IV), lignocaine (1.5 mg/Kg IV), and normal saline, respectively; al.
    [Show full text]
  • Atrial Fibrillation in the Surgical Patient
    DISCLAIMER: These guidelines were prepared by the Department of Surgical Education, Orlando Regional Medical Center. They are intended to serve as a general statement regarding appropriate patient care practices based upon the available medical literature and clinical expertise at the time of development. They should not be considered to be accepted protocol or policy, nor are intended to replace clinical judgment or dictate care of individual patients. NEW ONSET ATRIAL FIBRILLATION IN THE SURGICAL PATIENT SUMMARY Atrial fibrillation is a common postoperative arrhythmia and can represent a major source of morbidity and mortality. Treatment of atrial fibrillation is directed at three main objectives: controlling the ventricular response, preventing thromboembolism, and maintaining sinus rhythm. Therapeutic decisions also hinge on patients’ hemodynamic stability. In patients who are hemodynamically unstable, direct current cardioversion is the first line therapy and pharmacotherapy should be used as adjunctive treatment. In patients who are hemodynamically stable, pharmacologic treatment including class II (beta-blockers), class III (amiodarone), or class IV (nondihydropyridine calcium channel blockers) agents are viable options. RECOMMENDATIONS Level 1 Beta-blockade (esmolol or metoprolol), nondihydropyridine calcium channel blockers (diltiazem or verapamil), and amiodarone are pharmacologic options to manage new onset atrial fibrillation (see table for dosing). Beta-blockers are the first line therapy for postoperative atrial fibrillation to achieve rapid ventricular rate control and conversion to sinus rhythm. Diltiazem is second line rate control agent when beta-blocker therapy has failed. Both therapies should be avoided in hypotensive patients. Amiodarone can provide both rate and rhythm control and is an alternative therapy to beta-blockade for postoperative atrial fibrillation especially when the patient is hemodynamically unstable or has a known ejection fraction of < 40%.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • Drugs That Affect the Cardiovascular System
    PharmacologyPharmacologyPharmacology DrugsDrugs thatthat AffectAffect thethe CardiovascularCardiovascular SystemSystem TopicsTopicsTopics •• Electrophysiology Electrophysiology •• Vaughn-Williams Vaughn-Williams classificationclassification •• Antihypertensives Antihypertensives •• Hemostatic Hemostatic agentsagents CardiacCardiacCardiac FunctionFunctionFunction •• Dependent Dependent uponupon –– Adequate Adequate amountsamounts ofof ATPATP –– Adequate Adequate amountsamounts ofof CaCa++++ –– Coordinated Coordinated electricalelectrical stimulusstimulus AdequateAdequateAdequate AmountsAmountsAmounts ofofof ATPATPATP •• Needed Needed to:to: –– Maintain Maintain electrochemicalelectrochemical gradientsgradients –– Propagate Propagate actionaction potentialspotentials –– Power Power musclemuscle contractioncontraction AdequateAdequateAdequate AmountsAmountsAmounts ofofof CalciumCalciumCalcium •• Calcium Calcium isis ‘glue’‘glue’ that that linkslinks electricalelectrical andand mechanicalmechanical events.events. CoordinatedCoordinatedCoordinated ElectricalElectricalElectrical StimulationStimulationStimulation •• Heart Heart capablecapable ofof automaticityautomaticity •• Two Two typestypes ofof myocardialmyocardial tissuetissue –– Contractile Contractile –– Conductive Conductive •• Impulses Impulses traveltravel throughthrough ‘action‘action potentialpotential superhighway’.superhighway’. A.P.A.P.A.P. SuperHighwaySuperHighwaySuperHighway •• Sinoatrial Sinoatrial node node •• Atrioventricular Atrioventricular nodenode •• Bundle Bundle ofof
    [Show full text]
  • SUPPLEMENTARY MATERIAL 1: Search Strategy
    SUPPLEMENTARY MATERIAL 1: Search Strategy Medline search strategy 1. exp basal ganglia hemorrhage/ or intracranial hemorrhages/ or cerebral hemorrhage/ or intracranial hemorrhage, hypertensive/ or cerebrovascular disorders/ 2. ((brain$ or cerebr$ or cerebell$ or intracerebral or intracran$ or parenchymal or intraparenchymal or intraventricular or infratentorial or supratentorial or basal gangli$ or putaminal or putamen or posterior fossa or hemispher$ or pon$ or lentiform$ or brainstem or cortic$ or cortex$ or subcortic$ or subcortex$) adj5 (h?emorrhag$ or h?ematoma$ or bleed$)).tw 3. ((hemorrhag$ or haemorrhag$) adj6 (stroke$ or apoplex$ or cerebral vasc$ or cerebrovasc$ or cva)).tw 4. (ICH or ICHs or PICH or PICHs).tw 5. 1 or 2 or 3 or 4 6. exp blood pressure/ 7. exp hypertension/ 8. (blood pressure or bloodpressure).tw 9. ((bp or blood pressure) adj5 (lowering or reduc$)).tw 10. ((strict$ or target$ or tight$ or intens$ or below) adj3 (blood pressure or systolic or diastolic or bp or level$)).tw 11. (hypertension or hypertensive).tw 12. ((manage$ or monitor$) adj3 (hypertension or blood pressure)).tw 13. ((intense or intensive or aggressive or accelerated or profound or radical or severe) adj5 ((bp or blood pressure) adj5 (lowering or reduc$ or decreas$ or decrement or dimin$ or declin$))).tw 14. ((standard or normal or ordinary or guideline or guide line or guideline recommend$ or recommend$ or convention$ or usual or established) adj5 ((bp or blood pressure) adj5 (lowering or reduc$ or decreas$ or decrement or dimin$ or declin$))).tw 15. (antihypertensive adj2 (agent$ or drug$ or medicat$)).tw 1 16. 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 17.
    [Show full text]
  • Get in Rhythm with the Safe and Effective Use of Antiarrythmic Drugs
    Get in Rhythm with the Safe and Effective Use of Antiarrythmic Drugs Karen J. McConnell, Pharm.D., FCCP, BCPS- AQ Cardiology, ASH-CHC Clinical Director and Cardiology Subject Matter Expert, Cardinal Health Clinical Associate Professor, University of Colorado Skaggs School of Pharmacy and Shannon W. Finks, Pharm.D., FCCP, BCPS- AQ Cardiology, ASH-CHC Professor of Clinical Pharmacy, University of Tennessee College of Pharmacy Clinical Specialist Cardiology, Veterans Affairs Medical Center Memphis Disclosure The program chair and presenters for this continuing education activity have reported no relevant financial relationships. Objectives . Design patient-specific treatment and monitoring plans for antiarrhythmic drugs (AADs) to treat atrial fibrillation (AF) . Differentiate among appropriate monitoring strategies for various agents used in ventricular arrhythmia suppression . Avoid potential adverse drug events with AADs by identifying important drug interactions . Ensure safe and effective dosing of AADs based upon specific patient factors Rhythm Rule #1 . Pharmacists play a vital role in the appropriate use of AAD dosing, adverse effects, interactions, and monitoring. Treatment and Monitoring of Atrial Fibrillation Atrial Fibrillation • Most common type of serious arrhythmia • In U.S., affects 2-5 million patients • Frequently seen with comorbidities • AF complicates management of comorbidity • Comorbidity complicates management of AF • Associated with stroke, heart failure, death • Most common arrhythmia requiring hospitalization Case #1: Mary Rhythm 60 y/o AA woman with a PMH including . Laboratory data: HFrEF (EF 35%), atrial fibrillation(AF), CKD, 140 110 18 HTN 105 . Inpatient Medications: 4.7 22 1.6 apixaban 5 mg twice daily lisinopril 20 mg daily BP 115/78 mm Hg HT 67 in metoprolol succinate 50 mg/day HR 70 bpm WT 75 kg furosemide 40 mg twice daily spironolactone 25 mg/day .
    [Show full text]
  • A Comparison of Intravenous Esmolol Versus Intravenous Diltiazem in Atrial Fibrillation with Rapid Ventricular Response-A Study from an Academic Center
    Cardiol Cardiovasc Med 2020; 4 (4): 450-459 DOI: 10.26502/fccm.92920143 Research Article A Comparison of Intravenous Esmolol versus Intravenous Diltiazem in Atrial Fibrillation with Rapid Ventricular Response-A Study from An Academic Center Manjari R Regmi1*, Mohammad Al-Akchar2, Bishal Bhandari1, Abdisamad M Ibrahim1, Priyanka Parajuli1, Odalys Estefania Lara Garcia1, Basma Al-Bast1, Nitin Tandan1, Ruby Maini1, Warren Alexander Skoza1, Marissa Kircher1, Abigail Levy1, Joseph Pflederer1, Brendan Finnell1, Albert Botchway1, Vivek Prakash1, Abhishek Kulkarni2, Momin Siddique2, Mohamed Labedi2 1Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA 2Division of Cardiology, Southern Illinois University School of Medicine, Springfield, IL, USA *Corresponding Authors: Manjari Rani Regmi, Southern Illinois University School of Medicine, 701 North First Street, PO Box 19636, Springfield, IL 62794-9636, USA, Tel: 217-545-0193; F a x : 279-201-6023; E-m a i l : [email protected] Received: 03 August 2020; Accepted: 15 August 2020; Published: 26 August 2020 Citation: Manjari R Regmi, Mohammad Al-Akchar, Bishal Bhandari, Abdisamad M Ibrahim, Priyanka Parajuli, Odalys Estefania Lara Garcia, Basma Al-Bast, Nitin Tandan, Ruby Maini, Warren Alexander Skoza, Marissa Kircher, Abigail Levy, Joseph Pflederer, Brendan Finnell, Albert Botchway, Vivek Prakash, Abhishek Kulkarni, Momin Siddique, Mohamed Labedi. A Comparison of Intravenous Esmolol versus Intravenous Diltiazem in Atrial Fibrillation with Rapid Ventricular Response-A Study from An Academic Center. Cardiology and Cardiovascular Medicine 4 (2020): 450-459. Abstract Introduction: This study’s objective was to compare Methods: The measured parameters were the number of the differences in the effects of intravenous esmolol and hospital re-admissions, length of hospital stay, time diltiazem on patients having atrial fibrillation with taken for rate control, and side effects like hypotension RVR.
    [Show full text]
  • The Effect of Intraoperative Lidocaine Versus Esmolol Infusion On
    Bajracharya et al. BMC Anesthesiology (2019) 19:198 https://doi.org/10.1186/s12871-019-0874-8 RESEARCH ARTICLE Open Access The effect of intraoperative lidocaine versus esmolol infusion on postoperative analgesia in laparoscopic cholecystectomy: a randomized clinical trial Joshan Lal Bajracharya1, Asish Subedi2* , Krishna Pokharel3 and Balkrishna Bhattarai4 Abstract Background: As a part of multimodal analgesia for laparoscopic cholecystectomy, both intraoperative lidocaine and esmolol facilitate postoperative analgesia. Our objective was to compare these two emerging strategies that challenge the use of intraoperative opioids. We aimed to assess if intraoperative esmolol infusion is not inferior to lidocaine infusion for opioid consumption after laparoscopic cholecystectomy. Methods: In this prospective, randomized, double-blind, non-inferiority clinical trial, 90 female patients scheduled for elective laparoscopic cholecystectomy received either intravenous (IV) lidocaine bolus 1.5 mg/kg at induction followed by an infusion (1.5 mg/ kg/h) or IV bolus of esmolol 0.5 mg/kg at induction followed by an infusion (5– 15 μg/kg/min) till the end of surgery. Remaining aspect of anesthesia followed a standard protocol apart from no intraoperative opioid supplementation. Postoperatively, patients received either morphine or tramadol IV to maintain visual analogue scale (VAS) scores ≤3. The primary outcome was opioid consumption (in morphine equivalents) during the first 24 postoperative hours. Pain and sedation scores, time to first perception of pain and void, and occurrence of nausea/vomiting were secondary outcomes measured up to 24 h postoperatively. Results: Two patients in each group were excluded from the analysis. The postoperative median (IQR) morphine equivalent consumption in patients receiving esmolol was 1 (0–1.5) mg compared to 1.5 (1–2) mg in lidocaine group (p = 0.27).
    [Show full text]
  • Ep 2444077 A1
    (19) & (11) EP 2 444 077 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 25.04.2012 Bulletin 2012/17 A61K 31/00 (2006.01) A61K 31/215 (2006.01) A61P 3/10 (2006.01) (21) Application number: 12151969.8 (22) Date of filing: 24.01.2008 (84) Designated Contracting States: • Gollapudy, Reena, R. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 411 045 PUNE (IN) HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT • Deshpande, Supreet, K. RO SE SI SK TR 411 045 PUNE (IN) (30) Priority: 29.01.2007 IN MU19602007 (74) Representative: Ahner, Francis et al Cabinet Regimbeau (62) Document number(s) of the earlier application(s) in 20, rue de Chazelles accordance with Art. 76 EPC: 75847 Paris Cedex 17 (FR) 08720107.5 / 2 114 386 Remarks: (71) Applicant: Vlife Sciences Technologies Pvt Ltd. This application was filed on 20-01-2012 as a Pune 411 045, Maharashtra (IN) divisional application to the application mentioned under INID code 62. (72) Inventors: • Kulkarni, Sudhir, A. 411 045 PUNE (IN) (54) Pharmaceutical composition for treatment of diabetic complications (57) A method for treating diabetic complications by abetic complications, such as diabetic wounds, are dis- administration of a beta-blocker is disclosed. Diabetic closed. The present invention includes employing a top- complications arise from diabetes and have few or no ical formulation of a beta- blocker, having substantially no existing treatment options. The present invention de- antibacterial activity, to improve the process of diabetic scribes the use of a beta-blocker in the treatment of a wound healing.
    [Show full text]