DOCSLIB.ORG

Current and Potential Antiarrhythmic Drugs Targeting Voltage-Gated

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Current and Potential Antiarrhythmic Drugs Targeting Voltage-Gated maco har log P y: r O la u p c e n s a A v Perez-Neut et al., Cardiol Pharmacol 2015, 4:2 c o c i e d r s a s Open Access C Cardiovascular Pharmacology: DOI: 10.4172/2329-6607.1000139 ISSN: 2329-6607 Review Article OpenOpen Access Access Current and Potential Antiarrhythmic Drugs Targeting Voltage-Gated Cardiac Ion Channels Mathew Perez-Neut, Vidhya Rao, Lauren Haar, Keith W Jones and Saverio Gentile* Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Maywood, IL USA Abstract Voltage-gated ion channels play a fundamental role in the generation and propagation of the cardiac action potential by acting synergistically to produce an ionic current across cellular membranes. Abnormalities of heart ion channel activities that lead to loss or gain of function (channelopathies) are often associated with disruption of the coordinated propagation of electrical activity of the cardiac myocytes and can generate fatal arrhythmogenesis. Drugs that act on cardiac ion channels have long been used to restore normal rhythm and conduction in patients affected by cardiac arrhythmias and offered to basic scientists the possibility to characterize distinct ion channel classes. This review will explore the mechanisms and role of the current anti-arrhythmic drugs used in the clinic, and discuss recent development on ion channel openers as potential anti-arrhythmic drugs. Abbreviations: VGIC: Voltage gated ion channels; VGKC: Voltage gated potassium channels; KCNQ: Potassium Channel, Voltage-Gated, KQT-like subfamily; KCNH: Potassium channel voltage gated subfamily H; ATP: Adenosine tri phosphate; hERG1: human Ether-à-go-go-Related Gene; SCN: Sodium channel, voltage gated; CACNA: Calcium channel, voltage gated [gene]; CaV: Calcium channel, voltage gated [protein]; RyR: Ryanodine receptor Introduction (outward flow of positive charges) determines the initial descending deflection of the cardiac action potential (phase 1) [16]. This event Voltage-gated ion channels (VGIC) are pore forming is followed by a plateau (phase 2) in which an inward Ca2+ currents transmembrane proteins which are ion permeable and gated by changes resulting from activation of L-type calcium channels [17-19] is balanced of transmembrane voltage [1]. Activities of VGIC are characterized by an outward K+ current upon activation of KCNQ and KCNH type + by defined parameters ranging from distinct ion selectivity (e.g. Na , potassium channels [16]. During this phase, cells accumulate Ca2+ that + 2+ - K , Ca or Cl ) to ionic direction (inward or outward ionic flow; is used in conjunction with ATP during the activation of the contractile currents). Opening and closing of VGIC specifically expressed in machinery (systole). cardiac myocytes generate and propagate the electric signal to shape the waveform of a cardiac action potential [2]. While there are some Finally, closure of the Ca2+ channels determines the initiation of differences in the shape of action potentials among different cell types repolarization that is progressively accelerated by the full activation found in the myocardium, the myocyte action potential is composed by of potassium channels such as the KCNH2 (hERG1) channels (phase 5 phases (4-0-1-2-3) [3]. 3) [16]. As the membrane potential repolarizes, several potassium channels close resulting in restoring the resting membrane potential. In the resting state, when the cardiac muscle is relaxed (diastole) the At this point, the funny Na+ channels can re-open until a new phase + + activity of several pumps and ion transporters including Na /K pumps 4 initiates. [4], Na+/Ca2+ exchanger [5] and K+ ion channels (inwardly rectifying) [6] accumulate ions in the cytoplasm against their electrochemical Aberrant cardiac ion channel activities can often be associated with gradient. This results in the generation of a negative membrane generation of an abnormal action potential that results in arrhythmias potential that peaks around -85/-95 mV (phase 4; resting membrane [20-23]. For example, malfunction of several ion channels including potential. The membrane potential at resting state is unstable and Na+, K+ or Cl+ channels can lead to a pathological retardation in the slowly depolarizes (moves towards positive values) due to the activity repolarization of the cardiac action potential. This phenomenon is of a specific member of the Na+ channel family (“funny” Na+ channels) detected as prolonged QT interval measured by electrocardiogram [7] through which sodium ions slowly cross the membrane (Na+ (Long QT Syndrome, LQT) [24], and is the lead culprit in polymorphic currents) until the membrane potentials reach a value that activates ventricular tachycardia—the classical arrhythmia (Table 1). + + the fast Na channel [8]. Consequently, the rapid Na entry quickly Antiarrhythmic drugs aim to abolish the electrophysiological depolarizes the cell membrane (phase 0) reaching up to values of +20/25 mV. At this membrane potential, the inactivation gate of the fast Na+ channels closes (inactivated state) producing an impermeable channel that can re-open only when the membrane potential reaches *Corresponding author: Saverio Gentile, Department of Molecular Pharmacology the values at rest [9]. This phenomenon underlines the initiation of the and Therapeutics, Loyola University Chicago, Maywood, IL USA, E-mail: refractory period during which the cardiac cell cannot elicit another [email protected] action potential. However, although in the refractory period, random Received: April 15, 2015; Accepted: May 04, 2015; Published: May 10, 2015 + failure of inactivation can lead to generation of a small Na current (late Citation: Perez-Neut M, Rao V, Haar L, Jones KW, Gentile S (2015) Current and current, INaL) that appears to contribute minimally in shaping the action Potential Antiarrhythmic Drugs Targeting Voltage-Gated Cardiac Ion Channels. Cardiol potential of a normal cardiac myocyte but may play an important role Pharmacol 4: 139. doi:10.4172/2329-6607.1000139 in a diseased heart [10-12]. Copyright: © 2015 Perez-Neut M et al. This is an open-access article distributed + under the terms of the Creative Commons Attribution License, which permits un- Closing of the Na channels in addition to the slow opening of restricted use, distribution, and reproduction in any medium, provided the original Cl- (inward flow of negative charges) [13-15] and potassium channels author and source are credited. Cardiol Pharmacol ISSN: 2329-6607 CPO, an open access journal Volume 4 • Issue 2 • 1000139 Citation: Perez-Neut M, Rao V, Haar L, Jones KW, Gentile S (2015) Current and Potential Antiarrhythmic Drugs Targeting Voltage-Gated Cardiac Ion Channels. Cardiol Pharmacol 4: 139. doi:10.4172/2329-6607.1000139 Page 2 of 7 mechanisms that are responsible for the cardiac arrhythmias. These drugs cause inhibition of membrane permeability to Na+ by acting as drugs can exhibit diverse properties according to their effects on the Na+ channel blockers, thereby decreasing rate/velocity/magnitude of targeted ion channels as they and can be channel blockers (ligands that the depolarization that occurs in phase 0 of the cardiac action potential block ionic flows), gating inhibitors (ligand that inhibit channel gating [36]. Since activity of Na+ channel determines the speed through which either by acting on ion channel activation or inactivation) or activators a cardiac action potential depolarizes inhibition of Na+ channels is a (ligands that activate ion channels by direct binding) [25,26]. common strategy used to correct disturbances of the heart rhythm in which the heart rate is abnormally increased (pathological tachycardia/ + Pharmacology of the Cardiac Na Channel tachyarrhythmia). Members of the Class I antiarrhythmic drugs are Nine genes in the human genome (SCN1A through SCN9A) divided into three different categories (1A, 1B, 1C) and are defined by + + the different degree of Na channel blockage. encode for Na channels α subunit proteins named Nav1.1 through Nav1.9 and 4 β subunits (SCN1B-SCN4B). Although mRNA for Procainamide or quinidine is Class IA antiarrhythmic drugs several Nav channels have been found in the human heart, the product indicated for the treatment of sustained ventricular fibrillation. The + + of the SCNA5 gene, Nav1.5, is considered the main Na channel effects of these Na channel blockers is reduction of cell excitability that determines excitability and electrical conduction velocity in the by increasing the threshold for the rapid depolarization during phase cardiac myocytes. This conclusion is centered on the observation that 0. Consequently, termination of the refractory period of the atria and mutations of the Nav1.5 channel that cause partial or complete loss of ventricles is delayed. However, these drugs can also be pro-arrhythmic Nav1.5 activity can cause a delay of depolarization during phase 0 of the and are contraindicated by the presence of prolonged QT [37]. action potential [27-31]. This is hypothesized to occur by enhancing I which can lead to an abnormal Ca2+ entry during phase 2 or phase Lidocaine is one of the most commonly used class IB NaL , + 3 upon reactivation of Ca2+ channels that has been related to clinically antiarrhythmic. This drug blocks Na channel in the conduction system relevant cardiac arrhythmias such as Brugada syndrome (Table 1) [32- and in the muscle cells of the heart causing inhibition of spontaneous 34] . depolarization during diastole [38,39]. Na 1.5 channel blockers Flecainide and Propafenone are examples of class IC
Load more

Recommended publications
  • Table 2. 2012 AGS Beers Criteria for Potentially
    Table 2. 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Strength of Organ System/ Recommendat Quality of Recomm Therapeutic Category/Drug(s) Rationale ion Evidence endation References Anticholinergics (excludes TCAs) First-generation antihistamines Highly anticholinergic; Avoid Hydroxyzin Strong Agostini 2001 (as single agent or as part of clearance reduced with e and Boustani 2007 combination products) advanced age, and promethazi Guaiana 2010 Brompheniramine tolerance develops ne: high; Han 2001 Carbinoxamine when used as hypnotic; All others: Rudolph 2008 Chlorpheniramine increased risk of moderate Clemastine confusion, dry mouth, Cyproheptadine constipation, and other Dexbrompheniramine anticholinergic Dexchlorpheniramine effects/toxicity. Diphenhydramine (oral) Doxylamine Use of diphenhydramine in Hydroxyzine special situations such Promethazine as acute treatment of Triprolidine severe allergic reaction may be appropriate. Antiparkinson agents Not recommended for Avoid Moderate Strong Rudolph 2008 Benztropine (oral) prevention of Trihexyphenidyl extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. Antispasmodics Highly anticholinergic, Avoid Moderate Strong Lechevallier- Belladonna alkaloids uncertain except in Michel 2005 Clidinium-chlordiazepoxide effectiveness. short-term Rudolph 2008 Dicyclomine palliative Hyoscyamine care to Propantheline decrease Scopolamine oral secretions. Antithrombotics Dipyridamole, oral short-acting* May
    [Show full text]
  • The Pharmacology of Amiodarone and Digoxin As Antiarrhythmic Agents
    Part I Anaesthesia Refresher Course – 2017 University of Cape Town The Pharmacology of Amiodarone and Digoxin as Antiarrhythmic Agents Dr Adri Vorster UCT Department of Anaesthesia & Perioperative Medicine The heart contains pacemaker, conduction and contractile tissue. Cardiac arrhythmias are caused by either enhancement or depression of cardiac action potential generation by pacemaker cells, or by abnormal conduction of the action potential. The pharmacological treatment of arrhythmias aims to achieve restoration of a normal rhythm and rate. The resting membrane potential of myocytes is around -90 mV, with the inside of the membrane more negative than the outside. The main extracellular ions are Na+ and Cl−, with K+ the main intracellular ion. The cardiac action potential involves a change in voltage across the cell membrane of myocytes, caused by movement of charged ions across the membrane. This voltage change is triggered by pacemaker cells. The action potential is divided into 5 phases (figure 1). Phase 0: Rapid depolarisation Duration < 2ms Threshold potential must be reached (-70 mV) for propagation to occur Rapid positive charge achieved as a result of increased Na+ conductance through voltage-gated Na+ channels in the cell membrane Phase 1: Partial repolarisation Closure of Na+ channels K+ channels open and close, resulting in brief outflow of K+ and a more negative membrane potential Phase 2: Plateau Duration up to 150 ms Absolute refractory period – prevents further depolarisation and myocardial tetany Result of Ca++ influx
    [Show full text]
  • Tricyclic Antidepressant
    Princess Margaret Hospital for Children Emergency Department Guideline PAEDIATRIC ACUTE CARE GUIDELINE Poisoning – Tricyclic Antidepressant Scope (Staff): All Emergency Department Clinicians Scope (Area): Emergency Department This document should be read in conjunction with this DISCLAIMER http://kidshealthwa.com/about/disclaimer/ Poisoning – Tricyclic Antidepressant This guideline is a general approach to tricyclic antidepressant poisoning. For specific details please contact Poisons Information: 131126 or refer to the Toxicology Handbook. Agents: Amitriptyline Clomipramine Dothiepin Doxepin Imipramine Nortriptyline Trimipramine Background Tricyclic antidepressants (TCAs) act on a variety of receptors whose actions include: Noradrenaline reuptake inhibition Central and peripheral anticholinergic effect Fast sodium channel blockade in the myocardium Peripheral alpha1-adrenergic receptor blockade The life threatening effects of acute tricyclic antidepressant (TCA) overdose are: Rapid onset of coma Seizures Cardiac dysrhythmias Page 1 of 6 Emergency Department Guideline Poisoning – Tricyclic Antidepressant Hypotension and central and peripheral anticholinergic effects may also be seen Risk Assessment Most acute accidental paediatric exposures do not result in life threatening toxicity A 10kg child can develop life threatening poisoning with the ingestion of a single tablet (e.g. 150mg amitriptyline) Patients who ingest a large dose of TCA usually develop evidence of intoxication within 2-4 hours, and always within 6 hours If their is suspicion
    [Show full text]
  • Neurochemical Mechanisms Underlying Alcohol Withdrawal
    Neurochemical Mechanisms Underlying Alcohol Withdrawal John Littleton, MD, Ph.D. More than 50 years ago, C.K. Himmelsbach first suggested that physiological mechanisms responsible for maintaining a stable state of equilibrium (i.e., homeostasis) in the patient’s body and brain are responsible for drug tolerance and the drug withdrawal syndrome. In the latter case, he suggested that the absence of the drug leaves these same homeostatic mechanisms exposed, leading to the withdrawal syndrome. This theory provides the framework for a majority of neurochemical investigations of the adaptations that occur in alcohol dependence and how these adaptations may precipitate withdrawal. This article examines the Himmelsbach theory and its application to alcohol withdrawal; reviews the animal models being used to study withdrawal; and looks at the postulated neuroadaptations in three systems—the gamma-aminobutyric acid (GABA) neurotransmitter system, the glutamate neurotransmitter system, and the calcium channel system that regulates various processes inside neurons. The role of these neuroadaptations in withdrawal and the clinical implications of this research also are considered. KEY WORDS: AOD withdrawal syndrome; neurochemistry; biochemical mechanism; AOD tolerance; brain; homeostasis; biological AOD dependence; biological AOD use; disorder theory; biological adaptation; animal model; GABA receptors; glutamate receptors; calcium channel; proteins; detoxification; brain damage; disease severity; AODD (alcohol and other drug dependence) relapse; literature review uring the past 25 years research- science models used to study with- of the reasons why advances in basic ers have made rapid progress drawal neurochemistry as well as a research have not yet been translated Din understanding the chemi- reluctance on the part of clinicians to into therapeutic gains and suggests cal activities that occur in the nervous consider new treatments.
    [Show full text]
  • Calcium Current Block by (-)-Pentobarbital, Phenobarbital
    The Journal of Neuroscience, August 1993, 13(E): 321 l-3221 Calcium Current Block by (-)-Pentobarbital, Phenobarbital, and CHEB but not (+)-Pentobarbital in Acutely Isolated Hippocampal CA1 Neurons: Comparison with Effects on GABA-activated Cl- Current Jarlath M. H. ffrench-Mullen,’ Jeffery L. Barker,* and Michael A. Rogawski3 ‘Department of Pharmacology, Zeneca Pharmaceuticals Group, Zeneca Inc., Wilmington, Delaware 19897 and *Laboratory of Neurophysiology, and 3Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 Block of a voltage-activated Ca*+ channel current by pheno- Ca*+ current, whereas the sedative effects that occur at high- barbital (PHB), 5-(2-cyclohexylideneethyl)-5-ethyl barbituric er concentrations could reflect stronger Ca2+ current block- acid (CHEB), and the optical R(-)- and S(+)-enantiomers of ade. The powerful sedative-hypnotic action of (-)-PB may pentobarbital (PB) was examined in freshly dissociated adult reflect greater maximal enhancement of GABA responses guinea pig hippocampal CA1 neurons; the effects of the in conjunction with strong inhibition of Ca2+ current. The barbiturates on GABA-activated Cl- current were also char- convulsant action of CHEB is unlikely to be related to its acterized in the same preparation. (-)-PB, PHB, and CHEB effects on the Ca*+ current. produced a reversible, concentration-dependent block of the [Key words: calcium channel, GABA receptor, (-)-pen- peak Ca*+ channel current (3 mM Ba2+ as the charge carrier) tobarbital, (+)-pentobarbital, phenobarbital, CHEB [S-(2-cy- evoked by depolarization from -80 to - 10 mV (I&,, values, clohexylideneethyl)-S-ethyl barbituric acid], CA 1 hippocam- 3.5, 72, and 118 PM, respectively).
    [Show full text]
  • Flecainide Considerations For
    Flecainide (Tambocor) Considerations for Use* US/FDA Approved Indications: Heart Rhythm Control for Atrial Fibrillation Black Box Warning* Proarrhythmic. Increased mortality in patients with non-life-threatening ventricular arrhythmias, structural heart disease (ie, MI, LV dysfunction); not recommended for use with chronic atrial fibrillation. Mechanism of Action Depresses phase 0 depolarization significantly, slows cardiac conduction significantly (Class 1C). Dosing† Cardioversion: 200 to 300 mg PO‡1 Maintenance: 50 to 150 mg PO every 12 hrs Hepatic Impairment: Reduce initial dosage. Monitor serum level frequently. Allow at least 4 days after dose changes to reach steady state level before adjusting dosage. Renal Impairment: CrCl > 35 ml/min: No dosage adjustment is required. CrCl <= 35 ml/min: Initially, 100 mg PO once daily or 50 mg PO twice daily. Adjust dosage at intervals > 4 days, since steady-state conditions may take longer to achieve in these patient Contraindications cardiogenic shock sick sinus syndrome or significant conduction delay 2nd/3rd degree heart block or bundle brand block without pacemaker acquired/congenital QT prolongation patients with history of torsade de pointes Major Side Effects hypotension, atrial flutter with high ventricular rate, ventricular tachycardia, HF Dosage forms and Strengths PO: 50, 100, 150mg tablets Special Notes Close monitoring of this drug is required. When starting a patient on flecainide, it is prudent to do a treadmill stress test after the patient is fully loaded.4 Do not use in patients with ischemic heart disease or LV dysfunction; increases risk of arrhythmias. Additional AV nodal blocking agent may be required to maintain rate control when AF recurs.
    [Show full text]
  • A Proposal for the Clinical Use of Flecainide
    A Proposal for the Clinical Use of Flecainide JEFFREY L. ANDERSON, MD, JAMES R. STEWART, MD, and BARRY J. CREVEY, MD Effective antiarrhythmic therapy requires a carefully sponse rate is observed in preventing induction of considered approach, including an understanding sustained ventricular tachycardia, and these pa- of the arrhythmia, the underlying cardiac disease tients should be carefully selected. Flecainide is and the drug’s pharmacokinetics. Flecainide is a promising in the treatment of supraventricular new antiarrhythmic drug that may soon be released tachycardias using atrioventricular nodal or extra- for general use. Flecainide demonstrates unsur- nodal reentrant pathways, although this use is still passed efficacy in chronic ventricular arrhythmias investigational in the United States. The drug’s use in stable patients and may become a first-choice for arrhythmias during acute myocardial infarction drug because of its ease of administration, efficacy requires further study. Flecainide possesses modest and favorable tolerance. Twice-daily dosing with negative inotropic potential. Proarrhythmic or other 100 to 200 mg usually provides effective therapy. adverse reactions have occurred primarily in set- Clinical experience suggests flecainide to be indi- tings of high drug level, poor ventricular function cated in the treatment of uniform and multiform or refractory, malignant arrhythmias, suggesting ventricular premature complexes, coupled ven- caution in these groups. tricular premature complexes, and episodes of nonsustained
    [Show full text]
  • Amiodarone (As Hydrochloride)
    NEW ZEALAND DATA SHEET ARATAC 1. Product Name Aratac, 100 mg and 200 mg tablet. 2. Qualitative and Quantitative Composition Each Aratac tablet contains 100 mg or 200 mg of amiodarone (as hydrochloride). Aratac tablets contain lactose. For the full list of excipients, see section 6.1. Amiodarone hydrochloride is a fine white crystalline powder. It is slightly soluble in water and is soluble in alcohol and chloroform. It is an amphiphilic compound and contains iodine in its formulation. Each 200 mg tablet of amiodarone contains approximately 75 mg organic iodine. In the steady state, metabolism of 300 mg amiodarone yields 9 mg/day of iodine. 3. Pharmaceutical Form Amiodarone 100 mg Tablet: round, normal convex, white tablet, 8.5 mm diameter, imprinted “AM” | “100” on one side and “G” on the other. Amiodarone 200 mg Tablet: round, normal convex, white tablet, 10.0 mm diameter, imprinted “AM” | “200” on one side and “G” on the other. The tablet can be divided into equal doses. 4. Clinical Particulars 4.1 Therapeutic indications Treatment should be initiated only under hospital or specialist supervision. Tachyarrhythmias associated with Wolff-Parkinson-White Syndrome. Atrial flutter and fibrillation when other agents cannot be used. All types of tachyarrhythmias of paroxysmal nature including: supraventricular, nodal and ventricular tachycardias, ventricular fibrillation; when other agents cannot be used. Tablets are used for stabilisation and long term treatment. 4.2 Dose and method of administration Dose Due to poor absorption and wide inter-patient variability of absorption, the initial loading and subsequent maintenance dosage schedules of the medicine in clinical use has to be individually titrated.
    [Show full text]
  • Guideline for Preoperative Medication Management
    Guideline: Preoperative Medication Management Guideline for Preoperative Medication Management Purpose of Guideline: To provide guidance to physicians, advanced practice providers (APPs), pharmacists, and nurses regarding medication management in the preoperative setting. Background: Appropriate perioperative medication management is essential to ensure positive surgical outcomes and prevent medication misadventures.1 Results from a prospective analysis of 1,025 patients admitted to a general surgical unit concluded that patients on at least one medication for a chronic disease are 2.7 times more likely to experience surgical complications compared with those not taking any medications. As the aging population requires more medication use and the availability of various nonprescription medications continues to increase, so does the risk of polypharmacy and the need for perioperative medication guidance.2 There are no well-designed trials to support evidence-based recommendations for perioperative medication management; however, general principles and best practice approaches are available. General considerations for perioperative medication management include a thorough medication history, understanding of the medication pharmacokinetics and potential for withdrawal symptoms, understanding the risks associated with the surgical procedure and the risks of medication discontinuation based on the intended indication. Clinical judgement must be exercised, especially if medication pharmacokinetics are not predictable or there are significant risks associated with inappropriate medication withdrawal (eg, tolerance) or continuation (eg, postsurgical infection).2 Clinical Assessment: Prior to instructing the patient on preoperative medication management, completion of a thorough medication history is recommended – including all information on prescription medications, over-the-counter medications, “as needed” medications, vitamins, supplements, and herbal medications. Allergies should also be verified and documented.
    [Show full text]
  • Angiotensin Modulators/Calcium Channel Blocker Combinations Review 02/05/2009
    Angiotensin Modulators/Calcium Channel Blocker Combinations Review 02/05/2009 Copyright © 2004 - 2009 by Provider Synergies, L.L.C. All rights reserved. Printed in the United States of America. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage and retrieval system without the express written consent of Provider Synergies, L.L.C. All requests for permission should be mailed to: Attention: Copyright Administrator Intellectual Property Department Provider Synergies, L.L.C. 5181 Natorp Blvd., Suite 205 Mason, Ohio 45040 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Comments and suggestions may be sent to [email protected].
    [Show full text]
  • Treatment for Calcium Channel Blocker Poisoning: a Systematic Review
    Clinical Toxicology (2014), 52, 926–944 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2014.965827 REVIEW ARTICLE Treatment for calcium channel blocker poisoning: A systematic review M. ST-ONGE , 1,2,3 P.-A. DUB É , 4,5,6 S. GOSSELIN ,7,8,9 C. GUIMONT , 10 J. GODWIN , 1,3 P. M. ARCHAMBAULT , 11,12,13,14 J.-M. CHAUNY , 15,16 A. J. FRENETTE , 15,17 M. DARVEAU , 18 N. LE SAGE , 10,14 J. POITRAS , 11,12 J. PROVENCHER , 19 D. N. JUURLINK , 1,20,21 and R. BLAIS 7 1 Ontario and Manitoba Poison Centre, Toronto, ON, Canada 2 Institute of Medical Science, University of Toronto, Toronto, ON, Canada 3 Department of Clinical Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada 4 Direction of Environmental Health and Toxicology, Institut national de sant é publique du Qu é bec, Qu é bec, QC, Canada 5 Centre Hospitalier Universitaire de Qu é bec, Qu é bec, QC, Canada 6 Faculty of Pharmacy, Université Laval, Qu é bec, QC, Canada 7 Centre antipoison du Qu é bec, Qu é bec, QC, Canada 8 Department of Medicine, McGill University, Montr é al, QC, Canada 9 Toxicology Consulting Service, McGill University Health Centre, Montr é al, QC, Canada 10 Centre Hospitalier Universitaire de Qu é bec, Qu é bec, QC, Canada 11 Centre de sant é et services sociaux Alphonse-Desjardins (CHAU de Lévis), L é vis, QC, Canada 12 Department of Family Medicine and Emergency Medicine, Universit é Laval, Québec, QC, Canada 13 Division de soins intensifs, Universit é Laval, Qu é bec, QC, Canada 14 Populations
    [Show full text]
  • Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
    International Journal of Molecular Sciences Article Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model Monika Banach 1 , Monika Rudkowska 1, Agata Sumara 2 and Kinga Borowicz-Reutt 1,* 1 Independent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, Poland; [email protected] (M.B.); [email protected] (M.R.) 2 Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, Poland; [email protected] * Correspondence: [email protected] Abstract: Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activ- ity of oxcarbazepine and pregabalin. Amiodarone, given alone or in combination with oxcarbazepine, lamotrigine, or topiramate, significantly disturbed long-term memory in the passive-avoidance task in mice. Brain concentrations of antiepileptic drugs were not affected by amiodarone. However, the brain concentration of amiodarone was significantly elevated by oxcarbazepine, topiramate, and pregabalin. Additionally, oxcarbazepine and pregabalin elevated the brain concentration of desethylamiodarone, the main metabolite of amiodarone. In conclusion, potentially beneficial action of amiodarone in epilepsy patients seems to be limited by neurotoxic effects of amiodarone. Although results of this study should still be confirmed in chronic protocols of treatment, special precautions Citation: Banach, M.; Rudkowska, are recommended in clinical conditions.
    [Show full text]