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Med Res Rev 2018 07 5;38(4):1332-1403. Epub 2018 Jan 5.

Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové, Czech Republic.

Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. Read More

Am J Emerg Med 2015 Oct 29;33(10):1542.e1-2. Epub 2015 Jul 29.

Department of Emergency Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI, USA; Spectrum Health Hospitals, Grand Rapids, MI, USA; Grand Rapids Medical Education Partners Emergency Medicine Residency, Grand Rapids, MI, USA.

Flecainide is a class Ic antidysrhythmic agent used to prevent and treat tachydysrhythmias. Flecainide toxicity primarily causes cardiovascular and neurologic effects through sodium-channel blockade. There is scant evidence to support specific management, and recommended therapies have been extrapolated from management of other sodium-channel blocking drugs. Read More

Am J Ther 2014 Jul-Aug;21(4):244-9

Departments of 1Obstetrics and Gynecology and 2Medical Toxicology Service, Department of Emergency Medicine, San Antonio Military Medical Center, San Antonio, TX; 3Department of Emergency Medicine, School of Pharmacy, Concordia University, Mequon, WI; and 4Texas A & M University Health Science Center College of Medicine, Scott and White Hospital, Temple, TX.

Sodium nitrite and sodium thiosulfate are common cyanide antidotes. Hydroxocobalamin was approved for use in the United States in 2006. Our objective was to determine the frequency of antidote use as reported to the US poison centers from 2005 to 2009 and describe which antidotes were used in critically ill cyanide toxic patients. Read More

J Emerg Med 2013 Apr 13;44(4):781-3. Epub 2012 Sep 13.

New York University School of Medicine and Bellevue Hospital, New York, New York and New York City Poison Control Center, New York, NY 10016, USA.

Background: Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate. Read More

Pacing Clin Electrophysiol 2013 Mar 8;36(3):e87-9. Epub 2012 Aug 8.

Department of Emergency Medicine, Regions Hospital, St. Paul, MN 55101, USA.

Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR, QRS, and QTc prolongation on the electrocardiogram and development of life-threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid resuscitation and the administration of magnesium and sodium bicarbonate. We report a case of flecainide overdose associated with life-threatening hemodynamic compromise successfully treated with intravenous fat emulsion (IFE) therapy. Read More

J Pharmacol Exp Ther 2011 Feb 15;336(2):551-9. Epub 2010 Nov 15.

Department of Pharmacology and Toxicology, Queen’s University, Kingston, Ontario, Canada.

Amiodarone (AM) is a potent antidysrhythmic agent that can cause potentially life-threatening pulmonary fibrosis, and N-desethylamiodarone (DEA), an AM metabolite, may contribute to AM toxicity. Apoptotic cell death in nontransformed human peripheral lung epithelial 1A (HPL1A) cells was assessed by annexin V-fluorescein isothiocyanate (ann-V) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and necrotic cell death was assessed by propidium iodide (PI) staining. The percentage of cells that were PI-positive increased more than six times with 20 μM AM and approximately doubled with 3. Read More

J Med Toxicol 2005 Dec;1(1):11-8

Medical Toxicology Fellow, Rocky Mountain Poison and Drug Center and Denver Health Medical Center, Denver, CO.

Introduction: Cocaine is a common drug of abuse and use has been associated with ventricular dysrhythmias. Published guidelines suggest that amiodarone is the first line antidysrhythmic for ventricular tachycardia and fibrillation. However, the effects amiodarone in the setting of cocaine toxicity are unknown and unstudied. Read More

Phytomedicine 2004 Feb;11(2-3):121-9

Department of Human Physiology University of Durban-Westville, Durban, South Africa.

The cardiotonic and antidysrhythmic effects of four triterpenoid derivatives, namely oleanolic acid (OA), ursolic acid (UA), and uvaol (UV), isolated from the leaves of African wild olive (Olea europaea, subsp. africana) as well as methyl maslinate (MM) isolated from the leaves of Olea europaea (Cape cultivar) were examined. The derivatives showed low toxicity on brine shrimp test. Read More

Methods Find Exp Clin Pharmacol 2004 Jan-Feb;26(1):31-8

Department of Pharmacology, Faculty of Health Sciences, University of Durban-Westville, Durban, South Africa.

This study was undertaken to evaluate the involvement of delta- and kappa-opioid receptors in both ischemia- and reperfusion-induced arrhythmias, and to elucidate some of the plausible mechanisms conferring antidysrhythmic effects on opioid delta- and kappa-receptor agonists and antagonists. Different models of arrhythmia (calcium chloride [CaCl(2)]-, adrenaline-, and ischemia/reperfusion-induced arrhythmias) were employed. The following opioid agonists, antagonists and blockers were used in the study: [D-Ala(2), D-Leu(5)]enkephalin (DADLE), a selective delta-receptor agonist; trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U-50488H), a selective kappa-receptor agonist; Naltriben Methanesul-fonate (NTB), a selective delta(2)-antagonist with kappa-receptor agonist-like activity; natrindole, a non-selective delta(1)- and delta(2)-receptor antagonist; nor-binaltorphimine dehydrochloride (nor-BNI), a selective kappa-receptor antagonist; chelerythrine, a selective protein kinase C inhibitor, and glibenclamide, a selective blocker of ATP-sensitive K channel. Read More

Toxicol Sci 2003 Sep 27;75(1):169-80. Epub 2003 Jun 27.

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada K7L 3N6.

Pulmonary toxicity, including fibrosis, is a serious adverse effect associated with the antidysrhythmic drug amiodarone (AM). We tested the potential usefulness of pirfenidone against AM-induced pulmonary toxicity in the hamster model. Intratracheal AM administration resulted in pulmonary fibrosis 21 days posttreatment, as evidenced by an increased hydroxyproline content and histological damage. Read More

J Pharmacol Exp Ther 2003 Jan;304(1):277-83

Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada.

Amiodarone (AM) is an efficacious antidysrhythmic agent that can cause numerous adverse effects, including potentially life-threatening pulmonary fibrosis. The current study was undertaken to investigate potential protective mechanisms of vitamin E against AM-induced pulmonary toxicity (AIPT) in the hamster. Three weeks after intratracheal administration of AM (1. Read More

Am J Physiol Lung Cell Mol Physiol 2001 Nov;281(5):L1180-8

Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6.

Amiodarone (AM) is an antidysrhythmic agent with a propensity to cause pulmonary toxicity, including potentially fatal fibrosis. In the present study, the potential roles of c-Jun and transforming growth factor (TGF)-beta 1 in AM-induced inflammation and fibrogenesis were examined after intratracheal administration of AM (1.83 micromol/day on days 0 and 2) or an equivalent volume (0. Read More

Toxicology 2001 Sep;166(3):109-18

Department of Pharmacology and Toxicology, Botterell Hall Room 535, Queen's University, Ont., K7L 3N6, Kingston, Canada.

Amiodarone (AM) is a potent and efficacious antidysrhythmic agent that can cause potentially life-threatening pulmonary fibrosis. Vitamin E has been demonstrated to decrease AM-induced pulmonary fibrosis in vivo in hamsters. In the present in vitro study, we investigated the effects of vitamin E on cell death induced by AM and its primary metabolite, N-desethylamiodarone (DEA), in freshly isolated hamster lung cells. Read More

J Pharmacol Exp Ther 2001 Sep;298(3):1280-9

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

Amiodarone (AM), a potent antidysrhythmic agent, can cause potentially life-threatening pulmonary fibrosis. In the present investigation of mechanisms of initiation of AM lung toxicity, we found that 100 microM AM decreased mitochondrial membrane potential in intact hamster lung alveolar macrophages and preparations enriched in isolated alveolar type II cells and nonciliated bronchiolar epithelial (Clara) cells, following 2 h of incubation. This was followed by a drop in cellular ATP content (by 32--77%) at 4 to 6 h, and 30 to 55% loss of viability at 24 h. Read More

Toxicology 1999 Apr;133(2-3):75-84

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

Amiodarone (AM) is a potent antidysrhythmic agent that is limited in clinical use by its adverse effects, including potentially life-threatening AM-induced pulmonary toxicity (AIPT). The present study tested the ability of dietary supplementation with vitamin E (500 IU d,1-alpha-tocopherol acetate/kg chow) to protect against pulmonary damage following intratracheal administration of AM (1.83 micromol) to the male golden Syrian hamster. Read More

Toxicol Lett 1998 Sep;98(1-2):41-50

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

Amiodarone (AM) is an efficacious antidysrhythmic agent that is limited clinically by numerous adverse effects. Of greatest concern is AM-induced pulmonary toxicity (AIPT) due to the potential for mortality. Mitochondrial alterations and free radicals have been implicated in the etiology of AM-induced toxicities, including AIPT. Read More

Gen Pharmacol 1998 May;30(5):627-38

Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.

1. The review summarizes the most important data known so far on chemistry, pharmacodynamics, toxicology and clinics of the investigational agent, pyridoindole stobadine. 2. Read More

Rev Port Cardiol 1996 Oct;15(10):745-51

Serviço de Cardiologia do Hospital de Pulido Valente, Lisboa.

The pulmonary toxicity induced by amiodarone is one of the major complications that can limit the use of this potent antidysrhythmic agent. The authors perform a bibliographical revision concerning the toxic effects of amiodarone in the lung, pathogenesis, clinical, radiologic and pathologic features, diagnostic problems, risk factors and prognostic data. Read More

J Biochem Toxicol 1996 ;11(3):147-60

Department of Pharmacology, Queen's University, Kingston, Ontario, Canada.

Amiodarone (AM) is an effective antidysrhythmic agent, restricted in use by the development of adverse effects, including potentially fatal AM-induced pulmonary toxicity (AIPT). Although the pathogenesis of AIPT is unknown, an oxidant mechanism has been proposed. The present study evaluated the role of reactive oxygen species (ROS) in AM-induced toxicity. Read More

Anticancer Res 1996 Jan-Feb;16(1):327-32

Laboratorie de Pharmacologie Fondamentale, Faculté de Médecine, Besançon, France.

The electrophysiological effects of gallium chloride (Ga ) and its activity on arrhythmias induced by digitalis were investigated in guinea pig papillary muscle. KCl microelectrodes were used to record transmembrane electrical activity from Purkinje cells from the papillary muscle of guinea pig hearts during superfusion and electrical stimulation in vitro at 37 degrees C. Myocardial contractility was continuously monitored. Read More

Can J Physiol Pharmacol 1995 Dec;73(12):1675-85

Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada.

Although amiodarone is a highly efficacious antidysrhythmic agent, the drug produces numerous adverse effects. The most critical of these is pulmonary toxicity because of the potential for mortality. This review examines the experimental model systems used to study amiodarone toxicity, summarizes the current state of knowledge regarding the processes involved in amiodarone-induced pulmonary toxicity (AIPT), and includes a discussion of potential future directions. Read More

Anesthesiology 1995 Nov;83(5):992-9

Department of Anesthesiology, Osaka University Faculty of Medicine, Japan.

Background: Dexmedetomidine, an alpha 2-adrenergic agonist, can prevent the genesis of halothane/epinephrine dysrhythmias through the central nervous system. Because stimulation of alpha 2 adrenoceptors in the central nervous system enhances vagal neural activity and vagal stimulation is known to inhibit digitalis-induced dysrhythmias, dexmedetomidine may exert the antidysrhythmic property through vagal stimulation. To address this hypothesis, the effect of dexmedetomidine in vagotomized dogs was examined and compared with that in intact dogs. Read More

Korean J Intern Med 1995 Jul;10(2):155-9

Department of Internal Medicine, Anatomical Pathology, College of Medicine, Soon Chun Hy ang University, Seoul, Korea.

Amiodarone is an iodinated benzofuran derivative that represents a new and extremely effective therapy for certain life-threatening refractory cardiac arrgythmia. There are numerous side effects associated with amiodarone therapy, including corneal microdeposits. Skin reactions and others. Read More

Toxicol Lett 1994 Oct;74(1):51-9

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

Amiodarone is an effective antidysrhythmic agent, restricted in use by the development of pulmonary toxicity. Several in vivo animal models have been used to study amiodarone-induced pulmonary toxicity. Intratracheal administration of amiodarone to the hamster has been used as a model for the critical amiodarone-induced pulmonary fibrosis (AIPF). Read More

Toxicol Appl Pharmacol 1994 Aug;127(2):275-81

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

Amiodarone (AM) is an effective antidysrhythmic agent, the use of which is limited because of the drug's potential for causing life-threatening pulmonary fibrosis. Oxidative stress involving keto oxygen-derived free radical formation has been postulated to be responsible for initiating AM-induced pulmonary toxicity (AIPT). We have investigated whether des-oxo-amiodarone (DOAM), which has a methylene group in place of the keto oxygen group of AM, causes pulmonary fibrosis in an experimental animal. Read More

Cesk Farm 1993 Dec;42(6):260-4

Katedra farmakológie a toxikológie Farmaceutickej fakulty Univerzity Komenského, Bratislava, SR.

In a systematic study of the relationship between the chemical structure and beta-adrenolytic activity, eleven derivatives of the 4-alkoxysubstituted phenylcarbamic acids were prepared. The beta-adrenolytic efficiency of the compounds was studied in the isolated spontaneously beating guinea-pig atria and expressed as pA2 values against isoprenaline tachycardia. Negative chronotropic and antidysrhythmic activity were also evaluated. Read More

J Pharmacol Exp Ther 1990 Sep;254(3):1107-12

Department of Internal Medicine, Indiana University School of Medicine, Indianapolis.

Amiodarone is a potent antidysrhythmic drug that is associated with severe pulmonary toxicity. The mechanism of amiodarone pulmonary toxicity is poorly understood. To investigate the possible involvement of oxygen-derived metabolites in amiodarone-induced injury, 51Cr-labeled human pulmonary artery endothelial (HPAE) cells were incubated with amiodarone for 18 hr in the presence of various antioxidants and in hypoxic and hyperoxic conditions with cell injury quantified by 51Cr release, expressed as cytotoxic index. Read More

Mayo Clin Proc 1985 Sep;60(9):601-3

Use of amiodarone, an investigational antidysrhythmic agent, has been associated with cases of pulmonary toxicity. The mechanism of amiodarone pulmonary toxicity is unknown, and recommendations for the assessment and treatment of patients with this condition continue to evolve. In two patients with clinically diagnosed amiodarone pulmonary toxicity, a rapidly progressive and fatal adult respiratory distress syndrome developed after pulmonary angiography. Read More

Toxicol Lett 1985 Aug;26(2-3):107-10

Subchronic 1-month intravenous toxicity studies on indecainide, an antidysrhythmic agent, were conducted in rats and dogs. Rats (10 males, 10 females/group) were given daily intravenous (i.v. Read More

J Clin Pharmacol 1984 Jul;24(7):328-32

Assessments of efficacy of antidysrhythmic drugs at different clinical arrhythmia centers frequently produce discordant data, probably because of differences in patient population, technology to assess efficacy, study design, and concomitant drugs such as digitalis, diuretics, beta-adrenergic blocking agents, and calcium channel blockers. Furthermore, different doses employed may greatly influence the toxicity and efficacy of both conventional and experimental antiarrhythmic drugs. These variables make the design of studies in the field of antiarrhythmic therapy both difficult and of critical importance. Read More

Pacing Clin Electrophysiol 1984 Jan;7(1):109-24

Amiodarone hydrochloride is a relatively new antiarrhythmic agent, the properties of which differ in a significant manner electrophysiologically, pharmacokinetically and structurally from those of conventional as well as other investigational antidysrhythmic compounds. It is also pharmacologically unique in so far as its fundamental action on cardiac muscle following chronic therapy differs markedly from that found during the intravenous administration; its I.V. Read More

Med Clin North Am 1976 Mar;60(2):213-32

The often emergent nature of life-threatening cardiac dysrhythmias, the frequent seeming "resistance" of the abnormal heart rhythm to therapy, and the commonly encountered toxicity of antidysrhythmic agents combine to make treatment of cardiac dysrhythmias one of the strictest challenges to the practicing physician. Although electrophysiologic studies have markedly increased out understanding of dysrhythmogenesis and the actions of anti-dysrhythmic drugs, these numerous investigations have provided but little assistance to the practicing physician either as an intellectual framework or as a guide to patient care. The electrophysiologic classification of the antidysrhythmic drugs presented in this paper should be acceptable both to the electrophysiologist and the clinician since it is based on alterations in basic membrane properties and correlates well with clinical realities. Read More

Br J Pharmacol 1972 Jan;44(1):1-9

1. Kö 1173, 1-(2',6'-dimethyl-phenoxy)-2-amino-propane, was equal to lignocaine in potency as a local anaesthetic on stripped frog sciatic nerve at pH 7.5. Read More