Calcium Channel Blockers and Mortality in Elderly Patients with Myocardial Infarction

Total Page:16

File Type:pdf, Size:1020Kb

Calcium Channel Blockers and Mortality in Elderly Patients with Myocardial Infarction ORIGINAL INVESTIGATION Calcium Channel Blockers and Mortality in Elderly Patients With Myocardial Infarction James G. Jollis, MD; Ross J. Simpson, Jr, MD, PhD; Mridul K. Chowdhury, PhD; Wayne E. Cascio, MD; John R. Crouse III, MD; Mark W. Massing, MD, MPH; Sidney C. Smith, Jr, MD Background: Although calcium channel blockers are Results: Calcium channel blockers were widely pre- a useful therapy in relieving angina, lowering blood pres- scribed at hospital discharge to elderly patients with sure, and slowing conduction of atrial fibrillation, grow- myocardial infarction between 1994 and 1995 ing evidence has cast doubt on their safety in patients with (n = 51 921), the most commonly prescribed being dil- coronary disease. tiazem (n = 21 175), nifedipine (n = 12 670), amlo- dipine (n = 11 683), and verapamil (n = 3639). After Objective: To examine the association between cal- adjusting for illness severity and concomitant medica- cium channel blocker therapy at hospital discharge and tion use, patients who were prescribed calcium chan- mortality in a population-based sample of elderly pa- nel blockers at hospital discharge did not have tients hospitalized with acute myocardial infarction. increased risk for 30-day or 1-year mortality, with the exception of the few (n = 116) treated with bepridil. Design: Retrospective cohort study using data from medi- Bepridil differs from other calcium channel blockers cal charts and administrative files. because of its tendency to prolong repolarization, and its association with proarrhythmic effects in elderly Setting: All acute care hospitals in 46 states. patients. Patients: All Medicare patients with a principal diag- Conclusion: We did not identify a mortality risk in a nosis of acute myocardial infarction consecutively dis- large consecutive sample of elderly patients with myo- charged from the hospital alive during 8-month periods cardial infarction, which supports the need for addi- between 1994 and 1995 (N = 141 041). tional prospective trials examining calcium channel blocker therapy for ischemic heart disease. Main Outcome Measure: Mortality at 30 days and 1 year. Arch Intern Med. 1999;159:2341-2348 ALCIUM CHANNEL block- nel blocker therapy, and further studies in- ers represent a poten- volving large numbers of patients are tially useful therapy for needed to examine the safety of their use. elderly patients with coro- Given current apprehension among clini- nary artery disease, given cians regarding calcium channel blocker theirC ability to relieve angina, lower blood therapy, such studies are unlikely to be From the Duke Clinical pressure, and slow conduction of atrial fi- performed, particularly involving formu- Research Institute, Duke brillation. However, growing evidence has lations for which patents have expired. University, Durham, NC cast doubt on their safety. In post hoc Decisions regarding the use of calcium (Dr Jollis); Medical Review of analyses, the Multicenter Diltiazem Postin- channel blockers in the elderly are even North Carolina Inc, Cary farction Trial (MDPIT)1 found higher rates more difficult, given the relatively few (Drs Simpson and Chowdhury); of nonfatal reinfarction or cardiac death elderly patients enrolled in previous tri- Division of Cardiology associated with diltiazem treatment in pa- als. In 1995, calcium channel blockers— (Drs Simpson, Cascio, and tients with myocardial infarction (MI) and including nifedipine, diltiazem, and ver- Smith) and Department of pulmonary congestion or reduced ejec- apamil—were widely used among Epidemiology (Dr Massing), tion fraction. More recently, a meta- Medicare patients. We examined the re- University of North Carolina, 2 Chapel Hill; and the analysis of nifedipine therapy after acute lationship between calcium channel Department of Medicine, Wake MI identified higher mortality associated blocker use after acute MI and survival for Forest University School of with nifedipine therapy on a dose-re- 141 041 elderly patients, as part of the Medicine, Winston-Salem, NC sponse basis. These findings have led to Health Care Financing Administration’s (Dr Crouse). much uncertainty regarding calcium chan- Cooperative Cardiovascular Project (CCP). ARCH INTERN MED/ VOL 159, OCT 25, 1999 WWW.ARCHINTERNMED.COM 2341 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 1. Thirty-Day Mortality Logistic Regression Model* PATIENTS AND METHODS Variable Odds Variable Estimate x2 P . Ratio PATIENT POPULATION Intercept −3.57 727.79 .001 The CCP abstracted hospital charts of Medicare patients Age from 65 y 0.04 51.39 .001 1.04 Age from 65 y squared −0.0003 1.87 .17 1.00 withaprincipaldiagnosisofacuteMI(InternationalClas- Female −0.15 29.48 .001 0.86 sification of Diseases codes 410.x0 and 410.x1) consecu- Black −0.12 4.29 .04 0.89 tively discharged from the hospital during 8-month pe- Anterior infarction 0.18 38.56 .001 1.20 3-5 riods between 1994 and 1995, in 46 states. Informa- Inferior infarction −0.01 0.25 .62 0.99 tion collected for each Medicare patient included patient Non–Q wave infarction −0.19 45.80 .001 0.82 identifiers, hospitalization dates, demographics, chest Systolic blood pressure −0.007 263.17 .001 0.99 pain history, physical examination findings, medica- Pulse 0.003 31.62 .001 1.00 tions used, presence or absence of contraindications to Respiratory rate 0.01 23.06 .001 1.01 therapy,electrocardiograms,cardiacenzymelevels,treat- Rales or pulmonary congestion 0.15 26.23 .001 1.16 ment, complications, and survival status. Accuracy of Ejection fraction 40%-59% −0.53 206.58 .001 0.59 hospital chart abstraction was evaluated on a monthly Ejection fraction .60% −0.97 177.00 .001 0.38 basis by masked reabstraction, with agreement rates by Ejection fraction missing −0.14 16.32 .001 0.87 data element in the 85% to 95% range. Calcium chan- Previous myocardial infarction 0.03 1.30 .25 1.03 nel blockers were identified at 2 points in the CCP chart Previous congestive heart failure 0.08 6.82 .009 1.08 abstraction, according to discharge medications entered Previous bypass surgery 0.06 2.19 .14 1.06 by free text and by a specific variable for “calcium chan- Previous angioplasty −0.37 33.45 .001 0.69 Electrocardiogram—atrial 0.15 25.50 .001 1.16 nel blocker at discharge.” These 2 variables agreed for fibrillation 51 843 of 51 921 patients we identified as being treated Electrocardiogram—heart block 0.10 2.59 .11 1.11 with calcium channel blockers, and for 89 099 of 89 120 Electrocardiogram—myocardial 0.11 10.25 .001 1.12 patientsnotbeingtreated.Allpatientsolderthan65years infarction who were discharged from the hospital alive were in- Diabetes 0.13 20.32 .001 1.14 cludedinthepresentstudy.Datesofdeathwereobtained Hypertension −0.16 29.31 .001 0.86 from the Medicare Enrollment Database and the Social Previous stroke 0.06 2.96 .08 1.06 SecurityAdministration’sMasterBeneficiaryRecordFile. Peripheral vascular disease 0.10 7.62 .006 1.11 Obstructive pulmonary disease 0.08 5.57 .018 1.08 DATA ANALYSIS Current cigarette smoker 0.18 18.58 .001 1.20 Dementia 0.39 98.80 .001 1.48 The primary analysis of the present study compared Serum urea nitrogen level, ,5 −0.13 7.25 .007 0.88 the mortality of patients who were prescribed cal- mmol/L Serum urea nitrogen level, 7-8 0.19 19.05 .001 1.21 cium channel blockers at hospital discharge after acute mmol/L MI with that of patients discharged but not taking Serum urea nitrogen level, 9-10 0.24 24.63 .001 1.27 these drugs. Calcium channel blockers were classi- mmol/L fied as nifedipine, amlodipine, other dihydropteri- Serum urea nitrogen level, ,10 0.60 234.58 .001 1.82 dines, diltiazem, verapamil, and bepridil hydrochlo- mmol/L ride. Baseline characteristics and outcomes were Serum urea nitrogen level 0.17 5.15 .023 1.19 compared between treatment categories using x2 tests missing for categorical variables and analysis of variance for Walks with assistance 0.30 90.61 .001 1.35 continuous variables. Unable to walk 1.22 715.83 .001 3.39 Thirty-day and 1-year mortality after hospital dis- Unable to determine mobility 0.88 92.84 .001 2.41 charge were examined in logistic regression models Congestive heart failure 0.56 304.32 .001 1.74 after adjusting for illness severity, medications taken, Recurrent angina 0.23 64.10 .001 1.26 and propensity for treatment with calcium channel Shock 0.17 6.65 .01 1.19 blockers (propensity score). Logistic model vari- Reinfarction 0.24 11.49 .001 1.28 Stroke 0.55 93.28 .001 1.73 ables were selected on the basis of their association Hemorrhage −0.008 0.05 .82 0.99 with mortality according to previous work, strength Cardiac arrest 0.13 4.66 .03 1.14 of association, and clinical intuition (Table 1 and Discharged to nonacute hospital 0.74 448.40 .001 2.10 Table 2). Specific model components included age, Discharged to home health care 0.27 50.16 .001 1.30 sex, race, descriptors of MI and coronary disease se- Propensity decile 1 −0.73 68.36 .001 0.48 verity, comorbid illnesses, mobility at discharge, dis- Propensity decile 2 −0.48 35.28 .001 0.62 charge destination, and propensity score. Propen- Propensity decile 3 −0.27 12.42 .001 0.76 sity score was derived according to the methods of Propensity decile 4 −0.23 9.44 .002 0.79 Rubin6 using an additional logistic model to exam- Propensity decile 5 −0.19 6.87 .009 0.82 ine characteristics associated with being discharged Propensity decile 6 −0.22 9.29 .002 0.80 while taking a calcium channel blocker.7 Compo- Propensity decile 7 −0.14 3.97 .05 0.87 nent variables for the propensity model were se- Propensity decile 8 −0.10 1.89 .17 0.91 lected in a similar manner as those for the mortality Propensity decile 9 −0.05 0.56 .46 0.95 models, using association with calcium channel Discharged while taking calcium −0.04 2.20 .14 0.96 blocker therapy as the gauge of importance (Table 3).
Recommended publications
  • A Drug Repositioning Approach Identifies Tricyclic Antidepressants As Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors
    Published OnlineFirst September 26, 2013; DOI: 10.1158/2159-8290.CD-13-0183 RESEARCH ARTICLE A Drug Repositioning Approach Identifi es Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors Nadine S. Jahchan 1 , 2 , Joel T. Dudley 1 , Pawel K. Mazur 1 , 2 , Natasha Flores 1 , 2 , Dian Yang 1 , 2 , Alec Palmerton 1 , 2 , Anne-Flore Zmoos 1 , 2 , Dedeepya Vaka 1 , 2 , Kim Q.T. Tran 1 , 2 , Margaret Zhou 1 , 2 , Karolina Krasinska 3 , Jonathan W. Riess 4 , Joel W. Neal 5 , Purvesh Khatri 1 , 2 , Kwon S. Park 1 , 2 , Atul J. Butte 1 , 2 , and Julien Sage 1 , 2 Downloaded from cancerdiscovery.aacrjournals.org on September 29, 2021. © 2013 American Association for Cancer Research. Published OnlineFirst September 26, 2013; DOI: 10.1158/2159-8290.CD-13-0183 ABSTRACT Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformat- ics approach querying a large compendium of gene expression profi les to identify candidate U.S. Food and Drug Administration (FDA)–approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endog- enous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein–coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma.
    [Show full text]
  • Comparison of Electropharmacological Effects of Bepridil and Sotalol in Halothane-Anesthetized Dogs
    Circ J 2008; 72: 1003–1011 Comparison of Electropharmacological Effects of Bepridil and Sotalol in Halothane-Anesthetized Dogs Tomomichi Ishizaka, DVM*,**; Akira Takahara, PhD*; Hiroshi Iwasaki, MD*; Yoshitaka Mitsumori, MD*; Hiroaki Kise, MD*; Yuji Nakamura, MS*; Atsushi Sugiyama, MD*,** Background Bepridil is known to have a multiple ion channel-blocking property in the heart, which has been applied for the treatment of atrial fibrillation and drug-refractory ventricular tachyarrhythmias. In this study, the electro-pharmacological effects of bepridil were compared with those of dl-sotalol, a representative class III anti- arrhythmic drug, using the halothane-anesthetized canine model. Methods and Results Cardiovascular and electrophysiological variables were measured under the halothane anesthesia. Intravenous administration of bepridil (0.3mg/kg, n=4) delayed the intraventricular conduction and prolonged the ventricular effective refractory period, whereas dl-sotalol (0.3mg/kg, iv, n=4) inhibited atrioven- tricular conduction and prolonged the atrial and ventricular effective refractory period. The additional adminis- tration of 10 times the higher dose of bepridil or dl-sotalol (ie, 3mg/kg, iv, n=4 for each group) decreased blood pressure, suppressed ventricular contraction and sinus automaticity, and prolonged the atrial and ventricular effective refractory period and monophasic action potential duration, in addition to the effects of the low dose. Conclusions The electropharmacological effects of bepridil and dl-sotalol were similar,
    [Show full text]
  • Evaluation and Management of Chronic Hepatitis C Virus Infection
    EVALUATION AND MANAGEMENT OF CHRONIC HEPATITIS C VIRUS (HCV) INFECTION Federal Bureau of Prisons Clinical Guidance MAY 2017 Federal Bureau of Prisons (BOP) Clinical Guidance is made available to the public for informational purposes only. The BOP does not warrant this guidance for any other purpose, and assumes no responsibility for any injury or damage resulting from the reliance thereof. Proper medical practice necessitates that all cases are evaluated on an individual basis and that treatment decisions are patient- specific. Consult the BOP Health Management Resources Web page to determine the date of the most recent update to this document: http://www.bop.gov/resources/health_care_mngmt.jsp. Federal Bureau of Prisons Evaluation and Management of Chronic HCV Infection Clinical Guidance May 2017 WHAT’S NEW IN BOP GUIDANCE REGARDING HCV INFECTION? The major changes included in this May 2017 update to the BOP guidance on chronic HCV infection are based primarily on the April 2017 changes to the American Association for the Study of Liver Diseases (AASLD) guidelines, as follows: • The term resistance-associated substitutions (RASs) is now being used instead of resistance- associated variants (RAVs). • Anti-HBs and anti-HBc, in addition to HBsAg, are recommended for baseline testing of hepatitis B status (see LABORATORY TESTS under BASELINE EVALUATION). • Ledipasvir/sofosbuvir once daily for eight weeks is now an AASLD-recommended regimen for treatment in a subgroup of HCV-infected persons who have genotype 1a or 1b, have an HCV viral load <6 million IU/ml, and are treatment-naïve—but who are not black, are not HIV-coinfected, and do not have cirrhosis.
    [Show full text]
  • Comparison of In-Cell Immunoassay and Automated Electrophysiology for Assessment of Herg Trafficking Liability for New Drugs
    Comparison of in-cell immunoassay and automated electrophysiology for assessment of hERG trafficking liability for new drugs Yuri Kuryshev, Peter Hawryluk, Caiyun Wu, Abby Sewell, James Kramer, Carlos Obejero-Paz, Luke Armstrong, Arthur M. Brown Charles River, Cleveland, Ohio, USA IWB/PPC 1 h IWB/PPC 24 h 1.8 1.8 hERG-Lite 16 h hERG-Lite 1 h 1 3 1.6 Abstract Results 1.6 4 Summary 1.4 1.4 hERG-Lite® is an antibody-based chemiluminescent assay that identifies compounds that disrupt Voltage clamp population patch: functional assay for 1.2 1.2 trafficking or suppress expression of hERG channel protein. Electrophysiological recording from measuring relative changes in membrane surface hERG 1.0 1.0 hERG-Lite® : in-cell immunoassay for measuring relative single cell using the manual patch-clamp technique is more direct way to quantify hERG expression in 0.8 0.8 0.6 0.6 cell membrane but this method has critical limitations: low throughput and selection bias during choice channelAa levels Ab Vehicle Control Pentamidine changes in hERG channel surface levels 24 hr. 1 hr. 0.4 0.4 Fraction of Control Fraction of Control of cells for patching. Application of the automated population patch clamp technique for the hERG 1hr. 30 M/1 hr. 30 M 30 M 0.2 0.2 VC Pent. VC Pent. expression analysis provides a dramatic increase in throughput and eliminates the cell selection bias. 0.0 0.0 hERG-Lite WB* IWB/PPC We analyzed a panel of drugs (Amiodarone, Amitriptyline, Bepridil, Diphenhydramine, Dofetilide, 0.03 0.1 0.3 1 0.03 0.1 0.3 1 Amiodarone ↓ ↓ N.D.** Fluoxetine, Imipramine, Ouabaine, Pentamidine, Pimozide, Sunitinib and Verapamil) for chronic effects Pimozide, M Pimozide, M Amitriptyline ↓ ↓ ↓ on hERG channel trafficking and expression by the hERG-Lite® method and with IonWorks Barracuda IWB/PPC 1 h IWB/PPC 24 h hERG-Lite 1 h hERG-Lite 16 h (IWB), a population-based automated patch clamp platform.
    [Show full text]
  • Drug and Medication Classification Schedule
    KENTUCKY HORSE RACING COMMISSION UNIFORM DRUG, MEDICATION, AND SUBSTANCE CLASSIFICATION SCHEDULE KHRC 8-020-1 (11/2018) Class A drugs, medications, and substances are those (1) that have the highest potential to influence performance in the equine athlete, regardless of their approval by the United States Food and Drug Administration, or (2) that lack approval by the United States Food and Drug Administration but have pharmacologic effects similar to certain Class B drugs, medications, or substances that are approved by the United States Food and Drug Administration. Acecarbromal Bolasterone Cimaterol Divalproex Fluanisone Acetophenazine Boldione Citalopram Dixyrazine Fludiazepam Adinazolam Brimondine Cllibucaine Donepezil Flunitrazepam Alcuronium Bromazepam Clobazam Dopamine Fluopromazine Alfentanil Bromfenac Clocapramine Doxacurium Fluoresone Almotriptan Bromisovalum Clomethiazole Doxapram Fluoxetine Alphaprodine Bromocriptine Clomipramine Doxazosin Flupenthixol Alpidem Bromperidol Clonazepam Doxefazepam Flupirtine Alprazolam Brotizolam Clorazepate Doxepin Flurazepam Alprenolol Bufexamac Clormecaine Droperidol Fluspirilene Althesin Bupivacaine Clostebol Duloxetine Flutoprazepam Aminorex Buprenorphine Clothiapine Eletriptan Fluvoxamine Amisulpride Buspirone Clotiazepam Enalapril Formebolone Amitriptyline Bupropion Cloxazolam Enciprazine Fosinopril Amobarbital Butabartital Clozapine Endorphins Furzabol Amoxapine Butacaine Cobratoxin Enkephalins Galantamine Amperozide Butalbital Cocaine Ephedrine Gallamine Amphetamine Butanilicaine Codeine
    [Show full text]
  • Evaluation of Ruxolitinib and Pracinostat Combination As a Therapy for Patients with Myelofibrosis 2014-0445
    2014-0445 October 23, 2016 Page 1 Protocol Page EVALUATION OF RUXOLITINIB AND PRACINOSTAT COMBINATION AS A THERAPY FOR PATIENTS WITH MYELOFIBROSIS 2014-0445 Core Protocol Information Short Title Ruxolitinib and Pracinostat Combination Therapy for Patients with MF Study Chair: Srdan Verstovsek Additional Contact: Paula J. Cooley Sandra L. Rood Leukemia Protocol Review Group Department: Leukemia Phone: 713-792-7305 Unit: 428 Full Title: EVALUATION OF RUXOLITINIB AND PRACINOSTAT COMBINATION AS A THERAPY FOR PATIENTS WITH MYELOFIBROSIS Protocol Type: Standard Protocol Protocol Phase: Phase II Version Status: Terminated 06/01/2018 Version: 13 Submitted by: Sandra L. Rood--10/23/2017 2:12:37 PM OPR Action: Accepted by: Elizabeth Orozco -- 10/26/2017 1:34:18 PM Which Committee will review this protocol? The Clinical Research Committee - (CRC) 2014-0445 October 23, 2016 Page 2 Protocol Body EVALUATION OF RUXOLITINIB AND PRACINOSTAT COMBINATION AS A THERAPY FOR PATIENTS WITH MYELOFIBROSIS 1.0 HYPOTHESIS AND OBJECTIVES Hypothesis Ruxolitinib (also known as INCB018424), a JAK1/2 inhibitor, and pracinostat (a histone deacetylase inhibitor; HDACi) are effective and tolerable treatments for patients with myelofibrosis (MF). Combination of these agents in patients with MF can improve the overall clinical response to therapy without causing excessive toxicity. Objectives Primary: to determine the efficacy/clinical activity of the combination of ruxolitinib with pracinostat as therapy in patients with MF Secondary: to determine the toxicity of the combination of ruxolitinib with pracinostat as therapy in patients with MF Exploratory: to explore time to response and duration of response to explore changes in bone marrow fibrosis to explore changes in JAK2V617F (or other molecular marker) allele burden or changes in cytogenetic abnormalities 2.0 BACKGROUND AND RATIONALE 2.1 Myelofibrosis Myelofibrosis (MF) is a rare clonal proliferative disorder of a pluripotent stem cell.
    [Show full text]
  • Neuroleptics of the Diphenylbutylpiperidine Series Are Potent Calcium Channel Inhibitors
    Proc. Nati. Acad. Sci. USA Vol. 83, pp. 7513-7517, October 1986 Neurobiology Neuroleptics of the diphenylbutylpiperidine series are potent calcium channel inhibitors (fluspirilene/desmethoxverapamil/binding/voltage-clamp/skeletal muscle) JEAN-PIERRE GALIZZI, MICHEL FOSSET, GEORGES ROMEY, PIERRE LADURON*, AND MICHEL LAZDUNSKI Centre de Biochimie du Centre National de la Recherche Scientifique, Parc Valrose, 06034 Nice Cedex, France Communicated by Jean-Marie Lehn, June 5, 1986 ABSTRACT [1t4]Fluspirilene, a neuroleptic molecule of spirilene and directly demonstrate that molecules in the the diphenylbutylpiperidine series, binds to skeletal muscle DPBP series are among the most potent inhibitors of the transverse tubule membranes with a high affinity correspond- skeletal muscle Ca2+ channel. ing to a Kd of 0.11 * 0.04 nM. A 1:1 stoichiometry was found between [3H]fluspirilene binding and the binding of (-)- [3H]desmethoxyverapamil {(-)[3H]D888}, one of the most MATERIALS AND METHODS potent Ca2+ channel inhibitors. Ca2+ channel inhibitors such as D888, verapamil, gallopamil, bepridil, or diltiazem antag- Materials. (-)[3H]D888 (82 Ci/mmol; 1 Ci = 37 GBq) and onize [3H]fluspirilene binding besides antagonizing (-)[3H]- the 1,4-dihydropyridine (+)[3H]PN 200-110 (80 Ci/mmol) D888 binding. Neuroleptics, especially those of the diphenyl- were obtained from Amersham; (-)D888, verapamil, and butylpiperidine family, also antagonize both (-)[3H]D888 gallopamil were from Knoll AG (Ludwigshafen, F.R.G.); binding and [3H]fluspirilene binding. There is an excellent bepridil and the bepridil analogs 4205 {1-[(1-propynyl)- correlation between affinities found from [3H~fluspirilene bind- cyclohexyloxy]-2-(1-pyrrolidinyl)-3-[(2-methyl)propoxyjpro- ing experiments and those found from (-)[3H]D888 binding pane chlorhydrate} and 11787 [N-(4-chloro)phenylmethyl-N- experiments.
    [Show full text]
  • ( 12 ) United States Patent
    US010117881B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 117 ,881 B2 Helson (45 ) Date of Patent: * Nov. 6 , 2018 ( 54 ) PROTECTIVE EFFECT OF DMPC , DMPG , (58 ) Field of Classification Search DMPC /DMPG , LYSOPG AND LYSOPC None AGAINST DRUGS THAT CAUSE See application file for complete search history . CHANNELOPATHIES (71 ) Applicant: SignPath Pharma Inc. , Quakertown , ( 56 ) References Cited PA ( US) U . S . PATENT DOCUMENTS (72 ) Inventor: Lawrence Helson , Quakertown , PA 4 , 812 , 312 A 3 / 1989 Lopez -Berestein et al . (US ) 5 ,023 ,087 A 6 / 1991 Yau - Young 5 ,679 ,864 A 10 / 1997 Krackov et al . ( 73 ) Assignee : Signpath Pharma, Inc. , Sandy, UT 6 , 143 , 276 A 11/ 2000 Unger (US ) 6 , 787 , 132 B1 9 /2004 Gabison et al . 6 , 946 ,475 B1 9 / 2005 Lloyd ( * ) Notice : Subject to any disclaimer, the term of this 7 ,060 ,733 B2 6 / 2006 Pandol et al . patent is extended or adjusted under 35 7 , 067 , 159 B2 6 / 2006 Katz et al. U . S . C . 154 ( b ) by 0 days. 7 , 507 , 864 B2 3 / 2009 Miller et al. 7 ,674 , 820 B2 3 / 2010 Fedida et al. This patent is subject to a terminal dis 7 , 723 , 515 B1 5 / 2010 DiMauro claimer. 7 ,871 ,609 B2 1 / 2011 Ziff et al . 7 , 968, 115 B26 / 2011 Kurzrock et al . 8 , 062 ,663 B2 11/ 2011 Wang et al. ( 21) Appl . No. : 15 /347 , 381 8 , 153 , 172 B2 4 / 2012 Antony 8 , 202, 839 B1 6 / 2012 Sung (22 ) Filed : Nov . 9 , 2016 8 , 207 ,219 B2 6 / 2012 Fedida et al .
    [Show full text]
  • Prescription Medications, Drugs, Herbs & Chemicals Associated With
    Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus American Tinnitus Association Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form, or by any means, without the prior written permission of the American Tinnitus Association. ©2013 American Tinnitus Association Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus American Tinnitus Association This document is to be utilized as a conversation tool with your health care provider and is by no means a “complete” listing. Anyone reading this list of ototoxic drugs is strongly advised NOT to discontinue taking any prescribed medication without first contacting the prescribing physician. Just because a drug is listed does not mean that you will automatically get tinnitus, or exacerbate exisiting tinnitus, if you take it. A few will, but many will not. Whether or not you eperience tinnitus after taking one of the listed drugs or herbals, or after being exposed to one of the listed chemicals, depends on many factors ‐ such as your own body chemistry, your sensitivity to drugs, the dose you take, or the length of time you take the drug. It is important to note that there may be drugs NOT listed here that could still cause tinnitus. Although this list is one of the most complete listings of drugs associated with tinnitus, no list of this kind can ever be totally complete – therefore use it as a guide and resource, but do not take it as the final word. The drug brand name is italicized and is followed by the generic drug name in bold.
    [Show full text]
  • Medications to Avoid in Long QT Syndrome
    Jackie Crawford Cardiac Inherited Disease Co-ordinator C/- Paediatric Cardiology; Level 3 Starship; Auckland City Hospital Private Bag 92024; Auckland Cardiac Inherited Disease Registry Phone: (09) 3074949 ext 23634 www.cidg.org Fax: (09) 6309877 Email: [email protected] Medications to be avoided, or requiring special caution, in people with Long QT syndrome This list includes medications which prolong the QT interval and is meant as a guide for people with Long QT syndrome, or acquired long QT interval from heart muscle disease, and their parents or guardians. It should not be seen as all inclusive. Those prescribing any medication to someone with Long QT syndrome should always check the drug specifications and contra-indications. The list has been compiled by review of publications and/or drug advice sheets provided with medications. Check also www.SADS.org and www.Torsades .org. Antibiotics Erythromycin, Clarithromycin, Gatifloxacin, levofloxacin, Moxifloxacin Sulfamethoxazole-trimethoprim (Septrin/Bactrim), Spiramycin, Pentamidine Antihistamines Terfenadine, Astemizole, Diphenhydramine, (These are particularly to be avoided (even in normal subjects) in combination with Erythromycin or grapefruit juice or the antifungals ketoconazole, miconazole, fluconazole or itraconazole) [Antihistamines that may be used safely are loratidine, cetirizine and fexofenadine, and phenergan] Appetite suppressants Fenfluramine, phentermine, Sibutramine Asthma treatments The Beta-2 agonists (e.g. Terbutaline, Salbutamol, Salmeterol) both work against
    [Show full text]
  • Johansen 1..13
    RESEARCH ARTICLE EBOLA VIRUS A screen of approved drugs and molecular probes identifies therapeutics with anti–Ebola virus activity Lisa M. Johansen,1 Lisa Evans DeWald,2 Charles J. Shoemaker,3 Benjamin G. Hoffstrom,1 Calli M. Lear-Rooney,2 Andrea Stossel,2 Elizabeth Nelson,3 Sue E. Delos,3 James A. Simmons,3 Jill M. Grenier,1 Laura T. Pierce,1 Hassan Pajouhesh,1 Joseph Lehár,1,4 Lisa E. Hensley,2 Pamela J. Glass,2 Judith M. White,3 Gene G. Olinger2*† Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration–approved drugs spanning multiple mech- anistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections. INTRODUCTION as well as drugs acting through mechanisms that would not have been Filoviruses (Ebolavirus and Marburgvirus) are responsible for acute vi- predicted (11).
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]