DOCSLIB.ORG

Redalyc.Interactions Between Antihypertensive Drugs and Food

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Nutrición Hospitalaria ISSN: 0212-1611 info@nutriciónhospitalaria.com Grupo Aula Médica España Jáuregui-Garrido, B.; Jáuregui-Lobera, I. Interactions between antihypertensive drugs and food Nutrición Hospitalaria, vol. 27, núm. 6, noviembre-diciembre, 2012, pp. 1866-1875 Grupo Aula Médica Madrid, España Available in: http://www.redalyc.org/articulo.oa?id=309226791011 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative 11. INTERACTIONS:01. Interacción 29/11/12 14:38 Página 1866 Nutr Hosp. 2012;27(5):1866-1875 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Revisión Interactions between antihypertensive drugs and food B. Jáuregui-Garrido1 and I. Jáuregui-Lobera2 1Department of Cardiology. University Hospital Virgen del Rocío. Seville. Spain. 2Bromatology and Nutrition. Pablo de Olavide University. Seville. Spain. Abstract INTERACCIONES ENTRE FÁRMACOS ANTIHIPERTENSIVOS Y ALIMENTOS Objective: A drug interaction is defined as any alter- ation, pharmacokinetics and/or pharmacodynamics, Resumen produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. Objetivo: la interacción de medicamentos se define como These interactions can affect the antihypertensive drugs, cualquier alteración, farmacocinética y/o farmacodiná- altering their therapeutic efficacy and causing toxic mica, producida por diferentes sustancias, otros tratamien- effects. The aim of this study was to conduct a review of tos, factores dietéticos y hábitos como beber y fumar. Estas available data about interactions between antihyperten- interacciones pueden afectar a los fármacos antihipertensi- sive agents and food. vos, alterando su eficacia terapéutica y causando efectos Methods: The purpose of this review was to report an tóxicos. El objetivo de este estudio fue realizar una revisión update of main findings with respect to the interactions de los datos disponibles acerca de las interacciones entre los between food and antihypertensive drugs by way of a fármacos antihipertensivos y los alimentos. search conducted in PubMed, which yielded a total of 236 Métodos: El objetivo de esta revisión fue proporcionar articles initially. una puesta al día sobre los principales resultados con res- Results: After excluding different articles, which were pecto a las interacciones entre alimentos y fármacos antihi- not focusing on the specific objective, the main results pertensivos mediante una búsqueda realizada en PubMed, refer to interactions between antihypertensive drugs and que dio lugar inicialmente a un total de 236 artículos. food (in general) as well as between antihypertensive Resultados: Tras la exclusión de diferentes artículos agents and grapefruit juice. que no estaban centrados en el objetivo específico, los Discussion: Food may affect the bioavailability of anti- resultados principales se refieren a las interacciones entre hypertensive drugs and this should be carefully consid- los fármacos antiarrítmicos y alimentos en general y ered. Advising patients to remove the grapefruit juice entre dichos fármacos y el zumo de pomelo. from their diet when treatment with these drugs seems to Discusión: Los alimentos pueden afectar a la biodispo- be the best recommendation. Given these interactions nibilidad de los fármacos antihipertensivos y ello debe ser and the associated potential adverse effects the anamnesis considerado cuidadosamente. Advertir a los pacientes must include detailed information about the specific que supriman el zumo de pomelo en su dieta cuando están eating habits of the patients. en tratamiento con estos fármacos parece la mejor reco- (Nutr Hosp. 2012;27:1866-1875) mendación. Dadas estas interacciones y sus potenciales efectos adversos, la anamnesis debe incluir información DOI:10.3305/nh.2012.27.6.6127 detallada sobre los hábitos alimentarios de los pacientes. Key words: Antihypertensive drugs. Food-drugs interac- (Nutr Hosp. 2012;27:1866-1875) tions. Grapefruit juice. Diet. DOI:10.3305/nh.2012.27.6.6127 Palabras clave: Fármacos antihipertensivos. Interacciones entre alimentos y medicamentos. Zumo de pomelo. Dieta. Abbreviations AT1 receptor: Angiotensin 1 receptor. AUC: Area under the curve (Area under the plasma ACE: Angiotensin-converting enzyme. concentration time curve). ARBs: Angiotensin II receptor blockers. BA: Bioavailability. BP: Blood pressure. Correspondence: I. Jáuregui-Lobera. Cmax: Maximum plasma concentration. Bromatology and Nutrition. cGMP: cyclic guanosine monophosphate. Pablo de Olavide University. CYP: Cytochrome P450 gene family. Virgen del Monte, 31. 41011 Seville. Spain. DASH: Dietary Approach to Stop Hypertension. E-mail: [email protected] / [email protected] DBP: Diastolic blood pressure. Recibido: 21-VIII-2012. HT: Hypertension. Aceptado: 24-VIII-2012. IP3: Inositol triphosphate. 1866 11. INTERACTIONS:01. Interacción 29/11/12 14:38 Página 1867 NaCl: Sodium chloride, common salt. and inhibitors of the CYP system, so the association of OAT: Organic anion transporter. antihypertensive drugs with other drugs and/or food OCT: Organic cation transporter. which use the CYP for their metabolism may be toxic. P-gp: P-glycoprotein. Together with CYP, it should be noted, due to its meta- SBP: Systolic blood pressure. bolic importance, the P-glycoprotein (P-gp), a family of t1/2: Drug elimination half-life. membrane transporters located in the brush border of the tmax: Time after administration of a drug when the enterocytes’ membranes. In addition to mobilizing maximum plasma concentration is reached. endogenous substances, the P-gp mobilizes certain drugs including some antihypertensive drugs.9-11 Drug interactions are defined as any alteration, phar- Introduction macokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary Hypertension (HT), which is defined as a chronic factors and habits such as drinking and smoking.12 elevation of systolic and/or diastolic blood pressure These interactions may affect the antihypertensive (BP), is in all probability the most common chronic drugs, modifying their therapeutic efficacy and the disease today. The main clinical significance of HT, adverse effects. which is not a disease in the usual sense of the word, The aim of this study was to conduct a review of lies on the future risk of vascular disease. Apart from available data about interactions between antihyper- various causes of HT, the most frequent case is the tensive drugs and food. essential HT (up to 95%).1,2 In the regulation of BP, there are different involving factors (sympathetic nervous system, kidney, hormonal Method systems), one of them being the composition of the diet. Thus, sodium, potassium, magnesium, lipids and total The review was conducted through a PubMed search. energy intake influence the control of BP.3 In the largest The initial search term was “Interactions between antihy- international study on the relationship between sodium pertensive drugs and food,” which resulted in a total of and BP (INTERSALT),4 the analysis of more than 337 articles. Later, other specific searches were 10,000 participants showed that a variation of 100 mmol performed, by entering “ Interactions between loop sodium intake modified the systolic BP (SBP) 2.2 diuretics and food”, “ Interactions between calcium mmHg, being lower the effect on diastolic BP (DBP). As channel blockers and food”, “Interactions between ACE for diet, one of the most relevant studies (DASH: Dietary inhibitors and food”, “Interactions between ARBs and Approaches to Stop Hypertension)5 showed that BP food”, “Interactions between hydralazine and food” and levels decreased with a diet low in saturated fat, choles- “Interactions between grapefruit juice and antihyperten- terol and total fat and high in fruits, vegetables and sive agents”. Having excluded the repeated articles, a total skimmed or semi-skimmed milk, that is a diet rich in of 236 articles were considered. Then those that did not magnesium, calcium, potassium, protein and fibre. In a make specific reference to the object of the review were later study (DASH-sodium),6 it was observed that with rejected. Articles without an abstract were also excluded. any level of sodium, the greatest reduction in BP was With respect to case reports and letters, because of the achieved with the DASH diet and even better with a scarcity of articles focusing specifically on a subject, sodium intake of only 1,500 mg of sodium per day. some of them were considered. Apart from the articles Regarding the treatment of HT, it is correct when its included after the search, some other articles and/or chap- continued efficacy is proven and it has minimal side ters were considered due to its relevance. effects. The goal is to achieve and maintain a SBP below 140 mmHg and a DBP below 90 mmHg.7 Apart from general measures of treatment (stress manage- Results ment, moderate salt restriction, regular exercise and moderate reduction of other risk factors) 8 there is a full Interactions between food and diuretics arsenal of antihypertensive drugs: diuretics, alpha and beta-blockers, calcium channel blockers, angiotensin- The simultaneous intake of food and some loop converting enzyme (ACE) inhibitors, angiotensin II diuretics such as furosemide and bumetanide causes a receptor blockers (ARBs) and others such as sodium decrease
Recommended publications
  • (12) United States Patent (10) Patent No.: US 6,784,177 B2 Cohn Et Al

    (12) United States Patent (10) Patent No.: US 6,784,177 B2 Cohn Et Al

    USOO6784177B2 (12) United States Patent (10) Patent No.: US 6,784,177 B2 Cohn et al. (45) Date of Patent: Aug. 31, 2004 (54) METHODS USING HYDRALAZINE Massie et al., The American Journal of Cardiology, COMPOUNDS AND SOSORBIDE 40:794-801 (1977). DINTRATE OR ISOSORBIDE Kaplan et al., Annals of Internal Medicine, 84:639-645 MONONTRATE (1976). Bauer et al., Circulation, 84(1):35-39 (1991). (75) Inventors: Jay N. Cohn, Minneapolis, MN (US); The SOLVD Investigators, The New England Journal of Medicine, 327(10):685–691 (1992). Peter Carson, Chevy Chase, MD (US) Ziesche et al., Circulation, 87(6):VI56-VI64 (1993). Rector et al., Circulation, 87(6):VI71-VI77 (1993). (73) Assignee: Nitro Med, Inc., Bedford, MA (US) Carson et al., Journal of Cardiac Failure, 5(3):178-187 (Sep. 10, 1999). (*) Notice: Subject to any disclaimer, the term of this Dries et al, The New England Journal of Medicine, patent is extended or adjusted under 35 340(8):609-616 (Feb. 25, 1999). U.S.C. 154(b) by 18 days. Freedman et al, Drugs, 54 (Supplement 3):41-50 (1997). Sherman et al., Cardiologia, 42(2):177-187 (1997). (21) Appl. No.: 10/210,113 Biegelson et al., Coronary Artery Disease, 10:241-256 (1999). (22) Filed: Aug. 2, 2002 Rudd et al, Am. J. Physiol., 277(46):H732–H739 (1999). (65) Prior Publication Data Hammerman et al, Am. J. Physiol., 277(46):H1579–1592 (1999). US 2004/0023967 A1 Feb. 5, 2004 LoScalzo et al., Transactions of the American and Climato logical ASS., 111:158-163 (2000).
  • Stems for Nonproprietary Drug Names

    Stems for Nonproprietary Drug Names

    USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol
  • Grayanotoxin Poisoning in Humans from Honey Consumption HELENA COLOMA DÍEZ AUTONOMOUS UNIVERSITY of BARCELONA

    Grayanotoxin Poisoning in Humans from Honey Consumption HELENA COLOMA DÍEZ AUTONOMOUS UNIVERSITY of BARCELONA

    Grayanotoxin Poisoning in Humans from Honey Consumption HELENA COLOMA DÍEZ AUTONOMOUS UNIVERSITY OF BARCELONA Objectives Structure, Types and Isolation of GTX The main objective of this bibliographic research is compiling and announcing information Grayanotoxins are non-volatile diterpenes, a about grayanotoxin-containing honey and the toxic effects derived from its ingestion. This polyhidroxylated cyclic hydrocarbon with a 5/7/6/5 ring substance is believed to have medicinal properties, and the current increment of use of structure that does not contain nitrogen, as seen on figure 2. There are 25 known isoforms of grayanotoxins, natural products as dietetic complements with this finality may cause a rising in the number GTX-I and GTX-III being the most common and of intoxication cases. So it is important learning to recognise the clinical signs it causes and abundant ones, followed by GTX-II. their treatment, apart from finding out if it may have medicinal applications. TheGTXcanbeisolatedbytypicalextraction procedures for naturally occurring terpenes, such as paper electrophoresis, thin-layer chromatography (TLC), and gas chromatography (GC). They require derivatization before GC analysis due to the Introduction compound’s instability on heating and having low vapor pressure. Other identification techniques are based on The poisoning caused by grayanotoxin-containing honey, called “mad honey”, is known from infrared (IR), nuclear magnetic resonance (NMR), and antiquity. This toxic honey has been used for different purposes, such as biological weapon mass spectrometry (MS). or therapeutical product. Figure 2. Structure formulas (left pannel) and 3D The origin of this toxin relays in some plants of the Rhododendron genus, widespread all representations (right pannel) of GTX-I, II and III.
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
  • Mad Honey Poisoning: a Review Rakesh Gami1* and Prajwal Dhakal2 1All Saints University, St

    Mad Honey Poisoning: a Review Rakesh Gami1* and Prajwal Dhakal2 1All Saints University, St

    linica f C l To o x l ic a o n r l o u g o y J Gami and Dhakal, J Clin Toxicol 2017, 7:1 Journal of Clinical Toxicology DOI: 10.4172/2161-0495.1000336 ISSN: 2161-0495 Review article Open Access Mad Honey Poisoning: A Review Rakesh Gami1* and Prajwal Dhakal2 1All Saints University, St. Vincent and The Grenadines 2Michigan State University, East Lansing, MI, USA *Corresponding author: Rakesh Gami, Assistant Professor, Department of Epidemiology, College of Medicine, All Saints University, St. Vincent and The Grenadines, Tel: +1-443-854-8522; E-mail: [email protected] Received date: January 01, 2017, Accepted date: January 19, 2017; Published date: January 20, 2017 Copyright: © 2017 Gami R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Mad honey, which is different from normal commercial honey, is contaminated with grayanotoxins and causes intoxication. It is used as an alternative therapy for hypertension, peptic ulcer disease and is also being used more commonly for its aphrodisiac effects. Grayanotoxins, found in rhododendron plant, act on sodium ion channels and place them in partially open state. They also act on muscarinic receptors. Cardiac manifestations of mad honey poisoning include hypotension and rhythm disorders such as bradycardia, nodal rhythm, atrial fibrillation, complete atrioventricular block or even complete heart block. Additionally, patients may develop dizziness, nausea and vomiting, weakness, sweating, blurred vision, diplopia and impaired consciousness.
  • Pharmaceutical Appendix to the Tariff Schedule 2

    Pharmaceutical Appendix to the Tariff Schedule 2

    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
  • Medical Marijuana… Fact Versus Fiction

    Medical Marijuana… Fact Versus Fiction

    MEDICAL MARIJUANA… FACT VERSUS FICTION Thomas F. Jan, DO, FAOCPMR Subspecialty Certified– Pain Medicine Diplomate – American Board of Addiction Medicine MASSAPEQUA PAIN MANAGEMENT AND REHABILITATION ADMINISTRATIVE DIRECTOR-CHRONIC PAIN MANAGEMENT 4200 SUNRISE HIGHWAY MATHER HOSPITAL-NORTHWELL HEALTH MASSAPEQUA, NY 11758 PORT JEFFERSON, NY 516-541-1064 THE I LOVE ME SLIDE: THOMAS F. JAN, DO, FAOCPMR, FKIA • 20 years private practice, board certified in pain medicine and addiction medicine • Current Chair, American Osteopathic Pain Medicine Conjoint Exam Committee • Administrative Director for Chronic Pain Management, John T. Mather Hospital, Port Jefferson, NY • Core faculty, PM&R residency program, Mercy Medical Center, Catholic Health System • Leadership Council, Long Island Council on Alcoholism and Drug Dependence (LICADD) • Medical Director, LICADD Opioid Overdose Prevention Program • Member, Nassau County, NY, County Executive's task force on Heroin and Prescription drug abuse • Former Medical Director, Town of Babylon Drug and Alcohol Program Disclosures: Speaker Bureau, US WorldMeds, Lucemyra OBJECTIVES A brief history of marijuana and its medical uses throughout history How does one get certified to prescribe medical marijuana Discussion about the endocannabinoid system (ECS) What receptors are there and what are they purported to do How do the various options affect the body through the ECS What are the risks involved and some discussion about the science MEDICAL MARIJUANA FOR OPIATE ADDICTION “I prescribed the cannabis simply
  • Interactions Between Antihypertensive Drugs and Food B

    Interactions Between Antihypertensive Drugs and Food B

    11. INTERACTIONS:01. Interacción 29/11/12 14:38 Página 1866 Nutr Hosp. 2012;27(5):1866-1875 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Revisión Interactions between antihypertensive drugs and food B. Jáuregui-Garrido1 and I. Jáuregui-Lobera2 1Department of Cardiology. University Hospital Virgen del Rocío. Seville. Spain. 2Bromatology and Nutrition. Pablo de Olavide University. Seville. Spain. Abstract INTERACCIONES ENTRE FÁRMACOS ANTIHIPERTENSIVOS Y ALIMENTOS Objective: A drug interaction is defined as any alter- ation, pharmacokinetics and/or pharmacodynamics, Resumen produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. Objetivo: la interacción de medicamentos se define como These interactions can affect the antihypertensive drugs, cualquier alteración, farmacocinética y/o farmacodiná- altering their therapeutic efficacy and causing toxic mica, producida por diferentes sustancias, otros tratamien- effects. The aim of this study was to conduct a review of tos, factores dietéticos y hábitos como beber y fumar. Estas available data about interactions between antihyperten- interacciones pueden afectar a los fármacos antihipertensi- sive agents and food. vos, alterando su eficacia terapéutica y causando efectos Methods: The purpose of this review was to report an tóxicos. El objetivo de este estudio fue realizar una revisión update of main findings with respect to the interactions de los datos disponibles acerca de las interacciones entre los between food and antihypertensive drugs
  • Interaction of Batrachotoxin with the Local Anesthetic Receptor Site in Transmembrane Segment IVS6 of the Voltage-Gated Sodium Channel

    Interaction of Batrachotoxin with the Local Anesthetic Receptor Site in Transmembrane Segment IVS6 of the Voltage-Gated Sodium Channel

    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 13947–13952, November 1998 Pharmacology Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel NANCY J. LINFORD,ANGELA R. CANTRELL,YUSHENG QU,TODD SCHEUER, AND WILLIAM A. CATTERALL* Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195-7280 Contributed by William A. Catterall, September 28, 1998 ABSTRACT The voltage-gated sodium channel is the site these sodium channel binding sites are distinct, allosteric of action of more than six classes of neurotoxins and drugs interactions among the sites modulate drug and toxin binding that alter its function by interaction with distinct, allosteri- (10–15). Neurotoxin receptor site 2 binds neurotoxins that cally coupled receptor sites. Batrachotoxin (BTX) is a steroi- cause persistent activation of sodium channels, including ba- dal alkaloid that binds to neurotoxin receptor site 2 and trachotoxin (BTX), veratridine, aconitine, and grayanotoxin causes persistent activation. BTX binding is inhibited allos- (10, 12, 16). BTX is a steroidal alkaloid from the skin secre- terically by local anesthetics. We have investigated the inter- tions of South American frogs of the genus Phyllobates (16). action of BTX with amino acid residues I1760, F1764, and Binding of BTX shifts the voltage dependence of sodium Y1771, which form part of local anesthetic receptor site in channel activation in the negative direction, blocks inactiva- transmembrane segment IVS6 of type IIA sodium channels. tion, and alters ion selectivity (17–20). Its binding to site 2 is Alanine substitution for F1764 (mutant F1764A) reduces a nearly irreversible and is highly dependent on the state of the tritiated BTX-A-20- -benzoate binding affinity, causing a channel with a strong preference for open sodium channels.
  • The Organic Chemistry of Drug Synthesis

    The Organic Chemistry of Drug Synthesis

    THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS VOLUME 3 DANIEL LEDNICER Analytical Bio-Chemistry Laboratories, Inc. Columbia, Missouri LESTER A. MITSCHER The University of Kansas School of Pharmacy Department of Medicinal Chemistry Lawrence, Kansas A WILEY-INTERSCIENCE PUBLICATION JOHN WILEY AND SONS New York • Chlchester • Brisbane * Toronto • Singapore Copyright © 1984 by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada. Reproduction or translation of any part of this work beyond that permitted by Section 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. Library of Congress Cataloging In Publication Data: (Revised for volume 3) Lednicer, Daniel, 1929- The organic chemistry of drug synthesis. "A Wiley-lnterscience publication." Includes bibliographical references and index. 1. Chemistry, Pharmaceutical. 2. Drugs. 3. Chemistry, Organic—Synthesis. I. Mitscher, Lester A., joint author. II. Title. [DNLM 1. Chemistry, Organic. 2. Chemistry, Pharmaceutical. 3. Drugs—Chemical synthesis. QV 744 L473o 1977] RS403.L38 615M9 76-28387 ISBN 0-471-09250-9 (v. 3) Printed in the United States of America 10 907654321 With great pleasure we dedicate this book, too, to our wives, Beryle and Betty. The great tragedy of Science is the slaying of a beautiful hypothesis by an ugly fact. Thomas H. Huxley, "Biogenesis and Abiogenisis" Preface Ihe first volume in this series represented the launching of a trial balloon on the part of the authors. In the first place, wo were not entirely convinced that contemporary medicinal (hemistry could in fact be organized coherently on the basis of organic chemistry.
  • Signed Dissertation Title Page Debi Hudgens

    Signed Dissertation Title Page Debi Hudgens

    Di- and Mono- Phenyl Amine Based Sodium Channel Blockers for the Treatment of Pain Debjani Patangia Hudgens Little Rock, AR B.S., University of Arkansas, 2000 A Dissertation presented to the Graduate Faculty of the University of Virginia in Candidacy for the Degree of Doctor of Philosophy Department of Chemistry University of Virginia January, 2007 Acknowledgements I would like to thank the collaborative efforts of several groups who have made this body of work possible. Chapters 2 & 3 All of the [3H]-BTX and [3H]-norepinephrine binding assays were conducted by Novascreen Biosciences, Inc. A great deal of thanks goes the laboratory of Dr. Manoj K. Patel, particularly Catherine Taylor and Dr. Timothy Batts, for the electrophysiological work conducted on sodium channels. Merck, Division of Ion Channel Research, carried out all of the fluorescence based assay work in collaborative efforts with the Brown lab. The NIH screening program at NINDS was responsible for anticonvulsant and toxicity screening in animal models. I would also like to thank the work of Dr. Steve White’s lab, particularly Misty Smith-Yockman, whose efforts in conjunction with NIH has provided for screening in animal models of inflammatory pain. Chapter 5 I would like to thank my advisor, Dr. Milton Brown, for help with the CoMFA model and prediction of future analogues. All of the [3H]-BTX binding assays were conducted by Novascreen Biosciences, Inc. Electrophysiological screening in calcium channels was conducted in the laboratory of Dr. Yong Kim, with special thanks to Nathan Lewis and Maiko Sakai. Chapter 6 I would also like to thank Dr.
  • (12) United States Patent (10) Patent No.: US 6,635,273 B1 Loscalz0 Et Al

    (12) United States Patent (10) Patent No.: US 6,635,273 B1 Loscalz0 Et Al

    USOO6635273B1 (12) United States Patent (10) Patent No.: US 6,635,273 B1 LOScalZ0 et al. (45) Date of Patent: Oct. 21, 2003 (54) METHODS OF TREATING VASCULAR Dries et al, The New England Journal of Medicine, DISEASES CHARACTERIZED BY NITRIC 340(8):609-616 (Feb. 25, 1999). OXDE INSUFFICIENCY Freedman et al, Drugs, 54(Supp. 3):41-50 (1997). Sherman et al., Cardiologia, 42(2):177-187 (1997). (75) Inventors: Joseph Loscalzo, Dover, MA (US); Biegelson et al., Coronary Artery Disease, 10:241-256 Joseph A. Vita, Hingham, MA (US); (1999). Michael D. Loberg, Boston, MA (US); Rudd et al, Am. J. Physiol., 277(46):H732–H739 (1999). Manuel Worcel, Boston, MA (US) Hammerman et al, Am. J. Physiol., 277(46):H1579-H1592 (1999). (73) Assignees: Trustees of Boston University, Boston, LoScalzo et al., Transactions of the American and Climato MA (US); NitroMed, Inc., Bedford, logical ASS., 111:158-163 (2000). MA (US) Cohn et al, The New England Journal of Medicine, 325(5):303-310 (1991). (*) Notice: Subject to any disclaimer, the term of this Cohn et al, The New England Journal of Medicine , patent is extended or adjusted under 35 314(24): 1547–1552 (1986). U.S.C. 154(b) by 0 days. Carson et al., Circulation, Supplement I, 92(8):I31-I32, Abstract No. 0145 (1995). (21) Appl. No.: 09/697,317 (List continued on next page.) (22) Filed: Oct. 27, 2000 Primary Examiner-Jon P. Weber Related U.S. Application Data ASSistant Examiner-Kalash C. Srivastava (60) Provisional application No. 60/179,020, filed on Jan.