Drug Class Review on Calcium Channel Blockers

Total Page:16

File Type:pdf, Size:1020Kb

Drug Class Review on Calcium Channel Blockers Drug Class Review on Calcium Channel Blockers Final Report Update 2 March 2005 Original Report Date: September 2003 Update 1 Report Date: June 2004 A literature scan of this topic is done periodically The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Marian S. McDonagh, PharmD Karen B. Eden, PhD Kim Peterson, MS Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2005 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved. Note: A scan of the medical literature relating to the topic is done periodically (see http://www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/methods.cfm for scanning process description). Upon review of the last scan, the Drug Effectiveness Review Project governance group elected not to proceed with another full update of this report. Some portions of the report may not be up to date. Prior versions of this report can be accessed at the DERP website. Final Report Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION........................................................................................................................... 4 Scope and Key Questions........................................................................................ 5 METHODS ...................................................................................................................................... 5 Literature Search................................................................................................................. 5 Study Selection ................................................................................................................... 5 Data Abstraction ................................................................................................................. 6 Validity Assessment............................................................................................................7 Data Synthesis..................................................................................................................... 7 RESULTS ........................................................................................................................................ 7 Overview .......................................................................................................................................... 7 Key Question 1: Effectiveness........................................................................................................ 8 Essential Hypertension........................................................................................................8 Angina....................................................................................................................... ……18 Supraventricular Arrhythmias........................................................................................... 23 Systolic Dysfunction......................................................................................................... 25 Key Question 2: Safety and Adverse Events .............................................................................. 28 Essential Hypertension...................................................................................................... 29 Angina....................................................................................................................... ……31 Supraventricular Arrhythmias........................................................................................... 31 Systolic Dysfunction......................................................................................................... 32 Evidence from Observational Studies............................................................................... 34 Key Question 3: Subgroups.......................................................................................................... 39 Essential Hypertension...................................................................................................... 39 Angina....................................................................................................................... ……41 Supraventricular Arrhythmias........................................................................................... 41 Systolic Dysfunction......................................................................................................... 41 SUMMARY ................................................................................................................................... 42 REFERENCES.............................................................................................................................. 44 IN-TEXT TABLES Table 1. All-cause mortality in patients with hypertension ........................................................... 11 Table 2. Cardiovascular disease mortality in patients with hypertension ...................................... 12 Table 3. Myocardial infarction in patients with hypertension ....................................................... 13 Table 4. Stroke in patients with hypertension ................................................................................ 14 Table 5. Heart failure in patients with hypertension ...................................................................... 15 Table 6. End stage renal disease in patients with hypertension ..................................................... 15 Table 7. Quality of life in patients with hypertension .................................................................... 16 Table 8. Active control trials of chronic stable angina ................................................................... 21 Table 9. Placebo-controlled trials of systolic dysfunction.............................................................. 28 Table 10. Observational studies of mortality .................................................................................. 37 Table 11. Strength of the evidence by key question ....................................................................... 42 FIGURES Figure 1. Results of literature search .............................................................................................. 56 Figure 2. All-cause mortality in hypertensives (CCB vs diuretic and/or beta-blocker).................. 57 Figure 3. All-cause mortality in hypertensives (CCB vs ACE inhibitor) ....................................... 58 Figure 4. Mean change in weekly angina attacks ........................................................................... 59 Calcium Channel Blockers Update #2 Page 2 of 194 Final Report Drug Effectiveness Review Project Figure 5. Mean change in weekly nitroglycerin doses ................................................................... 60 Figure 6. Mean change in time to angina onset .............................................................................. 61 Figure 7. Final ventricular rate plot ................................................................................................ 62 Figure 8. Flushing in hypertensives ................................................................................................ 63 Figure 9. Dizziness in hypertensives............................................................................................... 64 Figure 10. Headache in hypertensives ............................................................................................ 65 Figure 11. Edema in hypertensives................................................................................................. 66 Figure 12. Withdrawals due to adverse events in hypertension active-controlled trials of CCBs vs diuretics or beta-blockers............................................................................... 67 Figure 13. Withdrawals due to adverse events in hypertension active-controlled trials of CCBs vs ACE inhibitors............................................................................................... 68 Figure 14. Overall AE incidence in head-to-head trials of patients with angina ............................ 69 Figure 15. Withdrawal due to AE in head-to-head trials of patients with angina........................... 70 Figure 16. Edema incidence in head-to-head angina trials ............................................................. 71 Figure 17. Edema incidence in systolic dysfunction trials.............................................................. 72 Figure 18. Withdrawal rates in systolic dysfunction trials.............................................................. 73 APPENDICES Appendix A. Search strategy .......................................................................................................... 74 Appendix B. Quality assessment methods for drug class reviews.................................................. 77 Appendix C. Reports of trials excluded.......................................................................................... 81 Appendix D. Articles available as abstracts only.......................................................................... 187 Appendix E. Studies of quality of life with duration
Recommended publications
  • Selective Mtorc2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival
    Author Manuscript Published OnlineFirst on January 22, 2018; DOI: 10.1158/0008-5472.CAN-17-2388 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Selective mTORC2 inhibitor therapeutically blocks breast cancer cell growth and survival Thomas A. Werfel1, 3, Shan Wang2, Meredith A. Jackson1, Taylor E. Kavanaugh1, Meghan Morrison Joly3, Linus H. Lee1, Donna J. Hicks3, Violeta Sanchez4, Paula Gonzalez Ericsson4, Kameron V. Kilchrist1, Somtochukwu C. Dimobi1, Samantha M. Sarett1, Dana Brantley-Sieders2, Rebecca S. Cook1,3,4* and Craig L. Duvall1* 1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232 USA 2Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.USA 3Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 USA 4Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 USA Running Title: A selective mTORC2 inhibitor blocks breast cancer growth Key Words: Breast Cancer, mTOR, Rictor, RNA interference, Nanomedicine *To whom correspondence should be addressed: Craig L. Duvall, PhD Vanderbilt University School of Engineering Department of Biomedical Engineering Nashville, TN 37232 Phone: (615) 322-3598 Fax: (615) 343-7919 Email: [email protected] Rebecca S. Cook, PhD Vanderbilt University Medical Center Department of Cancer Biology Nashville, TN 37232 Phone: (615) 936-3813 Fax: (615) 936-3811 Email: [email protected] Funding. This work was supported by Specialized Program of Research Excellence (SPORE) grant NIH P50 CA098131 (VICC), Cancer Center Support grant NIH P30 CA68485 (VICC), NIH F31 CA195989-01 (MMW), NIH R01 EB019409, DOD CDMRP OR130302, NSF GFRP 1445197, and CTSA UL1TR000445 from the National Center for Advancing Translational Sciences.
    [Show full text]
  • Angiotensin-Converting Enzyme (ACE) Inhibitors Single Entity Agents
    Therapeutic Class Overview Angiotensin-Converting Enzyme (ACE) Inhibitors Single Entity Agents Therapeutic Class Overview/Summary: The renin-angiotensin-aldosterone system (RAAS) is the most important component in the homeostatic regulation of blood pressure.1,2 Excessive activity of the RAAS may lead to hypertension and disorders of fluid and electrolyte imbalance.3 Renin catalyzes the conversion of angiotensinogen to angiotensin I. Angiotensin I is then cleaved to angiotensin II by angiotensin- converting enzyme (ACE). Angiotensin II may also be generated through other pathways (angiotensin I convertase).1 Angiotensin II can increase blood pressure by direct vasoconstriction and through actions on the brain and autonomic nervous system.1,3 In addition, angiotensin II stimulates aldosterone synthesis from the adrenal cortex, leading to sodium and water reabsorption. Angiotensin II exerts other detrimental cardiovascular effects including ventricular hypertrophy, remodeling and myocyte apoptosis.1,2 The ACE inhibitors block the conversion of angiotensin I to angiotensin II, and also inhibit the breakdown of bradykinin, a potent vasodilator.4 Evidence-based guidelines recognize the important role that ACE inhibitors play in the treatment of hypertension and other cardiovascular and renal diseases. With the exception of Epaned® (enalapril solution) and Qbrelis® (lisinopril solution), all of the ACE inhibitors are available generically. Table 1. Current Medications Available in Therapeutic Class5-19 Generic Food and Drug Administration
    [Show full text]
  • Drug Class Review Antianginal Agents
    Drug Class Review Antianginal Agents 24:12.08 Nitrates and Nitrites 24:04.92 Cardiac Drugs, Miscellaneous Amyl Nitrite Isosorbide Dinitrate (IsoDitrate ER®, others) Isosorbide Mononitrate (Imdur®) Nitroglycerin (Minitran®, Nitrostat®, others) Ranolazine (Ranexa®) Final Report May 2015 Review prepared by: Melissa Archer, PharmD, Clinical Pharmacist Carin Steinvoort, PharmD, Clinical Pharmacist Gary Oderda, PharmD, MPH, Professor University of Utah College of Pharmacy Copyright © 2015 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved. Table of Contents Executive Summary ......................................................................................................................... 3 Introduction .................................................................................................................................... 4 Table 1. Antianginal Therapies .............................................................................................. 4 Table 2. Summary of Agents .................................................................................................. 5 Disease Overview ........................................................................................................................ 8 Table 3. Summary of Current Clinical Practice Guidelines .................................................... 9 Pharmacology ............................................................................................................................... 10 Table 4. Pharmacokinetic Properties
    [Show full text]
  • Interactions Medicamenteuses Index Des Classes Pharmaco
    INTERACTIONS MEDICAMENTEUSES INDEX DES CLASSES PHARMACO-THERAPEUTIQUES Mise à jour avril 2006 acides biliaires (acide chenodesoxycholique, acide ursodesoxycholique) acidifiants urinaires adrénaline (voie bucco-dentaire ou sous-cutanée) (adrenaline alcalinisants urinaires (acetazolamide, sodium (bicarbonate de), trometamol) alcaloïdes de l'ergot de seigle dopaminergiques (bromocriptine, cabergoline, lisuride, pergolide) alcaloïdes de l'ergot de seigle vasoconstricteurs (dihydroergotamine, ergotamine, methylergometrine) alginates (acide alginique, sodium et de trolamine (alginate de)) alphabloquants à visée urologique (alfuzosine, doxazosine, prazosine, tamsulosine, terazosine) amidons et gélatines (gelatine, hydroxyethylamidon, polygeline) aminosides (amikacine, dibekacine, gentamicine, isepamicine, kanamycine, netilmicine, streptomycine, tobramycine) amprénavir (et, par extrapolation, fosamprénavir) (amprenavir, fosamprenavir) analgésiques morphiniques agonistes (alfentanil, codeine, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol) analgésiques morphiniques de palier II (codeine, dextropropoxyphene, dihydrocodeine, tramadol) analgésiques morphiniques de palier III (alfentanil, dextromoramide, fentanyl, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil) analogues de la somatostatine (lanreotide, octreotide) androgènes (danazol, norethandrolone, testosterone) anesthésiques volatils halogénés
    [Show full text]
  • Supplementary Information
    Supplementary Information Network-based Drug Repurposing for Novel Coronavirus 2019-nCoV Yadi Zhou1,#, Yuan Hou1,#, Jiayu Shen1, Yin Huang1, William Martin1, Feixiong Cheng1-3,* 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA 2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA 3Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA #Equal contribution *Correspondence to: Feixiong Cheng, PhD Lerner Research Institute Cleveland Clinic Tel: +1-216-444-7654; Fax: +1-216-636-0009 Email: [email protected] Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. Supplementary Table S2. Protein sequence identities across 5 protein regions in 15 coronaviruses. Supplementary Table S3. HCoV-associated host proteins with references. Supplementary Table S4. Repurposable drugs predicted by network-based approaches. Supplementary Table S5. Network proximity results for 2,938 drugs against pan-human coronavirus (CoV) and individual CoVs. Supplementary Table S6. Network-predicted drug combinations for all the drug pairs from the top 16 high-confidence repurposable drugs. 1 Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. GenBank ID Coronavirus Identity % Host Location discovered MN908947 2019-nCoV[Wuhan-Hu-1] 100 Human China MN938384 2019-nCoV[HKU-SZ-002a] 99.99 Human China MN975262
    [Show full text]
  • List of Union Reference Dates A
    Active substance name (INN) EU DLP BfArM / BAH DLP yearly PSUR 6-month-PSUR yearly PSUR bis DLP (List of Union PSUR Submission Reference Dates and Frequency (List of Union Frequency of Reference Dates and submission of Periodic Frequency of submission of Safety Update Reports, Periodic Safety Update 30 Nov. 2012) Reports, 30 Nov.
    [Show full text]
  • Health Reports for Mutual Recognition of Medical Prescriptions: State of Play
    The information and views set out in this report are those of the author(s) and do not necessarily reflect the official opinion of the European Union. Neither the European Union institutions and bodies nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein. Executive Agency for Health and Consumers Health Reports for Mutual Recognition of Medical Prescriptions: State of Play 24 January 2012 Final Report Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Acknowledgements Matrix Insight Ltd would like to thank everyone who has contributed to this research. We are especially grateful to the following institutions for their support throughout the study: the Pharmaceutical Group of the European Union (PGEU) including their national member associations in Denmark, France, Germany, Greece, the Netherlands, Poland and the United Kingdom; the European Medical Association (EMANET); the Observatoire Social Européen (OSE); and The Netherlands Institute for Health Service Research (NIVEL). For questions about the report, please contact Dr Gabriele Birnberg ([email protected] ). Matrix Insight | 24 January 2012 2 Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Executive Summary This study has been carried out in the context of Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross- border healthcare (CBHC). The CBHC Directive stipulates that the European Commission shall adopt measures to facilitate the recognition of prescriptions issued in another Member State (Article 11). At the time of submission of this report, the European Commission was preparing an impact assessment with regards to these measures, designed to help implement Article 11.
    [Show full text]
  • Mechanism of Action of Nicotine in Isolated Urinary Bladder of Guinea-Pig
    Br. J. Pharmacol. (1988), 95, 465-472 Mechanism of action of nicotine in isolated urinary bladder of guinea-pig Tetsuhiro Hisayama, Michiko Shinkai, lIssei Takayanagi & Toshie Toyoda Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1, Miyama, Funabashi, Chiba 274, Japan 1 Nicotine produced a transient contraction of isolated strips of guinea-pig urinary bladder. The response to nicotine was antagonized by the nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin. 2 The nicotine-induced contraction was potentiated by the cholinesterase inhibitor, physostig- mine, and was reduced to 50% and 70% by the muscarinic cholinoceptor antagonist, atropine and the sympathetic neurone blocking drug, guanethidine, respectively. Chemical denervation with 6- hydroxydopamine abolished the inhibitory effect of guanethidine. Simultaneous treatment with atropine and guanethidine did not abolish the response to nicotine, but the degree of inhibition was comparable to that obtained with atropine alone. 3 The nicotine-induced contraction was insensitive to bunazosin and yohimbine (al- and Cc2-adrenoceptor antagonists, respectively), and exogenously applied noradrenaline did not cause a contraction even in the presence of blockade of noradrenaline uptake mechanisms with desipramine and normetanephrine and of fi-adrenoceptors with propranolol, suggesting a non-adrenergic nature of the sympathomimetic effect of nicotine in this tissue. 4 The nicotine-induced contraction in the presence of atropine was abolished after desensitization of P2-purinoceptors with a, ,B-methylene adenosine 5'-triphosphate, a slowly degradable ATP ana- logue selective for P2-purinoceptors. By this desensitization, the response to ATP, but not to hista- mine, was also abolished. 5 A cyclo-oxygenase inhibitor flurbiprofen partially inhibited the nicotine-induced contraction.
    [Show full text]
  • Summary of Product Characteristics
    SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT *IPERTEN/ARTEDIL/MANYPER 10mg tablets IPERTEN/ARTEDIL/MANYPER 20mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION IPERTEN/ARTEDIL/MANYPER 10 mg tablets Each tablet contains: Manidipine hydrochloride 10mg Excipient with known effect: 119,61 mg lactose monohydrate/tablet IPERTEN/ARTEDIL/MANYPER 20 mg tablets Each tablet contains: Manidipine hydrochloride 20mg Excipient with known effect: 131,80 mg lactose monohydrate/tablet For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet IPERTEN/ARTEDIL/MANYPER 10mg: pale yellow, round, scored tablet; IPERTEN/ARTEDIL/MANYPER 20mg: yellow-orange, oblong, scored tablet. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Mild to moderate essential hypertension 4.2 Posology and method of administration The recommended starting dose is 10 mg once a day. Should the antihypertensive effect be still insufficient after 2-4 weeks of treatment, it is advisable to increase the dosage to the usual maintenance dose of 20 mg once a day. Elderly In view of the slowing down of metabolism in the elderly, the recommended dose is 10mg once daily. This dosage is sufficient in most elderly patients; the risk/benefit of any dose increase should be considered with caution on an individual basis. Renal impairment In patients with mild to moderate renal dysfunction care should be taken when increasing the dosage from 10 to 20mg once a day. Hepatic impairment Due to the extensive hepatic metabolisation of manidipine, patients with mild hepatic dysfunction should not exceed 10mg once a day (see also Section 4.3 Contraindications). Tablet must be swallowed in the morning after breakfast, without chewing it, with a few liquid.
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 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. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • WO 2012/044761 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date _ . 5 April 2012 (05.04.2012) WO 2012/044761 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 47/48 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/US201 1/053876 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, 29 September 201 1 (29.09.201 1) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (25) Filing Language: English NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (26) Publication Langi English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (30) Priority Data: ZM, ZW. 12/893,344 29 September 2010 (29.09.2010) US (84) Designated States (unless otherwise indicated, for every (71) Applicant (for all designated States except US): UNI¬ kind of regional protection available): ARIPO (BW, GH, VERSITY OF NORTH CAROLINA AT WILMING¬ GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, TON [US/US]; 601 South College Road, Wilmington, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, NC 28403 (US).
    [Show full text]
  • And Angiotensin II- Induced Changes by Calcium Antagonists in the Peripheral Circulation Ofanaesthetized Rabbits Robert P
    Br. J. Pharmac. (1985), 85, 75-87 Modification ofvasopressin- and angiotensin II- induced changes by calcium antagonists in the peripheral circulation ofanaesthetized rabbits Robert P. Hof Cardiovascular Unit of Preclinical Research, Sandoz Ltd, CH-4002 Basel, Switzerland 1 Investigations into the site of vasodilator and antivasoconstrictor activity of calcium antagonists previously performed in cats were extended to a second species, barbiturate-anaesthetized rabbits, and a second vasoconstrictor agent, vasopressin. 2 The dihydropyridine derivative darodipine (code name PY 108-068; 10, 30 and 100 pg kg-' i.v.) showed systemic haemodynamic effects comparable to those seen in cats at half these doses. Darodipine effected regional vasodilatation (measured with tracer microspheres) in the heart, brain and skeletal muscles as in cats. Only the vessels of the adrenals (dilated in rabbits but not in cats), and the kidneys and skin (constricted in rabbits but not in cats) responded differently to darodipine. 3 Angiotensin II (A II; 0.15 and 1.5 yg kg- min ')constricted the same vascular beds in rabbits as in cats, namely the heart, kidneys, small intestine, pancreas, spleen, skin and arterio-venous shunts (inferred from microspheres reaching the lungs), the only exceptions being the vessels of the stomach and liver (constriction only in cats) and the adrenals (constriction only in rabbits). 4 Darodipine (30 and 100 yg kg-') attenuated the A II-induced vasoconstriction in the same vascular beds in rabbits as in cats including the kidneys, which were constricted after administration of the antagonist alone. 5 These results indicate surprisingly small species differences for the vasodilator effects of darodipine as well as the attenuation of the vasoconstrictor effects of A II.
    [Show full text]