High-Yield Pharmacology, Third Edition - MU-medical
Weiss FM i-xiv.qxd11/5/082:12 PMPage iHigh-YieldPharmacologyTHIRD EDITIONTM
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Weiss FM i-xiv.qxd11/5/082:12 PMPage iiiHigh-YieldTMPharmacologyTHIRD EDITIONStephanie T. Weiss, PhDCleveland Clinic Lerner College of MedicineCase Western Reserve UniversityCleveland, OhioFirst and Second Editions byDaryl Christ, PhDAssociate Professor of PharmacologySouth Bend Center for Medical EducationIndiana University School of MedicineNotre Dame, Indiana
Weiss FM i-xiv.qxd11/5/082:12 PMPage ivAcquisitions Editor: Charles W. MitchellManaging Editor: Kelley A. SquazzoMarketing Manager: Emilie MoyerAssociate Production Manager: Kevin P. JohnsonDesigner: Holly McLaughlinCompositor: International Typesetting and CompositionThird EditionCopyright 2009, 2004, 1999 Lippincott Williams & Wilkins, a Wolters Kluwer business.Second edition 2004, First edition 1999351 West Camden StreetBaltimore, MD 21201530 Walnut StreetPhiladelphia, PA 19106Printed in the United States of AmericaAll rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, orutilized by any information storage and retrieval system without written permission from the copyrightowner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this bookprepared by individuals as part of their official duties as U.S. government employees are not covered by theabove-mentioned copyright. To request permission, please contact Lippincott Williams & Wilkins at 530Walnut Street, Philadelphia, PA 19106, via email at permissions@lww.com, or via website at lww.com(products and services).9 8 7 6 5 4 3 2 1Library of Congress Cataloging-in-Publication DataWeiss, Stephanie T.High-yield pharmacology. — 3rd ed. / Stephanie T. Weiss.p. ; cm. — (High-yield series)Rev. ed. of: High-yield pharmacology / Daryl Christ. 2nd ed. c2004.Includes index.ISBN-13: 978-0-7817-9273-8ISBN-10: 0-7817-9273-81. Pharmacology—Outlines, syllabi, etc. I. Christ, Daryl. High-yield pharmacology.II. Title. III. Series.[DNLM: 1. Pharmacology—Outlines. QV 18.2 W429h 2009]RM301.14.C48 2009615'.1—dc222008032468DISCLAIMERCare has been taken to confirm the accuracy of the information present and to describe generally acceptedpractices. However, the authors, editors, and publisher are not responsible for errors or omissions or forany consequences from application of the information in this book and make no warranty, expressed orimplied, with respect to the currency, completeness, or accuracy of the contents of the publication.Application of this information in a particular situation remains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universalrecommendations.The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage setforth in this text are in accordance with the current recommendations and practice at the time of publication.However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drugfor any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug.Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)clearance for limited use in restricted research settings. It is the responsibility of the health care provider toascertain the FDA status of each drug or device planned for use in their clinical practice.To purchase additional copies of this book, call our customer service department at (800) 638-3030 or faxorders to (301) 223-2320. International customers should call (301) 223-2300.Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkinscustomer service representatives are available from 8:30 am to 6:00 pm, EST.
Weiss FM i-xiv.qxd11/5/082:12 PMPage vThis book is dedicated to the spirit of the Cleveland Clinic Lerner College of Medicine.
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Weiss FM i-xiv.qxd11/5/082:12 PMPage viiPrefaceThe discipline of pharmacology encompasses both how drugs affect the body (pharmacodynamics), as well as how the body affects drugs (pharmacokinetics). Because it is such an interdisciplinary field, pharmacology necessarily is built upon a foundation consisting of nearly every otherbasic science discipline that is part of a medical school curriculum. You must have a good grasp ofphysiology, pathology, biochemistry, microbiology, and molecular biology in order to study pharmacology. Even many disciplines that people have not traditionally associated with pharmacologyare turning out to be essential for understanding pharmacology, such as anatomy and genetics. Infact, one of the hottest areas in pharmacology right now is pharmacogenomics, where a patient’streatment is tailored based upon his or her unique genetic makeup.This edition of High-Yield Pharmacology has been substantially updated and revised. Specifically,new sections on biologics have been added in the appropriate chapters, as well as several new figures and tables. In addition, the cardiovascular pharmacology chapter has been expanded and splitin half, reflecting the rapid growth in the pharmacology of this area. Readers who desire a very briefreview can read the bolded printed text, which highlights the most important concepts in eachchapter. In addition, the index can be used to help you review the class of every drug in the book.It is unfortunate that many medical students approach pharmacology as just a list of drug namesand side effects that must be memorized for the United States Medical Licensing Examination. Youmay be using this book to review pharmacology for Step 1 of the USMLE, and I hope you will findit helpful as you prepare. But I also hope that it will give you at least an inkling of how interestingand dynamic the field of pharmacology is. Please feel free to contact me at weisss@ccf.org if youhave any comments or suggestions about the book.Stephanie T. Weissvii
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Weiss FM i-xiv.qxd11/5/082:12 PMPage ixAcknowledgmentsI would like to acknowledge the generosity of all the people whose help and support made thisbook possible.My reviewers:Lisa Potts, PharmDMike Militello, PharmDDan Sessler, MDKathy Franco, MDBill Stewart, MDMike Lincoff, MDAtul Khasnis, MDMario Skugor, MDGerri Hall, PhDBelinda Yen-Lieberman, PhDChristopher Lowe, PharmDFrank Peacock, MDPranaya Mishra, MPharm, PhDDonald Weiss, DOManaging Editor Kelley Squazzo and the staff at Lippincott Williams & WilkinsThe Weiss family: Alicia, Donald, Shelly, and Peanutix
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Weiss FM i-xiv.qxd11/5/082:12 PMPage xiContentsPreface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .viiAcknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ix1 General PrinciplesI.II.III.IV.V.VI.VII.VIII. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1Pharmacokinetics: General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1Pharmacokinetics: Administration and Absorption of Drugs . . . . . . . . . . . . . . . . . . . .1Pharmacokinetics: Distribution of Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4Pharmacokinetics: Metabolism of Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5Pharmacokinetics: Elimination of Drugs and Drug Metabolites . . . . . . . . . . . . . . . . . .6Pharmacodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8Age-Dependent Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11Regulations Governing the Development of New Drugs . . . . . . . . . . . . . . . . . . . . . . .122 Peripheral Neuropharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14I.II.III.IV.V.VI.VII.VIII.IX.X.XI.Overview of the Autonomic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14Parasympathomimetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17Cholinesterase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19Parasympathetic Blocking Drugs (Antimuscarinics) . . . . . . . . . . . . . . . . . . . . . . . . . .20Ganglionic Blocking Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21Neuromuscular Blocking Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22Sympathomimetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24α-Adrenoceptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26β-Adrenoceptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28Adrenergic Neuron-Blocking Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29Drugs for Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .303 Central Neuropharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31I.II.III.IV.V.VI.VII.VIII.Principles of General Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31Inhalation Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32Intravenous Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .34Local Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36Sedative–Hypnotic and Antianxiety Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38Anticonvulsants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40Antipsychotic Drugs (Neuroleptics) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42Lithium Carbonate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43xi
Weiss FM i-xiv.qxdxii11/5/082:12 PMPage xiiCONTENTSIX.X.XI.XII.Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .44CNS Stimulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46Drugs for Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47Drugs for Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .494 Substance Abuse and PainI.II.III.IV.V.VI.VII.VIII.IX.X.XI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50General Features of Substance Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50Sedative-Hypnotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50Cigarettes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53CNS Stimulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54Anabolic Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54Hallucinogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55Marijuana . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55Gamma-Hydroxybutyric Acid (GHB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56Narcotic Analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .57Analgesic Antipyretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .595 Cardiovascular PharmacologyI.II.III.IV.V.VI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62Calcium Channel Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .64Antihypertensives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65Drugs for Angina Pectoris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .70Drugs for Congestive Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .72Antiarrhythmics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .746 Pharmacology of Blood and Blood Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .80I.II.III.IV.V.VI.Anticoagulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .80Fibrinolytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84Antiplatelet Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84Antibleeding Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86Drugs for Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86Antihyperlipidemics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .877 Autacoids, Drugs for Inflammatoryand Gastrointestinal Disorders, and Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90I.II.III.IV.V.VI.VII.VIII.IX.X.XI.Definition of Autacoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90Histamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90Histamine Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90Antiasthmatic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91Eicosanoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .93Drugs for Migraine Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95Drugs for Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95Drugs for Gout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97Drugs for Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98Drugs for Gastrointestinal Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .99
Weiss FM i-xiv.qxd11/5/082:12 PMPage xiiiCONTENTS8 Endocrine PharmacologyI.II.III.IV.V.VI.VII.VIII.IX.X.xiii. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102Pituitary Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102Adrenocortical Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .104Female Sex Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106Fertility Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .108Male Sex Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109Thyroid Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109Calcium and Phosphate Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111Drugs for Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .113Drugs for Hypoglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116Drugs for Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1179 Drugs for Bacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . nciples of Bacterial Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .118Cell Wall Inhibitors: Penicillins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119Cell Wall Inhibitors: Cephalosporins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123Cell Wall Inhibitors: Other β-Lactams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125Cell Wall Inhibitors: Non β-Lactams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125Protein Synthesis (30S Ribosome) Inhibitors:Aminoglycosides and Spectinomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .126Protein Synthesis (30S Ribosome) Inhibitors: Tetracyclines . . . . . . . . . . . . . . . . . . .127Protein Synthesis (50S Ribosome) Inhibitors: Macrolides . . . . . . . . . . . . . . . . . . . .128Other Protein Synthesis (50S Ribosome) Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . .128DNA Gyrase Inhibitors: Quinolones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129Tetrahydrofolic Acid Synthesis Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .130Miscellaneous Antimicrobials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .132Drugs for Mycobacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13210 Drugs for Infections from Eukaryotic Organisms and Viruses . . . . . . . . . . . . . . . . . . .134I.II.III.IV.Antifungal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134Antiprotozoal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .136Anthelmintics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .137Antiviral Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13811 Cancer Chemotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142I. Principles of Cancer Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142II. Anticancer Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144III. Immunomodulators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14912 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .152I. Emergency Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .152II. Heavy Metal Toxicity and Chelators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .154III. Other Toxic Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .159
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Weiss Ch01 001-013.qxd8/27/0810:10 AMPage 1Chapter 124GeneralCervical PrinciplesNeoplasia and CancerIPharmacokinetics: General PrinciplesA. PHARMACOKINETICS is the study of the movement of drugs into and out of the body,including absorption (bioavailability), distribution, metabolism (biotransformation),and elimination (ADME).B. Clinical pharmacokinetics, which involves the mathematical description of theprocesses of ADME, is useful to predict the serum drug concentrations under variousconditions.C. PHARMACOKINETICS can be thought of as what the body does to the drug.IIPharmacokinetics: Administration and Absorption of DrugsA. Many routes of drug administration can be used.1. The oral route (PO) is usually preferred.a. Advantages include:i. Convenienceii. A large surface area for absorptioniii. Fewer abrupt changes of serum drug concentrations than with parenteral administrationb. Disadvantages include:i. First-pass metabolism by the liver(a) All the blood flow from the intestinal tract goes initially to the liverthrough the portal vein; therefore the drug may be metabolizedbefore being distributed to the other tissues in the body(b) First-pass metabolism of a drug can be avoided by parenteral administration of the drug and partially avoided by rectal administration.ii. Systemic exposure to the drug2. The parenteral routes of administration are technically more difficult and usuallymust be performed by a health care professional. Common methods are inhalation, sublingual, intravenous (IV), intramuscular (IM), and subcutaneous (SQ)administration.a. Advantages include:i. A faster onset (usually)ii. More reliable absorptioniii. No first-pass metabolismb. Disadvantages include:i. More difficult administration1
Weiss Ch01 001-013.qxd28/27/0810:10 AMPage 2CHAPTER 1ii.iii.iv.v.Pain or necrosis at the site of infectionPossibility of infectionToxicity from a bolus intravenous (IV) injectionNecessity of dissolving the drug if given intravenouslyB. Some drugs are actively or passively transported by carrier proteins, but the movementof drugs across cell membranes usually occurs passively by diffusion.C. THE RATE OF DIFFUSION IS HIGH IF:1. The unionized form of a drug has a high lipid solubility.a. Lipid solubility is related to the oil-water partition coefficient.b. Cell membranes are basically lipoidal in nature, and only lipid soluble substances will diffuse through them.2. A large proportion of the drug is present in the unionized form.a. Only the unionized form can cross cell membranes, because the ionizedform will have a very low solubility in lipids.b. The equilibrium between the ionized (A ) and unionized (HA) forms of a weakacid is:HA 4 H A c. The equilibrium constant (Ka) for the dissociation of an acid is defined as:Ka [A ][H ][HA]d. By taking the negative log (–log) of both sides of the Ka expression and rearranging, we can get the Henderson–Hasselbalch equation for a weak acid: pH pKa log [A ][HA]e. The proportion of unionized drug will depend on the pH and can be determined with the Henderson–Hasselbalch equation.f. Weak bases also dissociate, and the equation for dissociation of the conjugateacid of a weak base is:HB 4 H Bg. The equilibrium constant (Ka) for the dissociation of the conjugate acid of aweak base is defined as:Ka [B][H ][HB ]h. By taking the negative log (–log) of both sides of the Ka expression and rearranging, we can get the Henderson–Hasselbalch equation for a weak base:pH pKa log[B][HB ]i. Note that the conjugate base should always go in the numerator, while the conjugate acid belongs in the denominator.j. When the pH equals the pKa, 50% of a drug will be ionized and 50% will beunionized.k. The most dramatic changes in the amounts of ionized and unionized drugoccur with pH changes near the pKa.
Weiss Ch01 001-013.qxd8/27/0810:10 AMPage 3GENERAL PRINCIPLES3.4.5.6.7.3The membrane is thin.The membrane is porous. Porosity is especially important for water-soluble drugs.The surface area of the membrane is large.The difference in concentrations on the two sides of the membrane is large.The diffusion constant, based on molecular size, molecular shape, andtemperature, is large.D. At the basic pH in the small intestine1. Weak bases are well absorbed because most of the drug is unionized.2. Weak acids are poorly absorbed because most of the drug is ionized.3. The opposite scenario occurs in the acidic environment of the stomach; however,the stomach does not have a very large absorptive capability.E. ION TRAPPING occurs with weak acids and weak bases if there is a difference in pHon the two sides of a membrane.1. The ionized form of the drug will be trapped on one side.a. The ionized form of a weak base will be protonated and trapped on the sidewith the lower pH.b. The ionized form of a weak acid will be deprotonated and trapped on the sidewith the higher pH.2. Figure 1-1 illustrates ion trapping for a weak acid with a pKa of 6.4. At equilibrium,the unionized concentrations on either side of the membrane will be equal, but91% of the drug will be in the compartment at pH 7.4.F.STRONG BASES AND STRONG ACIDS are totally dissociated or ionized in solution;thus, they are poorly absorbed at any pH. Quaternary ammonium compounds arecompletely ionized at physiological pHs and therefore are also poorly absorbed.G. ABSORPTION OF A DRUG IS USUALLY FAST, as compared to the elimination; thus,it is often ignored in kinetic calculations. The rate of gastric emptying can affect theabsorption and bioavailability of a drug.H. BIOAVAILABILITY is the fraction of drug administered that reaches the systemiccirculation without being metabolized.1. Bioavailability (F) equation:F [drug] in the systemic circulation after oral administration[drug] in the systemic circulation after IV administrationCell membraneH A(100)pH 7.4HAHAH A-(10)(10)(1)pH 5.4 Figure 1-1 Ion trapping of a weak acid (pKa 6.4) on the side of the cell membrane with the higher pH. The numbersin parentheses represent the relative concentrations of each form of the weak acid under steady-state conditions.
Weiss Ch01 001-013.qxd48/27/0810:10 AMPage 4CHAPTER 1a. The bioavailability after oral administration depends oni. The disintegration of a tabletii. The dissolution of the drug in the intestinal contentsiii. Gastrointestinal and first-pass metabolismb. A drug that is administered by IV will be 100% bioavailable.2. Bioequivalence occurs when drugs with equal F have the same drug concentration versus time relationship (i.e., similar rate and extent of drug absorption).3. Therapeutic equivalence (TE) is commonly said to occur when two drugs havethe same maximal response; it may be different than bioequivalence. (Note that theFDA defines TE as having the same ingredients, dosage form, route of administration, and concentration.)IIIPharmacokinetics: Distribution of DrugsA. THE INITIAL DISTRIBUTION of a drug to the tissues is determined by the relative bloodflows to the tissues. Sites with high blood flows will initially receive more of the drug.B. THE VOLUME OF DISTRIBUTION Vd is an approximation of the hypothetical fluidvolume that a drug appears to distribute in.1. It can be very large, even larger than the total body volume, if a drug is highly boundto tissues. This makes the serum drug concentration very low and the Vd very large.2. The Vd must be calculated at the time of administration.a. Apparent volume of distribution equation:Vd amount of drug administeredserum [drug]b. For the drugs illustrated in Figure 1-2, if the same amount of each was administered, the concentration of drug A at time 0 will be lower; thus, it will havethe larger Vd (the numerator is constant, but the denominator is smaller for Athan for B). This occurs because more of drug A than drug B is distributed inextravascular tissue.10,000Plasma [drug]1,000100A10B10.10246Hours810 Figure 1-2 Relationship of plasma drug concentration versus time for two drugs. Drug A has the larger apparentvolume of distribution.
Weiss Ch01 001-013.qxd8/27/0810:10 AMPage 5GENERAL PRINCIPLES53. The loading dose for a drug is based on the Vd.V COral loading dose dFwhere C is the desired or target serum drug concentration and F is the bioavailability (fraction of administered drug in the blood).C. The final apparent volume of distribution (Vd) will be affected by1. The lipid solubility of a drug, which, if high, will result in good penetration intocells and a high Vd2. Plasma protein binding and tissue bindinga. Plasma protein binding, especially to albumin, will reduce the Vd.b. Tissue binding will increase the Vd.c. Both types of binding act as reservoirs for the drug, as only the unbound drugcan activate pharmacological receptors. Thus binding willi. Slow the onset of drug actionii. Prolong the duration of drug action, if the drug is eliminated by glomerular filtration in th
This edition of High-Yield Pharmacology has been substantially updated and revised. Specifically, new sections on biologics have been added in the appropriate chapters, as well as several new fig-ures and tables. In addition, the cardiovascular pharmacology chapter has been expanded and split
Small Grains and Grain Sorghum 39 their straw yield as much as on grain yield. In a study we did at DeKalb, we found that straw yield was affected both by plant height and by yield. The formula to predict straw yield based on height and grain yield was as follows: Straw yield (tons per acre) 0.018 grain yield
General Pharmacology Drugs acting on Autonomic Nervous System Cardiovascular Pharmacology Drugs acting on GI, respiratory system & CNS Endocrine pharmacology Chemotherapeutic & immunopharmacology Geriatric & Pediatric Pharmacology Lectures/Large Group Discussions Pharmacy: preparat
11. A Complete Textbook of Medical Pharmacology 2nd edition by Dr. S. K. Srivastava published by APC Avichal Publishing Company, 2017. 12. K.D. Tripathi, Essentials of Medical Pharmacology, 8th edition, Jaypee Brothers Medical Pub, 2018. 13. Modern Pharmacology with Clinical Applications, 6th edition, Craig Charles R. & Stitzel Robet E.,
Figure 3 Leveraged Loan Yield vs High Yield Bond Yield January 1992 - December 2012 Source: Credit Suisse 5 8 11 14 17 20 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 Y ield (%) Correlation 0.88 HY Yield-to-Worst CS Lev Loan Index Yield (Assumes 3-yr Re ) 12/31/12 6.25% 5.93% Figure 4 Cumulative Returns of Bonds, Loans and Equities
RP 2K, Second Edition RP 2L, Third Edition RP 2M, First Edition Bul 2N, First Edition RP 2P, Second Edition RP 2Q, Second Edition RP 2R, First Edition RP 2T, First Edition Bul 2U, First Edition Bul 2V, First Edition Spec 2W, First Edition RP 2X, First Edition, with Supp 1 Spec 2Y, First Edition
Meanwhile, the median high-yield EDF metric increased from January 17's 0.30% to March 11's 0.94%. The latter is the highest median high-yield EDF since the 0.95% of February 11, 2016. Despite February 11, 2016's very wide 899 bp high-yield bond spread, March 11's median high-yield EDF favors a narrower 594
announcement in class, on the Pharmacology Canvas site, and/or through Outlook. A ‘current’ version of the schedule is posted on the Canvas pharmacology course site (Modules: Pharmacology . pharmacological agents and evolving concepts of therapeutics and assimilate that understanding into practice throughout your professional career.
including ANSI A300. A good practice in mixed planting areas is to plant trees first followed by the larger shrubs, low shrubs and finally with ground cover plants. This prevents damage to the smaller plants; however the Contractor is responsible for sequencing. Check that plants are moist at the time of planting. Verify that trees or shrubs if marked with compass orientation are planted in .
