Basic and Clinical Pharmacology / Edition 5

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Overview

This best selling book delivers the most current,complete,and authoritative pharmacology information to students and practitioners. All sections are updated with new drug information and references. New! Many new figures and diagrams,along with boxes of highlighted material explaining the "how and why" behind the facts.

Current. Comprehensive. Concise. Always.
*The most current and authoritative information available
*Concise and thorough introduction to basic and clinical pharmacology
*All chapters rigorously updated with the latest drug information and references
*New chapter on botanicals (herbal medications) and nutritional supplements
*Features include special-interst boxes and lists of common preparations and dosage information
*More than 600 illustrations and tables
*Ideal pharmacology text for medical students and students in other health-related professions This well-respected and influential text is known for clarity,comrehensiveness,and student-friendly features
*Basic and clinical pharmacology from the most authoritative source
*Organized by drug groups and prototypes
*Mechanism of action and toxicities of traditional and newer drugs
*Treatment strategies and drugs of choice for all major diseases

The book contains predominantly black-and-white illustrations, with some color illustrations.

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Editorial Reviews

Eric M. Scholar
This is the eighth edition of this editor's long-standing pharmacology textbook. It is designed to be a complete, authoritative, current, and readable pharmacology textbook. This book is written for medical, pharmacy, and health science students as well as house officers and clinicians. The information is presented in a sequence similar to many pharmacology books, starting with basic principles. Within each chapter, emphasis is placed on drug groups and prototypes. Clinical pharmacology has been made an integral part of this text. At the end of each chapter are lists of commercial preparations available, including trade and generic names as well as the dosage formulations available. In addition to a description of new drugs added since the last edition (1998), this edition contains a new chapter on botanicals and food supplements. Several of the chapters have been revised since the last edition and several new figures have been added. As found in the last edition, the book contains two appendixes, one on biologic products and one on important drug interactions. The editor is well qualified to write this text as are the authors of the different chapters. This is a very good textbook, as were the previous editions. It is a pharmacology book that is complete but that does not contain all the details that some pharmacology books do. The editor achieves a midpoint between books that provide extensive detail and some of the newer ones that are oversimplified. Fortunately, the editor avoids that latter trend in this book. The new chapter on botanicals is an excellent addition considering the widespread use of these drugs in recent years. I thought the editor exaggerated theadditions made in this new edition in his preface. He stated that several chapters underwent major revision but upon detailed examination it appeared that the changes were, in most cases, small. Overall, though, it is a very good book.
From The Critics
Reviewer: Eric M. Scholar, PhD (University of Nebraska Medical Center)
Description: This is the eighth edition of this editor's long-standing pharmacology textbook.
Purpose: It is designed to be a complete, authoritative, current, and readable pharmacology textbook.
Audience: This book is written for medical, pharmacy, and health science students as well as house officers and clinicians.
Features: The information is presented in a sequence similar to many pharmacology books, starting with basic principles. Within each chapter, emphasis is placed on drug groups and prototypes. Clinical pharmacology has been made an integral part of this text. At the end of each chapter are lists of commercial preparations available, including trade and generic names as well as the dosage formulations available. In addition to a description of new drugs added since the last edition (1998), this edition contains a new chapter on botanicals and food supplements. Several of the chapters have been revised since the last edition and several new figures have been added. As found in the last edition, the book contains two appendixes, one on biologic products and one on important drug interactions. The editor is well qualified to write this text as are the authors of the different chapters.
Assessment: This is a very good textbook, as were the previous editions. It is a pharmacology book that is complete but that does not contain all the details that some pharmacology books do. The editor achieves a midpoint between books that provide extensive detail and some of the newer ones that are oversimplified. Fortunately, the editor avoidsthat latter trend in this book. The new chapter on botanicals is an excellent addition considering the widespread use of these drugs in recent years. I thought the editor exaggerated the additions made in this new edition in his preface. He stated that several chapters underwent major revision but upon detailed examination it appeared that the changes were, in most cases, small. Overall, though, it is a very good book.
From Barnes & Noble
This bestselling pharmacology text emphasizes drug groups and prototypes rather than individual drugs though general and trade preparations are provided at the end of each chapter. Two-color and black-and-white charts, figures, and diagrams throughout highlight examples and special information. Expanded coverage of molecular biology; new receptors; neurotransmitters; drug interactions; the clinical management of asthma, congestive heart failure, Alzheimer's, and other diseases; more.

3 Stars from Doody
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Product Details

  • ISBN-13: 9780838505625
  • Publisher: Appleton & Lange
  • Publication date: 3/1/1992
  • Edition number: 5
  • Pages: 1017

Read an Excerpt

Chapter 1: Introduction

Pharmacology can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. These substances may be chemicals administered to achieve a beneficial therapeutic effect on some process within the patient or for their toxic effects on regulatory processes in parasites infecting the patient. Such deliberate therapeutic applications may be considered the proper role of medical pharmacology, which is often defined as the science of substances used to prevent, diagnose, and treat disease. Toxicology is that branch of pharmacology that deals with the undesirable effects of chemicals on living systems, from individual cells to complex ecosystems.

History

Prehistoric people undoubtedly recognized the beneficial or toxic effects of many plant and animal materials. The earliest written records from China and from Egypt list remedies of many types, including a few still recognized today as useful drugs. Most, however, were worthless or actually harmful. In the 2500 years or so preceding the modern era there were sporadic attempts to introduce rational methods into medicine, but none were successful owing to the dominance of systems of thought that purported to explain all of biology and disease without the need for experimentation and observation. These schools promulgated bizarre notions such as the idea that disease was caused by excesses of bile or blood in the body, that wounds could be healed by applying a salve to the weapon that caused the wound, and so on.

Around the end of the 17th century, reliance onobservation and experimentation began to replace theorizing in medicine, following the example of the physical sciences. As the value of these methods in the study of disease became clear, physicians in Great Britain and elsewhere in Europe began to apply them to the effects of traditional drugs used in their own practices. Thus, materia medica, the science of drug preparation and the medical use of drugs, began to develop as the precursor to pharmacology. However, any understanding of the mechanisms of action of drugs was prevented by the absence of methods for purifying active agents from the crude materials that were available and-even more-by the lack of methods for testing hypotheses about the nature of drug actions. However, in the late 18th and early 19th centuries, Francois Magendie and later his student Claude Bernard began to develop the methods of experimental animal physiology and pharmacology. Advances in chemistry and the further development of physiology in the 18th, 19th, and early 20th centuries laid the foundation needed for understanding how drugs work at the organ and tissue levels. Paradoxically, real advances in basic pharmacology during the 19th century were accompanied by an outburst of unscientific promotion by manufacturers and marketers of worthless "patent medicines." It was not until the concepts of rational therapeutics, especially that of the controlled clinical trial, were reintroduced into medicine-about 50 years ago-that it became possible to accurately evaluate therapeutic claims.

About 50 years ago, there also began a major expansion of research efforts in all areas of biology. As new concepts and new techniques were introduced, information accumulated about drug action and the biologic substrate of that action, the receptor. During this half-century, many fundamentally new drug groups and new members of old groups have been introduced. The last 3 decades have seen an even more rapid growth of information and understanding of the molecular basis for drug action. The molecular mechanisms of action of many drugs have now been identified, and numerous receptors have been isolated, structurally characterized, and cloned. Much of that progress is summarized in this book.

The extension of scientific principles into everyday therapeutics is still going on, though the medicationconsuming public, unfortunately, is still exposed to vast amounts of inaccurate, incomplete, or unscientific information regarding the pharmacologic effects of chemicals. This has resulted in the faddish use of innumerable expensive, ineffective, and sometimes harmful remedies and the growth of a huge "alternative health care" industry. Conversely, lack of understanding of basic scientific principles in biology and statistics and the absence of critical thinking about public health issues has led to rejection of medical science by a segment of the public and a tendency to assume that all adverse drug effects are the result of malpractice.

The Nature of Drugs

In the most general sense, a drug may be defined as any substance that brings about a change in biologic function through its chemical actions. In the great majority of cases, the drug molecule interacts with a specific molecule in the biologic system that plays a regulatory role, ie, a receptor molecule. The nature of receptors is discussed more fully in Chapter 2. In a very small number of cases, drugs known as chemical antagonists may interact directly with other drugs, while a few drugs (eg, osmotic agents) interact almost exclusively with water molecules. Drugs may be synthesized within the body (eg, hormones) or may be chemicals not synthesized in the body, ie, xenobiotics (from Gr xenos "stranger"). Poisons are drugs. Toxins are usually defined as poisons of biologic origin, ie, synthesized by plants or animals, in contrast to inorganic poisons such as lead and arsenic.

In order to interact chemically with its receptor, a drug molecule must have the appropriate size, electrical charge, shape, and atomic composition. Furthermore, a drug is often administered at a location distant from its intended site of action, eg, a pill given orally to relieve a headache. Therefore, a useful drug must have the necessary properties to be transported from its site of administration to its site of action. Finally, a practical drug should be inactivated or excreted from the body at a reasonable rate so that its actions will be of appropriate duration.

A. The Physical Nature of Drugs: Drugs may be solid at room temperature (eg, aspirin, atropine), liquid (eg, nicotine, ethanol), or gaseous (eg, nitrous oxide). These factors often determine the best route of administration. For example, some liquid drugs are easily vaporized and can be inhaled in that form, eg, halothane, amylnitrite. The common routes of administration are listed in Table 3-3. The various classes of organic compounds-carbohydrates, proteins, lipids, and their constituents-are all represented in pharmacology. Many drugs are weak acids or bases. This fact has important implications for the way they are handled by the body, because pH differences in the various compartments of the body may alter the degree of ionization of such drugs (see below).

B. Drug Size: The molecular size of drugs varies from very small (lithium ion, MW 7) to very large (eg, alteplase [t-PA], a protein of MW 59,050). However, the vast majority of drugs have molecular weights between 100 and 1000. The lower limit of this narrow range is probably set by the requirements for specificity of action. In order to have a good "fit" to only one type of receptor, a drug molecule must be sufficiently unique in shape, charge, etc, to prevent its binding to other receptors. To achieve such selective binding, it appears that a molecule should in most cases be at least 100 MW units in size. The upper limit in molecular weight is determined primarily by the requirement that drugs be able to move within the body (eg, from site of administration to site of action). Drugs much larger than MW 1000 will not diffuse readily between compartments of the body (see Permeation, below). Therefore, very large drugs (usually proteins) must be administered directly into the compartment where they have their effect. In the case of alteplase, a clot-dissolving enzyme, the drug is administered directly into the vascular compartment by intravenous infusion.

C. Drug Reactivity and Drug-Receptor Bonds: Drugs interact with receptors by means of chemical forces or bonds. These are of three major types: covalent, electrostatic, and hydrophobic. Covalent bonds are very strong and in many cases not reversible under biologic conditions. Thus, the covalent bond formed between the activated form of phenoxybenzamine and the a receptor for norepinephrine (which results in blockade of the receptor) is not readily broken. The blocking effect of phenoxybenzamine lasts long after the free drug has disappeared from the bloodstream and is reversed only by the synthesis of new a receptors, a process that takes about 48 hours. Other examples of highly reactive, covalent bond-forming drugs are the DNA-alkylating agents used in cancer chemotherapy to disrupt cell division in the neoplastic tissue.

Electrostatic bonding is much more common than covalent bonding in drug-receptor interactions. Electrostatic bonds vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds and very weak induced dipole interactions such as van der Waals forces and similar phenomena. Electrostatic bonds are weaker than covalent bonds.

Hydrophobic bonds are usually quite weak and are probably important in the interactions of highly lipidsoluble drugs with the lipids of cell membranes and...

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Table of Contents

Schedule of Controlled Drugs
Preface
The Authors
1 Introduction 1
2 Drug Receptors & Pharmacodynamics 9
3 Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action 35
4 Drug Biotransformation 51
5 Basic & Clinical Evaluation of New Drugs 64
6 Introduction to Autonomic Pharmacology 75
7 Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs 92
8 Cholinoceptor-Blocking Drugs 107
9 Adrenoceptor-Activating & Other Sympathomimetic Drugs 120
10 Adrenoceptor Antagonist Drugs 138
11 Antihypertensive Agents 155
12 Vasodilators & the Treatment of Angina Pectoris 181
13 Cardiac Glycosides & Other Drugs Used in Congestive Heart Failure 200
14 Agents Used in Cardiac Arrhythmias 219
15 Diuretic Agents 245
16 Histamine, Serotonin, & the Ergot Alkaloids 265
17 Vasoactive Peptides 292
18 The Eicosanoids: Prostaglandins, Thromboxanes, Leukotrienes, & Related Compounds 311
19 Nitric Oxide, Donor, & Inhibitors 326
20 Drugs Used in Asthma 333
21 Introduction to the Pharmacology of CNS Drugs 351
22 Sedative-Hypnotic Drugs 364
23 The Alcohols 382
24 Antiseizure Drugs 395
25 General Anesthetics 419
26 Local Anesthetics 436
27 Skeletal Muscle Relaxants 446
28 Pharmacologic Management of Parkinsonism & Other Movement Disorders 463
29 Antipsychotic Agents & Lithium 478
30 Antidepressant Agents 498
31 Opioid Analgesics & Antagonists 512
32 Drugs of Abuse 532
33 Agents Used in Anemias; Hematopoietic Growth Factors 549
34 Drugs Used in Disorders of Coagulation 564
35 Agents Used in Hyperlipidemia 581
36 Nonsteroidal Anti-Inflammatory Drugs, Disease-Modifying Antirheumatic Drugs, Nonoploid Analgesics & Drugs Used in Gout 596
37 Hypothalamic & Pituitary Hormones 625
38 Thyroid & Antithyroid Drugs 644
39 Adrenocorticosteroids & Adrenocortical Antagonists 660
40 The Gonadal Hormones & Inhibitors 679
41 Pancreatic Hormones & Antidiabetic Drugs 711
42 Agents That Affect Bone Mineral Homeostasis 735
43 Beta-Lactam Antibiotics & Other Inhibitors of Cell Wall Synthesis 754
44 Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins 774
45 Aminoglycosides & Spectinomycin 784
46 Sulfonamides, Trimethoprim, & Quinolones 793
47 Antimycobacterial Drugs 803
48 Antifungal Agents 814
49 Antiviral Agents 823
50 Miscellaneous Antimicrobial Agents; Disinfectants, Antiseptics, & Sterilants 845
51 Clinical Use of Antimicrobial Agents 854
52 Basic Principles of Antiparasitic Chemotherapy 869
53 Antiprotozoal Drugs 882
54 Clinical Pharmacology of the Anthelmintic Drugs 903
55 Cancer Chemotherapy 923
56 Immunopharmacology 959
57 Introduction to Toxicology: Occupational & Environmental 987
58 Heavy Metal Intoxication & Chelators 999
59 Management of the Poisoned Patient 1011
60 Special Aspects of Perinatal & Pediatric Pharmacology 1025
61 Special Aspects of Geriatric Pharmacology 1036
62 Dermatologic Pharmacology 1045
63 Drugs Used in Gastrointestinal Diseases 1064
64 Therapeutic & Toxic Potential of Over-the-Counter Agents 1077
65 Botanicals ("Herbal Medications") & Nutritional Supplements 1088
66 Rational Prescribing & Prescription Writing 1104
App. I Vaccines, Immune Giobulins, & Other Complex Biologic Products 1113
App. II Important Drug Interactions & Their Mechanisms 1122
Index 1135
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Preface

This book is designed to provide a complete, authoritative, current, and readable pharmacology textbook for medical, pharmacy, and other health science students. It also offers special features that make it useful to house officers and practicing clinicians.

Information is organized according to the sequence used in many pharmacology courses: basic principles; autonomic drugs; cardiovascular-renal drugs; drugs with important actions on smooth muscle; central nervous system drugs; drugs used to treat inflammation, gout, and diseases of the blood; endocrine drugs; chemotherapeutic drugs; toxicology; and special topics. This sequence builds new information on a foundation of information already assimilated. For example, early presentation of autonomic pharmacology allows students to integrate the physiology and neuroscience they know with the pharmacology they are learning and prepares them to understand the autonomic effects of other drugs. This is especially important for the cardiovascular and central nervous system drug groups. However, chapters can be used equally well in courses that present these topics in a different sequence.

Within each chapter, emphasis is placed on discussion of drug groups and prototypes rather than offering repetitive detail about individual drugs. Selection of the subject matter and the order of its presentation are based on the accumulated experience of teaching this material to thousands of medical, pharmacy, dental, podiatry, nursing, and other health science students.

Major features that make this book especially useful to professional students include sections that specifically address the clinical choice and use of drugs in patients and themonitoring of their effects-in other words, clinical pharmacology is an integral part of this text. Lists of the commercial preparations available, including trade and generic names and dosage formulations, are provided at the end of each chapter for easy reference by the house officer or practitioner writing a chart order or prescription.

The nomenclature of recognized receptors is still somewhat unstable at present. In order to minimize discrepancies, we have in most cases chosen to use the receptor names given in the 1999 and 2000 issues of Receptor Nomenclature Supplement (special annual issue of Trends in Pharmacological Sciences). Enzymes are named according to the contributor's judgment of the best current usage, usually that of 1992 Enzyme Nomenclature, Academic Press, 1992.

Significant revisions in this edition include the following:

  • A new chapter on botanicals (herbal medications) and food supplements-an area of increasing importance for health practitioners
  • Major revision of the chapter on anti-inflammatory drugs, including important new disease-modifying agents
  • Major revision of the chapter on anemia and colony-stimulating factors
  • Major revision of the chapter on the treatment of clotting disorders
  • Major revision of the chapters on steroid drugs
  • Major revision of the chapter on antiprotozoal drugs
  • New figures, most in color, that help to clarify important concepts in pharmacology
  • New special-interest text boxes that provide working examples of the text material or serve to point out items of particular interest
  • Continuing expansion of the coverage of general concepts relating to receptors and listings of newly discovered receptors
  • Recent changes in the clinical management of antibiotic-resistant infections, AIDS, asthma, and congestive heart failure
  • Descriptions of important new drugs released through March 2000
  • Revised bibliographies with many new references through March 2000

An important related source of information is Pharmacology: Examination & Board Review, 5th ed. (Katzung BG, Trevor AJ: Appleton & Lange/McGraw-Hill, 1998). This book provides a succinct review of pharmacology with one of the largest available collections of sample examination questions and answers. It is especially helpful to students preparing for board-type examinations.

The widespread acceptance of the first seven editions of Basic & Clinical Pharmacology over more than 15 years suggests that this book fills an important need. We believe that the eighth edition will satisfy this need even more successfully. Spanish, Portuguese, Italian, and Indonesian translations are available. Translations into other languages are under way; the publisher may be contacted for further information.

I wish to acknowledge the ongoing efforts of my contributing authors and the major contributions of the staff at Appleton & Lange and more recently at McGraw-Hill, and of our editor, James Ransom. I also wish to thank my wife, Alice, for her expert proofreading contributions since the first edition.

Suggestions and comments about Basic & Clinical Pharmacology are always welcome. They may be sent to me at the Department of Cellular & Molecular Pharmacology, Box 0450, S-1210, University of California, San Francisco, CA 94143-0450.

San Francisco
September 2000

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