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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.
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...
|Schedule of Controlled Drugs|
|2||Drug Receptors & Pharmacodynamics||9|
|3||Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action||35|
|5||Basic & Clinical Evaluation of New Drugs||64|
|6||Introduction to Autonomic Pharmacology||75|
|7||Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs||92|
|9||Adrenoceptor-Activating & Other Sympathomimetic Drugs||120|
|10||Adrenoceptor Antagonist Drugs||138|
|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|
|16||Histamine, Serotonin, & the Ergot Alkaloids||265|
|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|
|27||Skeletal Muscle Relaxants||446|
|28||Pharmacologic Management of Parkinsonism & Other Movement Disorders||463|
|29||Antipsychotic Agents & Lithium||478|
|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|
|50||Miscellaneous Antimicrobial Agents; Disinfectants, Antiseptics, & Sterilants||845|
|51||Clinical Use of Antimicrobial Agents||854|
|52||Basic Principles of Antiparasitic Chemotherapy||869|
|54||Clinical Pharmacology of the Anthelmintic Drugs||903|
|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|
|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|
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:
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.