Introduction to the Pharmaceutical Sciences: An Integrated Approach PDF
Preview Introduction to the Pharmaceutical Sciences: An Integrated Approach
LWBK942-FM.qxd 6/25/11 8:45 AM Page x Introduction to the Pharmaceutical Sciences An Integrated Approach S e c o n d e d i t i o n Nita K. Pandit, B.S. Pharm, PhD Professor of Pharmaceutics College of Pharmacy and Health Sciences Drake University Des Moines, Iowa Robert Soltis, B.S. Pharm, PhD Professor of Pharmacology College of Pharmacy and Health Sciences Drake University Des Moines, Iowa LWBK895-FM_pi-viii.indd 1 20/07/11 10:10 PM Acquisitions Editor: David B. Troy Product Manager: Jennifer Ajello Developmental Editor: Laura Bonazzoli Senior Marketing Manager: Joy Fisher-Williams Designer: Teresa Mallon Compositor: Aptara, Inc. Second Edition Copyright © 2011 Lippincott Williams & Wilkins, a Wolters Kluwer business 351 West Camden Street Two Commerce Square Baltimore, MD 21201 2001 Market Street Philadelphia, PA 19103 Printed in China All rights reserved. This book is protected by copyright. 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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 drug for 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 to ascertain 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 fax orders to (301) 223-2320. International customers should call (301) 223-2300. Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST. LWBK895-FM_pi-viii.indd 2 20/07/11 10:10 PM P r e f a c e Think simple as my old master used to say, meaning reduce the whole of its parts to the simplest terms, getting back to first principles. —Frank Lloyd Wright This is the second edition of Introduc- readers have at least 2 years of college-level tion to the Pharmaceutical Sciences; the science and mathematics, with a basic first edition was published in 2007. Many background in general chemistry, organic improvements have been made in the chemistry, biology, and algebra. Some second edition, the most important being knowledge of introductory biochemistry the addition of a distinguished coauthor, and calculus is helpful but not required. Dr. Robert Soltis, a Drake colleague who Physiological concepts are introduced as team-teaches the Introduction to the Phar- needed. maceutical Sciences course with me. His In our experience, students who under- expertise in pharmacology has greatly stand the language of the pharmaceutical sci- improved many chapters in the book. ences, the key concepts, and links between The philosophy of the second edition these concepts are better able to appreci- remains unchanged. It is an introductory ate more advanced material in specialized book that provides a simple, integrated, courses that come later. They are less likely and coherent overview of pharmaceuti- to treat each discipline as a silo and often cal science concepts for the beginner or find connections that faculty miss! nonspecialist. We introduce and explain The text could be used for a one- fundamental principles that underlie all semester or a full-year course, depending pharmaceutical science disciplines, reveal on the desired depth of coverage. All topics the connections between them, and point may not be necessary for a one-semester to their pharmaceutical and therapeutic course; selection of material could depend applications. on the course objectives and subsequent The integration of various disciplines curriculum. A full-year course may use the is particularly important to us and is entire book with detailed discussion and reflected in the new subtitle “An Inte- additional readings as desired. For a phar- grated Approach.” Pharmacists must be macy student, an understanding of the basic able to integrate their knowledge of the concepts in this book will be followed by pharmaceutical and clinical sciences to courses in pharmacology, pharmaceutics, solve drug therapy problems. Pharma- pharmacokinetics, and medicinal chemis- ceutical scientists in drug discovery and try. For graduate students, this book will development must have a broad under- provide a broad context in which to study standing of the field as they participate in and investigate problems in their chosen interdisciplinary project teams. pharmaceutical specialty. Although this The target audiences are first-year phar- book is written as a text, it will be valu- macy students, junior-level science under- able to scientists new to the pharmaceuti- graduates, and other scientists new to cal industry who need a simple overview the pharmaceutical field. We assume that of the pharmaceutical sciences. iii LWBK895-FM_pi-viii.indd 3 20/07/11 10:10 PM iv Preface It is important to state what this book to students. We hope that this feature is not intended to be. It is not meant to enhances student learning and problem- be an encyclopedia of the pharmaceutical solving abilities. sciences, a “how-to” book for laboratory researchers, or a book for the specialist Cases in one of the pharmaceutical science dis- Cases at the end of many chapters are ciplines. Because we wish to emphasize an important new addition to the sec- common concepts underlying this field, ond edition. Cases are multifaceted and discussion of special topics and details of realistic scenarios that teach students any one discipline are generally limited. to apply their knowledge to solve prob- There are several other courses and excel- lems. Some background information is lent books that fill these needs, and sug- provided, and students are led through a gestions are provided at the end of each series of increasingly complex questions. chapter. Clinical application of basic pharmaceuti- We continue to aim for simplicity, cal science concepts is introduced wher- clarity, and brevity so that students will ever appropriate. Cases in early chapters actually read the book. Historical devel- are fairly short and increase in complex- opment of theories and hypotheses has ity through the book, requiring students been omitted. To provide coherence and to integrate knowledge from preceding readability, material is not referenced chapters. Instructors will be provided to primary literature; however, every with detailed answers and suggestions on attempt has been made to ensure that ways to expand the case discussions. statements reflect generally accepted sci- entific views. Need-to-know concepts are emphasized; nice-to-know content and Key Concepts and Review material that will be taught later in phar- Questions macy curricula or that is not directly rel- Key Concepts are summarized at the end evant have been minimized. of each chapter so that readers know what they should have learned from a particu- Features lar chapter. A list of Review Questions is provided at the end of each chapter. These Every chapter has received critical atten- broad questions test understanding of the tion and has been updated. A couple of concepts rather than the details. chapters were eliminated, while others were combined to improve the flow. Like Additional Reading the first edition, each chapter builds on previous material, so we recommend that All chapters include a list of Additional the sequence in the book be followed for Reading at the end to which a reader can best outcomes. turn for further information on a topic. We hope that this text will make it Practice Problems easier for faculty to develop and teach Practice problems have been added to a truly integrated course in the phar- more chapters, if appropriate. These ele- maceutical sciences. We would also like ments help students to work with material to see this book used in other degree discussed and to develop their quantita- programs so that students in chemis- tive and problem-solving skills. Solutions try, biology, or premedical programs can are provided only to the instructor to appreciate the applications of pharma- retain control over how to use the prob- ceutical sciences and see this field as a lems (homework, in-class discussion) career opportunity. Lastly, we want to and when and how to reveal solutions emphasize that this book continues to LWBK895-FM_pi-viii.indd 4 20/07/11 10:10 PM Preface v be a “work in progress”; feedback from In addition, purchasers of the text can readers is always welcome. access the searchable Full Text Online by going to the Introduction to Pharmaceuti- Resources for Instructors cal Sciences, second edition Web site at https://thepoint.lww.com/Pandit2e. See Approved adopting instructors will be the inside front cover of this text for more given access to the following additional details, including the passcode you will resources: need to gain access to the site. • Answers to practice problems • Answers to case study questions in the Nita K. Pandit, PhD text Robert Soltis, PhD • Additional integrated case studies not included in the text LWBK895-FM_pi-viii.indd 5 20/07/11 10:10 PM a c k n o w l e d g m e n t S As with any book, this text has ben- ences outside Drake. Their input has efited from contributions of many been valuable in making the book suit- people. Students at Drake have been our able not just to the needs of Drake stu- primary audience, and we thank them for dents but to students, teachers, and read- their suggestions in shaping the second ers elsewhere. edition. We are also grateful to our col- We particularly thank the wonderful leagues at the Drake University College of people at Lippincott Williams & Wilkins, Pharmacy for their support and encour- whose enthusiasm, commitment, profes- agement in this endeavor. sionalism, and patience made this a reward- The second edition has also improved ing undertaking. as a result of feedback from our audi- vi LWBK895-FM_pi-viii.indd 6 20/07/11 10:10 PM c o n t e n t S Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi . 1 . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Part I: Drug Chemistry 7 . 2 . Drugs and Their Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 . 3 . Ionization of Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 . 4 . Solubility and Lipophilicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Part II: Drug Delivery 58 . 5 . Transport Across Biological Barriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 . 6 . Drug Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 . 7 . Drug Delivery Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Part III: Drug Disposition 119 . 8 . Drug Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 . 9 . Drug Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 .10 . Drug Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 .11 . Pharmacokinetic Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 Part IV: Drug Action 200 .12 . Ligands and Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 .13 . Mechanisms of Drug Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 .14 . Dose–Response Relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 Part V: Drug Therapy 262 .15 . Therapeutic Variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263 .16 . Drug Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278 .17 . Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 Part VI: Special Topics 313 .18 . Biopharmaceutical Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 .19 . Drug Discovery and Approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340 Index.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 vii LWBK895-FM_pi-viii.indd 7 20/07/11 10:10 PM LWBK895-FM_pi-viii.indd 8 20/07/11 10:10 PM
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