(Solution Manual) Hand book of Food-Drug Interactions latest 2022

McCabe,Frankel,Wolfe, 1

Nursing

Solution Manual

1st Edition

• $15.00 $50.00

---

Description

Solution Manual for Hand book of Food-Drug Interactions latest 2022, The downloadable file consists of 532 pages, and the total size of the file is 4.33 MB. Purchase now only for highly discounted price.

Author(s): McCabe, Frankel, Wolfe

---

---

Study Note Preview

CRC PRESS Boca Raton London New York Washington, D.C.FOOD -DRUG INTERACTIONSHandbook of Edited by Beverly J. McCabe Eric H. Frankel Jonathan J. Wolfe © 2003 by CRC Press LLCThis book contains information obtained from authentic and highly regarded sour ces. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the va lidity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior perm ission in writing from the publisher. All rights reserved. Authorization to phot ocopy items for internal or personal use, or the personal or internal use of specific clients, may be granted by CRC Press LLC, provided that $1.50 per page photocopied is paid directly to Copyright Cl earance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. The fee code for users of the Transact ional Reporting Se rvice is ISBN 0-8493-1531-X/03/$0.00+$1.50. The fee is subject to change without noti ce. For organizations that have be en granted a photocopy license by the CCC, a separate system of payment has been arranged. The consent of CRC Press LLC does not extend to c opying for general distribution, for promotion, for creating new works, or for resale. Specific permissi on must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 N. W. Corporate Blvd., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be tradem arks or registered trademarks, and are used only for identifica tion and explanation, with out intent to infringe. Visit the CRC Press Web site at www.crcpress.com © 2003 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-8493-1531-X Library of Congress Card Number 2002041312 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paperLibrary of Congress Cataloging-in-Publication Data Handbook of food-drug interactions / edited by Beverly J. McCabe, Jonathan J. Wolfe, Eric H. Frankel. p. cm. Includes bibliographical references and index. ISBN 0-8493-1531-X 1. Drug-nutrient interactions—Handbooks, manuals, etc. I. McCabe, Beverly J. II. Wolfe, Jonathan James, 1944- III. Frankel, Eric H. RM302.4.H36 2003 615′.7045—dc21 2002041312 Preface As health professionals from different di sciplines, we learn the basic concepts, terminology, and procedures that are central to our areas of expertise. In doing so, we become acculturated to th inking, interacting, networki ng, and learning with peers from the same discipline. When we begi n to interact as me mbers of healthcare teams, we bring our own jargon and mores. Often we assume that others may understand us as fully and completely as ou r professional peers, but we fail to grasp different meanings or focus that others may have on a given subject, case, or problem. The term multidisciplinary is used to defi ne teams in which different disciplines are represented but tend to function in isolatio n of each other. Inte rdisciplinary means that teams combine their unique talents an d knowledge to create a working unit. This book is written by an interdisciplinary team of authors and contributors representing the fields of nutrition, pharma cy, dietetics, medicine, and technology. Each chapter and appendix was viewed from the aspect of different disciplines: “Is this something everyone knows, or is this something that one discipline is unlikely to know or is likely to view differently?” “What type of information would be helpful for all disciplines to have readil y available?” The book attempts to bring the detailed and discipline-specific knowledge to other disciplines. In providing common concepts, communi cations among different disciplines can be improved and, in turn, improve health care. The authors of each chapter have worked from a perspective of generic drug names in ever y case. Example trade names have been provided solely for the convenience of r eaders. In no case do the authors or the editors intend any endorsement, or imply that the example trademark names possess any advantage over equivalent generic products. The first six chapters introduce basic co ncepts from pharmacy and from nutrition for all disciplines. In jointly authored chapters involving more than one discipline, comparisons are sometimes made between th e thinking and focus of one discipline with the other. For example, Chapter 6 is written by two pharmacists and a dietitian and reflects both similarities an d differences in approaches. Chapters 7 through 13 present specific deta iled topics of diseases, disorders, and lifestyle choices. Chapters 14 throug h 17 represent guidance in planning and implementing counseling prog rams, meeting accreditation requirements, and appli - cation of technology. The appendices provide valuable reference materials, com - prehensive summaries of drug and dietary details, and suggested tools that may aid the practitioner regardless of the discipline. © 2003 by CRC Press LLCThe Editors Beverly J. McCabe, Ph.D., R.D., L.D., as a young psychiatric dietitian, began the study of food and drug interactions involving monoamine oxidase inhibitor (MAOI) drugs and pressor amines. In the following years, she found that many facilities and review articles recommend un necessary restrictions based on ill-con - ceived extrapolation from one food to others. Today, with a compilation of tyremine and other pressor amine values in foods dr awn from a comprehensive review of the world literature, she works closely with physicians an d pharmacists to reduce the risks of adverse food and drug interactions . She has published more than 20 articles, monographs, and book chapters, and her students’ abstracts now number over 50 from national and international meeting presentations in the last 18 years. Currently, Dr. McCabe serves on the board of editors of the Journal of the American Dietetic Association. She has served as a reviewer for the Journal of Clinical Psychiatry for nutrition articles and as a national officer and on the board of directors of the American Dietetic Association. She established the list serve for the Dietetic Educators of Pr actitioners Dietetic Practice Group and received the first outstanding service award from this group in recognition of her contribution. More recently, she was named outstanding dietit ian in Arkansas for 2002. She has also been honored by the Arkansas affiliate of the American H eart Association for statewide workshops and presentations on nutrition in heart di sease and for devel - opment of educational materials. Dr. McCabe has been an innovator in the application of technology to the practice of nutrition counseling and diet etic education. With a fe deral grant, she developed an interactive compressed video program to teach healthier cooking techniques to rural food service personnel in the Arkansas delta counties. Through a grant of the Arkansas Rural Hospital Program, she also pioneered individual and group nutrition counseling of rural patients on diets for weight control, diabetes, hypertension, and other conditions using the interactive comp ressed video network that reaches some 50 rural hospitals and clinic s. Additionally, Dr. McCabe has team counseled with pharmacy faculty using a long-distance co unseling technique known as Telehealth and Telenutrition. A dedicated educator, Dr. McCabe has made numerous presentations to lay audiences including television and radio interviews. She has been active in the National Nutrient Databank Co nferences and has a strong interest in food composi - tion and analysis. Her most recent research grant is for the study of the stability of biotin in frozen foods. Dr. McCabe received her bachelor of sc ience degree from the University of Arkansas at Fayetteville, her dietetic intern ship at the University of Kansas Medical Center, her master of science from the Un iversity of Kansas, and her Ph.D. from the University of Iowa. Eric H. Frankel, M.S.E., Pharm.D., B.C.N.S.P., is the nutritional support service coordinator for Covenant Health System (formerly Methodist Hospital and St. Mary of the Plains Hospital and Rehabilitation Ce nter) in Lubbock, Texas. He has practiced © 2003 by CRC Press LLCin nutritional support for 22 years. Prior to his pharmacy career, Dr. Frankel earned a bachelor of science in psycholo gy and a master of science in education from the City College of New York, after which he taught at the secondary level for several years. Dr. Frankel received his bachelor of pharmacy degree from Arnold and Marie Schwartz College of Pharmacy in New York City and went on to earn a doctor of pharmacy degree in 1979 from Mercer University. Still an educator, Dr. Frankel has taught in pharmacy school and served as a preceptor for doctor of pharmacy candidates and for dietetic interns. He is currently the director of a residency program for pharmacy practice specializing in nutritional support and is a clinical assistant professor for Texas Tech University Health Sciences Center School of Pharmacy, as well as an adjunct professor for the School of Human Sciences, Division of Nutrition, in Lubbock. In addition, Dr. Frankel has taught classes for physical therapists, dietitians, an d respiratory therapists at Texas Tech as well as Emory University, Georgia State Univ ersity, and Georgia T ech, all in Atlanta. Besides teaching, he serves as a consulta nt for home care patien ts receiving nonvo - litional nutrition outside the hospital and has been appointed to represent the Texas Pharmacy Association to the U.S. Pharmaco peial Convention. He has been an author of several articles in the nutritional support and pharmacy literature, and has spoken at numerous local, state, and national meetings. Jonathan J. Wolfe, Ph.D., R.Ph., is currently associate dean of the College of Pharmacy at the University of Arkansas for Medical Sciences in Little Rock. His teaching responsibilities within the college include profe ssional ethics, history of pharmacy, and intravenous therapy. He also works with an interdisciplinary faculty to offer a course in death and dying. Hi s current research in terests are medication error reduction and history. He recently serv ed as guest curator for an exhibit at the Old State House Museum in Little Rock: Me dical Education at th e Old State House: From Flexner to New Deal . Dr. Wolfe was educated first as an hist orian, completing hi s doctorate at the University of Virginia in Charlottesville. After 3 years of teaching college courses, he returned to school and earned his de gree in pharmacy. His practice experiences include hospital pharmacy and home infusion pharmacy. He joined the faculty at the pharmacy college full time in 1991. His other service reflects his interest in pain treatmen t and end-of-life care. He was a cofounder of the Arkansas Cancer Pain Initiative and has served on the board of the American Association of State Cancer Pain Initiatives. In addition, he was appointed a delegate to the U.S. Pharmacopeia in 1995, continuing to serve in that capacity through February 2003. © 2003 by CRC Press LLCContributors Albert Barrocas, M.D., F.A.C.S., F.A.C.N. Pendleton Memorial Methodist Hospital Tulane University New Orleans, Louisiana Tiffany R. Bolton, Pharm.D. DCH Regional Medical Center Tuscaloosa, Alabama Nancy Carthan, Pharm.D., C.D.E. Southeast Dallas Health Center Dallas, Texas Ronni Chernoff, Ph.D., R.D., F.A.D.A. Arkansas Center on Aging Geriatrics Research, Education and Clini cal Center, Central Arkansas Veterans Healthcare System College of Public Health University of Arkansas for Medical Sciences Little Rock, Arkansas Howell Foster, Pharm.D. Arkansas Poison Control Center College of Pharmacy University of Arkansas for Medical Sciences Little Rock, Arkansas Eric H. Frankel, M.S.E., Pharm.D., B.C.N.S.P. Covenant Health System Texas Tech University Health Sciences Center Department of Food and Nutrition, College of Human Sciences Texas Tech University Lubbock, Texas Paul O. Gubbins, Pharm.D. Department of Pharmacy Pr actice, College of Pharmacy University of Arkansas for Medical Sciences Little Rock, Arkansas © 2003 by CRC Press LLCBill J. Gurley, Ph.D. Department of Pharmaceutical Sciences, College of Pharmacy University of Arkansas for Medical Sciences Little Rock, Arkansas Dorothy W. Hagan, Ph.D., R.D., L.D., F.A.D.A. Oregon Health Sciences University Portland, Oregon Reza Hakkak, Ph.D. Department of Dietetics and Nutrition, College of Health Related Professions University of Arkansas for Medical Sciences Little Rock, Arkansas Jan K. Hastings, Ph.D. Department of Pharmacy Pr actice, College of Pharmacy University of Arkansas for Medical Sciences Little Rock, Arkansas John W. Holladay, Ph.D. Prescription Compounding of Sumter Sumter, South Carolina Charles W. Jastram, Jr., Pharm.D., B.C.N.S.P. University of Louisiana at Monroe Medical Center of Louisiana— Charity Campus New Orleans, Louisiana Kim E. Light, Ph.D. Department of Pharmaceuti cal Sciences and Department of Interdisciplinary Toxicology and Pharmacology University of Arkansas for Medical Sciences Little Rock, Arkansas Razia Malik, Pharm.D. Niles, Michigan Beverly J. McCabe, Ph.D., R.D., L.D. Department of Dietetics and Nutrition College of Health Related Professions and College of Public Health University of Arkansas for Medical Sciences Little Rock, Arkansas © 2003 by CRC Press LLCBeth Miller, Pharm.D. Methodist University Pain Institute Memphis, Tennessee Kathleen M. Strausburg, M.S, R.Ph., B.C.N.S.P. Lakewood, Colorado Pete Tanguay Rock-Pond Solutions, Inc. Conway, Arkansas Jonathan J. W olfe, Ph.D., R.Ph. Associate Dean, College of Pharmacy University of Arkansas for Medical Sciences Little Rock, Arkansas Fantahun Yimam, Pharm.D., B.C.N.S.P. Covenant Health System Lubbock, Texas © 2003 by CRC Press LLCContents Chapter 1 Pharmacy: Basic Concepts Eric H. Frankel Chapter 2 Biopharmaceutics of Orally Ingested Products John W. Holladay Chapter 3 Drug Interactions: Basic Concepts Eric H. Frankel Chapter 4 Nutrition and Metabolism Ronni Chernoff Chapter 5 Food and Nutrition Update Beverly J. McCabe Chapter 6 Monitoring Nutritional Status in Drug Regimens Beverly J. McCabe, Eric H. Frankel, and Jonathan J. Wolfe Chapter 7 Gastrointestinal and Metabolic Di sorders and Drugs Fantahun Yimam and Razia Malik Chapter 8 Drug Interactions in Nutrition Supp ort Kathleen M. Strausburg Chapter 9 Alcohol and Nutrition Kim E. Light and Reza Hakkak Chapter 10 Nutrition and Drug Regimens in Older Persons Albert Barrocas, Charles W. Jastram, and Beverly J. McCabe Chapter 11 Obesity and Appetite Drugs Tiffany R. Bolton Chapter 12 Nonprescription Drug and Nutrient Interactions Beth Miller and Nancy Carthan Chapter 13 Herbal and Dietary Supplement In teractions with Drugs Bill J. Gurley and Dorothy W. Hagan Chapter 14 Dietary Counseling to Prevent Food–Drug Interactions Beverly J. McCabe © 2003 by CRC Press LLCChapter 15 Prevention of Food–Drug Interactions Jonathan J. Wolfe and Jan K. Hastings Chapter 16 Drug–Nutrient Interactions and JCAHO Standards Dorothy W. Hagan and Beverly J. McCabe Chapter 17 Computers in Nutrient–Drug Interaction Management: Understanding the Past and the Present, Building a Framework for the Future Pete Tanguay and Howell Foster Appendix A.1 Drug Side Effects Appendix A.2 Brand Name Medications and Side Effects Appendix A.3 Generic Name Medications and Side Effects Appendix A.4 Most Commonly Prescribed Trade Name Drugs Appendix A.5 Most Commonly Prescribed Gene ric Drugs Appendix A.6 pH of Bodily Fluids Appendix A.7 Weight–Mass Conversions Appendix A.8 Approximate V olume Conversions Appendix A.9 Electrolyte Content of Common IV Solutions Appendix B.1 Milliequivalent/Milligram Conversions for Commonly Used Salts Appendix B.2 Average pH Values of Some Common Beverages and Foods Appendix B.3 Commonly Used Electrolyte Additives for Intravenous Therapy Appendix B.4 Commonly Used Micronutrient Additives for Intravenous Therapy Appendix C.1 Food Storage Guidelines for the General Population and for High-Risk Populations Appendix C.2 Guidelines for Drug Approval (U.S. Food and Drug Administration) © 2003 by CRC Press LLCAppendix C.3 Grapefruit Juice–Drug Inte ractions and Their Clinical Significance Appendix C.4 Guide to Gliadin in Drugs Appendix C.5 Foods Containing Gliadin Appendix C.6 Food Carbohydrate Replacements for Illness or Hypoglycemia Appendix D.1 Tyramine Content of Foods and Beverages in µg/g or µg/mL Appendix D.2 Histamine Content of Foods and Beverages in µg/g or µg/mL Appendix D.3 Calcium Content of Selected Foods Appendix D.4 Vitamin K1 (Phylloquinone) Content of Foods in µg/100 g and µg/serving (in g or mL) Appendix D.5 Iron Content in Selected Foods Appendix D.6 Magnesium Content in Selected Foods Appendix D.7 Phosphorus Content in Selected Foods Appendix D.8 Potassium Content in Selected F oods Appendix D.9 Sodium Content in Selected Foods Appendix D.10 Zinc Content in Selected Foods Appendix D.11 Oxalate Content by High, Moderate, and Little or No Oxalate Categories Appendix D.12 Dietary Caffeine and Other Methylxanthines Appendix D.13 Caffeine Content of Common Beverages and Foods Appendix D.14 Theobromine in Foods Appendix D.15 Alcohol (Ethanol) Content of Alcoholic Beverages Appendix D.16 Purine-Yielding Foods © 2003 by CRC Press LLCAppendix E.1 Nutrition Monitoring Screen Appendix E.2 Critical Points in Physical Assessment for Nutrition Status Appendix E.3 Sample Questionnaire for Assessing Dietary Factors Affecting Potential for Biogenic Amines Interactions Appendix E.4 General Dietary Scr eening for Food and Drug Reactions Appendix E.5 Guidelines for Estimating Energy Needs and Desirable Body Weight Appendix E.6 Competency Checklist for Nutr ition Counselors © 2003 by CRC Press LLCCHAPTER 1 Pharmacy: Basic Concepts Eric H. Frankel CONTENTS Background View of Drugs The Perfect Medication Drug Delivery and Administration Dosage Forms Pills and Powders Tablets, Capsules, and High Tech Liquids Rectal Dosage Forms Topical Agents Injections Pharmaceutical Elegance: Coats to Disguise, Protect, and Increase Duration Compounding: What’s Old Is New Again Pharmacokinetics Absorption Distribution Metabolism Elimination Pharmacodynamics Reference Materials Textbooks and References Drugs Manuals and References Internet-Based Resources © 2003 by CRC Press LLCBasic information about pharmaceutics, pharmacology, pharmacokinetics, and pharmacodynamics is discussed in this chapte r. The information will allow readers to appreciate the mechanisms that can result in interactions between drugs and nutrients. BACKGROUND VIEW OF DRUGS Animals are dependent on food for their very existence. Man is no exception. Man, as hunter and gatherer and later as agronomist, looked to plants and animals for more than just food. Animals and plants provided tools, shelter, clothing, and transportation, as well as labor. Early man manifested an intelligence that led him to attempt to influence the external world and to change things to hi s advantage. Inevitabl e injury and illness were treated by means influenced by lo gic and intelligence. The means readily available to preliterate mankind included experimentation with plant and animal materials in the immediate en vironment. The trial and er ror method, combined with oral traditions and later written record k eeping, produced diverse local practices of medicinal arts. “The desire to take medicine is perhaps the greatest fe ature which distinguishes man from animals.” William Osle r (1849–1919), Canadian writer, lecturer, and physician. Pharmacognosy, the study of the origin, na ture, properties, and effects of natural products on living organisms, grew from such instinctive responses to disease. Pharmacology, the study of the origin, nature, properties, and effects of various substances (naturally occurring and synthetic ) on living organisms, grew from roots grounded for centuries in these primitive practices. It is interesting to note that there is a recent resurgence of interest in natural products for medical use. With this new interest in natural products, keep in mind that efficacy, purity, and active ingredient concentration of substan ces sold as nutritional supplements are not regulated by any arm of the U.S. federa l government. Recently, the U.S. Pharma - copeial (USP) Convention began a voluntary program for the certification of purity and active ingredient concentr ation of nutritional supplements. The USP is a private, not-for-profit entity founded in 1820 and entirely independent from the government. Except for products certified by this process, a potential for variance still exists between manufacturers, between lots from the same manufacturer, and even within the same lot. THE PERFECT MEDICATION Ideally, medications should be extremely specific in their effects, have the same predictable effect for all patients, never be affected by concomitant food or other medications, exhibit linear potency, be totally nontoxic in any dosage, and require only a single dose to effect a permanent cu re. Unfortunately, that “perfect” drug has yet to be discovered. The concept has fascinated pharmacists and physicians since Galen of Kos expressed it nearly 18 centuries ago. © 2003 by CRC Press LLCIn reality, most drugs have multiple effects on the host. Those actions may even vary among hosts, depending upon factors as diverse as genetics and local environ - ments. A drug is usually taken for one de sired pharmacological action, but this is often accompanied by other, usually undesired, reactions referred to as side effects. Even drugs genetically engineered and ch emically close to an endogenous chemical may fall short of the ideal profile. Exogenous administration of a “normally occurring substance” may disturb or fail to match a pa rticular patient’s internal control mecha - nisms for homeostasis, the balance of physio logy. Part of the interest in natural products is motivated by the wish to produce a desirable effect with fewer side effects. However, on a philosophical level, the reality of pharmacology is that all substances in high amounts, including even oxygen or water, can be toxic. From this viewpoint, drugs can be likened to poisons that may have desirable side effects. If health profes - sionals adopt this viewpoint in using, prescribing, or recommending medications, iatrogenic drug misuse, misadventures, ab use, and nosocomial-medication-related errors could be minimized. In many cases, knowledge of both the indicated use of a product and its reported side-effect profile allow the caregiver to select among similar agents for an individual patient in order to minimize undesired side effects. DRUG DELIVERY AND ADMINISTRATION Prior to discussing basic pharmacology and pharmacokinetics, some exposure to pharmaceutics is helpful. This area of pharmacy knowledge focuses on dosage forms and routes of administ ration. Knowledge of pharmaceu tics is required in order to begin to understand how drugs work. For a medication to be effective, it firs t needs to reach a target location in the organism. Some type of delivery system is needed for this to occur. This requires use of a specific route of administration. Ro utes of administration are more numerous than people outside the medical professions would think. Thanks to technological advances, both routes for drug administration and dosage forms (a term describing the specific physical form of the drug’s active and inactive ingredients) exhibit more variety today than ever before. Three major routes are used for drug deli very: topical, enteral, and parenteral. The topical route (cutaneous) can be used to apply a drug for its local activity at the area of application. Antifungal me dications, such as miconazole creams for athlete’s foot, serve as examples. Drugs ma y also be applied topically (transcutane - ous) to a site from which they can be abso rbed to exert a systemic effect. Nitroglyc - erin ointment or patches, used to prevent angina pain, are examples of this route. Vaginal creams and suppositories are examples of topical drugs used in contact with mucous membranes rather than the epidermi s. Topical drugs are also used for the eye (ophthalmic), ear (otic), and nose (intra nasal). Finally, certa in topical drugs can be delivered into the lung (inhalation) for both local and systemic effects. The most common and convenient route for drug administration is via the gas - trointestinal tract. The oral route ( per os, PO) is the most common enteral route, but not the sole one. Medication may be admin istered sublingually (SL), using tablets formulated for SL administrati on. Nitroglycerin is available as a sublingual tablet. This © 2003 by CRC Press LLCdosage form is rapidly absorbed into th e bloodstream. Medication can also be admin - istered buccally (in contact wi th the oropharyngeal mucosa), as in the case of nystatin oral suspension; and rectally. When medication is given via the gastrointestinal tract, mechanisms usually involved in the absorption of nutrients are “borrowed” to transport the drug into the body. In effect, the gastrointestinal tract takes on an added function. This is possible because abso rbable drugs have some chemical features in common with nutrients. This facilitates the active or passive absorption of the drug. The nasoen - teric and percutaneous enteral tubes, familiar to many for delivery of nutrition, may, with appropriate precautions, also be pres sed into service for enteral drug delivery. The most invasive route for drug administr ation is the parenteral route. Whereas, technically, parenteral means not via the gast rointestinal tract, it is commonly used to refer to routes requiring some form of injection. Once again, a variety of routes come under this umbrella. The routes include injection into the bloodstream, most commonly intravenously (IV), or into a vein. This can be done rapidly (IV push), over a limited time (IV piggy back), or over a longer time (IV infusion). Occasionally, the blood vessel may be an artery instead of a vein. Arteries are sometimes used as the injection site for provision of intrahepatic chemotherapy. This is referred to as intraarterial injection. Medication can be injected into the su bcutaneous tissue (SQ), muscle tissue (intramuscularly, IM), or the skin (intraderm al). Medication may also be injected into the spinal canal or into the dura surrounding the spinal cord. This is done mainly for pain control. The techniques here are in trathecal and subdural, respectively. Occa - sionally, chemotherapy for cancer or infection is given intr athecally in an attempt to decrease systemic side effects while maxi mizing central nervous system (CNS) effec - tiveness or to compensate for poor pa ssage of many medications across the blood/brain barrier from the bloodstream into the cerebrospinal fluid. Antiinflamma - tory steroids, used for severe arthritis, ma y be injected into th e space within a joint. This is called synovial injection. Occasio nally medication, particularly hydration fluids, may be given by slow infusion subcutaneously rather than into a vein. This is called hypodermoclysis, and it is no longer commonly used for large volumes. Small volumes are sometimes given this way. An example of this would be insulin delivered by a pump. Medication can also be given directly into the peritoneum (intraperito - neal), directly into the wall of the heart or into one of its chambers (intracardiac), and sprayed into the trachea (i ntratracheal). The latter two routes may be used during cardiopulmonary resusc itation. Occasionally, drugs can be given via catheter into the ventricles of the brain. This is called intraventricular administration. During gestation, drugs may even be administered to a fetus in utero or into the amniotic fluid, referred to as intrauterine injection. Finally, there is a route of injection called intraosseous, where the injection is done into the bone marrow of long bones such as the tibia. This may be useful in children with poor veins and relatively soft bones. DOSAGE FORMS In order to take advantage of this multitude of medication administration routes, a similarly diverse number of dosage forms have been devised. Some, such as urethral © 2003 by CRC Press LLCbougies, are no longer in common use, wh ile others, such as the transcutaneous patch and metered dose inhalers (MDI), are becoming increasingly popular. Pills and Powders When the general public thinks of an oral dosage form, the word pill is commonly used. The pill is act ually an archaic dosage form. Pills consist of medication com - bined with inactive ingredients to form a gelatinous (doughy) mass. This mass is then divided, rolled into cylinders on a pill tile, and then cut into individual pills. The pills are then dried prior to use. Currently, few medications are truly pills. Carter’s Little Liver Pills ® and Lydia Pinkham’s Pills® are among the last of a once popular dosage form for both manufactured and extemporaneously prepared medi - cations. Powder papers (a small, precis ely measured quantity of medication and diluent inside a folded piece of paper) were once a popular method of drug delivery. Two over-the-counter (OTC) popular medications are available in this form: BC Powders ® and Goody’s Powders®. Tablets, Capsules, and High Tech The most common dosage form is the tablet. It is prep ared from a dry mixture of active and inactive ingredients (excipients). The excipients include binders, lubri - cants, diluents, and coloring agents. This mixture is m echanically compressed into solid tablets in various shapes. The excipien ts are considered in ert ingredients, but can occasionally cause difficulty in indivi dual patients. Lactos e is commonly used as a diluent. The quantity is usually too small to cause adverse effects, even in a lactose intolerant individual. Tartrazine, commonly called FD&C yellow dye No. 5, is a coloring agent. Serious allergic react ions are possible to this agent and to medications colored with it. Capsules are the other most common oral dosing form. Active ingredients, diluents, and lubricants (to improve the flow of the powder through the equipment) are put into preformed, hard gelatin shells that are then mated with a second gelatin shell. Liquid medication can also be sealed into a capsular shell. Several variations on the manufacturing of tablets and capsules can result in delayed or extended medication re lease into the gastrointestinal tract. The absorption of the drug into the bloodstr eam and the pharmacological effect of the drug will be affected by this alteration in the release of the medicine. The most advanced oral dosage forms use semiperm eable membranes or laser technology to produce dosage forms that release medicati on into the gastrointestinal tract at a controlled rate. Some drugs may be absorbed from the capil lary beds in the mouth. Nitroglycerin tablets are designed to dissolve under the tongue and will be absorbed sublingually. Recently, rapid dissolving tablets have b een developed to deliver medications into the gastrointestinal tract. The medication is released in the oral cavity but is absorbed at numerous locations in the gastrointestinal tract. This results in a quicker onset of action. Rapid disintegration (RD) is frequent ly associated with this type of dosage form. Other medications may be designed for absorption from the inner aspect of the cheek. These are referred to as buccal dosage forms. Lozenges may be used to © 2003 by CRC Press LLCdeliver medication into the oral cavity for both local and syst emic action. Local anesthetics for treating a sore throat can be put into a lozenge. A powerful pain medication, fentanyl, is available in a lozenge on a stick form for transmucosal absorption. Cough suppressants are also available as lozenges. Liquids Of course, oral liquids remain a popul ar dosage form. This category includes solutions such as teas (infusions and deco ctions), fluid extracts, syrups, drops, and tinctures, as well as emulsions and powders ready for reconstitution with water. With the popularity of “natural remedies,” the use of teas and homemade preparations has increased. All oral liquids are relatively s imple in comparison to oral liquid nutritional supplements. The supplements are generally oil-based solutions emulsified within water-based solutions with some of their ingredients suspended in a colloidal form. Recently, the introduction of foods havi ng desirable pharm acological properties has further blurred the distinction among dr ugs, nutritional supplements, and foods. Benecol® (contains plant stanol esters) and Take Control® (plant sterol-enriched spread) are the best examples of this, bu t even the marketing of oatmeal and oat bran ventures into this newly gr ayed area separating drugs and foods. Rectal Dosage Forms Other enteral dosage forms are designed for absorption in the sigmoid colon and may be solid dosage forms (suppositories), liquids (enemas), or aerosols (foams). Again, both local and systemically acting medications may be given via this route. Hemorrhoid treatments, antiemetics, laxatives, and antipyretics (medications used to treat fever) are all commonly given in these forms. Topical Agents Topical dosage forms are similarly dive rse. Ointments (oil base) may deliver topical medications. Creams (w ater-soluble base), gels, and mustards (pasty sub - stance spread on a cloth and wrapped around a body part) also do so. Shampoos, soaps, solutions, and topical patches may also deliver medication in a useful manner. Nasal, ophthalmic, and otic (for the ear) solutions and suspensions are available. Aerosols, sprays, nebulized medications, metered dose inhalers, and powders for inhalation are used to deliver medication to the respiratory tract. Intravaginal sup - positories (also called vaginal tablets), creams, douches, and sponges are used to deliver medications. Injections Parenteral dosage forms are mainly water-based solutions, but a few novel approaches are used. These include solution s in solvents other than water, oil-in- © 2003 by CRC Press LLCwater emulsions, and even drug-impregnated solids used as subdermal implants. Recently, drugs have even been delivered inside liposomes in a parenteral liquid. Pharmaceutical Elegance: Coats to Disguise, Protect, and Increase Duration Coatings have been used on tablets to hide bad tastes (e.g., E-Mycin—erythro - mycin). One liquid suspension (Biaxin®—clarithromycin) consists of film-coated granules. The coating again hides the taste of the medicine. Interestingly, this is a liquid medication that should not be given via a small-bore feeding tube. The granules can “logjam” at the curves in the tube and occlude it. Other coatings, referred to as enteric coatings, are used to prevent dissolution and inactivation of the drug in the stomach by ga stric secretions. Extensive efforts have been made to engineer dosage forms that change the absorp tion of medications. The goal is usually to extend the duration of action for a drug with a relatively short half-life. Repetabs ® provide an example of tablets designed to provide a quantity of quickly released medication followed by a quantity of drug released slowly over time. Capsules can contain pellets coated with varying thickness of slowly dissolving excipients to achieve a timed-release bioavailability. Si nce medications are sometimes crushed before administration, one needs to know why the coating was on the tablet, where the drug will enter the gastrointestinal tract, and how removing the coating will affect the bioavailability of the dosage form. COMPOUNDING: WHAT’S OLD IS NEW AGAIN As can be seen from the preceding info rmation, the history of pharmacy goes back to production of medication by a ph armacist rather than a commercial manu - facturer. Today, many pharmacists are ente ring a niche market meeting individualized needs with individualized products. Co mpounding of pharmaceutical products pro - vides such an opportunity. In this area, pharmacists with knowledge of product and patient work as problem solvers to provide a solution to a medical problem not amenable to treatment with off-the-shelf approaches. Dosage forms, which are prepared by compounding pharmaci sts, parallel com - mercial dosage forms. Capsules, topical prep arations including tr ansdermal gels with enhanced ability to penetrate the skin, ophthalmic ointments, suppositories, troches, medicinal lollipops, and oral suspensions are among the dosage forms used by compounding pharmacists. Flavoring of liquid oral preparations is another area of expertise used by these practitioners. Dosage forms containing multiple drugs can also be prepared to increase patient compliance and alleviate problems in patients who have difficulty swallowing cap - sules, tablets, or liquid me dications. Specially prepared lozenges that slowly dissolve and release small volumes of medications in to the gastrointestinal tract are useful for this purpose. Preparati ons that may have a therapeutic advantage but also have limited stability, and hence require short expiration dating, are poorly suited for © 2003 by CRC Press LLClarge-scale manufacturing operations. A compounding pharmacy may be the only source for these types of preparations. PHARMACOKINETICS In order to understand drug in teractions and drug interac tions with nutrients, one needs to have a basic knowledge of pharmacokinetics. Pharmacokinetics is a science that deals with the progressive movement and alteration of chemical substances within the body. Bioavailability is important when reviewing the effects or pharma - cology of a drug. In order for a drug to have an effect, it needs to be physically present at the site where it exerts its pha rmacological action. First, the drug needs to be absorbed, and then it needs to be distributed or transported to a receptor—the site of action. The drug may then exert it s pharmacological eff ect. Subsequently, the drug may be metabolized and then excreted . The acronym ADME is used to help people remember the pharmacokinetic aren as of absorption, distribution, metabo - lism, and elimination. Keep in mind that drugs are usually substances not commonly ingested. All the pharmacokinetic mechanisms for each of the four ADME processes probably did not evolve to handle drugs. Drugs can be likened to a “Trojan Horse.” Most fre - quently, drugs enter the body via the gastrointestinal tract, a route that clearly serves the purpose of absorbing food. Drugs have to be chemically similar to food sub - stances in order to be absorbed, but dissimilar enough to avoid digestion. For example, the reason that insulin must be injected is that it is a polypeptide. If ingested, insulin would be digested into smaller peptides and amino acids and lack the pharmacological action expected from insulin. In order to understand drug dosing, one needs to appreciate how the amount of drug in the bloodstream changes after admi nistration of the drug. Pharmacologists will frequently employ a graph of serum concentrations of a drug vs. time in order to describe the drug’s bioavailability. Th e serum concentration is affected by each ADME component. The relative amount of absorbed drug compared with adminis - tered drug is referred to as the drug’s bioavailability. Total bioavailability and the time course of absorption aff ect drug action. Even while the drug is being absorbed, the processes of distribution, metabolism, and elimination are al ready at work affect - ing serum levels. When a drug leaves th e bloodstream and accumulates in another tissue, this lowers the serum level. Sometimes, this will increase the activity of the drug, particularly for drugs that exert th eir effects in tissues other than the blood - stream. General anesthetics and antidepressa nts have their effects in the CNS. Other drugs may accumulate in adipose tissue, only to be released slowly over an extended time. A graph of the serum concentration of a typically orally administered drug plotted against time is de picted in Figure 1.1. Absorption Many factors affect absorption. The prin cipal factors are the route of adminis - tration, the dosage form, the chemical nature of the drug, and the local environment © 2003 by CRC Press LLCat the site of absorption (i.e., pH, blood flow, physiological changes of tissue, etc.). One general principle to remember is th at drugs are generally absorbed in an unionized form. Weakly acidic drugs are, th erefore, generally absorbed in the stom - ach, while weakly basic drugs are absorbed in the small intestine. Most drugs are weakly basic. Binding to other chemicals in the gastrointestinal tract may interfere with absorption. Distribution Once the drug enters the body, it travels within the bloodstream. Depending on its chemical nature, the drug may preferenti ally concentrate in a particular tissue. Many water-soluble drugs remain in the fluid compartment. Other drugs may pref - erentially accumulate in adip ose tissue or muscle. This affects the serum levels of the drug. Theoretically, the co ncentration of a drug put in a solvent should be equal to the amount of the drug divided by the volume of the solvent. If you think of the organism as the solvent for a drug, then the amount of the drug absorbed divided by the volume of the organism should equal the measured drug concentration. Since the organism is not a single solvent, this does not work. A theoretical construct called volume of distribution (Vd) is used to reconcile the measured serum level and the amount of drug absorbed. A volume of distribution of 0.6 L/kg indicates that the drug is distributed principally in the fluid compartm ent that accounts for about 60% of our body weight. A lower Vd would indicate that the drug is prefer - entially found in the bloodstream. Higher Vds indicate that the drug is sequestered in tissues other than the bloodstream (i.e., muscle, bone, CNS, etc.). Metabolism When a drug enters the body, it will encounter metabolic processes that may alter its chemistry. As a general rule, the metabolic processes in the body tend to decrease toxicity and enhance the eliminat ion of foreign chemicals. These paired processes are achieved by three principa l mechanisms: (1) increasing the water solubility of these chemicals, (2) decreas ing the size of the foreign molecules, and Figure 1.1 Serum concentration of a typically orally administered drug plotted against time.Hours0 8 16 246 4 2 0 © 2003 by CRC Press LLC(3) binding the drugs to larger molecules (conjugation). The end products of these processes are referred to as metabolites . Metabolism can happen in the peripheral tissue of the body or in a specific organ. The liver is frequently the organ involved in this process. Many enzymes participate in drug metabolism; one group of liver enzymes responsible for much of this act ivity is the cytochrome P450 enzymes. Furthermore, many subgroups of enzymes ex ist in this class. One drug or nutrient may alter the action of these enzymes on a second drug or nutrient by binding to or having a greater affinity for the enzyme s than the other substance. This may result in drug–drug or drug–nutrient interactions. Changes in liver func tion may also affect drug metabolism. Age alone, in the absen ce of liver pathology, will affect drug metabolism. This will be elaborated in later chapters of the text. Elimination Several organs are involved in eliminating drugs from the body. The kidneys are the most important organs in this regard. These organs of homeostasis remove drugs and drug by-products from circulation by both passive action (filtration) and by active processes involving secretion and resorp tion of substances from the plasma. The lungs, the liver, the skin, and various glands may also help in the elimination of chemicals from the body. Once again, age will be a factor because renal function declines as a function of normal aging. Substances processed by the kidney may be actively or passively secreted into the urine as it traverses the nephron, which is the functional unit of the kidney. Substances can also be activel y or passively reabsorbed into the blood - stream before leaving the nephron. This pr ocess can be affected by the pH of the urine and can be enhanced or inhibited by the presence of other substances in the urine or the blood. Drugs that alter urine production, such as diuretics, may also affect the urinary excretion of drug and drug metabolites, and this may result in interactions. PHARMACODYNAMICS The study of the actions of drugs is called pharmacodynamics. Drugs can be categorized as exerting an action in a ge neral or a specific manner. Drugs with general, nonspecific effects may affect al l body tissues and cells. Drugs with specific effects will have a target substrate that th ey act on, in one or more organ systems. The fewer systems affected by the drug, the more specific its action. Specifically acting drugs are generally considered better to work with from a pharmacodynamic perspective. In contrast to the serendipitous manner in which drugs were developed in the past, drug development now focuses on chemical specificity based on drug and receptor structure. Drugs or foods that interfere dir ectly with another drug’s action would cause a drug–drug or drug–nutrient interaction. Drugs with an effect similar to another drug may cause a great er than additive pharmacological effect. This type of interaction is called syne rgism. Drugs with opposing pharmacological effects may negate the benefits of one of the agents . © 2003 by CRC Press LLCREFERENCE MATERIALS This chapter has presented a brief overvie w of some ways th at pharmacists tend to categorize and think about pharmacology, drugs, and drug interactions. For readers who wish to know more about these concepts, the following references provide in-depth and authoritative information. Textbooks and References Merck Manual, 17th edition, Beers, M.H. and Be rkow, R., Eds., Merck Research Laboratories, Whitehouse Sta tion, NJ, 1997. (A concise guide to medical science designed for the lay public, th is reference gene rally provides quick cursory infor - mation about illness. It is a valuable t ool that may rapidly provide information about unfamiliar me dical conditions.) Hansten & Horn’s Drug Interact ions Analysis and Management, Hansten, P.D. and Horn, J.R., Eds., Facts & Comparisons, In c., St. Louis, MO., updated quarterly. (This text details the mechanism of various drug interactions. It is useful for someone who wants more than a superfic ial understanding of how drugs interact.) Goodman and Gilman's The Pharmaco logical Basis of Therapeutics, 10th ed., Hard - man, J.F. and Limbird, L.E., Eds., McGr aw-Hill, New York, 2001. (This is the classic reference for pharmacology.) Drugs Manuals and References Readers who wish to know more about a particular drug or class of drugs would do well to refer to the following references. Drug Facts and Comparisons, Facts & Comparisons, Inc., St. Louis, MO; updated monthly. (This is the drug reference most extensively used by pharmacists. It is somewhat more oriented to community practi ce. A loose-leaf format that is updated monthly, a hardbound format that is upd ated annually, and a CD-ROM are all marketed. The CD-ROM can be made access ible on a computer network. It covers over 10,000 products and includes compar ison charts betwee n similar products. Both over the counter (OTC) and prescrip tion products are covered. It provides information about sugar-free and alcohol -free formulations. Information regarding the relative costs of drugs is include d. Both FDA-approved and non–FDA-approved (off-label) uses of drugs are covered. Information is presented on a large number of, but not all, investigational agen ts. The monthly update s highlight product changes. Manufacturer addr esses, normal lab values, and pharmaceutical abbrevi - ations are included. It includes the in formation that is commonly required by practitioners about medications. Pharmacology, ph armacokinetics , adverse reac - tions, drug interactions, and food interactions are all covered.) AHFS Drug Information 2003, McEvoy, G.K., Ed., American Society of Health- System Pharmacists, Bethesda, MD, 2003. (This reference provides detailed mono - graphs on most drugs and includes bot h FDA-approved and non–FDA-approved (off-label) uses and information on the stability and incomp atibility of drugs. Monographs cover pharmacology, pharmacok inetics, dosages, contraindi cations, precautions, adverse effects, and intera ctions. Quarterly updates are issued, but most revisions are done annua lly. This reference is also available in hard- and © 2003 by CRC Press LLCsoftcover editions as well as on CD-ROM and online. The soft cover edition usually gets dog-eared after a year in a busy pha rmacy department. It is most commonly found in hospital pharmacy settings beca use the American Society of Health- System Pharmacists is the publisher. The information on each agent in this refer - ence is more extensive than Facts and Comparisons. One shortcoming is that it does not include every marketed medication.) Drug Information Handbook APhA, Lacy, C.F. et al., Eds. , Lexi-Comp, Inc., Hudson, OH, 2002. (A handbook-sized but rather wei ghty paperback that can fit in a lab coat pocket, this referenc e includes concise monographs of all drugs, and it is updated annually. Comparison charts of va rious agents are included, and the appen - dix contains therapy recommendations. Useful if information is needed in a very portable form.) Drug Interaction Facts, Tatro, D.S., Ed., Facts & Comparisons, Inc., St. Louis, MO, updated quarterly. (Providing extensive information about drug–drug and drug–food interactions, this reference examines mechanis m, clinical significance, timing, and management of interactions. The informati on is quite clear and acces - sible. Case and stu dy descriptions are provided, and the information is referenced. It is available in a hardbound format and also is computerized. Subscribers are provided with quarterly updates.) Drug-Induced Nutrient Depletion Handbook, Pelton, R., et al., Eds., Lexi-Comp, Inc., Hudson, OH, 2001. (This unique reference is designed to assist healthcare profes - sionals in guiding patients receiving medications on the selection of appropriate nutritional supplem entation. The Drug-Induced Nutrie nt Depletion Handbook con- tains a complete and up-to-date listing of the drugs known to deplete the body of nutritional compounds and identifies symptoms that may result from the depletion of specific nutrients. The re ference section includes summ aries of selected findings organized by individual drugs.) Drugs in Pregnancy and Lactation, Briggs, G.G., Freeman, R.K., and Yaffe, S.J., Eds., Williams & Wilkins, Baltimore, MD, 2001. (Thi s text is a complete reference on the use of drugs in pregnancy and lactation, including classification of risk. Summaries of available studies are included, and the information is very carefully referenced.) Evaluations of Dr ug Interactions, V ol. 1, II (EDI), Zucchero, F.J., et al., Eds., First DataBank, St. Louis, MO, 20 02. (This book is a comprehe nsive reference for both prescription and OTC drug conflicts. It co vers more than 34,000 drug interactions. Each interaction is outlined in a m onograph format. The monographs include severity coding of the interaction, a summary of the overall effect of the interaction, and a synopsis of documented cases. Mechanisms of action and related agents that are chemically similar to the interacting drugs are discussed. Helpful recommen - dations, when available, of acceptable alternative th erapies supported by primary literature are also included. ED I is updated six times a year.) Geriatric Dosage Handbook, Semla, T.P., Beizer, J.L., and Higbee, M.D., Eds., Lexi- Comp, Inc., Hudson, OH, 2002. (This guid e provides information on medications for the elderly. Informative monographs, compiled from current literature and clinical experiences, cover 800 commonl y used drugs. The appendix includes additional clinical drug info rmation (charts, ta bles, and graphs) relevant to the practice of geriatri c pharmacotherapy.) King Guide to Intravenous Admixtures, Catania, P.N., Ed., Ki ng Guide Publications, Inc., St. Louis, MO, updated quarterly. (This re ference contains information on the stability and compatibility of parenteral drugs. It is in loose-leaf format and is updated quarterly. The information is presented in tabular form.) © 2003 by CRC Press LLCHandbook on Injectable Drugs, 11th ed., Trissel, L.A., American Society of Health- System Pharmacists, Bethesda, MD, 2000. ( Handbook on Injectable Drugs con- tains stability and compatib ility information on roughly 300 drugs that are com - mercially available as well as investigational drugs, with references.) Ident-A-Drug Reference, Therapeutic Research Cent er, Stockton, CA, 2001. (This reference, updated annually, allows you to quickly identify prescription and OTC tablets and capsules by the code number imprinted on them. The latest version has more than 25,000 drug listings. It lists the code number, physical description, dose, ingredients, National Drug Code (NDC) universal identification number, Drug Enforcement Administra tion (DEA) class number, and manufacturer of each drug. Brand name and generi c products available in the U.S. and in Canada are covered.) Micromedex , Greenwood Village, CO. (A multiple CD-ROM or Internet-based com - prehensive drug info rmation reference, Micromedex allows electronic searches of its database. Besides the info rmation available in the pr inted references, it also provides citations for the primary inform ation sources used to compile the mono - graphs. It can be networked within an institution for availability at multiple work - stations. This reference helps the user tr ack down hard to find information without consulting the primary literature. Unappr oved but literature-supported uses for medications are well documented in this re ference, and the cita tions are included. The CD-ROM contains multip le references. A user may subscribe to all or only part of the services, as practice require ments dictate. Subscr iptions are available for all the modules at additional cost . The available modules are DRUGDEX, POISINDEX, IDENTIDEX, EMERGINDEX, PDR, MARTINDALE, TOMES, and DRUG-REAX. Identidex is a feature of Micromedex that can help identify drugs based on the color, shape, and marki ngs on the tablets. It is particularly helpful when trying to identify generic drugs and products of foreign origin.) Pediatric Dosage Handbook, 8th ed., Taketomo, C.K., Hoddi ng, J.H., and Kraus, D.M., Eds., Lexi-Comp, Hudson, OH, 2001. (This handbook is one of the best references for pediatric drug information. It incl udes more than 615 monographs featuring compilations of recommended pediatric doses found in the literature. Administra - tion guidelines are provided for the proper administration of oral and parenteral medications. Directions fo r preparing extemporaneously compounded liquid dos - age forms for oral administration are prov ided along with appropriate references. This may be useful for patients with fe eding tubes after cons ulting a pharmacist about other issues. Guidelines for monito ring patients with laboratory tests and other parameters to assess the efficacy and toxicity of selected medications are provided. Food interactions, describing the interactions between the drug listed in the monograph and food or nutritional subs tances, are also presented. The hand - book is available in soft cover and fits in a laboratory coat pocket.) Physician’s Desk Reference, Medical Economics Inc., Montvale, NJ, 2002. (Known as the PDR, this reference consists of paid advertisements placed by pharmaceutical companies. The advertisement for each drug is limited to the package labeling (package insert) approved by the Fede ral Food and Drug Administration (FDA). The limitations of the information exceed its benefits for he alth professionals. Literature-supported but unapproved uses of drugs are not covered. The information is current only as of the last time the package insert was changed (possibly when the drug was first introduced for sale in th e U.S.). Drugs that are widely marketed in generic versions but no longer mark eted by the originator company may not appear at all, even though they are useful and cost-effective agents (i.e., phenobar - bital). One helpful feature of the PDR is the drug identification section with color © 2003 by CRC Press LLC