McKenna's Pharmacology for Nursing, 2e

M c KENNA’S PHARMACOLOGY FOR NURSING AND HEALTH PROFESSIONALS SECOND EDITION Lisa McKenna RN, RM, BE d S t , ME d S t , GD Health Admin & InfoSys, GD LFAH, P h D, MACN Professor, School of Nursing and Midwifery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia

Anecita Gigi Lim RN, BS c (Nursing), MHS c , GD Science Pharmacology, PGD Social Science, P h D, FCN Senior Lecturer, School of Nursing, University of Auckland, Auckland, New Zealand

Original US edition

Focus on Nursing Pharmacology Amy M. Karch RN, MS Associate Professor of Clinical Nursing, University of Rochester School of Nursing, Rochester, New York

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National Library of Australia Cataloguing-in-Publication entry Title: McKenna’s pharmacology for nursing and health professionals/ANZ adaptation by Professor Lisa McKenna, Dr Anecita Gigi Lim; original US edition by Amy Karch. Edition: Second edition. ISBN: 9781920994983 (paperback) 9781922228031 (ebook) Notes: Includes bibliographical references and index.

Subjects: Pharmacology—Australia—Handbooks, manuals, etc. Drugs—Australia—Administration—Handbooks, manuals, etc. Nursing—Study and teaching—Handbooks, manuals, etc. Midwifery—Study and teaching—Handbooks, manuals, etc. Other Authors/Contributors: McKenna, Lisa. Lim, Anecita Gigi. Karch, Amy. Dewey number: 615.10993

Every effort has been made to trace and acknowledge copyright. Should any infringement have occurred, the authors and publisher tender their apologies and invite the copyright holders to contact the publisher at the publisher’s address given above. References to websites were checked for accuracy at the time of going to press. However, the authors and publisher are not responsible for the content, currency, accuracy or reliability of material on any sites that are referenced. Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editor and publisher are not responsible for errors or omissions or any consequences from application of the information in this book and make no warranty, express or implied, with respect to the content of the publication. The authors, editor and publisher have exerted every effort to ensure that any drug selection and dosage set forth in this text are in accordance with the current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations and the constant flow of information relating to drug therapy and drug reactions, the reader is advised to check the package 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 an infrequently employed drug. Some drugs and medical devices presented in this publication have clearance for limited use in restricted research settings from the Australian Therapeutic Goods Administration (TGA), the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) and the United States Food and Drug Administration (FDA). It is the responsibility of the healthcare provider in Australia and New Zealand to ascertain the TGA or Medsafe status of each drug or device planned for use in his or her clinical setting.

Reviewers, Australia and New Zealand

Genevieve BRIDESON RN, RM, BN (Hons), P h D (cand.) Lecturer, School of Nursing and Midwifery, Flinders University, Adelaide, South Australia Petra CZARNIAK BP harm , MP harm , D ip T each , GC ert (DiabEd), MPS, AACPA Senior Lecturer, School of Pharmacy, Curtin University, Perth, Western Australia Julie HANSON RN, BN, PGC ert (Advanced Nursing Practice), P h D (cand.) Lecturer, School of Nursing and Midwifery, University of the Sunshine Coast, Maroochydore, Queensland Karole HOGARTH RN, BS c (Hons), PGC ert (Tertiary Teaching), P h D Senior Lecturer, School of Nursing, Otago Polytechnic Te Kura Matatini ki Otago, Dunedin, New Zealand Heather JOSLAND RN, BN, MA (Hlth Sci), PGC ert (Clin Tchg) Senior Nursing Lecturer, Department of Nursing and Human Services, Christchurch Polytechnic Institute of Technology, Christchurch, New Zealand Snezana KUSLJIC BS ci (Hons), P h D Senior Lecturer, Pharmacologist, Department of Nursing, The University of Melbourne, Melbourne, Victoria; Honorary Senior Research Fellow, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria Victoria KAIN RN, MN, P h D Senior Lecturer, School of Nursing and Midwifery, Griffith University, Brisbane, Queensland Catherine KING MP harm , P h D Senior Lecturer, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia Patricia LOGAN BS c , MA pp S c , GC ert (Uni Tech & Learn), P h D, ANMT Lecturer in Health Science, School of Biomedical Science, Charles Sturt University, New South Wales

Rosie MacLEAVY RN, BN, GD ip (Paediatrics), MCN (Paediatrics) Lecturer, Unit Coordinator, School of Health Sciences, University of Tasmania, Hobart, Tasmania; Board of Directors, Australian College of Children and Young People’s Nurses (ACCYPN) Michael J. McGIVERN RGN, RMN, BN, D i PHE, PGD ip HS c (Advanced Nursing), NCAET, C ert M gmt Clinical Nursing Tutor, NorthTec School of Nursing Tai Tokerau Wa– nanga, Whangarei, Northland, New Zealand Andrea MILLER BN (Hons), MCN, ME d Clinical Lecturer, School of Health Sciences, University of Tasmania, Hobart, Tasmania Kate NORRIS RN, BN, MA (Nursing), PGC ert (HlthSci), CAT Senior Nursing Lecturer, Department of Nursing and Human Services, Christchurch Polytechnic Institute of Technology, Christchurch, New Zealand Nadim RAHMAN RN, BN, MBBS, AMC (Primary Assessment), PGT (General Practice), GCHPE Lecturer, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria Joanne RAMSBOTHAM RN, EM, C ert A dult E d , MN C hild H ealth , P h D Lecturer, School of Nursing, Queensland University of Technology, Brisbane, Queensland David STANLEY RN, RM, N urs D, BA N g , MS c HS, D ip HE (Nursing), GC ert (HPE) Associate Professor, School of Population Health, The University of Western Australia, Perth, Western Australia Jenny WILKINSON BS c (Hons), G rad D ip (FET), MHE d , P h D Associate Professor, School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales Cecilia YEBOAH RN, RM, MN, P h D, MRCNA Lecturer/International Academic Advisor—Nursing, School of Nursing, Midwifery and Paramedicine (Melbourne Campus), Australian Catholic University, Victoria

Contents

 9 Antibiotics 90

Preface  vii To the student using this text  xii Acknowledgements xii  PART 1   Introduction to nursing pharmacology 1  1 Introduction to drugs 2

Bacteria and antibiotics 91 Bacteria and resistance to antibiotics 94 Aminoglycosides 95

Carbapenems 97 Cephalosporins 99 Macrolides 103 Lincosamides 104 Monobactam antibiotic  104 Fluoroquinolones 106 Penicillins and penicillinase-resistant antibiotics 108 Sulfonamides 112 Tetracyclines 114 Antimycobacterials 118 New classes of antibiotics and adjuncts 121 10 Antiviral agents 126 Agents for influenza A and respiratory viruses 130 Agents for herpes and cytomegalovirus 132 Agents for HIV and AIDS 134

Sources of drugs 3 Drug evaluation 5 Legal regulation of drugs 8 Sources of drug information 11

 2 Drugs and the body 15 Pharmacodynamics 16 Pharmacokinetics 19

Factors influencing drug effects 25 Optimal therapeutic effect 28

 3 Toxic effects of drugs 31 Adverse events, adverse drug events and adverse drug reactions 31 Adverse drug effects 32 Drug allergy 33 Drug-induced tissue and organ damage 33  4 Clinical decision making in drug therapy  42 Nursing: Art and science 43 Midwifery: Art and science 43 The clinical decision making process 43 Prevention of medication errors 46  5 Mathematics and dosage calculations 53 Basic mathematical calculations 54 Measuring systems 55 Calculating dose 55  6 Challenges to effective drug therapy 60 Consumer awareness 61 Over-the-counter drugs 62 Alternative therapies and herbal medicine 63 Off-label uses 64 Costs of healthcare and the importance of teaching 64 Drug abuse 66 Protecting the environment 68  PART 2  Chemotherapeutic agents 71  7 Introduction to cell physiology 72 The cell 73 Cell properties 75 Cell cycle 78  8 Anti-infective agents 81 Anti-infective agents 82

Anti-hepatitis B and C agents 144 Locally active antiviral agents 146

11 Antifungal agents 150 Systemic antifungals 151 Topical antifungals 157 12 Antiprotozoal agents 163 Malaria 164 Antimalarials 166 Other protozoal infections 170 Other antiprotozoal agents 172 13 Anthelmintic agents 179

Intestine-invading worm infections 180 Tissue-invading worm infections 181 Anthelmintics 183

14 Antineoplastic agents 190 Cancer 191 Antineoplastic drugs 192

Alkylating agents 195 Antimetabolites 200 Antineoplastic antibiotics 205 Mitotic inhibitors 209 Hormones and hormone modulators 212

Cancer cell–specific agents 218 Miscellaneous antineoplastics 222  PART 3  Drugs acting on the immune system 227 15 Introduction to the immune response and inflammation 228 Body defences 229 Pathophysiology involving the immune system 237

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Contents

16 Anti-inflammatory, antiarthritis and related agents 240 Anti-inflammatory, antiarthritis and related agents 241 Salicylates 241 Non-steroidal anti-inflammatory and related agents 246 Antiarthritis agents 252 17 Immune modulators 258 Immune stimulants 259 Immune suppressants 263 18 Vaccines and sera 272 Immunity 273 Immunisation 273 Vaccines 278 Immune sera 285  PART 4  Drugs acting on the central and peripheral nervous systems 291 19 Introduction to nerves and the nervous system 292 Physiology of the nervous system 293 Central nervous system 297 Clinical significance of drugs that act on the nervous system 301 20 Anxiolytic and hypnotic agents 303 States affected by anxiolytic and hypnotic drugs 304 Benzodiazepines used as anxiolytics 305 Barbiturates used as anxiolytic/hypnotics 310 Other anxiolytic and hypnotic drugs 312 21 Antidepressant agents 316 Depression and antidepressants 317 Tricyclic antidepressants 317 Monoamine oxidase inhibitors 323 Selective serotonin reuptake inhibitors 325 Other antidepressants 330 22 Psychotherapeutic agents 334 Mental disorders and their classification 335 Antipsychotic/neuroleptic drugs 336 Antimanic drugs 344 Central nervous system stimulants 347 23 Antiseizure agents 352 Nature of seizures 353 Drugs for treating generalised seizures 356 Drugs for treating partial seizures 365 24 Antiparkinsonism agents 372 Parkinson’s disease and Parkinsonism 373

27 General and local anaesthetic agents 416 General anaesthesia 417 General anaesthetic agents 419 Local anaesthesia 424 Local anaesthetic agents 425 28 Neuromuscular junction blocking agents 432 The neuromuscular junction 433 Neuromuscular junction–blocking agents 434  PART 5  Drugs acting on the autonomic nervous system 443 29 Introduction to the autonomic nervous system 444 Structure and function of the autonomic nervous system 445 The sympathetic nervous system 446 The parasympathetic nervous system 450 30 Adrenergic agonists 455

α- and β-adrenergic agonists 456 α-specific adrenergic agonists 462 β-specific adrenergic agonists 465

31 Adrenergic blocking antagonists 469 Non-selective adrenergic blocking agents 470 Non-selective alpha-adrenergic blocking agents 474 Alpha 1 -selective adrenergic blocking agents 475 Non-selective beta-adrenergic blocking agents 477 Beta 1 -selective adrenergic blocking agents 482 32 Cholinergic agonists 487

Direct-acting cholinergic agonists 488 Indirect-acting cholinergic agonists 491

33 Anticholinergic agents 501

Anticholinergics/parasympatholytics 501

 PART 6  Drugs acting on the endocrine system 511 34 Introduction to the endocrine system 512 Structure and function of the endocrine system 513 The hypothalamus 514 The pituitary gland 515 Endocrine regulation 517 35 Hypothalamic and pituitary agents 521 Drugs affecting hypothalamic hormones 522 Drugs affecting anterior pituitary hormones 525 Drugs affecting posterior pituitary hormones 530 36 Adrenocortical agents 536 The adrenal glands 537 Adrenocortical agents 539 37 Thyroid and parathyroid agents 551 The thyroid gland 552 Thyroid agents 556 The parathyroid glands 562 Parathyroid agents 565 38 Agents to control blood glucose levels 572

Dopaminergic agents 374 Anticholinergic agents 379 Adjunctive agents 382 25 Muscle relaxants 385 Nerves and movement 386

Neuromuscular abnormalities 387 Centrally-acting skeletal muscle relaxants 388 Direct-acting skeletal muscle relaxants 390 26 Opioids, opioid antagonists and antimigraine agents 397 Pain 398 Opioids 400

Glucose regulation 573 Diabetes mellitus 576 Insulin 578 Sulfonylureas and other hypoglycaemic agents 585 Glucose-elevating agents 591

Migraine headaches 409 Antimigraine agents 410

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Contents

 PART 7   Drugs acting on the reproductive system 595 39 Introduction to the reproductive system 596 Female reproductive system 597 Male reproductive system 601 The human sexual response 603 40 Drugs affecting the female reproductive system 606 Sex hormones and oestrogen receptor modulators 607 Fertility drugs 617 Uterine motility drugs 620 41 Drugs affecting the male reproductive system 627 Androgens 628 Anabolic steroids 631 Drugs for treating penile erectile dysfunction 634  PART 8  Drugs acting on the cardiovascular system 641 42 Introduction to the cardiovascular system 642 Structure and function of the heart 643 Electrocardiography 646 Circulation 649 43 Drugs affecting blood pressure 657 Review of blood pressure control 658

51 Diuretic agents 803 Diuretics 804 52 Drugs affecting the urinary tract and the bladder 819 Urinary tract anti-infectives 820 Urinary tract antispasmodics 824 Bladder protectant agent 826 Drugs for treating benign prostatic hyperplasia 828  PART 10  Drugs acting on the respiratory system 833 53 Introduction to the respiratory system 834 Structure and function of the respiratory system 835 Respiratory pathophysiology 837 54 Drugs acting on the upper respiratory tract 842 Antitussives 843 Decongestants 846 Antihistamines 852 Expectorants 857 Mucolytics 859 55 Drugs acting on the lower respiratory tract 864 gastrointestinal system 887 56 Introduction to the gastrointestinal system 888 Structure and function of the gastrointestinal system 889 Gastrointestinal reflexes 892 57 Drugs affecting gastrointestinal secretions 896 Drugs used to treat gastro-oesophageal reflux disease and ulcer disease 897 Digestive enzymes 912 58 Drugs affecting gastrointestinal motility 916 Laxatives 917 Antidiarrhoeals 923 Irritable bowel syndrome drugs 926 59 Antiemetic agents 929 Antiemetic agents 930  APPENDICES  A Answers to questions 939 B Parenteral agents 945 C Topical agents 949 D Ophthalmic agents 955 E Vitamins 959 F Complementary and alternative (CAM) therapies 962 Bronchodilators/antiasthmatics 866 Drugs affecting inflammation 875 Lung surfactants 881 Other drugs used to treat lower respiratory tract disorders 883  PART 11  Drugs acting on the

Antihypertensive agents 662 Antihypotensive agents 676 44 Cardiotonic agents 681 Heart failure 682 Cardiotonic agents 685 45 Antiarrhythmic agents 696 Arrhythmias 697 Antiarrhythmic agents 701 46 Antianginal agents 713 Coronary artery disease 714 Antianginal agents 715 47 Lipid-lowering agents 729 Coronary artery disease 730

Fat and biotransformation (metabolism) 731 Lipid-lowering agents 735 Combination therapy 746 Future therapies 746 48 Drugs affecting blood coagulation 750 Blood coagulation 751 Disorders affecting blood coagulation 754 Drugs affecting clot formation and resolution 755 Drugs used to control bleeding 767 49 Drugs used to treat anaemias 774 Anaemia 775 Erythropoiesis-stimulating agents 777 Agents used for iron-deficiency anaemia 782 Agents used for other anaemias 787  PART 9  Drugs acting on the renal system 793 50 Introduction to the kidneys and the urinary tract 794 The kidneys 795 The urinary tract 800

Index 968

Preface

P harmacology is regarded by some as a difficult area to teach in standard nursing, midwifery and professional healthcare curricula, whether it be at the diploma, undergraduate or graduate level. Many related pharma- cology texts are large and burdensome, mainly because they need to cover not only the basic pharmacology, but also the particulars included in each area considered. Teachers are scarce, and time and money often dictate that the invaluable content is incorporated into other courses. As a result, the content is often lost. At the same time, changes in healthcare delivery— more outpatient and home-based care, shorter hospital stays and more self-care—have resulted in additional legal and professional responsibilities for nurses, mid­ wives and other health professionals, making them ever more responsible for the safe and effective delivery of drug therapy. Pharmacology should not be seen as such a formi- dable obstacle in nursing and professional healthcare curricula. The study of drug therapy incorporates physiology, pathophysiology, chemistry and clinical fun- damentals—subjects that are already incorporated into curricula in most schools. OUR PHILOSOPHY McKenna’s Pharmacology for Nursing and Health Pro- fessionals is a text for nursing and professional healthcare students that approaches pharmacology as an under- standable, teachable and learnable subject. It is based on the premise that students first need to have a solid and clearly focused concept of the principles of drug therapy before they can easily grasp the myriad details associated with individual drugs. Armed in advance with this fun- damental knowledge of pharmacology, the student can then appreciate and use the specific details that are so readily available in many annually updated and published drug guides, such as Wolters Kluwer Health’s McKenna’s Drug Handbook for Nursing and Midwifery . With this goal in mind, McKenna’s Pharmacology for Nursing and Health Professionals provides a concise and uncluttered text for today’s student, presenting the subject in a user-friendly and understandable manner. Because this text is designed to be used in conjunction with a handbook of current drug information, it remains streamlined.

Thoroughly revised and updated, the second edition of McKenna’s Pharmacology for Nursing and Health Professionals emphasises “need-to-know” concepts. The text reviews and integrates previously learned knowledge of physiology, chemistry and clinical fun- damentals into chapters focused on helping students to conceptualise what is important to know about each group of drugs. Illustrations and tables sum up concepts to enhance learning. Carefully designed pedagogical features further focus student learning on clinical application, critical thinking, safety, lifespan issues related to drug therapy, evidence-based practice, individual and family teaching, and case-study-based critical thinking exercises that incorporate clinical reasoning principles. Check your understanding sections at the end of each chapter provide review questions to help the student master the material and prepare for examinations. ORGANISATION McKenna’s Pharmacology for Nursing and Health Pro- fessionals is organised following a “simple-to-complex” approach, much like the syllabus for a basic pharma- cology course. Because students learn best “from the bottom up”, the text is divided into 11 distinct parts. Part 1 begins with an overview of basic pharmacol- ogy, including challenges such as street drugs, herbal therapies and information overload. Each of the other parts begins with a review of the physiology of the system affected by the specific drugs being discussed. This review refreshes the information for students and provides a quick and easy reference when they are reading about drug actions. Part 2 introduces the drug classes, starting with chemotherapeutic agents—both antimicrobial and antineoplastic drugs. Because the effectiveness of these drugs depends on their interference with the most basic element of body physiology—the cell—students can easily understand the pharmacology of this class. Mastering the pharmacotherapeutic effects of this drug class helps students to establish a firm grasp of the basic principles taught in Part 1. Once the easiest pharmaco- logical concepts are understood, students are enabled to move on to the more challenging physiological and pharmacological concepts.

5

C H A P T E R 1 Introduction to drugs

viii

Preface

1 ■■ Phase II studies test potential drugs on individuals who have the disease the drugs are designed to treat. ■■ Phase III studies test dr gs in the clinical setting to determine any unanticipated effects or lack of effectiveness. ■■ TGA pregnancy categories indicate the potential or actual teratogenic effects of a drug. ■■ Generic drugs are sold under their chemical names, not brand names; they may be cheaper but are not necessarily as safe as brand-name drugs. This is followed by a series of review exercises in the Check your understanding s ction, to h lp focus student learning on the s minal i formatio presented in the chapter. This section assists students in testing their knowledge and preparing for examinations. Paul, S. P., Dewdney, C. & Lam, C. (2012). Managing children with constipation in the community. Nurse Prescribing, 10(6) , 274–284. Porth, C. M. (2011). Essentials of Pathophysiology: Concepts of Altered Health States (3rd edn). Philadelphia: Lippincott Williams & Wilkins. Porth, C. M. (2009). Pathophysiology: Concepts of Altered Health States (8th edn). Philadelphia: Lippincott Williams & Wilkins. Prynn, P. (2011). Managing adult constipation. Practice Nurse, 41(17) , 23–28. Sarre, R. (2005). Bowel pre aration. Australian P escriber, 28 , 16–17. Answers to the questions in this chapter can be found in Appendix A at the back of this book. MULTIPLE CHOICE Select the best response to the following. 1. Laxatives are drugs that are used to: DRUG EVALUATION After a chemical that might have therapeutic value is identified, it must undergo a series of scientific tests to evaluate its actual therapeutic and toxic effects. This process is tightly controlled by the Therapeutic Goods Administration (TGA) , an agency of the Australian Department of Health and Ageing that regulates the development and sale of drugs. TGA-regulated tests are designed to ensure the safety and reliability of any drug approved in this country. For every 100,000 chemicals that are identified as being potential drugs, only about five end up being marketed. Before receiving final TGA The text of each chapter ends with a summary of important concepts . CHAPTER SUMMARY ■■ Drugs are chemicals that are intro uced into the body to bring about some sort of chang . ■■ Drugs can come from many sources: plants, animals, inorganic elements nd synthetic prepar tions. ■■ Th TGA regulates the development and marketing of drugs safety and efficacy in Australia. ■■ Preclinical trial involve testing of potential drugs on laboratory an mals to determine their therapeutic and adverse effects. ■■ Phase I studies test potential drugs on healthy human subjects. P A R T 1 1 Drugs acting on the gastrointestinal system poractant alfa → → dipalmitoylphosphatidylcholine Curosurf Chapter openings also include a glossary of key terms and a list of featured drugs . Test your current knowledge of drugs with a PrepU Practice Quiz! Glossary of key terms azoles: a group of drugs used to treat fungal infections Candida : fungus that is normally found on mucous membranes; can cause yeast infection immunosuppressed individuals ergosterol: steroid-type protein found in the cell embrane of fungi; similar in c nfigurat fungus: a cellular organism with a hard cell wall that contains chitin and many polysaccha contains rgosterols mycosis: disease ca sed by a fungus tin a: fungus called ringworm that causes such infections as at l te’s foot, jo k itch and o ■■ TABLE 1.2 Elements us d for their therapeu ic effects Element Therapeutic use Aluminium Antacid to decrease gastric acidity Management of hyperphosphataemia Prevention of the formation of pho ph te urinary stones Fluorine (as fluoride) Prev nti n of dental cavities Prevention of osteoporosis Gold Treatment of rheumatoid arthritis Iron Treatment of iron deficiency anaemia 12 P A R T 1 Introduction to nursing pharmacology Therapeutic Guideli es provides a wid rang of drug i formation a series of systematic guid s, such as tibiotics and astrointestinal pharmacology. These guidelines draw upon a range of evaluated literature and research. McKenna’s Drug Handbook for Nursing and Mid- wifery has drug monographs organised alphabetically and includes care implications and important teaching points specifically relevant to nursing and midwifery practice. ■■ Orpha drug discov red to are not financ drugs. ■■ OTC drugs a self-treatment ■■ Information a variety of sou books, journ Glossary of key terms adverse effects: drug effects that are not the desired therapeutic effects; may be unple brand name: name given to a drug by the pharmaceutical company that developed it; chemical name: name that reflects the chemical structure of a drug drugs: chemicals that are introduced into the body to bring about some sort of change generic drugs: drugs sold by their chemical name; not brand (or trade) name products generic name: the original designation that a drug is given when the drug company th genetic engineering: process of altering DNA, usually of bacteria, to produce a chemic New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE): a busine authority responsible for the regulation of therapeutic products in New Zealand orphan drugs: drugs that have been discovered but would not be profitable for a drug treat only a small number of people; these orphans can be adopted by drug compani over-the-counter (OTC) drugs: drugs that are available without a prescription for self-tr be safe when used as directed pharmacology: the study of the biological effects of chemicals pharmacotherapeutics: clinical pharmacology—the branch of pharmacology that deal medicine for the treatment, prevention and diagnosis of disease in humans phase I study: a pilot study of a potential drug conducted with a small number of select phase II study: a clinical study of a proposed drug by selected doctors using actual peo to treat; the subjects must provide informed consent phase III study: use of a proposed drug on a wide scale in the clinical setting with peopl to treat phase IV study: continual evaluation of a drug after it has been released for marketing post-marketing surveillance: monitoring the safety of medicines and medical devices i preclinical trials: initial trial of a chemical thought to have therapeutic potential; uses la teratogenic: having adverse effects on the fetus Therapeutic Goods Administration (TGA): Australian commonwealth government ag enforcement of drug evaluation and distribution policies SYSTEMIC ANTIFUNGALS Azole antifungals fluconazole itraconazole ketoconazole posaconazole terbi afine voriconazole Echinocandin antifungals anidulafungin caspofungin Other antifungals amphotericin B flucytosine griseofulvin nystatin TOPICAL ANTIFUNG Azole topical antifu butoconazole clotrimazole econazole ket conazole iconazole terbinafine each of which has slightly different properties, making a particular drug more desirable in a specific situa- tion. hroughout this book, the icon will be used to desig ate those drugs of a class that are considered the prototype of the class, the original drug in the class or the drug that has emerged as the most effective. For example, the cephalosporins are a large group of antibiotics derived from the same chemical structure. Alterations in th ch mical ri gs or attachments to that structure m ke it possible for some of these drugs to be absorbed orally, whereas others must e given par- enterally. Some of these drugs cause severe toxic effects (e.g. renal tox city), but others do not. KEY POINTS ■■ Clinical pharmacology is he s udy of drugs used to treat, diagno e or preven a disease. ■■ Drugs are chemicals that are introd ced into the body and affect the body’s chemical processes. ■■ Drugs can come from plants, foods, animals, salts of inorganic compounds or synthetic sources. KEY POINTS Numerous other drug handbooks are also on the market and readily available for nurs s and midwives to use. Journals Various journals can be us d to obtain drug informa- tion. For example, the Medical Letter is a monthly review of new drugs, drug classes and sp cific treat- ment protocols. Many clinical nursing and midwifery journals offer information on new drugs, drug errors and care implications. Australian Prescriber is a useful source of easily interpreted pharmacology information and is freely available online. Internet information Many individuals now use the Internet as a source of medical information and advice. Nur es and midwives need t become familiar with w a is available on the Internet and what people may be referencing, and have skills in critiquing the credibility of these sources. Knowi study m to find o ONLIN An extensive rang and learning and t b found online at thePoint at http:// Learn videos, Con review questions, Test your current knowledge of antifungal agents with a PrepU Practice Quiz! Key poin s appear pe iodically throughout each chapter to summarise important concepts. WEB LI Healthcare pro the following In www.anztpa.or Home page of t Product Agency www.australia Australian Pres www.medsafe.g Home page of www.nps.org.a Home page of Service. www.tga.gov.a Home page of t BIBLIOGRA Shah, S. B. & Hanauer, S. B. (2007). Treat pat ents w th inflammatory bowel diseas Reviews in Gastroenterology Disorders, Tobias, N., Mason, D., Lutkenhoff, M., Sto (2008). Management and principles of o childhood constipation. Journal of Pedi 12–23. Wang, M., Szucs, T. D. & Steffen, R. (2008 traveler’s diarrhea. Journ l of Travel Me Selby, W. (2010). Managing constipation in Prescriber, 33 , 116–119. Barton, J. H. & Em pharmaceutical potential refor Cardinale, V. (199 directions. Dru Davies, C. A. (200 of the regulatio devices in Austr Dempsey, J., Hilleg C H E C K Y O U R U N D E R S T A N D I N G C U MULTIPLE RESPONSE Select all that apply.

Part 3 focuses on drugs affecting the immune system, because recent knowledge about the immune system has made it the cornerstone of modern therapy. All of the immune system drugs act in ways in which the immune system would act if it were able. Recent immu- nological research has contributed to a much greater understanding of this system, making it important to position information about drugs affecting this system close to the beginning of the text instead of at the end, as has been the custom. Parts 4 and 5 address drugs that affect the nervous system, the basic functioning system of the body. Following the discussion of the nervous system, and closely linked with it in Part 6 , is the endocrine system. The sequence of these parts introduces students to the concept of control, teaches them about the inter­ relatedness of these two systems and prepares them for understanding many aspects of shared physiological function and the inevitable linking of the two systems into one: the neuro-endocrine system. Parts 7, 8 and 9 discuss drugs affecting the repro- ductive, cardiovascular and renal systems, respectively. The sequencing of cardiovascular and renal drugs is logical because most of the augmenting cardiovascular drugs, such as diuretics, affect the renal system. Part 10 covers drugs that act on the respiratory system, which provides the link between the left and right ventricles of the heart. Part 11 addresses drugs acting on the gastrointes- tinal system. The gastrointestinal system stands on its own; it does not share any actions with any other system. FEATURES OF THIS EDITION The text’s features are skilfully designed to support the text discussion, encouraging the student to look at the whole person and to focus on the essential informa- tion about each drug class. Important features focus on incorporating basic clinical skills, person safety, critical thinking and application of the material learned to the clinical scenario, helping the student to understand the pharmacology material. Chapter structure Each chapter opens with a list of learning objectives for that chapter, helping the student to understand what the key learning points will be. ■■ TABLE 1.1 Drugs derived from plants Plant Product Ricinus c mmunis Digitalis p rpurea (foxglove plant) Leaves Dried leaves Digitalis leaf Papaver somniferum (poppy plant) l -thyroxine,T 4 ← Eut oxsig, Oroxine ←

Seed Oil Castor oil (Neolid)

Unripe capsule Juice Opium Morphine (MS Contin, Ordine) Codeine Papaverine

pigs. Now genetic engineering —the process of altering DNA—permits scientists to produce human insulin by altering Escherichia coli bacteria, making insulin a better product without some of the impurities that come with animal products. Thyroid drugs and growth hormone preparations also may be obtained from animal thyroid and hypo- thalamic tissues. Many of these preparations are now created synthetically, however, and the synthetic prep rations are considered to be purer and safer than preparations derived from animals. Inorganic compounds Salts of various chemical elements can have therapeu- tic effects in the hum body. Aluminium, fluoride, iron and even gold are used to treat various conditions. The effects of these elements were usually discovered acci- dentally when a cause–effect relationship was observed. Table 1.2 shows examples of some elements used for their therapeutic eff cts. Synthetic sources Today, many drugs are developed sy thetically after chemicals in plants, animals or the environment have been tested and found to have therapeutic activity. Scien- tists use genetic engineering to alter bacteria to produce chemicals that are therapeutic and effective. Other tech- nical advances allow scientists to alter a chemical with proven therapeutic effectiveness to make it better. Some- times, a small change in a chemical’s structure can make that chemical more useful as a drug—more potent, more stable, less toxic. These techn l gic l advances have led to the development of groups o si il r drugs, all of which are derived from an original prototype, but 928

■■ TABLE 1.3 Comparison of generic, chemical, and brand names of drugs thyroxine sodium ← generic name →

chemical name brand names

Learning objectives Upon completion of this chapter, you should be able to: 1. Define the word pharmacology. 2. Outline the steps involved in developing and approving a new drug in Australia and New Zealand. 3. Describe the legislative controls on drugs that have abuse potential. 4. Differentiate between generic and brand-name drugs, over-the-counter and prescription drugs. 5. Explain the benefits and risks associated with the use of over-the-counter drugs. Introduction to drugs

Nursing and Mi (2nd Australian Williams & Wil 1. A nurse or midwife is preparing a person who has been prescribe teaching plan should include wh a. the importance of proper diet b. the need to take the drug for the full effect c. the importance of exercise d. the need to take advantage of by providing privacy and tim to work e. the need to limit fluids f. the importance of limiting th laxative use 2. A nurse or midwife might expec paraffin for which person? a. a debilitated person low on n b. a person with haemorrhoids c. a person with recent rectal su

a. increase the quantity of wastes excreted. b. speed the passage of the intestinal contents through the GI tract. c. increase digestion of intestinal contents. d. increase the water content of the intestinal contents. 2. The laxative of choice when mild stimulation is needed to prevent straining is: a. senna. b. castor oil. c. bisacodyl. d. magnesium sulphate. 3. Cathartic dependence can occur when: a. people do not use laxatives routinely and

Alpha-adrenergic blockers phenoxybenzamine phentolamine Alpha 1 -blockers doxazosin

ered to it by a series of liver reak the drug into metabo- tive and cause effects in the are deactivated and can be lt, a large percentage of the his point and never reaches on is known as the first-pass drug that gets through the to the circulatory system for dy. gs absorbed from sites other a similar biotransformation e liver. Because some of the a chance to reach the respon- the liver, the injected drug is er dose than the oral equiva- d dose for oral drugs can be e recommended dose for par- st-pass effect into account. valence e proportion of drug that circulation after oral admin- ount both absorption and lates to the total proportion stemic circulation. The use bility is limited as it relates of the drug that reaches the glects the rate of absorption. e decisions about the “generic roducts. The concept of bio- provide evidence that a new y similar to the existing one ut causing clinical problems al changes that can sed blood volume, sorption, reduced anges in receptor- ten have a variety can be receiving a o be evaluated for ith various central heimer’s disease or ficulty swallowing dication. Through- ross the Lifespan to the drug class fically to children, . These boxes high- ife should consider each age group. ion r handbook relation to the ssment provides before giving that te the effects of should supplement ich include social, ther factors. and peripheral nervous systems ovement of a drug to the As with absorption, factors include the drug’s lipid solu- e perfusion of the responsive rfusion is a factor in caring who has a lower-leg infec- o destroy the bacteria in the drugs may not be effective process involves changes in ed blood flow to some areas, bs. If there is not adequate e antibiotic can be delivered iotic effect will be seen. g drug name, inistration; fects; warning lems; safety etting g making rtant papers; luation to ut drug . drug (relief of anges, GI rrhythmias,

Links to Laerdal clinical simulations enable students to link theory to practice, prepare for clinical placement and acquire the knowledge and skills essential for pro- fessional practice. Test your curr nt knowledge of antibiotics with a PrepU Practice Quiz! Many drugs are bound to proteins and are not lipid soluble. These drugs cannot be distributed to the central nervous system (CNS) because of the effective blood– brain barrier (see later discussion), which is highly selective in allowing lipid solubl substances to pass into the CNS. Pharmacology: Di tr bution and set of interventions. H althcare priorities reflect identified alterations in a person’s function based on the assessment of the clinical situation. Because drug therapy is nly a small part of the verall person’s situ- ation, priorities that are related to drug therapy must be incorporated into a total picture of the pers . Implementation nvolves taking th information ga red and synthesised to plan care. This process includes setting goals and desired outcomes to assure safe and effective drug therapy. These outcomes usually involve ensuring effective response to drug therapy, minimising adverse effects and understanding the drug regimen. Three types of interventions are frequently involved in drug therapy: drug dministration, provision of comfort easures and education of the person and their family. Proper drug administration T he cardiovascular sy tem is a closed sys m of blood vessels that is responsible for delivering oxy enated bl od to the tissues an removing waste products from the tiss es. The blood in this system flows from areas f higher pressure to areas of lower pr ssure. The area of highest pressure in th system is always e left ventri- cle during systole. The pr ssure in this area p opel the blood out of the aorta and into the system. The lowest pressure is in the right atrium, which collects all of the deoxygenated blood fr m the body. The maint nance of this pressure system is controlled by specific areas of the brain nd various hormones. If the pressure becomes too high, t person is said to be hypertensive. If the pressure becomes to low and blood cannot be delivered effectively, the person is said to be hypotensive. Helping the erson t maintain the blood pressure within ormal limits is the oal of drug therapy. Cardiovascular health is one of the Australia g vernment’s nine National Health Priority Areas (AIHW, 2013). Assessing blood pressure Thiazide and thiazide-like diuretics chlorthalidone hydrochlorothiazide indapamide Potassium-sparing diuretics amiloride spiron lactone triamterene Beta-blockers atenolol betaxolol metoprolol nadolol nebivolol pindolol propranolol timolol Alpha- a d beta-blockers carvedilol prazosin terazosin Alpha 2 clonidine methyldopa moxonidine TABLE 38.2 Drug name insuli (various typ s) Glossary of key terms aerobic: bacteria that depend on oxygen for survival Icons for Concepts in action animations depicting pharmacological concepts, Watch and learn video clips, Practice and learn activities and clinical simulation case studies guide students to online resources to further enhance understanding of complex topics. Many drugs are extensively bound to proteins and it should be noted that only the unbound fraction of the drug can reach the site of action in responsive tissues. Some drugs compete with each other for protein binding sites, al ering effectiveness or causing toxicity wh n the two drugs are given together. The toxicity is attributed to sudden increase in the fraction of the previously pro- tein-bound drug that is now free. Pharmacology: Drug binding Nurses and midwives must consider a ser es of points, or “rights”, t ensure safe and effective drug admin- istration. These are correct drug and person, correct storage of drug, correct and most effective route, corr ct dose, correct preparation, correct timing and correct ec r ing of admin s r i n. Se the later section on the prevention of medication errors for a det iled xplana- tion of the nurse’s and midwife’s role in implementing these rights. Remembering to review each point before administering a drug will help to prevent medication errors and improve care outcomes. Medications: The Three Checks and the Five Ri hts of Medication Administration AMINOGLYCOSIDES amikacin framycetin gentamicin neomycin tobramycin CARBAPENEMS doripenem ertapenem imipenem-cilastatin meropenem Blood–brain barrier The blood–brain barrier is a protective system of cellular membranes that keep many things (e.g. foreign invaders, poisons) away from the CNS. The fundamental structural difference of the membranes forming the blood-brain barrier is the use of so called tight-junctions between cells, leaving no gaps between the cells. Drugs that are highly lipid soluble are more likely to pass through the blood–brain barrier and reach the CNS. Drugs that are not lipid soluble are not able to pass the blood–brain barrier. This is clinically significant in treating a brain infection with antibiotics. Almost all antibiotics are not lipid soluble and cannot cross the blood–brain barrier. Effective antibiotic treatment can occur only when the infection is severe enough to damage the blood–brain barrier and allow antibiotics to cross. Although many drugs can cause adverse CNS effects, these are often the result of indirect drug effects and not the actual reaction of the drug with CNS tissue. For example, alterations in glucose levels and electro- lyte changes can interfere with nerve functioning and produce CNS effects such as dizziness, confusion or changes in thinking ability. CEPHALOSPORINS First-generation cefalotin cephalexin cephazolin Second-generation cefaclor cefoxitin cefuroxime Contraindications and cautions Opioid antagonists are contraindicated in the presence of any know allergy to any opioid antagonist to avoid hypersensitivity react ons . Caution should be used in the following circumstances: duri g pregn ncy and breastfeeding because of potential adverse effects on the f tus and neonate ; with opioid addiction because of the precipitation of a withdrawal syndrome ; and with cardiovascular (CV) disease, which could be exacerbated by the reversal of the depressive effects of opioids. Adverse effects The most frequently seen adverse effects associated with these drugs relate to the blocking effects of the opioid receptors. The most common effect is an acute opioid abstinence syndrome that is characterised by nausea, vomiting, sweating, tachycardia, hypertension, tremu- lousness and feelings of anxiety. A naloxone challenge should be administered before giving naltrexone to help to avoid acute reactions. CNS excitement and reversal of analgesia are espe- cially c mmon after surgery. Cardiovascular (CV) effects related to the reversal of the opioid depr ssion can inclu e tac yc rdia, blood pressure changes, dys- rhythmias and pul onary oedema. Drug–d ug interacti ns To reverse the effects of buprenorphine or dextropro- poxyphene, larger doses of opioid antagonists may be needed. therapeutic effect from drugs intended to react with those tissues. REVIEW OF BLOOD PRESSURE CONTROL Text highlights • In the Care considerations section of each chap er, italics highlight the rationale for each a e intervention, helping the student to apply the information in a clinical situation. Elsewhere in the text, the rationale is consistently provided for therapeutic drug actions, co traindicati ns and adverse effects. The pressure in the cardiovascular system is determined by three elements: • Heart rate • Stroke volume , or the amount of blood that is pumped out of the ventricle with each heartbeat (primarily determined by the volume of blood in the system) • Total peripheral resistance , or the resistance of the muscular arteries to the blood being pumped through. The small arterioles are though to be the most important factors in determini g peripheral resistance. Because they have the smallest diameter, they are able to almost stop blood flow into capillary beds when they constrict, building up tremendous pressure in the arteries Car considerations for people receiving antimigraine agents Assessment: History and examination ■ ■ Assess for contraindications or cautions: any known allergies to any components of the dr gs to avoid hypersensitivity reactions ; history of MI, CAD or hypertension, which may be exacerbated by the drug ; hepatic or renal dysfunction, which could alter the metabolism and excretion of the drug ; pruritus or malnutrition, which could be exacerbated by ergot derivatives ; and current status of pregnancy and breastfeeding, which would be cautions to the use of these drugs . ■ ■ Perform a physical assessment to establish baseline status before beginning therapy, determine drug effectiveness and evaluate for any potential adverse effects. ■ ■ Assess neurological status, including level of orientation, affect and reflexes, to evaluate CNS effects of the drugs . ■ ■ Monitor for complaints of extremity numbness and tingling to identify effects on vascular constriction. ■ ■ Inspect the skin for localised oedema, itching or breakdown with ergot derivatives to evaluate potential dermatological effects. ■ ■ Assess vital signs, including pulse rate and blood pressure; obtain an ECG as appropriate to evaluate cardiac status for changes. • In the Drug list at the beginning of each chapter, a special icon appears next to the drug that is considered the prototype drug of each class. In each chapter, prototype summary boxes spotlight need-to- morphine oxycodone pethidine remifentanil tapentadol tramadol Opioid agonists–antagonists buprenorphine Opioid antagonists aloxon naltrexone ANTIMIGRAINE AGENTS Ergot derivatives ergotamine naratriptan rizatriptan sumatriptan zolmitriptan Prototype summary: Naloxone Indications: Complete or partial reversal of opioid depression; diagnosis of suspected opioid overdose. Actions: Pure opio d antagonist; re rses the effects of the opioids, including respiratory depression, sedation and hypotension. Pharmacokinetics: Route Peak Onset Duration

Preface 5–30 mg PO q 6 hours or 30 mg PR q 6–8 hours as needed Adult: 5–20 mg IM or SC or 15–30 mg PO q 4–6 rs Paediatric: 0.1–0.2 g/kg IM or SC Adult: 25–100 mg IM, SC or 25–50 mg slow IV q 3–4 hours Paediatric: 0.5–2 g/kg IM or SC q 3–4 hours Adult a chil ren >2 years: dos determined by general anaesthetic being used

midodrine Sympathetic adrenergic agonists or vasopressors adrenaline dobutamine ADULTS Adults being treated for acute pain should be reassured that the risk of add tion to an opioid during treatment is remote.They should b encouraged to ask for pain medication before the pain is acute, to get better coverage for their pain. Many institutions allow people to self-regulate intravenous drips to control their pain postoperatively. PREGNANCY AND BREASTFEEDING The opioid ar contraindicated or should only be used with caution during pregnancy because of the potential for morphine (Anamorph, Kapanol, MS Contin) oxycodone (OxyContin, Oxynorm, Endone, Proladone) pethidine (generic) remifentanil (Ultiva) dopamine ephedrine • Drugs in focus tables clearly summarise and identify the drugs within a class, highlighting them by generic and trade names, usual dosage and indications. The icon appears in these tables next to each drug that is considered to be the prototype for its specific class. isoprenaline metaraminol noradrenaline phenylephrine

5. Outline care considerations for people receiving each class of antibiotic.

ix Because older impairment, they levels of the drug and excretion.Th measures in effec ambulate—when hospital setting. effects associated nervous system, effects.

-blockers

Simulation-based learning On completion of the chapter, explore the scenario of Kenneth Bronson (Part 1) who has been diagnosed with a strep throat. Continue onto the second scenario (Part 2) as his condition deteriorates into an emergency situation. Consider the medication management of Kenneth’s condition throughout his episode of care. What learning from the chapter, can be applied to the case? Protein binding Most drugs are bound to some extent to proteins in the blood to be carri d into circulation. The protei –drug complex is relatively large and c nnot enter into capil- laries and then into tissues to react. The drug m st be freed from the protein’s binding site at the tissues. DRUGS IN FOCUS Insulin TABLE 26.1 Drug ame tapentadol (Pal xia SR) tramadol (Durotram XR, Lodam) 94 P A R T 2 Chemotherapeutic agents

579

C H A P T E R 3 8 Agents to control blood glucose levels

Adult: 50 mg PO b.d.

DRUGS IN FOCUS Opioids

Usual indications Adult: rapid relief of pain: 50-100 mg PO q 4–6 hours to a maximum 400 mg/day Chronic pain: 25 mg/day PO titrated slowly to a maximum 400 mg/day Dosage/route

Third-generation cefotaxime ceftazidime ceftriaxone Fourth-generation cefepime Fifth-generation ceftaroline Baroreceptors As the blood leaves the left ventricle through the aorta, it influences specialised cells in the arch of the aorta called baroreceptors (pressure receptors). Similar cells are lo ated in the carotid arteries, which deliver blood to the brain. If ther is sufficient pressure in these vessels, the baroreceptors are stimulated, sending that informa- tion t the brain. If the pressure falls, the stimulation of the barorec ptors falls off. That information is also sent to the brain. The sensory input from the baroreceptors is received in the medulla in an area called the cardiovascular centre or vasomotor centre. If the pressure is high, the medulla stimul tes vasodilation and a decrease in cardiac rate and ou put, causing the pressure in the system to drop. If the p essure is low, the medulla directly stimulates an increase i cardiac rate and output, and vasoconstriction; this increases total peripheral resistance and raises the blood pressure. The medulla mediates these effects through the autonomic nervous system (see Chapter 29). Th baroreceptor reflex functions continually to maintain blood pressure within a predetermined range of normal. For example, if you have been lying down flat and suddenly stand up, the blood will rush to your feet (an effect of gravity). You may even feel light-headed or dizzy for a short time. When you stand and the blood flow drops, the baroreceptors are not stretched. The medulla senses this drop in stimulation of the baroreceptors and stimulates a rise in heart rate and cardiac output, and C H A P T E R 2 6 Opioids, opioid antagonists and antimig aine agents 413 ■ ■ Provide thorough teaching, including drug name, prescribed dose and schedule for administration; measures to avoid adverse effects; warning dextropropoxyphene (Doloxene) fentanyl (Actiq, Duragesic, Sublimaze) naltrexone (ReVia) 24 Drug swallowed Safe medication administration The e idence BOX 9.3 BOX 31.1 Adren rgic blocking agents CHILDREN behind t em a they prevent t e blood fro flowing through. The arterioles are very responsive to stimula- tion from the sympathetic nervous system; they constrict when the sympathetic system is stimulated, increasing total peripheral resistance and blood pressure. The body us s th s responsiveness to regulate blood pressure on a onstant basis, to ensure that there is enough pressure in the system to deliver sufficient blood to the brain. Dosage/route Varies based on response, diet, and activity level Opioid agonists alfentanil (Rapifen) codeine (generic) Opioid agoni ts–antagonists buprenorphine (Norspan, Temgesic) BACTERIA AND RESISTANCE TO ANTIBIOTICS

pathogens, such antibiotics (parti bacteria in the

PENICILLINS AND PENICILLINASE-RESISTANT ANTIBIOTICS Penicillins benzathine penicillin benzylpenicillin synthesis of glycogen from glucose, of fats from lipids and of proteins from amino acids. Insulin does these things by reacting with specific receptor sites on the cell. Figure 38.3 shows the sites of action of replacement insulin and other drugs used to treat diabetic conditions. See Table 38.2 for indications. Pharmacokinetics Various preparations of insulin are available to provide short- and long-term coverage. These preparations are processed within the body like endogenous insulin. However, the peak, onset and duration of each vary because of the placement or addition of glycine and/or arginine chains. Maintenance doses are given by the subcutaneous route only, and injection sites need to be rotated regularly to avoid damage to muscles and to pr vent subcutaneous atrophy. Regular insulin is given intramuscularly or intravenously in emergency situations. Insulin is available in various preparations with a wide range of peaks and durations of action. A person may receive a combination of regular and isophane insulin in the morning to cover the glucose peak from breakfast (regular onset, 30 to 60 minutes) and the lunch and dinner glucose peaks. The person may then require another injection before bed. The types of insulin used are determined by the anticipated eating and exercise activities of any particular individual. It is very important to make sure that one is using the correct insulin preparation when administering the drug. Insulin glargine ( Lantus ) and insulin detemir ( Levemir ) cannot be mixed in solution with any other drug, including other insulins. Contraindications and cautions Because insulin is used as a replacement hormone, there are no contraindications. Care should be taken during surgery; 0.05–0.1 mg postop ratively; 5 mcg/kg transmucosally; for transdermal patch, calculate the previous day’s opioids need and use table to convert to patch strength; ionic delivery system, 40 mcg over 10 minutes Paediatric (>2 years): 2–3 mcg/kg IM or IV; base transmucosal dose on weight and do not exceed 400 mcg well-being. Thes sives and as adj rapid analgesia, Indications for acute or chronic during anaesthe depending on th usual indication culation of a dos In deciding uation, it is imp the person’s con most effective in effects. Each p to a drug is als Half-lif The half-life of a of drug in the b it previously ac 20 mg of a dru the drug will r Two hours later, level); in 2 more information is i ate timing for a of a drug’s effec calculations.) The absorpt the speed of bio excreted are ll mining the half indicated in an a healthy pers estimate the half or liver dysfunct formation and drug), allowing dosing schedule. The timing achieve the mo midwives can u explain the imp administration i shows the effects concentration of Not dissolved, lost in faeces Lost in acid Lost in food, acid, digestion Biotransformed to non-effective state Bound to plasma proteins Determining drug levels A person is taki You are trying to drug will be gon • In 12 hours, ha body. BOX 2.1 ■■ The goal of an population of human immun ■■ Bacteria can b f und in respir (frequently fou also be classifi or aerobic (de ■■ Culture and se antibiotic is ch that may help resistant-strai KEY POINTS regimen ofte le b cteria. Using people saving u infections or to s • Tell people that exposures to cer to people that sa they think they n development of tests that could i • Offer other medi decongestants, request antibioti something to ta respond to antib people who re The publicity t bacteria have rece message across t course of an antib they are app opri C H A P T E R (MI). Table 31. these agents. Drug therap across the lifespan m re centr l nerv other adrenergic complications alr while taking an a a different agent. PREGNANCY AN In ge eral, there a of adre ergic bloc and th y shoul b the benefit to the fetu or ne nate. and babies born t adverse cardiovas Many of these dru Because of a simil breastfeeding mot baby if an adrener OLDER ADULTS Older people are effects ass ciated GI a d respirator also have renal or likely to have toxi in metabolism an be started on low monitored very cl or blood pressure choice for older p for hypertension problems in the e be used. Herbal and alternative therapies Treatment of type 1 diabetes mellitus; treatment of type 2 diabetes mellitus in people whose diabetes cannot be controlled by diet or other agents; treatment of severe ketoacidosis or diabetic coma; treatment of hyperkalaemia (in conjunction with a glucose infusion to produce a shift of potassium into the cells [polarising solution]); also used for short courses of therapy during periods of stress (e.g. surgery, disease) in people with type 2 diabetes, for newly diagnosed people being stabilised, for people with poor control of glucose levels, and for people with gestational diabetes Spontaneous ventilation: 7 mcg/kg by slow IV injection Controlled ventilation: 20-50 mcg/kg by slow IV injection Adult: 15–60 mg PO, IM, IV or SC q 4–6 hours; 10–20 mg PO q 4–6 hours for cough Paediatric: 0.5 mg/kg PO, IM or SC q 4–6 hours; 2.5–10 mg PO q 4–6 hours for cough 100 mg PO q 4 hours as needed Adult: 0.05–0.1 mg IM, 30–60 minutes before surgery; 0.002 mg/kg IV or IM during 200–400 mcg SL q 6–8 hours, 300–600 mcg M or IV q 6–8 hours or 1 transdermal patch every 7 days Adult: 0.4–2 mg IV, IM or SC q 2–3 minutes as needed Paediatric: 0.01 mg/kg IV, IM or SC Neonatal: 0.01 mg/kg IV, IM or SC q 2–3 minutes or 0.06 mg/kg IM immed at birth opportunistic inv are destroyed o nothing to preve In most cases th effect (e.g. vagina but in some case t an the infectio ment of the sup and the potentia cycle of treatmen

FLUOROQUINOLONES ciprofloxacin moxifloxacin norfloxacin ofloxacin dysfunction can lead to toxic lev ls of a drug in the bod because he drug nnot be excreted. Figure 2.3 outlines the pharmacokinetic proc ss that occur when a drug is administe ed orally. Pharmacology: Excretion Bacteria have survived for hundreds of years because they can adapt to their environment. They do this by altering their cell wall or enzyme systems to become r sistant to (i.e. protect themselves from) unfavourable conditions or situations. Many species of bacteria have developed resistance to certain antibiotics. For example, bacteria that were once very sensitive to penicillin have devel ped an enzyme called penicillinase, which effec- tively inactivates many of the penicillin-type drugs. New drugs have had to be developed t effectively reat infec- tions involving these once-controlled bacteria. It is very important to use these drugs only when the identity and se sitivity of he offending bacterium h ve been est b- lished. Indiscriminate use of these new drugs can lead to the dev lopment of more re istant strains for which there is no effective antibiotic (see later discussion of new antibiotics for additio al information on linezolid). The longer an antibio ic has been i se, the great r is the chance that the bacteria will develop into a resist- ant strain. Efforts to control the mergence of r sistant strains involve intensive educational programs that advocate the use of antibiotics only when necessary and effective and not for the treatment of viral infections such as the common cold (Box 9.3). In addition, the use of antibiotics may result in the devel ment of superinfections or overgrowth of resistant Children are at greater risk for complications associated with the use of adrenergic blocking agents, including bradycardia, difficulty breathing and ch ges in gluco e metabolism.The safety and efficacy for use of these drugs has not been established for children younger than 18 years of age. If one f these drugs is used, the do e for these agents needs to be calculated from the child’s ody weight and age. It is good practice to have a second person check t e dose calculation before administering the drug to avoid potential toxic effects.Two adrenergic blocking agents have es a li hed paediatric doses, and the migh be he drugs to c nsider whe one is eeded: praz s n is used to t eat hypert nsi n, and phentolamine, which is used during surgery for phaeochromocytoma. Children should be carefully monitored and supported when these drugs are given. ADULTS Adults being treated with adrenergic blocking agents should be cautioned about the many adverse effects a sociated with the rugs. People with diabetes need to be re-educated about ways to m nitor themselves f r hyperglyca mia and hypoglycaemia because the sympathetic reaction (sweating, feeling tense, increased heart rate, rapid breathing) usually alerts people that there is a problem with their glucose levels. People with severe thyroid disease are also at high risk for serious adverse effects when taking these drugs, and if one of the is need d, the person sh uld be monitored very closely. Propranolol and metoprolol are associated with control is determined by the relative ability of each drug to cause physical dependence. Opioid agonists include alfentanil ( R pifen ), c dei e (ge eric), dextro- propoxyphene ( Doloxe e ), fentanyl ( Actiq , Duragesic , Sublimaze ), hydromorphone ( Dilaudid , Jurnista ), meth- adone ( Biodone , Physeptone ), morphine ( Anam rph , Sevredol , MS Contin and others), oxyco one ( Endone , OxyContin , Oxynorm , Proladone ), pethidine (generic), remifentanil ( Ultiva ), tapent d l ( Palexia SR ) (not avail- able in New Zealand) and tramadol ( Durotram XR , Lodam , Tramal and others). Therapeutic actions and indications The opioid agonists act at specific opioid receptor sites in the CNS to produce analgesia, sedation and a sense of Adult: 50 mg/day PO • Focu on s fe medication admini tration boxes present important safety information to help keep the person safe, prevent medication errors and increase the therapeutic effectiveness f the drugs. The liver is very important in metabolising drugs in the body and the kidneys are responsible for a large part of the excretion of drugs from the body. One should get into the habit of always checking a person’s live nd renal fu ction before they start a drug r gimen. If the liver is not functioning properly, the drug may no be metabolised correctly and may reach toxic levels in the body. If the kidneys are not functioning properly, the drug may not be excreted properly and could accumulate in the body. Dose djustment ne ds to be considered if a person has problems with either the liver or the kidneys. • Focus on the evidence boxes compile information based on research to identif th best clinical practices assoc ated with specific rug therapy. P A R T 1 Introduction to nursing pharmacol gy Usi g antibiotics properly In 2003, the US Food and Drug Administration (FDA) nd Centers for Disease Control and Prevention (CDC) joined efforts to educate the public and healthcare providers about the dangers of inappropr ate use of antibiotics. The evidence-based practice guidelines combine data fro many studies to outline the most efficacious use of antibiotics.To review some of the studies, review the references listed in the Bibliography. Nurs s and mi wives should include some of th following points about the risks and dangers of antibiotic abuse in each person’s education plan: • Explain clearly that a particular antibiotic is effective against only certain bacteria and that a culture needs to be taken to identify the bacteria. • Explain that bacteria can develop resistant strains that will not be affected by antibiotics in the future, so use of antibiotics now may make them less effective in situations in which they are really necessary. • Ensure that people understand the importance of taking the full course of medication as prescribed, even if they feel better. Stopping an antibiotic midway through a • Focus on herbal and alternative therapies boxes highlight known eract n with sp cific herbs or alternative therapies that could affect the actions of the drugs being discussed. signs that may indicate possible problems; signs of ergotism if taking ergot derivatives; safety measures such as avoiding driving and avoiding overdose; and importance of follow-up monitoring nd evaluation to enhance the person’s knowledge about drug therapy and to promote compliance. Evaluation ■ ■ Monitor the person’s response to the drug (relief of acu e migraine headaches). ■ ■ Monitor for adverse effects (CV changes, arrhythmias, hypertension, CNS changes). ■ ■ Evaluate the effectiveness of the teaching plan (person can give the drug name and dosage and describe possible adverse effects to watch for, specific measures to prevent them and warning signs to report). ■ ■ Monitor the effectiveness of comfort measures and compliance with the regimen. Drug dissolved in gastrointestinal fluids Dissolved drug reaches intestine Drug absorbed by portal system Drug in liver Drug in circulation Drug distributed throughout body • Celery, coriander, Di huang, fenugreek, goldenseal, Java plum, xuan seng—lower blood glucose (increased risk of severe hypoglycaemia) • Saw palmetto—increased urinary tract complications People who are pr cribe n adrenergic blocking drug should be cautioned about the use of herbs, teas and alternative medicines. If a person feels that one of Broken down in tissues Bound to plasma proteins People who use alternative therapies as part of their daily regimen should be cautio ed abou potential increased adren rgic blocking effects if the f llowing alternative therapi s are combi ed with adrenergic blocking agents: • Ginseng, age—increased antihypertensive effects (risk of hypotensio and increased CNS effects) • Xuan shen, nightshade—slow heart rate (risk of severe bradycardia and reflex arrhythmias) Reaches reactive tissue Excreted by kidneys, lungs, skin, etc. Bound to f t tissue ■■ Migraine headaches are severe, throbbing headaches on one side of the head that may be associated with an aura or warning syndrome. These headaches are thought to be caused by arterial dilation and hyperperfusion of the brain vessels. Drug “does its thing”

anaerobic: bacteria that survive without oxygen, which are often seen when blood flow is cut off to an area of the body antibiotic: chemical that is able to inhibit the growth of specific bacteria or cause the death of susceptible bacteria gram-negative: bacteria that accept a negative stain and are frequently associated with infections of the genitourinary or GI tract gram-positive: bacteria that take a positive stain and are frequently associated with infections of the respiratory tract and soft tissues synergistic: drugs that work together to increase drug effectiveness Opioid antagonists nal xone (Narcan)

of insulin delivery that are available or under study for future use. Hyperglycaemic crisis Therapeutic actions and indications Insulin is a hormone that promotes the storage of the body’s fuels, facilitates the transport of various metabo- lites and ions acr ss cell membranes and stimul tes the In 2009, l nte insulin was removed from the market as name confusion had occurred between Lantus insulin and lente insulin. The pharmacokinetics and dose of insulins vary greatly. Use caution to make sure you know which insulin is intended for the individual person. Lantus and Levemir insulin cannot be mixed in a syringe with any other insulin or any other drug. Use particular caution when working with these two insulins. The DHBNZ Safe and Quality Use of Medicines has released an alert informing healthcare professionals to take extra care when giving insulin Humalog preparation. There are three Humalog preparations available in Australia and New Zealand: Humalog, Humalog Mix25 and Humalog Mix50. Potential harm can result if a person is given Humalog rapid release as opposed to Humalog intermediate release. The Australian Commission on Safety and Quality in Health Care (ACSQHC) has developed 10 National Safety and Quality Health Service Standards. These Standards aim to improve the quality of health service provision across Australia and provide a national statement of the level of care consumers should be able to expect from health services. Awareness and knowledge of Standard 4 on Medication Safety is an important part of the nurse’s and midwife’s clinical repertoire. For more information, see www.safetyandquality.gov.au/our-work/accreditation/nsqhss. Triptans eletriptan BOX 31.2 Safe medication administration

hing plan dosage and atch for, d warning

measures and

know information for each prototype drug. acting on the central and peripheral nervous systems

drugs that bind t activate them. eceptors and are ny opioids in the include naloxon ReVia ).

• In another 12 h would remain i • After 36 hours, • After 48 hours, remain. • After 60 hours, • After 72 hours, • After 84 hours, • Twelve more h reduce the dru • Finally, 12 mor amount of the would be quite Pharmacokinet These drugs are are distributed t orally. Th y re faeces and urine. drug and prepar Contraindicatio The non-selecti contraindicated tivity to any co serious hyperse

hene

ptors and reverse tory depression, potension.

KEY POINTS

, is a sensory and emotional experi- actual or potential tissue damage. pain is part of the clinical pres- isorders and is one of the hardest sal of the adverse atory depression id overdose. (See ch opioid antag- do ot have an ividual who are

the tissue damage has occurred. In some cases so-called referred pain occurs. A person experiencing pain f om damage to the heart muscle may actually feel the pain in the neck or jaw. The sensation of pain is experienced in