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Clinical Pharmacy and Therapeutics Commissioning Editor: Pauline Graham Development Editor: Nicola Lally Project Manager: Kerrie-Anne McKinlay Designer/Design Direction: Kirsteen Wright Illustration Manager: Bruce Hogarth Illustrators: David Graham/Andrew Bezear Clinical Pharmacy and Therapeutics...

Clinical Pharmacy and Therapeutics Commissioning Editor: Pauline Graham Development Editor: Nicola Lally Project Manager: Kerrie-Anne McKinlay Designer/Design Direction: Kirsteen Wright Illustration Manager: Bruce Hogarth Illustrators: David Graham/Andrew Bezear Clinical Pharmacy and Therapeutics Edited by Roger Walker  BPharm, PhD, FRPharmS, FFPH Professor of Pharmacy Practice, Welsh School of Pharmacy, Cardiff University, Cardiff UK and Chief Pharmaceutical Officer, Welsh Government, Cardiff, UK Cate Whittlesea BSc, MSc, PhD, MRPharmS Senior Lecturer, Institute of Pharmaceutical Science Kings College London, London, UK FIFTH EDITION Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2012 © 2012 Elsevier Ltd. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher's permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). First edition 1994 Second edition 1999 Third edition 2003 Fourth edition 2007 Fifth edition 2012 ISBN 978-0-7020-4293-5 International ISBN – 978-0-7020-4294-2 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Printed in China Preface In both primary and secondary care the use of medicines is landmark study was published adding to, or perhaps ­altering, the most common intervention in healthcare. Medicines use, the evidence base for a specific treatment. Together with however, is not without risk. Drug selection and prescribing the ­ongoing publication of national guidelines and frame- is increasingly complex and demanding, and undertaken as works, the face of therapeutics is ever changing. It is there- part of a multi-disciplinary process that involves pharmacists, fore ­inevitable that some sections of this book will date more some of whom are now prescribers in their own right, along quickly than others. with doctors, nurses and other members of the healthcare In practice many licensed drugs are used ‘off label’ or “near team. All must strive to promote safe, appropriate and cost- label” when prescribed for a certain indication or used in a effective prescribing that respects patient choice and promotes ­specific patient group such as children. To omit reference to adherence. This book has been written to help the reader these agents in the relevant chapter would leave an apparent gap understand and address many of these issues. It is unasham- in therapeutic management. As a consequence we have encour- edly written from a pharmacy perspective, although we do aged our authors to present details of all key drugs used along hope those from other disciplines will also find it of use. with details of the prescribed regimens even if not licensed for We have made considerable effort to update each chapter that specific indication. There is, however, a downside to this and ensure the content is relevant to current practice. Selected approach. The reader must always use this text critically and website addresses have been included to assist those who want with caution. If this is done the book will serve as a valuable to obtain further information and many references are now learning resource and help the reader understand some of the available electronically and this has been indicated where principles of therapeutics. We hope that, in some small way, appropriate. However, knowledge in therapeutics progresses this will also assist in achieving ­positive patient outcomes. rapidly, changes to dose regimens and licensed indications are frequent, safety issues emerge with established drugs and Roger Walker new medicines appear at regular intervals. Yesterday another Cate Whittlesea v Acknowledgements In 2011, as in 1994 when the first edition was published, one exception to this rule. The administrative support from undergraduate and postgraduate students help sustain our Marilyn Meecham has been invaluable. She has co-ordinated enthusiasm and commitment while continuing to be the this new edition from the outset and was often called upon ­inspiration and the raison d’etre for this book. To all those to present the polite face of two chastened editors. Thanks who have ­provided feedback in the past, thank you. For Marilyn. those who would like to comment on this edition, we welcome It was with great sadness that in November 2010 we heard your ­feedback; please contact us at [email protected] or of the untimely death of Professor Steve Hudson. Steve was [email protected]. a friend and colleague who had a broad knowledge of clinical We remain indebted to all authors who, through their hard pharmacy and was one of the movers, shakers and thinkers work, patience and tolerance, have contributed to the fifth central to the establishment of clinical pharmacy in the UK edition of this book. We are particularly grateful to those who in the 1980’s. He contributed to the first edition of this book have again contributed to another edition of this textbook and in 1994 and his most recent update is included in the current who strive, along with us, to produce an ever ­better book. To edition. It is our loss that he will be unable to review his latest our first-time authors, we are very grateful that you agreed to contribution in print. contribute, that you accepted our cryptic editorial comments Finally, and on a personal note, we would like thank our in good faith and still managed to submit on time. We hope close families for their support and tolerance with our indul- that you will continue to work with us on future editions. gence in editing this text. At times it may have appeared that A textbook of this size cannot, of course, be produced everything in our lives took second place to ‘the book’. We without the invaluable help, support and occasional com- are eternally grateful for their understanding, particularly ments of numerous colleagues, particularly those within the when we got our priorities in life wrong. Without the unfail- Public Health Wales, the Welsh School of Pharmacy, Cardiff ing support of Ann and Alex, this book would never have University, and the Institute of Pharmaceutical Science, materialized. King’s College London. It would be invidious to name indi- viduals who have helped us, in part for fear of offending Roger Walker anyone we might miss. We do, however, continue to make Cate Whittlesea vi Contributors Alya Abdul-Wahab BSc MB BS MRCP Geraldine Brough MB ChB FRCP Dermatology Registrar, St John's Institute of Dermatology, Associate Specialist in Rheumatology and Honorary Guys & St Thomas' NHS Trust, London, UK Lecturer, Royal Free Hospital, London, UK 57. Eczema and psoriasis 53. Rheumatoid arthritis and osteoarthritis Christopher Acomb BSc MPharm MRPharmS David J. Burn MD FRCP MA MB BS Clinical Pharmacy Manager (Professional Development), Professor of Movement Disorder Neurology and Pharmacy Department, St James's University Hospital, Honorary Consultant Neurologist, Institute for Leeds, UK Ageing and Health, Newcastle University, Newcastle 49. Anaemia upon Tyne, UK 32. Parkinson's disease Sharon D. Andrew BSc MPharm MRPharmS Regional Scientific Services Manager, Allergan Ltd. Marlow, Susan Calvert FRCOG Buckinghamshire, UK Consultant Obstetrician and Gynaecologist, 55. Glaucoma Bradford Royal Infirmary, Bradford, UK 45. Menstrual cycle disorders Sotiris Antoniou BPharm MSc DipMgt IPresc MRPharmS 46. Menopause Consultant Pharmacist, Cardiovascular Medicine, Barts and the London NHS Trust, North East London Cardiovascular Laura Cameron BPharm DipPharmPractice MRPharmS and Stroke Network, London, UK Haematology Pharmacist, Guy's & St Thomas' NHS 22. Arrhythmias Foundation Trust, London, UK 51. Lymphomas David Baldwin MB BS DM FRCPsych Professor of Psychiatry, University of Southampton, Southampton, UK Neil J.B. Carbarns BSc MB ChB FRCPath 28. Anxiety disorders Consultant Medical Microbiologist, Aneurin Bevan Health Board, Nevill Hall Hospital, Catrin Barker BSc MSc PGDipClinPharm Abergavenny, Wales, UK Acting Deputy Chief Pharmacist, Pharmacy 36. Urinary tract infections Department, Alder Hey Children's NHS Foundation Trust, Liverpool, UK Paul Cockwell MB BCh PhD MRCP FRCP 10. Paediatrics Consultant Nephrologist, Queen Elizabeth Hospital, Birmingham, UK Andrew Berrington MRCP FRCPath 17. Acute kidney injury Consultant Microbiologist, City Hospitals Sunderland, 18. Chronic kidney disease and end-stage renal disease Sunderland, UK 35. Respiratory infections Jonathan Cooke MPharm PhD MRPharmS Director of Research and Development, Stephen Bleakley BPharm, MSc MCMHP Clinical Director of Pharmacy and Medicines Locality Lead Pharmacist, Royal Hants Hospital, Management, School of Pharmacy and Pharmaceutical Southampton, UK Sciences, Faculty of Medical and Human Sciences, 27. Insomnia University of Manchester, South Manchester University 28. Anxiety disorders Hospitals NHS Trust, Wythenshawe Hospital, Manchester, UK; Visiting Professor in the Infectious David Branford PhD MRPharmS Diseases and Immunity Section, Division of Infectious Chief Pharmacist, Derbyshire Mental Health Services, Diseases, Department of Medicine, Imperial College, Derby, UK London, UK 30. Schizophrenia 8. Pharmacoeconomics vii  contributors Allan Cosslett BPharm, MRPharmS Clive Edwards BPharm PhD MRPharmS FICR(Hon) Lecturer/Disability Officer/Deputy Admissions Officer Formerly Prescribing Adviser, North Tyneside Primary Care & Director of Undergraduate Studies, Welsh School of Trust, Newcastle upon Tyne, UK Pharmacy, Cardiff University, Cardiff, UK 6. Laboratory data 7. Parenteral nutrition Bridget Featherstone BSc DipClinPharm IP Anthony Cox Bsc(Hons) DipClinPharm PhD MRPharmS Lead Pharmacist for Transplantation, Addenbrooke's NHS Lecturer in Clinical Therapeutics, Pharmacy Practice Trust, Cambridge, UK Group, Aston University, Birmingham, UK 15. Adverse effects of drugs on the liver 5. Adverse drug reactions Martin Fisher MB BS BSc FRCP Daniel Creamer BSc MD FRCP Consultant Physician HIV/AIDS, Brighton and Sussex Consultant Dermatologist, Kings College Hospital NHS University Hospitals NHS Trust, Brighton, UK Foundation Trust, London, UK 41. HIV infection 56. Drug-induced skin disorders Ray Fitzpatrick BSc PhD FRPharmS Duncan Cripps BPharm PGDipHospPharm MEd Clinical Director of Pharmacy, Royal Wolverhampton Education and Training Pharmacist, Plymouth Hospitals Hospitals NHS Trust; Professor of Clinical Pharmacy, NHS Trust, Plymouth, UK Wolverhampton University, Wolverhampton, UK 25. Asthma 3. Practical pharmacokinetics 26. Chronic obstructive pulmonary disease Kevin P. Gibbs BPharm, DipClinPharm Cert Health Econ, Sarah Cripps BPharm MSc MRPharmS (IPresc) PgC Evidence-based Hth Care PgC Law & Ethics MRPharmS Gastroenterology Pharmacist, Oxford Radcliffe Hospitals Clinical Pharmacy Manager, Bristol Royal Infirmary, NHS Trust, Oxford, UK Bristol, UK 13. Inflammatory bowel disease 25. Asthma 26. Chronic obstructive pulmonary disease Amy Cunnington MPharm Dip Pharm Prac Education & Training Pharmacist, Chapel Allerton Peter Golightly Hospital, Leeds, UK Director, West Midlands and Trent Regional Medicines 54. Gout and hyperuricaemia Information Centre, Good Hope Hospital NHS Trust, West Midlands, UK J. Graham Davies BPharm MSc PhD FRPharmS 47. Drugs in pregnancy and lactation Professor of Clinical Pharmacy and Therapeutics, Kings College London, London, UK Elena Grant BPharm MSc MRPharmS 1. Clinical pharmacy process Senior Medicines Information Pharmacist, West Midlands Medicines Information Centre, Good Hope Hospital, Heart Nemesha Desai MBBS BSC MRCP PGCHE of England NHS Foundation Trust, West Midlands, UK Consultant Dermatologist, St John's Institute of 47. Drugs in pregnancy and lactation Dermatology, Guys & St Thomas' NHS Trust, London, UK James W. Gray MRCP FRCPath 57. Eczema and psoriasis Consultant Microbiologist, The Birmingham Children's Hospital NHS Trust, Diana, Princess of Wales Children's Soraya Dhillon MBE BPharm PhD FRPharmS Hospital, Birmingham, UK Foundation Professor Head, School of Pharmacy, 37. Gastro-intestinal infections University of Hertfordshire, Hatfield, UK 38. Infective meningitis 31. Epilepsy Elizabeth Hackett BSc (hons) MSc Tobias Dreischulte MSc MRPharmS Principal Pharmacist for Diabetes, University Hospitals Research Pharmacist, University of Dundee, Dundee, UK Leicester, Leicester, UK 21. Chronic heart failure 44. Diabetes mellitus Alexander Dyker MBChB Bsc MSc MD FRCP(Glasgow) Keith Harding MB ChB FRCGP FRCP FRCS Consultant in Medicine, Clinical Pharmacology Sub Dean of Innovation & Engagement / Head of Section and Stroke Medicine, Newcastle Hospitals, Newcastle of Wound Healing, Department of Dermatology & Wound upon Tyne, UK Healing, Cardiff University, Cardiff, UK 19. Hypertension 58. Wounds viii contributors  Susanna Harwood BPharm(hons) DipClinPharm IPresc Roger Knaggs BSc BMedSci PhD MRPharmS Pharmacist, University Hospital of Wales, Cardiff, UK Specialist Pharmacist in Anaesthesia and Pain Management, 7. Parenteral nutrition Queens Medical Centre, Nottingham, UK 33. Pain Tina Hawkins Bsc(Hons) ClinDipPharm IPresc Advanced Clinical Pharmacist, Chapel Allerton Andrzej Kostrzewski MSc MMedEd PhD MRPharmS FHEA Hospital Leeds Teaching Hospital NHS Trust, Academic Lead for Clinical Development, University of Leeds, UK Herefordshire, Hatfield, UK 54. Gout and hyperuricaemia 3. Practical pharmacokinetics Gregory J. Hobbs BMBS FRCA FFPMRCA Janet Krska BSc PhD MRPharmS Consultant in Pain Medicine, Nottingham University Professor of Pharmacy Practice, School of Pharmacy and Hospitals NHS Trust, Nottingham, UK Biomolecular Sciences, Liverpool John Moores University, 33. Pain Liverpool, UK 5. Adverse drug reactions Samantha Holloway MSc CertEd(FE) RN Senior Professional Tutor / Course Director, Dept of Alan Lamont BMedSci(Hons) MBChB FRCR FRCP (Edinburgh) Dermatology and Wound Healing, Cardiff University, Consultant Oncologist, Colchester General Hospital, Cardiff, UK Essex, UK 58. Wounds 52. Solid tumours Philip Howard BPharm(Hons) DipClinPharm IPresc MRPharmS Heather Leake Date BSc MSc IPresc MRPharmS Consultant Antimicrobial Pharmacist, Leeds Teaching Consultant Pharmacist HIV/Sexual Health, Brighton and Hospital NHS Trust, Leeds, UK Sussex University Hospitals NHS Trust, Brighton, UK 39. Surgical site infection and antimicrobial and Honorary Senior Lecturer, University of Brighton, prophylaxis Brighton, UK 41. HIV infection Steve A. Hudson MPharm BPharm FRPharmS Deceased Catherine Loughran BPharm MSc MRPharmS(IPresc) Professor of Pharmaceutical Care, Strathclyde Lead Pharmacist Haematology, Leicester Royal Infirmary, Institute of Biomedical Sciences, Glasgow, UK Leicester, UK 21. Chronic heart failure 51. Lymphomas Graham Jackson MA MB BS FRCP FRCPath MD John J. McAnaw BSc PhD MRPharmS Consultant Haematologist, Freeman Hospital, Head of Pharmacy, NHS 24; Honorary Lecturer in Clinical Newcastle upon Tyne, UK Practice, Strathclyde Institute of Pharmacy & Biomedical 50. Leukaemia Sciences, Glasgow, UK 21. Chronic heart failure Stephen Jackson MA, FRCP Consultant, Leicester General Hospital, Leicester, UK Duncan McRobbie MSc MRPharmS 44. Diabetes mellitus Associate Chief Pharmacist, Clinical Services and Lead Cardiac Pharmacist, Gail Jones MD MRCP FRCPath Guy's and St Thomas' Hospital NHS Foundation Trust, Consultant Haematologist, Freeman Hospital, Newcastle London, UK upon Tyne, UK 1. Clinical pharmacy process 50. Leukaemia 20. Coronary Heart disease Patrick T.F. Kennedy MB BCh BAO BMedSci MRCP MD John Marriott PhD BSc MRPharmS Senior Lecturer & Consultant Hepatologist, Barts and The Professor of Clinical Pharmacy, School of Clinical and London School of Medicine, London, UK Experimental Medicine, University of Birmingham, 16. Liver disease Birmingham, UK 17. Acute kidney injury Moira Kinnear Bsc MSc ADCPT MRPharmS 18. Chronic kidney disease and end-stage renal disease Head of NHS Lothian Pharmacy Education, Research and Development, Western General Hospital, Edinburgh; Helen Marlow BPharm(Hons) MRPharmS Dip Clin Pharm Lecturer in Clinical Practice, University of Strathclyde, Visiting Lecturer, Non-Medical Prescribing, Kings College Glasgow, UK London, London, UK 12. Peptic ulcer disease 2. Prescribing ix  contributors Kay Marshall BPharm PhD FRPharmS MBA Philip A. Routledge OBE MD FRCP FRCPE FRCGP(Hon) FBTS Head of the Bradford School of Pharmacy, University of Professor, Section of Pharmacology, Therapeutics and Bradford, Bradford, UK Toxicology, Cardiff University, Cardiff, UK 45. Menstrual cycle disorders 23. Thrombosis 46. Menopause 34. Nausea and vomiting Emma Mason BSc MB ChB MRCP Paula Russell BA Mod (Chem) MApplSc MRPharmS Honorary Senior Lecturer in Palliative Medicine and Principal Pharmacist, Regional Drugs and Therapeutics Pharmacology, University College of Medicine, Centre, Newcastle upon Tyne, UK Cardiff, UK 47. Drugs in pregnancy and lactation 34. Nausea and vomiting Paul Rutter BPharm PhD MRPharmS Maria Martinez MPharm(hons) DipClinPharm MSc MRPharmS Principal Lecturer, Department of Pharmacy, University Renal Transplant, Nephrology and Urology Specialist of Wolverhampton, Wolverhampton, UK Pharmacist, University Hospitals of Leicester, 14. Constipation and diarrhoea Leicester, UK 48. Prostate disease Josemir W. Sander MD MRCP PhD Professor of Neurology, Queen Square, London, UK Manjusha Narayanan MBBS, MD, FRCPath 31. Epilepsy Consultant Microbiologist, Royal Victoria Infirmary, Newcastle upon Tyne, UK Robyn Sanderson MPharm(Hons), PG Dip Pharm Practice, MRPharmS 42. Fungal infections Specialist Pharmacist, St James University Hospital, Leeds, UK Lika K. Nehaul LRCPI LRCSI MSc FFPH 49. Anaemia Consultant in Communicable Disease Control, National Public Health Service for Wales, Mamhilad House, Jonathan Sandoe MB ChB, PhD, FRCPath Pontypool, UK Consultant Microbiologist, Leeds Teaching Hospitals NHS 40. Tuberculosis Trust, Leeds, UK 39. Surgical site infection and antimicrobial prophylaxis Anthony J Nunn BPharm, FRPharmS, HonFRCPCH Associate Director, NIHR Medicines for Children Research Mini Satheesh MPharm, MSc(Clin.Pharm), MRPharmS(IPresc) Network, University of Liverpool, UK. Renal and Urology Specialist Pharmacist, University 10. Paediatrics Hospitals Leicester, Leicester, UK 48. Prostate disease John O'Grady MD FRCPI Consultant Hepatologist, Institute of Liver Studies, King's College Hospital, London, UK Hamsaraj G.M. Shetty BSc MB BS FRCP(London), FRCP(Edin) 16. Liver disease Consultant Physician & Honorary Senior Lecturer, University Hospital of Wales & Cardiff University, Mike Page MD FRCP Cardiff, UK Consultant Physician, Royal Glamorgan Hospital, 11. Geriatrics Llantrisant, Wales, UK 23. Thrombosis 43. Thyroid and parathyroid disorders Michele Sie BPharm MSc IPresc MCMHP Dee Pang BPharm Consultant Pharmacist, St Bernards Hospital, West London Principal Pharmacist - Medicine, Royal Free Hospital, Mental Health NHS Trust, London, UK London, UK 27. Insomnia 53. Rheumatoid arthritis and osteoarthritis Simon Sporton BSc MD FRCP Peter Pratt BSc MPhil MRPharmS Consultant Cardiologist, Bart's and The London NHS Chief Pharmacist, Community Health Sheffield, Michael Trust, London, UK Carlisle Centre, Sheffield, UK 22. Arrhythmias 29. Affective disorders Stephanie Stringer MBChB, MRCP Ali Robb MRCP FRCPath Clinical Fellow in Nephrology, Queen Elizabeth Hospital, Consultant Microbiologist, Newcastle upon Tyne Hospitals, Birmingham, UK Newcastle upon Tyne, UK 17. Acute kidney injury x 35. Respiratory infections 18. Chronic kidney disease and end-stage renal disease contributors  Lucy C. Titcomb BSc MRPharmS MCPP Cate Whittlesea BSc (Pharmacy) MSc Econ PhD MRPharmS Lead Ophthalmic Pharmacist, Birmingham and Midland Senior Lecturer Pharmacy Practice, Kings College London, Eye Centre, Birmingham, UK London, UK 55. Glaucoma 2. Prescribing Ruben Thanacoody MD FRCP(Edin) Helen Williams BPharm(Hons) PGDip(Cardiol) MRPharmS IPresc Consultant Physician, Royal Victoria Infirmary; Honorary Consultant Pharmacist for Cardiovascular Disease, Clinical Senior Lecturer, Institute of Cellular Medicine, Southwark Health and Social Care, London, UK Newcastle University, Newcastle-upon-Tyne, UK 24. Dyslipidaemia 4. Drug interactions Netty Wood DipPharmPract, MRPharmS (IPresc) Sean Turner BPharm MSc DipClinPharm Lead Pharmacist, Essex Cancer Network, Essex, UK Director of Pharmacy, Children, Youth and Women's 52. Solid tumours Health Service, Adelaide, South Australia, Australia 10. Paediatrics Ken Woodhouse MD FRCP FHEA Professor of Medicine and Geriatric Medicine, School Roger Walker BPharm PhD FRPharmS FFPH of Medicine, Cardiff University, Cardiff, UK Professor of Pharmacy Practice, Welsh School of Pharmacy, 11. Geriatrics Cardiff University; Consultant in Pharmaceutical Public Health, Public Health Wales, Cardiff, UK Hilary Wynne MA MD FRCP 24. Dyslipidaemia Consultant Physician, Freeman Hospital, Newcastle upon Tyne, UK Sarah Walsh MB BCh BAO BMedSci MRCP 6. Laboratory data Consultant Dermatologist, King's College Hospital, London, UK Laura Yates MBChB DRCOG MRCPCH PhD 56. Drug-induced skin disorders Head of Teratology, UK Teratology Information Service, Newcastle upon Tyne, UK Martin P. Ward Platt MB ChB MD FRCP FRCPCH 47. Drugs in pregnancy and lactation Consultant Paediatrician and Honorary Clinical Reader in Neonatal and Paediatric Medicine, Royal Victoria Infirmary, Newcastle upon Tyne, UK 9. Neonates David Webb BPharm MSc MRPharmS HonFCPP Director, East & South East England Specialist Pharmacy Services; Visiting Professor, School of Pharmacy, University of London, London, UK 1. Clinical pharmacy process xi Contents 16. Liver disease   238 Section 1 General   1 P. Kennedy, J.G. O'Grady 1. Clinical pharmacy process   2 17. Acute kidney injury   255 D.G. Webb, J.G. Davies, D. McRobbie P. Cockwell, S. Stringer, J. Marriott 2. Prescribing   14 18. Chronic kidney disease and end-stage renal H. Marlow, C. Whittlesea disease   272 J. Marriott, P. Cockwell, S. Stringer 3. Practical pharmacokinetics   32 R. Fitzpatrick, A. Kostrzewski 19. Hypertension   295 A.G. Dyker 4. Drug interactions   50 H.K.R. Thanacoody 20. Coronary heart disease   312 D. McRobbie 5. Adverse drug reactions   62 J. Krska, A.R. Cox 21. Chronic heart failure   333 S.A. Hudson, J. McAnaw, T. Dreischulte 6. Laboratory data   76 H.A. Wynne, C. Edwards 22. Arrhythmias   354 S. Sporton, S. Antoniou 7. Parenteral nutrition   96 S.J. Harwood, A.G. Cosslett 23. Thrombosis   376 P.A. Routledge, H.G.M. Shetty 8. Pharmacoeconomics   116 J. Cooke 24. Dyslipidaemia   389 R. Walker, H. Williams 25. Asthma   412 K.P. Gibbs, D. Cripps Section 2 Life stages   123 26. Chronic obstructive pulmonary disease   431 9. Neonates   124 D. Cripps, K.P. Gibbs M.P. Ward Platt 27. Insomnia   446 10. Paediatrics   132 S. Bleakley, M. Sie C. Barker, A.J. Nunn, S. Turner 28. Anxiety disorders   454 11. Geriatrics   149 S. Bleakley, D. Baldwin H.G.M. Shetty, K. Woodhouse 29. Affective disorders   465 J.P. Pratt 30. Schizophrenia   479 Section 3 Therapeutics   161 D. Branford 12. Peptic ulcer disease   162 31. Epilepsy   489 M. Kinnear J.W. Sander, S. Dhillon 13. Inflammatory bowel disease   185 32. Parkinson's disease   507 S.E. Cripps D.J. Burn 14. Constipation and diarrhoea   209 33. Pain   519 P. Rutter R.D. Knaggs, G.J. Hobbs 15. Adverse effects of drugs on the liver   222 34. Nausea and vomiting   535 B.E. Featherstone E. Mason, P.A. Routledge xii  Contents 35. Respiratory infections   545 49. Anaemia   769 A. Robb, A.W. Berrington C. Acomb, R. Sanderson 36. Urinary tract infections   561 50. Leukaemia   786 N.J.B. Carbarns G. Jackson, G. Jones 37. Gastro-intestinal infections   573 51. Lymphomas   803 J.W. Gray L. Cameron, C. Loughran 38. Infective meningitis   584 52. Solid tumours   818 J.W. Gray N. Wood, A. Lamont 39. Surgical site infection and antimicrobial 53. Rheumatoid arthritis prophylaxis   596 and osteoarthritis   832 P. Howard, J.A.T. Sandoe D.J. Pang, G.M. Brough 40. Tuberculosis   608 54. Gout and hyperuricaemia   848 L.K. Nehaul T. Hawkins, A. Cunnington 41. HIV infection   621 55. Glaucoma   861 H. Leake Date, M. Fisher L.C. Titcomb, S.D. Andrew 42. Fungal infections   654 56. Drug-induced skin disorders   880 M. Narayanan S. Walsh, D. Creamer 43. Thyroid and parathyroid disorders   669 57. Eczema and psoriasis   893 M.D. Page A. Abdul-Wahab, N. Desai 44. Diabetes mellitus   685 58. Wounds   910 Elizabeth A. Hackett, Stephen N.J. Jackson S. Holloway, K. Harding 45. Menstrual cycle disorders   711 K. Marshall, S. Calvert 46. Menopause   725 Section 4 Appendices   927 K. Marshall, S. Calvert Appendix 1 Medical abbreviations   928 47. Drugs in pregnancy and lactation   739 Appendix 2 Glossary   938 P. Russell, L. Yates, E. Grant, P. Golightly 48. Prostate disease   753 Index   944 M. Martinez, M. Satheesh xiii This page intentionally left blank Section 1 general general 1 Clinical pharmacy process D. G. Webb, J. G. Davies and D. McRobbie Key points Development of clinical practice Clinical pharmacy comprises a set of functions that promote in pharmacy the safe, effective and economic use of medicines for individual patients. The emergence of clinical pharmacy as a form of practice The emergence of clinical pharmacy has allowed pharmacists has been attributed to the poor medicines control systems to shift from a product-oriented role towards direct that existed in hospitals during the early 1960s (Cousins and engagement with patients and the problems they encounter Luscombe, 1995). Although provoked by similar hospital- with medicines. centred problems, the nature of the professional response The practice of clinical pharmacy is generally an essential ­differed between the USA and the UK. component of pharmaceutical care. In the USA, the approach was to adopt unit dose dispens- Pharmaceutical care is a co-operative, patient-centred system for achieving specific and positive patient outcomes from the ing and pursue decentralisation of pharmacy services. In the responsible provision of medicines. UK, the unification of the prescription and the administra- The three key elements of the care process are patient tion record meant this document needed to remain on the assessment, determining the care plan and evaluating the hospital ward and required the pharmacist to visit the ward to outcome. order medicines. Clinical pharmacy thereby emerged from the The ability to consult with patients is a key process presence of pharmacists in these patient areas and their inter- in the delivery of pharmaceutical care and requires est in promoting safer medicines use. This was initially termed regular review and development regardless ‘ward pharmacy’ but participation in medical ward rounds in of experience. the late 1970s signalled the transition to clinical pharmacy. The clinical pharmacy process has been incorporated into Medication safety may have been the spur but clinical phar- a professional development framework that can be used to enhance skills and knowledge. macy in the 1980s grew because of its ability to promote cost- effective medicines used in hospitals. This role was recognised by the UK government, which, in 1988, endorsed the imple- mentation of clinical pharmacy services to secure value for money from medicines. Awareness that support depended, Clinical pharmacy, unlike the discipline of pharmacy, is a to an extent, on the quantification of actions and cost sav- comparatively recent and variably implemented form of prac- ings led several groups to develop ways of measuring phar- tice. It encourages pharmacists and support staff to shift their macists' clinical interventions. Coding systems were necessary focus from a solely product-oriented role towards more direct to aggregate large amounts of data in a reliable manner and engagement with patients and the problems they encoun- many of these drew upon the eight steps (Table 1.1) of the ter with medicines. Over the past 20 years there has been an drug use process (DUP) indicators (Hutchinson et al., 1986). emerging consensus that the practice of clinical pharmacy The data collected from these early studies revealed that itself should grow from a collection of patient-related func- interventions had very high physician acceptance rates, were tions to a process in which all actions are undertaken with the made most commonly at the ‘select regimen’ and ‘need for intention of achieving explicit outcomes for the patient. In drug’ stages of the DUP, and were influenced by hospital ward doing so, clinical pharmacy moves to embrace the philosophy type (intensive care and paediatrics having the highest rates), of pharmaceutical care (Hepler and Strand, 1990). pharmacist grade (rates increasing with grade) and time spent This chapter provides a practical framework within which on wards (Barber et al., 1997). a knowledge and understanding of therapeutics and prac- Despite the level of activity that intervention monitoring tice can be best utilised. It describes a pragmatic approach to revealed, together with evidence of cost containment and a applying both the principles of pharmaceutical care and the broadly supportive health care system, frustrations began specific skills of clinical pharmacy in a manner that does not to appear. These, in part, stemmed from a lack of certainty depend on the setting of the practitioner or patient. about the fundamental purpose of clinical pharmacy and 2 © 2012 Elsevier Ltd. All rights reserved. Clinical pharmacy process 1 Table 1.1 Drug use process (DUP) indicators Table 1.2 Definitions of clinical pharmacy, pharmaceutical care and medicines management DUP stage Action Term Definition Need for a drug Ensure there is an appropriate indication for each drug and that all medical Clinical pharmacy Clinical pharmacy comprises a set problems are addressed therapeutically of functions that promote the safe, effective and economic use of Select drug Select and recommend the most medicines for individual patients. appropriate drug based upon the Clinical pharmacy process requires ability to reach therapeutic goals, with the application of specific knowledge consideration of patient variables, of pharmacology, pharmacokinetics, formulary status and cost of therapy pharmaceutics and therapeutics to patient care Select regimen Select the most appropriate drug regimen for accomplishing the desired Pharmaceutical care Pharmaceutical care is a co-operative, therapeutic goals at the least cost patient-centred system for achieving without diminishing effectiveness or specific and positive patient outcomes causing toxicity from the responsible provision of medicines. The practice of clinical Provide drug Facilitate the dispensing and supply pharmacy is an essential component in process so that drugs are accurately the delivery of pharmaceutical care prepared, dispensed in ready-to- administer form and delivered to the Medicines management Medicines management encompasses patient on a timely basis the way in which medicines are selected, procured, delivered, Drug administration Ensure that appropriate devices prescribed, administered and reviewed and techniques are used for drug to optimise the contribution that administration medicines make to producing informed and desired outcomes of patient care Monitor drug therapy Monitor drug therapy for effectiveness or adverse effects in order to determine whether to maintain, modify or discontinue for a given individual and the provision not only of the drug Counsel patient Counsel and educate the patient or required but also the ­necessary services to assure ­optimally caregiver about the patient's therapy to safe and effective therapy' had been established previously ensure proper use of medicines (Brodie et al., 1980). The delivery of pharmaceutical care is dependent on the Evaluate effectiveness Evaluate the effectiveness of the patient's practice of clinical pharmacy but the key feature of care is drug therapy by reviewing all the that the practitioner takes responsibility for a patient's drug- previous steps of the drug use process related needs and is held accountable for that commitment. and taking appropriate steps to ensure that the therapeutic goals are achieved None of the definitions of pharmaceutical care is limited by reference to a specific professional group. Although phar- macists and pharmacy support staff would expect to, and clearly can, play a central role in pharmaceutical care, it is from tensions between the drive towards specialisation in essentially a co-operative system that embraces the contri- clinical pharmacy and the need to improve services of a more bution of other professionals and patients (Table 1.2). The general level in hospitals and other care settings. avoidance of factionalism has enabled pharmaceutical care to permeate community pharmacy, particularly in Europe, in a way that clinical pharmacy and its bedside connotations Pharmaceutical care did not. It also anticipated health care policy in which cer- tain functions, such as the prescribing of medicines, have The need to focus on outcomes of medicines use rather than been extended beyond their traditional professional origins dwelling only on the functions of clinical pharmacy became to be undertaken by those trained and identified to be com- apparent (Hepler and Strand, 1990). The launch of pharma- petent to do so. ceutical care as the ‘responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a Medication-related problems patient's quality of life' was a landmark in the topography of pharmacy practice. In reality, this was an incremental step for- When the outcome of medicines use is not optimal, a classi- ward, rather than a revolutionary leap, since the foundations fication (Box 1.1) for identifying the underlying ­medication-­ of pharmaceutical care as ‘the determination of drug needs related problem (MRP) has been proposed (Hepler and 3 1 general participation in physician ward rounds has been shown to Box 1.1 Categories of medication-related problems reduce adverse drug events by 78% and 66% in general med- Untreated indication ical (Kucukarslan et al., 2003) and intensive care settings Treatment without indication (Leape et al., 1999), respectively. A study covering 1029 US Improper drug selection hospitals was the first to indicate that both centrally based Too little drug and ­patient-specific clinical pharmacy services are associated Too much drug Non-compliance with reduced mortality rates (Bond et al., 1999). The services Adverse drug reaction involved were medicines information, clinical research per- Drug interaction formed by pharmacists, active pharmacist participation in resuscitation teams and pharmacists undertaking admission medication histories. Strand, 1990). Some MRPs are associated with significant In the UK, the focus has been also on prevention and man- morbidity and mortality. Preventable medication-related agement of medicine-related problems. Recognition that hospital admissions in the USA have a prevalence of 4.3%, many patients either fail to benefit or experience unwanted ­indicating that gains in public health from improved medi- effects from their medicines has elicited two types of cines management would be sizeable (Winterstein et al., 2002). response from the pharmacy profession. The first response In the UK too, preventable ­medication-related morbidity has has been to put in place, and make use of, a range of post- been associated with 4.3% of admissions to a medical unit. In graduate initiatives and programmes to meet the develop- nearly all cases, the underlying MRP was linked to prescrib- mental needs of pharmacists working in clinical settings. ing, monitoring or adherence (Howard et al., 2003). The second has been the re-engineering of pharmaceutical In prospective studies, up to 28% of accident and emergency services to introduce schemes for medicines management at department visits have been identified as medication related, an organisational level. These have ranged from specific ini- of which 70% are deemed preventable (Zed, 2005). Again, the tiatives to target identified areas of medication risk, such most frequently cited causes were non-adherence and inap- as pharmacist involvement in anticoagulation services, to propriate prescribing and monitoring. The cost of drug-related more general approaches where the intention is to ensure morbidity and mortality in the US ambulatory care (out- consistency of medicines use, particularly across care patient) population was estimated in 2000 to be $177 billion. interfaces. Medicines reconciliation on hospital admission Hospital admission accounted for 70% of total costs (Ernst and ensures that medicines prescribed to in-patients correspond Grizzle, 2001). In England, adverse drug reactions (ADRs) have to those that the patient was taking prior to admission. been identified as the cause of 6.5% of hospital admissions Guidance in the UK recommends that medicines reconcili- for patients over 16 years of age. The median bed stay with ation should be part of standard care and that pharmacists patients admitted with an ADR was 8 days representing 4% should be involved as soon as possible after the patient has of bed capacity. The projected annual cost to the NHS was been admitted (NICE and NPSA, 2007). Medicines recon- £466 million, the equivalent of seven 800-bed hospitals occupied ciliation has been defined as: by patients admitted with an ADR (Pirmohamed et al., 2004). Collecting information on medication history using the The rate for adverse drug events among hospital inpatients most recent and accurate sources of information to create in the USA has been quantified as 6.5 per 100 admissions. a full, and current, list of medicines; Overall, 28% of events were judged preventable, rising to 42% Verifying this list against the hospital drug chart and ensuring of those classified as life-threatening or serious (Bates et al., that any discrepancies are identified and acted upon; 1995). The direct cost of medication errors, defined as pre- Documenting and communicating any changes, omissions ventable events that may cause or lead to inappropriate medi- or discrepancies. cines use or harm, in NHS hospitals has been estimated to lie between £200 and £400 million per year. To this should be This process requires the name of medicines, dosage, frequency added the costs arising from litigation (DH, 2004). and route of administration to be established for all medicines The scale of the misadventure that these findings reveal, taken prior to admission. The information collected as part coupled with increasing concerns about the costs of drug ther- of medicines reconciliation is a pre-requisite for medication apy, creates an opportunity for a renaissance in clinical phar- review, which is a process which considers the appropriateness macy practice, providing that it realigns strongly with patient of treatment and the patient's medication-taking behaviour. safety, cost-effectiveness and prevention of ill health. In prac- tice, community pharmacists may be uniquely placed to help reduce the level of medication-related morbidity in primary care by virtue of their accessibility and existing relationships. Pharmaceutical consultation Structured postgraduate education has served to improve the knowledge of clinical pharmacists but fully achieving Benefits of pharmaceutical care the goals of pharmaceutical care has proved more challeng- The ability to demonstrate that clinical pharmacy practice ing. Part of the difficulty has been the requirement to place improves patient outcomes is of great importance to the phar- the patient at the heart of the system, rather than being a 4 maceutical care model. In the USA, for example, ­pharmacists' relatively passive recipient of drug therapy and associated Clinical pharmacy process 1 i­nformation. To deliver pharmaceutical care requires more Medicines-taking behaviour than scientific expertise. It mandates a system that describes The need for a care process which ensures that the patient is the role and responsibilities of the pharmacist and provides involved at all stages has become clearer as the extent of non- the necessary infrastructure to support them in this role and, adherence has been revealed. Significant proportions (between secondly, a clear process by which the pharmacist can deliver 30% and 50%) of patients with chronic conditions do not their contribution to patient care. take their prescribed medicines as directed. Many factors are Pharmaceutical care is predicated on a patient-centred thought to influence a patient's decision to adhere to a pre- approach to identifying, preventing or resolving medicine- scribed regimen. These include the characteristics of the dis- related problems. Central to this aim is the need to estab- ease and the treatment used to manage it, the patient's beliefs lish a therapeutic relationship. This relationship must be a about their illness and their medicines, as well as the quality of partnership in which the pharmacist works with the patient the interaction between the patient and health care practitio- to resolve medication-related issues in line with the patient's ner. Non-adherence can be categorised broadly into two types: wishes, expectations and priorities. Table 1.3 summarises the intentional and unintentional. Unintentional non-adherence three key elements of the care process (Cipolle et al., 1998). may be associated with physical or sensory barriers to taking Research in chronic diseases has shown that self-management medicines, for example, not being able to swallow or unable is promoted when patients more fully participate in the goal- to read the labels, forgetfulness or poor comprehension. setting and planning aspects of their care (Sevick et al., 2007). Traditionally, pharmacists have played a key role in helping These are important aspects to consider when pharmacists patients overcome these types of problems, but have been less consult with patients. In community pharmacy, one approach active in identifying and resolving intentional non-adherence. to help patients used their medicines more effectively is medi- Intentional (or deliberate) non-adherence may be due to cines use review (MUR). This uses the skills of pharmacists to a number of factors. Recent work in health psychology has help patients understand how their medicines should be used, shaped our understanding of how patients perceive health why they take them and to identify any problems patients and illness and why they often decide not to take their medi- have in relation to their medicines, providing feedback to the cines. When people receive information about illness and its prescriber if necessary. Two goals of MUR are to improve the treatment, it is processed in accordance with their own belief adherence of patients to prescribed medicines and to reduce systems. Often patients' perceptions are not in tune with the medicines wastage. medical reality and when this occurs, taking medicines may Clinical guidance on medicines adherence emphasises the not make sense to the individual. For example, a patient diag- importance of patient involvement in decisions about medi- nosed with hypertension may view the condition as one that cines (NICE, 2009). is caused by stress and, during periods of lower stress, may Recommendations include that health care professionals not take their prescribed medicines (Baumann and Leventhal, should: 1985). Consequently, a patient holding this view of hyperten- adapt their consultation style to the needs of individual sion may be at increased risk of experiencing an adverse out- patients come such as a stroke. consider any factors which may affect patients' More recent research has shown that patient beliefs about involvement in the consultation the necessity of the prescribed medication and concerns establish the most effective way of communicating with about the potential long-term effects have a strong influence each patient on medicines-taking behaviour (Horne, 2001). However, a encourage patients to ask about their condition and patient's beliefs about the benefits and risks of medicines are treatment rarely explored during consultation, despite evidence of an be aware that consultation skills can be improved to association between non-adherence and the patient's satisfac- enhance patient involvement. tion with the consultation process adopted by practitioners (Ley, 1988). Table 1.3 Key elements of the care process Consultation process Element Purpose There are several comprehensive accounts of the functions required to satisfy each stage of the DUP, but few go on to Assessment The main goal is to establish a full medication explore how the pharmacist might create a therapeutic rela- history and highlight actual and potential drug-related problems tionship with their patient. The ability of a pharmacist to consult effectively is fundamental to pharmaceutical care and Care plan This should clearly state the goals to optimise care this includes establishing a platform for achieving adherence/­ and the responsibilities of both the pharmacist concordance. Nurturing a relationship with the patient is and the patient in attaining the stated goals essential to understanding their medication-related needs. Descriptions of pharmaceutical consultation have been Evaluation This reviews progress against the stated patient confined largely to the use of mnemonics such as WWHAM, outcomes AS METTHOD and ENCORE (Box 1.2). These approaches 5 1 general provide the pharmacist with a rigid structure to use when to grasp the essential components of consultation tech- questioning patients about their symptoms but, although nique. Research into patients' perceptions of their illness useful, serve to make the symptom or disease the focus of and treatment has demonstrated that they are more likely the consultation rather than the patient. A common miscon- to adhere to their medication regimen, and be more satis- ception is that health care professionals who possess good fied with the consultation, if their views about illness and communication skills are also able to consult effectively with treatment have been taken into account and the risks and patients; this relationship will not hold if there is a failure benefits of treatment discussed. The mnemonic approach to consultation does not address adequately the complex inter- action that may take place between a patient and a health Box 1.2 Mnemonics used in the pharmacy consultation process care practitioner. WWHAM Undertaking a pharmaceutical consultation can be consid- Who is it for? ered as a series of four interlinked phases, each with a goal What are the symptoms? and set of competencies (Table 1.4). These phases follow a How long has it been going on? problem-solving pattern, embrace relevant aspects of adher- Action taken? ence research and attempt to involve the patient at each stage Medicines taken? in the process. For effective consultation, the practitioner AS METTHOD also needs to draw upon a range of communication behav- Age of the patient? iours (Box 1.3). This approach serves to integrate the agendas Self or for someone else? of both patient and pharmacist. It provides the vehicle for Medicines being taken? agreeing on the issues to be addressed and the responsibilities Exactly what do you mean (by the symptom)? accepted by each party in achieving the desired outcomes. Time and duration of the symptom The ability to consult with patients is a key process in the Taken any action (medicine or seen the doctor)? History of any disease? delivery of pharmaceutical care and consequently requires Other symptoms? regular review and development, regardless of experience. To Doing anything to alleviate or worsen the symptom? ensure these core skills are developed, individuals should use trigger questions to prompt reflection on their approach to ENCORE consulting (Box 1.4). Evaluate the symptom, its onset, recurrence and duration. No medication is always an option. Care when dealing with specific patient groups, notably the elderly, the young, nursing mothers, pregnant women, those receiving specific medication such as methotrexate and Box 1.3 Consultation behaviours anticoagulants, and those with particular disease, for example, renal impairment. Active listening Observe the patient for signs of systemic disturbance and ask Appropriate use of open and closed questions about presence of fever, loss of weight and any accompanying Respect patient physiological disturbance. Avoid jargon Refer when in doubt. Demonstrate empathy Explain any course of action recommended. Deal sensitively with potentially embarrassing or sensitive issues Table 1.4 Pharmaceutical consultation process Element Goal Examples of associated competencies Introduction Building a therapeutic Invites patient to discuss medication or health-related issue relationship Discusses structure and purpose of consultation Negotiates shared agenda Data collection and Identifying the patient's Takes a full medication history problem identification medication-related needs Establishes patient's understanding of their illness Establishes patient's understanding of the prescribed treatment Identifies and prioritises patient's pharmaceutical problems Actions and solutions Establishing an acceptable Involves patient in designing management plan management plan with Tailors information to address patient's perception of illness and treatment the patient Checks patient's understanding Refers appropriately Closure Negotiating safety netting Provides information to guide action when patient experiences problems with strategies with the patient management plan Provides further appointment or contact point 6 Clinical pharmacy process 1 Box 1.4 Key postconsultation questions Step 1. Establishing the need for drug therapy For independent prescribers this step includes establishing a Do I know more now about the patient? Was I curious? diagnosis and then balancing the risks and benefits of treat- Did I really listen? ment against the risks posed by the disease. Current practice Did I find out what really mattered to them? for most pharmacists means that another professional, most Did I explore their beliefs and expectations? frequently a doctor, will have diagnosed the patient's present- Did I identify the patient's main medication-related problems? ing condition and any co-existing disease. The pharmacist's Did I use their thoughts when I started explaining? role, therefore, is often one of providing information to the Did I share the treatment options with them? independent prescriber on the expected benefits and risks of Did I help my patient to reach a decision? Did I check that they understood what I said? drug therapy by evaluating both the evidence base and individ- Did we agree? ual patient factors. Pharmacists also draw on these concepts Was I friendly? as they become more involved in prescribing and adjusting therapy for patients under their care. The evidence for one specific mode of therapy may not be conclusive. In this circumstance, the pharmacist will need to call on their understanding of the principles of ­pharmaceutical science and on clinical experience to provide the best advice Clinical pharmacy functions and possible. knowledge Step 1.1. Relevant patient details The following practical steps in the delivery of pharmaceuti- cal care are based largely on the DUP. The ‘select regimen’ Without background information on the patient's health and and ‘drug administration’ indicators have been amalgamated social circumstances (Table 1.5) it is difficult to establish the at step 3. existence of, or potential for, MRPs. When this information is Table 1.5 Relevant patient details Factor Implications Age The very young and the very old are most at risk of medication-related problems. A patient's age may indicate their likely ability to metabolise and excrete medicines and have implications for step 2 of the drug use process Gender This may alter the choice of the therapy for certain indications. It may also prompt consideration of the potential for pregnancy or breast feeding Ethnic or religious Racially determined predispositions to intolerance or ineffectiveness should be considered with certain classes background of medicines, for example, ACE inhibitors in Afro-Caribbean people. Formulations may be problematic for other groups, for example, those based on blood products for Jehovah's Witnesses or porcine-derived products for Jewish patients Social history This may impact on ability to manage medicines and influence pharmaceutical care needs, for example, living alone or in a care home or availability of nursing, social or informal carers Presenting complaint Symptoms the patient describes and the signs identified by the doctor on examination. Pharmacists should consider whether these might be attributable to the adverse effects of prescribed or purchased medicines Working diagnosis This should enable the pharmacist to identify the classes of medicines that would be anticipated on the prescription based on current evidence Previous medical Understanding the patient's other medical conditions and their history helps ensure that management of the history current problem does not compromise a prior condition and guides the selection of appropriate therapy by identifying potential contraindications Laboratory or physical The focus should be on findings that may affect therapy, such as findings renal function liver function full blood count blood pressure cardiac rhythm Results may convey a need for dosage adjustment or presence of an adverse reaction 7 1 general lacking a review solely of prescribed medicines will probably Box 1.5 Key components of a medication history be of limited value and risks making a flawed judgement on the appropriateness of therapy for that individual. 1. Introduce yourself to the patient and explain the purpose of Current and co-existing conditions with which the patient the consultation. presents can be established from various sources. In medi- 2. Identify any allergies or serious adverse reactions and record these on the prescription chart, care notes or patient cal notes, the current diagnosis (Δ) or differential diagnoses medication record. (ΔΔ) will be documented, as well as any previous medical his- 3. Ascertain information about prescribed and non-prescribed tory (PMH). Other opportunities to gather information come treatments from: from discussion with the patient and participation in medical the patient's recall rounds. In primary care, general medical practitioners' com- medicines in the patient's possession puter systems carry information on the patient's diagnosis. referral letter (usually from the patient's primary care Once the diagnosis and PMH are established it is then pos- doctor) copy of prescriptions issued or a repeat prescription list sible to identify the medicines that would be expected to be medical notes prescribed for each indication, based on contemporary evi- contact with the appropriate community pharmacist or dence. This list of medicines may be compiled from appropri- primary care doctor. ate national or international guidelines, local formularies and 4. Ensure the following are recorded: knowledge of current practice. generic name of medicine (unless specific brand is required) dose Step 1.2. Medication history frequency duration of therapy. A medication history is the part of a pharmaceutical consul- 5. Ensure items such as inhalers, eye drops, topical medicines, tation that identifies and documents allergies or other serious herbal and homeopathic remedies are included, as patients adverse medication events, as well as information about how often do not consider these as medicines. medicines are taken currently and have been taken in the past. 6. Ascertain the patient's medication-taking behaviour. It is the starting point for medicines reconciliation and medi- 7. Consider practical issues such as swallowing difficulties, cation review. ability to read labels and written information, container preferences, ordering or supply problems. Obtaining accurate and complete medication histories has 8. Document the history in an appropriate format. been shown to have a positive effect on patient care and phar- 9. Note any discrepancies between this history and that macists have demonstrated that they can compile such histo- recorded by other health care professionals. ries with a high degree of precision and reliability as part of 10. Ascertain if these discrepancies are intentional (from patient, medicines reconciliation. The benefit to the patient is that pre- nursing staff, medical staff or medical notes). scribing errors of omission or transcription are identified and 11. Communicate non-intentional discrepancies to the prescriber. 12. Document any other important medication-related information corrected early, reducing the risk of harm and improving care. in an appropriate manner, for example, implications of chronic Discrepancies between the history recorded by the medical renal failure, dialysis, long-term steroid treatment. team and that which the pharmacist elicits fall into two cat- egories: intentional (where the medical team has made a deci- sion to alter the regimen) or unintentional (where a complete conditions. Types of drug–patient interactions may include record was not obtained). Discrepancies should be clarified allergy or previous ADR, the impact of abnormal renal or with the prescriber or referred to a more senior pharmacist. hepatic function or chronic heart failure on the systemic avail- Box 1.5 lists the key components of a medication history. ability of some medicines, and patients' preferences for certain treatment options, formulations or routes of administration. Step 2. Selecting the medicine The issues to be tackled at this stage include clinical and cost- Step 2.2. Identify drug–disease interactions effective selection of a medicine in the context of individual A drug–disease interaction may occur when a medicine has the patient care. The list of expected treatments generated at step 1 potential to make a pre-existing condition worse. Older people is now scrutinised for its appropriateness for the patient. This are particularly vulnerable due to the co-existence of several requires three separate types of interaction to be identified: chronic diseases and exposure to polypharmacy. Prevention drug–patient, drug–disease and drug–drug. The interactions of drug–disease interactions requires an ­understanding of the should be prioritised in terms of likelihood of occurrence and pharmacodynamic properties of medicines and an apprecia- the potential severity of outcome should they occur. tion of their contraindications. Step 2.1. Identify drug–patient interactions Step 2.3. Drug–drug interactions Many medicines have contraindications or cautions to their use Medicines may affect the action of other medicines in a num- that relate to age groups or gender. Potential drug–patient inter- ber of ways. Those with similar mechanisms of action may actions should be identified that may arise with any of the med- show an enhanced effect if used together whilst those with 8 icines that could be used to treat the current and pre-­existing opposing actions may reduce each other's effectiveness. Clinical pharmacy process 1 Metabolism of one medicine can be affected by a second Table 1.6 Pharmaceutical considerations in the administration that acts as an inducer or inhibitor of the cytochrome P450 of medicines enzyme system. The practitioner should be able to identify common drug Dose Is the dose appropriate, including adjustments interactions and recognise those medicines with increased for particular routes or formulations? risk of potential interaction, such as those with narrow Examples: differences in dose between intravenous and oral metronidazole, therapeutic indices or involving hepatic P450 metabolic intramuscular and oral chlorpromazine, and pathways. It is important to assess the clinical significance digoxin tablets compared with the elixir of drug interactions and consider the options for effective management. Route Is the prescribed route available (is the The list of potential, evidence-based treatments should be patient nil by mouth?) and appropriate for the reviewed for possible drug–patient, drug–disease and drug– patient? drug interactions. The refined list can then be compared Examples: unnecessary prescription of an intravenous medicine when the patient can with the medicines that have been prescribed for the patient. swallow, or the use of a solid dosage form The practitioner should explore any discrepancies to ensure when the patient has dysphagia the patient does not experience an MRP. This may neces- sitate consultation with medical staff or other health care Dosage form Is the medicine available in a suitable form for professionals, or referral to a more senior pharmacist. administration via the prescribed route? Documentation Is documentation complete? Do nurses or Step 3. Administering the medicine carers require specific information to administer Many factors influence the effect that a medicine has at its the medicine safely? locus of action. These include the rate and extent of absorp- Examples: appropriateness of crushing tablets for administration via nasogastric tion, degree of plasma protein binding and volume of distri- tubes, dilution requirements for medicines bution, and the routes of metabolism or excretion. Factors given parenterally, rates of administration affecting bioavailability may include the extent of absorption and compatibilities in parenteral solutions of the drug from the gastro-intestinal tract in relation to food (including syringe drivers) and other medicines, or the amount adsorped onto intrave- nous infusion bags and giving sets when used to administer Devices Are devices required, such as spacers for medicines parenterally. inhalers? The liver has extensive capacity for drug metabolism, even when damaged. Nevertheless, the degree of hepatic impair- ment should be assessed from liver function tests and related Although simple regimens (once- or twice-daily administra- to potential changes in drug metabolism. This is particularly tion) may facilitate adherence, some medicines possess short important for medicines that require activation by the liver half-lives and may need to be given more frequently. The prac- (pro-drugs) or those whose main route of elimination is trans- titioner should be familiar with the duration of action of reg- formation into water-soluble metabolites. ularly encountered medicines to ensure dosage regimens are Table 1.6 summarises the main pharmaceutical consider- designed optimally. ations for step 3. At this point, the practitioner needs to ensure the following tasks have been completed accurately. Step 4. Providing the medicine Step 3.1. Calculating the appropriate dose Ensuring that a prescription is legal, legible, accurate and Where doses of oral medicines require calculation, this is unambiguous contributes in large measure to the right usually a straightforward process based on the weight of the patient receiving the right medicine at the right time. For patient. However, medicines to be administered parenterally the majority of ­pharmacists this involves screening pre- may require more complex calculations, including knowledge scriptions written by other professionals, but those acting as of displacement values (particularly for paediatric doses) and supplementary and independent prescribers need to be cog- determination of appropriate concentrations in compatible nisant of guidance on prescribing, such as that contained fluids and rates of infusion. within the British National Formulary, when generating their prescriptions. In providing a medicine for an individual, due account Step 3.2. Selecting an appropriate regimen must be taken of the factors that influence the continued Giving medicines via the oral route is the preferred method availability and supply of the medicine within the hospi- of administration. Parenteral routes carry significantly more tal or community setting, for example, formulary and drug risks, including infection associated with vascular access. This tariff status, primary/secondary shared care arrangements, route, however, may be necessary when no oral formulation and whether the prescribed indication is within the prod- exists or when the oral access is either impossible or inappro- uct licence. This is particularly important with unlicensed or priate because of the patient's condition. non-formulary medicines when information and agreement 9 1 general on continuation of prescribing, ­recommended monitoring patient and their family or carers. In addition, patients often and availability of supply are transferred from a hospital to require specific information to support their daily routine of primary care setting. taking medicines. All written information, including medi- Risks in the dispensing process are reduced by attention cines reminder charts, should be dated and include contact to products with similar names or packaging, patients with details of the pharmacist to encourage patients to raise fur- similar names, and when supplying several family members at ther queries or seek clarification. the same time. Medicines should be labelled accurately, with clear dosage instructions and advisory labels, and presented Step 7. Evaluating effectiveness appropriately for patients with specific needs, for example, the ­visually impaired, those unable to read English or with lim- The provision of drug therapy for the purpose of achiev- ited dexterity. ing definite outcomes is a fundamental objective of ­pharmaceutical care. These outcomes need to be identified at the outset and form the basis for evaluating the response Step 5. Monitoring therapy to treatment. Practitioners delivering pharmaceutical care Monitoring criteria for the effectiveness of treatment and its have a responsibility to evaluate th

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