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Integrated PharmacyCase Studies

SALLY-ANNEFRANCIS

FELICITYSMITH

JOHNMALKINSON

ANDREWCONSTANTI

KEVINTAYLOR

PublishedbyPharmaceuticalPress

1LambethHighStreet,LondonSE17JN,UK

PharmaceuticalPressisthepublishingdivisionoftheRoyal PharmaceuticalSociety

TypesetbyDataStandardLimited,UK

PrintedinGreatBritainbyAshfordColourPressLtd,Gosport, Hampshire

PrintISBN978-0-85369-884-5

PDFISBN978-0-85711-045-9

ePubISBN978-0-85711-219-4

mobiISBN978-0-85711-220-0

Allrightsreserved.Nopartofthispublicationmaybe reproduced,storedinaretrievalsystem,ortransmittedinany formorbyanymeans,withoutthepriorwrittenpermissionof thecopyrightholder.

TherightsofSally-AnneFrancis,FelicitySmith,John Malkinson,AndrewConstantiandKevinTaylortobeidentiﬁed astheeditorsofthisworkhavebeenassertedbythemin accordancewiththeCopyright,DesignsandPatentsAct1988.

AcataloguerecordforthisbookisavailablefromtheBritish Library.

Althoughconsiderableeﬀortshavebeenmadetocheckthe materialin IntegratedPharmacyCaseStudies,theauthorsand publishermakenorepresentation,expressorimplied,with regardtotheaccuracyoftheinformationcontainedinthis bookandcannotacceptanylegalresponsibilityorliabilityfor anyerrorsoromissionsthatmaybemade.Also,thereaderis assumedtopossessthenecessaryknowledgetointerpretthe informationprovided.Itistheresponsibilityofpractitionerand readerstointerpret IntegratedPharmacyCaseStudies inlight ofprofessionalknowledgeandrelevantcircumstancesandto supplementitasnecessarywithspecialistpublicationsandby referencetoproductliterature,codesofconductandsafety regulations.

ForewordbyCatherineDuggan " vii

Acknowledgements " viii

Abouttheeditors " ix

Listofcontributors " x

Abbreviations " xiii

Introduction " xvii

1 Gastrointestinal,liverandrenal cases " 1

INTRODUCTION " 1

1Uninvestigateddyspepsia " 3

2Inﬂammatoryboweldisease " 7

3Treatmentofthreadworm " 10

4Liverdiseaseinanelderlypatient " 13

5Alcoholiclivercirrhosis " 15

6Liverdiseasewithascites " 19

7Managementofparacetamoloverdosewith acetylcysteine " 22

8Chronickidneydisease " 26

9Haemoﬁltration " 31

10Renalreplacementtherapy " 35

2 Cardiovascularcases " 39

INTRODUCTION " 39

1Atrial ﬁbrillation " 43

2Anginamanagement " 49

3Heartfailure " 52

4Acutecoronarysyndromes " 56

5Managementofhypertensioninblack patients " 61

6Cardiovascular(bloodpressure)supportin anelderlyhypotensivepatient " 66

7Deepveinthrombosisandwarfarin " 70

8Treatmentofacuteischaemicstroke " 75

9Secondarystrokeprevention " 78

10Druginteractions " 82

3 Respiratorycases " 87

INTRODUCTION " 87

1Asthma " 89

2Treatinganacutesevereasthma exacerbation " 93

3Nebulisedtherapyforchronicobstructive pulmonarydisease " 97

4Paediatriccystic ﬁbrosis " 101

5Cough " 108

4 Centralnervoussystemcases " 113

INTRODUCTION " 113

1Typesofanxiety,theirtreatmentand associatedissues " 116

2Treatmentoptionsinschizophrenia –antipsychoticsandsideeﬀects " 118

3Bipolardisorderanditstreatment " 122

4Treatment-resistantdepressioninapatient onhaemodialysis " 124

5Self-medicationofdepressionwithStJohn’ s wort,aherbalremedy " 128

6Extemporaneouspreparationof methadone " 131

7Neuropathicpain " 134

8Diﬀerentialindicatorsformigraineand medication-overuseheadache " 138

9Epilepsy " 142

10Phenytoinandacutetherapeutics " 146

11DrugtherapyofParkinson’sdisease " 149

12Smokingcessationincommunity pharmacy " 153

13Dementia/Alzheimer’sdisease " 159

14Dementiaanditspharmacotherapy " 163

5 Infectionscases

" 169

INTRODUCTION " 169

1CellulitisandMRSA " 173

2Typhoid " 178

3Community-acquiredpneumonia " 183

4Urinarytractinfection " 187

5Uncomplicatedgenital Chlamydia trachomatis infection " 189

6Surgicalantibioticprophylaxis " 193

7Diarrhoeaandantibiotictreatment " 196

8 ‘Feverwithnofocus’ inayounginfant " 198

9Managementoftuberculosisandits complications " 202 [continuedover]

10ManagementoflatentTBinfectionand pharmacyinterventions " 205

11Inﬂuenza " 207

12ChronichepatitisC " 210

13PrimaryHIVInfection " 215

14Immunisationsagainstinfectiousdiseases andmalariachemoprophylaxis " 221

6 Endocrinologycases " 225

INTRODUCTION " 225

1Insulinpumpuseinachild " 228

2Hypoglycaemiaduringinsulintherapy " 232

3Type2diabetesmellitus " 235

4Seriouslacticacidosisinducedby metformin " 239

5AnunusualcaseofCushing’ s syndrome " 242

6Addisoniancrisis " 248

7Hypothyroidism " 254

8Osteoporosisinayoungerwoman " 258

9Osteoporosisinanelderlywoman " 262

10TreatmentforHypercalcaemia " 266

7 Malignantdisease, immunosuppressionandhaematology cases " 271

INTRODUCTION " 271

1Lungcancer " 274

2Theuseofantimetabolitesinthetreatment ofbreastcancer " 278

3Clinicalveriﬁcationofprescriptionsfororal anticancermedicines " 282

4Thromboprophylaxisinapatientundergoing surgeryforcancer " 287

5Febrileneutropeniainpaediatric oncology " 291

6Managingchemotherapy-inducednauseaand vomitinginapatientwithlungcancer " 295

7Drugtherapyofmultiplesclerosis " 299

8Managementofvaso-occlusivecrisisinsickle celldisease " 304

8 Musculoskeletalandjointdisease cases " 309

INTRODUCTION " 309

1Gout " 311

2Approachestotheeﬀectivetreatmentof non-speciﬁc,lowbackpain " 314

3DMARDsandtreatmentforrheumatoid arthritis " 317

4Glucosaminesupplementsforosteoarthritis andjointstiﬀness " 324

5Treatingjuvenileidiopathicarthritisinyoung people " 327

6Systemiclupuserythematosus " 331

9 Eye,noseandthroatcases " 335

INTRODUCTION " 335

1Conjunctivitisinpregnancy " 337

2Chronicopen-angleglaucoma " 341

3Wetage-relatedmaculardegeneration " 345

4Sorethroat " 348

5Hayfever " 352

Skincases

" 357

INTRODUCTION " 357

1Atopiceczema " 359

2Contactdermatitis " 363

3Managementofanacute ﬂareof psoriasis " 366

4Acne " 369

5Antibacterialtreatmentofacneinyoung people " 372

6Fungalinfectionofthefoot " 376

7Treatmentofheadlice " 380

11 Specialcases " 383

INTRODUCTION " 383

1Paediatricpharmacokineticsinanewborn preterminfant " 385

2Fallsandcareofelderlypeople " 389

3Treatingapatientwithbenignprostatic hyperplasia " 396

4Painmanagementusingstrongopiatesin palliativecare " 399

5Humanpapillomavirusandcervical cancer " 404

6Blackcohoshformenopausal symptoms " 406

Index " 411

Foreword

Formanyyearstherehasbeenadebateacrosstheprofessionof pharmacyaboutthe ‘divide’ betweenscienceandpractice.The argumenthasoftencentredontheapparentdilutionofthesciencein pharmacy,alongsideastrengtheningclinicalrolewhereas,infact,the oppositeistrue.Clinicalpractitionersusetheirscienceateverystage ofeverydruginterventionandpatientencounter,andareableto demonstratetheiruniquecontributionasadirectresult.These contributionsformthebasisfortheinteractionsthatpharmacists havewithpatientseveryday:fromthedrugandformulationchoice, tomanagingdrugstabilityissues;fromassessingthepatient’sability toswallow,torecommendingthebestrouteofadministration;the assessmentoftheimpactofprescribedandnon-prescribeddrugson thepharmacokineticsofanewlyprescribeddrug;allthistogether withdoingthebestfortheconfusedpatient,nomatterwhattheage orstageoflife,understandingthechallengesbehindmedicine preparationandtaking.

Acrosstheprofession,wewanttoensurethatclinicalpracticeis strengthenedbytheintegrationofpharmaceuticalscience. Integrated PharmacyCaseStudies isahugelyvaluableanduniquetext,covering majordiseasesystems,rareandcommon,providingatextforall:for thoselearningtheconceptsfromscratch,aswellasforthoseat experiencedstagesofcareerdevelopment.Eachcasestudypresented isusefullysetoutwithclearlearningoutcomesandquestionsthat targettheneedsofthepatientthroughtheunderlyingscience.The focusisonthepatient,whereasthetextprovidesdetailsand informationonthedisease/condition,thedrugsinvolvedinits management,theirpharmacologicalmechanismofaction(according tocurrentunderstanding),theirchemicalstructuresandactive groups,formulations,stabilityandinteractions,relevanttothecasein hand.Thecasesnavigatetheissuesbehindthescience, pharmacokinetics,interactionsandsideeﬀectsandarefollowedby somepertinentquestions,referencesandfurtherreadingforthe readertoconsult.Theworkisatruecollaborationbetweenacademic pharmacistsandpractitionerssothattheclinicalcasesareusedto illustrateclearlythatthebestpatientcareresultsfromclinical practicebeingtrulyintegratedwiththepharmaceuticalsciences.

DRCATHERINEDUGGAN PhD,FRPharmS,DirectorofProfessionalDevelopmentandSupport RoyalPharmaceuticalSociety

Acknowledgements

Theeditorswouldliketotakethisopportunitytoacknowledgethose whohaveassistedinthepreparationofthisbook.Wearevery indebtedtothefollowing:

Theauthors:forthetimeandeffortthattheyhaveputintotheir respectivecasediscussions.Professionallifeprovidesfewspare moments,sothetimethattheseindividualshavemadeavailableto makesuchknowledgeablecontributionsisgreatlyvalued.Thenature ofthisbookhasmeantthatthecasesreturnedtotheoriginalauthors forapprovalwereoftenverydifferentfromthoseoriginallysubmitted, astheyhadbeeneditedandaddedto,toensurethattheymetthe objectivesofthisproject.Theauthors’ flexibilityandpositive responsesatallstageshavebeengreatlyappreciated.

CatherineBaumber (PharmaceuticsDepartment,UCLSchoolof Pharmacy):forherconsiderablesecretarial,administrativeand organisationalsupportthroughoutthisbook’spreparationfrom inceptiontosubmissiontothepublisher.

Ourrespectivepartnersandfamilies:fortheirhelp,support, patienceandtoleranceasthisbookwaswritten,editedandprepared inwhateuphemisticallymightbecalledour ‘sparetime’ .

Abouttheeditors

SALLY-ANNEFRANCIS ,BPharm,PhD,MRPharmS, FHEAisanHonorarySeniorLecturerinthe DepartmentofPracticeandPolicyatUCLSchool ofPharmacy,havingpreviouslyheldacademic appointmentsattheschoolfor10years.During thistime,shewasresponsibleforthecurriculum designanddeliveryofpostgraduateMSc programmesinClinicalPharmacy;shehasalso taughtandexaminedontheMPharmandPhD programmesofstudy.Sheisco-authorof InternationalResearchinHealthcare,atextbook forstudentsandresearchersundertaking multicentreresearchprojectsinhealthservices, medicinesuseandprofessionalpractice.

FELICITYSMITH ,BPharm,MA,PhD,FRPharmSis currentlyProfessorofPharmacyPracticeatUCL SchoolofPharmacy.Afterafewyearsinhospital andthencommunitypharmacy,shecompletedan MAinAfricanStudiesatSOASandaPhDatSt Bartholomew’sMedicalCollege.Shethenjoined theacademicstaﬀ oftheSchoolofPharmacy, UniversityofLondon,nowUCLSchoolof Pharmacy.ProfessorSmithhas25years’ experienceinteachingandresearchinpharmacy practice.Duringthistimeshehasbeenactively involvedincurriculumdesignandteachingin pharmacypracticeacrossall4yearsofthe MPharmdegree,aswellasMScandPhD programmes.Sheisauthorofothertextsincluding ConductingYourPharmacyPracticeResearch Project whichisintendedforstudentsorother ﬁrst-timeresearchersinpharmacy.

JOHNMALKINSON ,BPharm,PhD,MRPharmS, MRSC,CChem,FHEAisSeniorLecturerin PharmaceuticalScienceAppliedtoPracticeat UCLSchoolofPharmacy.DrMalkinsonregistered asapharmacistin1997,beforecompletingaPhD inpharmaceuticalchemistryandthenpostdoctoralresearchattheUniversityofLondon.Dr Malkinsonhasnearly15yearsofteaching experienceacrossall4yearstheMPharm programmeandonseveralMScprogrammes.His teachingfocusesprimarilyonorganicand medicinalchemistryandonappliedscienceina clinicalcontext.Hehasanactiveinterestinthe applicationoftechnologyfortheenhancementof

teachingandlearningandisaFellowofthe HigherEducationAcademy.

ANDREWCONSTANTI ,BSc(Pharm),PhD,FBPhSis aReaderinPharmacologyintheDepartmentof PharmacologyattheUCLSchoolofPharmacy.He studiedforhisPhDwhileemployedasaResearch AssistantatStBartholomew’sMedicalCollegeand receivedhisPhDinPharmacologyfromthe UniversityofLondonin1975.Hethenjoinedthe academicstaﬀ oftheSchoolofPharmacy, UniversityofLondon(nowUCLSchoolof Pharmacy)asateachingfellow,laterbeing promotedtolecturer,seniorlecturerandreader. DrConstantihas40yearsofexperiencein teachingandadministrationinall4yearsofthe MPharmdegreecourseaswellascontributingto MSccoursesandthetrainingofPhDstudents.He isalsoaVisitingProfessorofNeuroscienceatthe UniversityofTrieste,Italy,wherehecurrently teachesintheinternationalneuroscienceMSc course.Hisresearchinneuropharmacology/ neuronalelectrophysiologyhasledtothe publicationofover100originalarticlesinrefereed journalsandhewasthemainauthorofthe textbook BasicEndocrinology:forstudentsof pharmacyandalliedhealthsciences,intended primarilyforpharmacyundergraduates.Heisa memberofthePhysiologicalSocietyandan electedFellowoftheBritishPharmacological Society.

KEVINTAYLOR ,BPharm,PhD,FRPharmSis ProfessorofClinicalPharmaceuticsatUCLSchool ofPharmacy.ProfessorTaylorhasmorethan25 years ’ experienceinteachingandresearchinthe areasofformulationscience,medicines manufactureanddrugdelivery.Duringthistime hehasbeenactivelyinvolvedincurriculumdesign andteachinginpharmaceuticsacrossall4yearsof theMPharmdegreeaswellasMScandPhD programmes.Hehasbeenexternalexaminerfora numberofMPharmprogrammesintheUK.Heis co-authororco-editorofseveralothertexts, including Aulton’sPharmaceutics and Pharmacy Practice,whichareintendedforuseby undergraduatepharmacystudents.

Listofcontributors

BOTHAINABJERAGHALHADDAD ,BSc,MSc,PhD|Assistant ProfessorandLecturerinClinicalPharmacy,Departmentof PharmaceuticalSciences,PublicAuthorityforApplied EducationandTraining,Shwaikh,Kuwait

FATEMAHMOHAMMADALSALEH ,BPharm,MSc,PhD|Assistant Professor,DepartmentofPharmacyPractice,Facultyof Pharmacy,KuwaitUniversity,Kuwait

SOTIRISANTONIOU ,MRPharmS,MSc,DipMgt|Independent prescriber;ConsultantPharmacist,CardiovascularMedicine, Bart’sHealthNHSTrust,London,UK

ANAARMSTRONG ,BPharm,PgDipClinPharm|LeadPharmacist, MedicalDivision,SurreyandSussexHealthcareNHSTrust, UK

NELARON Č EVI Ć ASHTON ,BSc,PgDip|ClinicalTutor,Schoolof PharmacyandBiomedicalSciences,UniversityofCentral Lancashire;AdvancedPrimaryCarePharmacist,Cumbria andLancashireClinicalSupportUnit,UK

ZOEASLANPOUR ,BPharm,PhD|MemberofUKPHR,FRSPH, HeadofPharmacyandPublicHealthPractice,Universityof Hertfordshire;ConsultantinPublicHealth,NHS Bedfordshire,UK

PAULBAINS ,DipClinPharm,MRPharmS|Independent prescriber;SeniorLeadPharmacistforMedicine,Imperial CollegeHealthcareNHSTrust,PharmacyDepartment, HammersmithHospital,London,UK

JOANNEBARTLETT ,BPharm,ClinDipPharm|SpecialistClinical Pharmacist,EndofLifeCare,JohnTaylorHospice, Birmingham,UK

GORDONBECKET ,BPharm,PhD,MRPharmS,MRSC,FNZCP |ProfessorofPharmacyPractice,SchoolofPharmacyand BiomedicalSciences,UniversityofCentralLancashire, Preston,Lancashire,UK

SIÂNBENTLEY ,BPharm,MRPharmS,DipClinPharm|Specialist Pharmacist,Paediatrics,RoyalBromptonandHareﬁeldNHS FoundationTrust,London,UK

RANIABETMOUNI ,BPharm,DipClinPharm|Independent prescriber;MScQualityandSafetyinHealthcare,Clinical Pharmacist – BUPACromwellHospital,London,UK

ANNETTBLOCHBERGER ,DipClinPharm|Independentprescriber; LeadPharmacist,Neurosciences,StGeorge’sNHS HealthcareTrust,London,UK

LISABOATENG ,BSc,MSc,MRPharmS,CertiﬁcateinClinical Pharmacy|Independentprescriber;HighlySpecialised Pharmacist,AntimicrobialsandInfectionControl,London, UK

MARKBORTHWICK ,MPharmS,MSc|ConsultantPharmacist, CriticalCare,JohnRadcliﬀeHospital,OxfordUniversity HospitalsNHSTrust,Oxford,UK

SIMONEBRACKENBOROUGH ,BSc,DipClinPharm|Independent prescriber;SeniorLeadPharmacistforMedicineatImperial CollegeHospitalsNHSTrust(StMary’sHospitalSite), London,UK

NADIABUKHARI ,BPharm,MRPharmS,PgDipFHEA|Clinical Lecturer,MPharmStudentSupportManager&Pre RegistrationCoordinator,UCLSchoolofPharmacy,London, UK

MEE-ONNCHAI ,MSc,DipClinPharm,BPharm|Clinical Pharmacist,TeamLeader – RenalServices,King’sCollege HospitalNHSFoundation,London,UK

BARBARACLARK ,MPharm(Hons),GPhC,ClinDip|LeadClinical Pharmacist,LondonBridgeHospital;ChairUKCPA Haemostasis,AnticoagulationandThrombosis(HAT) Group,London,UK

JESSICACLEMENTS ,MPharm,CertPharmPract,DipPharmPract, CertIndependentprescribingpractice|HighlySpecialised PharmacistHIVatMedwayMaritimeHospital,Gillingham, Kent,UK

LOUISECOGAN ,BSc,MRPharmS,PgDipFHEA|Teacher Practitioner,UniversityofCentralLancashire,Preston, Lancashire,UK

ANDREWCONSTANTI ,BSc,PhD,FBPharmacolS|Readerin Pharmacology,UCLSchoolofPharmacy,London,UK

SHANICORB ,MRPharmS,MSc|Independentprescriber;Lead Pharmacist,PaediatricOncology,RoyalAlexandraChildren’ s Hospital,BSUHNHSTrust,Brighton,Sussex,UK

JOYETADAS ,MPharm,DipClinPharm|Independentprescriber; LeadPharmacist,Hepatology,ImperialCollegeLondonNHS Trust,London,UK

HALAMFADDA ,MPharm,PhD|AssistantProfessor,Collegeof PharmacyandHealthSciences,ButlerUniversity, Indianapolis,IN,USA

JOSEPHINEFOLASADEFALADE ,BPharm,MSc,FHEA|Highly SpecialistPharmacist,Bart’sHealthNHSTrust;Clinical Lecturer,UCLSchoolofPharmacy,London,UK

SALLY-ANNEFRANCIS ,BPharm,PhD,MRPharmS,FHEA |HonorarySeniorLecturer,UCLSchoolofPharmacy, London,UK

CLAIREGOLIGHTLY ,MPharmClinDipHosp,PGCertEd |LecturerinProfessionalPractice,BradfordSchoolof Pharmacy,UniversityofBradford,Bradford,UK

LARRYGOODYER ,PhD,MRPharmS,FFTMRCPS(Glas),FRGS |Professor,HeadoftheLeicesterSchoolofPharmacy, FacultyofHealthandLifeSciences,DeMontfortUniversity, Leicester,UK

NICOLAJGRAY ,BSc,PhD,MRPharmS,FHEA,FSAHM(US) |Independentpharmacistresearcher;Director,GreenLine ConsultingLimited,Manchester,UK

KATIEGREENWOOD ,MRPharmS,PGCertTLHE,FHEA |LecturerinPharmacyPractice,PlacementCo-ordinatorand Pre-RegistrationFacilitator,SchoolofPharmacyand BiomedicalSciences,UniversityofCentralLancashire, Preston,Lancashire,UK

ELIZABETHHACKETT ,BSc,MSc|Independentprescriber; PrincipalPharmacistforDiabetes,UniversityHospitals Leicester,Leicester,UK

DELYTHHIGMANJAMES ,PhD,MSc,BPharm,MRPharmS, AMBPsS,FHEA|SeniorLecturer,ProgrammeDirector,MSc inPharmacyClinicalPractice(CommunityandPrimary Care),Cardiﬀ,SouthWales,UK

TIMHILLS ,MRPharmS,DipClin|Independentprescriber;Lead PharmacistAntimicrobialsandInfectionControl, NottinghamUniversityHospitalsNHSTrust,Nottingham, UK

STEPHENHUGHES ,MPharm|SpecialistRenalPharmacist, CentralManchesterFoundationTrust,Manchester,UK

LYNNHUMPHREY ,BPharm,DipPharmPrac,IPP|SeniorLead Pharmacist – Cardiovascular,ImperialCollegeHealthcare NHSTrust,London,UK

ANDYHUSBAND ,DProf,MSc,BPharm,MRPharmS|Deanof Pharmacy,DurhamUniversity,Durham,UK

MATTHEWDJONES ,MPharm,PhD,MRPharmS|Senior Pharmacist – MedicinesInformation,RoyalUnitedHospital BathNHSTrust,Bath,UK

SARAHCJONES ,MPharm,MSc,MRPharmS|LocalityLead Pharmacist,AvonandWiltshireMentalHealthPartnership NHSTrust,Bath,UK

NAVEEDIQBAL ,MPharm,PGClinDip,MSc|TeachingFellow, AstonUniversity;PrescribingSupportPharmacistforNHS, BirminghamCrossCityCCG;communitypharmacist

KUMUDKANTILAL ,BSc(Pharm),DipPharmPract,Postgraduate awardinclinicaloncology|MacmillanPrincipalPharmacist, LeadforCancerEducationandTraining,Guy’sandSt Thomas’ NHSFoundationTrust,London,UK

NAZANINKHORSHIDI ,MPharm,PGDip|HighlySpecialist Pharmacist;OrthopaedicsandPlasticsatGuy’sandSt Thomas’ NHSFoundationTrust,London,UK

STEPHANIEKIRSCHKE ,PhD|SeniorLeadPharmacist Haematology,ImperialCollegeHealthcareNHSTrust, London,UK

ROGERDAVIDKNAGGS ,BSc,BMedSci,PhD,MRPharmS |AssociateProfessorinClinicalPharmacyPractice, UniversityofNottingham;AdvancedPharmacyPractitioner – PainManagement,NottinghamUniversityHospitalsNHS Trust,Nottingham,UK

SARAHKNIGHTON ,MPharm,MPharmS|Independent prescriber;ClinicalPharmacyTeamLeader,LiverandPrivate PatientServices,King’sCollegeHospitalNHSFoundation Trust,London,UK

ROMANLANDOWSKI ,BSc(Pharm),DipClinPharm|Ward Pharmacist,MaternityCareUnit,UniversityCollege Hospital,London,UK

JEREMYLEVY ,MBBChir,PhD,FHEA,FRCP|Consultant Nephrologist,ImperialCollegeHealthcareNHSTrust, London,UK

NATALIELEWIS ,MPharm,ClinDipPharm,PGCertEd|Senior Pharmacist – TeacherPractitioner,AstonUniversityand UniversityHospitalsBirminghamNHSFoundationTrust, Birmingham,UK

TRACYLYONS ,BSc(Pharm),MSc|LeadPharmacist,Infection, ImperialCollegeHealthcareNHSTrust,London,UK

FIONAMACLEAN ,MSc,MRPharmS|Independentprescriber; LeadClinicalPharmacist,CancerandNeurosciences,NHS GreaterGlasgowandClyde,Glasgow,UK

JANETEMCDONAGH ,MBBS,MD,FRCP|ClinicalSenior LecturerinPaediatricandAdolescentRheumatology, UniversityofBirminghamandBirminghamChildren’ s HospitalNHSFoundationTrust,Birmingham,UK

DUNCANMCROBBIE ,MSc,FRPharmS|AssociateChief Pharmacist,Guy’sandStThomas’ NHSHospitalTrust; ClinicalReader,KingsCollegeLondon,London,UK;Visiting Professor,UCL,UK

CARLMARTIN ,PhD,GPhCregistrant,MRPharmS,PGCHE |SeniorClinicalTeacher,DepartmentofPracticeandPolicy, UCLSchoolofPharmacy,London,UK

JAYMIMISTRY ,MPharm,DipGPP|HighlySpecialistPharmacist – AcuteMedicine(generalmedicine)andMedicinesSafety, London,UK

SANDEEPSINGHNIJJER ,MPharm,MBA,GPhC|Pharmacist,UK

LELLYOBOH ,BPharm,DipClinPharm|Independentprescriber; ConsultantPharmacist,CareofOlderPeople,Guy’sandSt Thomas’ CommunityHealthServices,London,UK

JIGNESHPATEL ,PhD,MRPharmS|ClinicalSeniorLecturer/ HonoraryConsultantPharmacist,Anticoagulation,King’ s CollegeLondon/King’sCollegeHospital,London,UK

NEILPOWELL ,MPharm,ClinDip,MRPharmS|Antibioticand HIVPharmacist,RoyalCornwallHospitalTrust,Truro,UK

ANNAPRYOR ,MPharm,MRPharmS|LeadPharmacist,A&E andAdmissions,ImperialCollegeHealthcareNHSTrust(St Mary’ssite),London,UK

GEMMAQUINN ,PGDip,MRPharmS|CourseDirectorMSc ClinicalPharmacy(Hospital)andMPharmStageTutor (Stage4),UniversityofBradford,Bradford,UK

TIMOTHYRENNIE ,MPharm,PhD|HeadofSchoolofPharmacy (AssociateDean),UniversityofNamibia,Namibia,Africa

IANROWLANDS ,MRPharmS,DipClinPharm|Independent prescriber;LeadPharmacistStrokeServices,ImperialCollege HealthcareNHSTrust,London,UK

IMOGENSAVAGE ,BPharm,PhD,MRPharmS|SeniorLecturer (retired),UCLSchoolofPharmacy,London,UK

JENNYSCOTT ,BSc,PhD,MRPharmS|Independentprescriber; SeniorLecturerinPharmacyPractice,UniversityofBath, Bath,UK

LOUISESEAGER ,BPharm,ClinDipPharm,MRPharmS|Senior SpecialistClinicalPharmacistEndofLifeCare,JohnTaylor Hospice,Birmingham,UK

RITASHAH ,BPharm,MRPharmS,MSc|SeniorClinical Pharmacist,CriticalCare,King’sCollegeHospitalNHS FoundationTrust,London,UK

KATESHARDLOW ,MBBS,BPharm,MRCGP|GPandspeciality doctoringenitourinarymedicine,Chelmsford,Essex,UK

NEELAMSHARMA ,BA,PGCertPsychiatricTherapeutics |RegisteredPharmacyTechnician,ChiefPharmacy Technician,MedicinesManagementandE&T,SouthLondon andMaudsleyNHSFoundationTrust,London,UK

ROBSHULMAN ,BScPharm,MRPharmS,DipClinPharm,DHC (Pharm)|LeadPharmacist – CriticalCare,Pharmacy Department,UniversityCollegeHospital;HonoraryAssociate ProfessorinClinicalPharmacyPractice,UCLSchoolof Pharmacy;HonoraryLecturer,DepartmentofMedicine, UniversityCollegeLondon,London,UK

MERVYNSINGER ,MBBSMDMRCP|ProfessorofIntensive CareMedicine;Head,ResearchDepartmentofClinical Physiology,DivisionofMedicine,UniversityCollegeLondon, UK

TIMOTHYJSNAPE ,PhDMSciMRSC,CChemCSci|Lecturerin MedicinalChemistry,UniversityofCentralLancashire, Preston,Lancashire,UK

NUTTANKANTILALTANNA ,MRPharmS,DComP,PhD |PharmacistConsultant,Women’sHealthandOlderPeople, Women’sServicesandaﬃliatedwiththeArthritisCentre, NWLondonHospitalsNHSTrust,London,UK

NEILTICKNER ,MPharm,MRPharmS,PGDipClinPharm|Lead PharmacistPaediatrics,StMary’sHospital,ImperialCollege HealthcareNHSTrust,London,UK

ADAMTODD ,MPharm,PhD,MPharmS,MRSC|Lecturerin PharmacyPractice,DivisionofPharmacy,Durham University,Durham,UK

MARKTOMLIN ,PhD,FRPharmS|Independentprescriber; ConsultantPharmacistCriticalCare,SouthamptonGeneral Hospital,Southampton,UK

STEPHENTOMLIN ,BPharm,FRPharmS|ConsultantPharmacist – Children’sServices,London,UK

CHARLESTUGWELL ,BPharm,MSc,MRPharmS,MCLIP |SpecialistClinicalPharmacist,Neurology/Neurosurgery, RoyalLondonHospital,Bart’sHealthNHSTrust,London, UK

SINEADTYNAN ,MPharm,IP,ClinDip,MSc,MRPharmS|Senior ClinicalPharmacist – LiverServices,King’sCollegeHospital, London,UK

SAMIRVOHRA ,BPharm|LecturerinClinicalPharmacyPractice, SchoolofPharmacyandBiomedicalScience,Universityof CentralLancashire,Preston,Lancashire,UK

PETERSWHITTON ,BSc,MSc,PhD|SeniorLecturerin Pharmacology,UCLSchoolofPharmacy,London,UK

HELENWILLIAMS ,BPharm,PGDip(Cardiol),MRPharmS |Independentprescriber;ConsultantPharmacistfor CardiovascularDisease,SouthLondon,hostedbySouthwark CCG,London,UK

ELIZABETHMWILLIAMSON ,BSc,PhD,MRPharmS,PhD,FLS |ProfessorofPharmacyandDirectorofPractice,University ofReadingSchoolofPharmacy,Reading,UK

KEITHAWILSON ,BSc,PhD|Professor,AstonUniversity, Birmingham,UK

STEWARTWILSON ,BPharm,ClinDipPharm|LeadPharmacist Cardiology,ImperialCollegeNHSHealthcareTrust,London, UK

KAYWOOD ,BSc,DipClinPharm,PhD,MRPharmS,PGPCTL |SeniorLecturerinClinicalPharmacy,Birmingham,UK

KIRSTYWORRALL ,BSc,MRPharmS|TeacherPractitioner workingwithBootsandUCLSchoolofPharmacy,London, UK

PAULWRIGHT ,MRPharmS,MSc|SpecialistCardiacPharmacist, Bart’sHealthNHSTrust,London,UK

Abbreviations

18 F-FDG [18F]ﬂuorodeoxyglucose

5ARI 5a-reductaseinhibitor

5-FdUMP 5-ﬂuorodeoxyuridinemonophosphate

5FU 5-ﬂuorouracil

5-HT 5-hydroxytryptamine/serotonin

A&E accidentandemergency

Ab amyloid-b

AAD autoimmuneAddison’sdisease

ABG arterialbloodgas

ABMS AbbreviatedMentalTestScore

ABPA allergicbronchopulmonaryaspergillosis

ABPM ambulatorybloodpressuremonitoring

ABW actualbodyweight

ACE angiotensin-convertingenzyme

acetyl-CoA acetyl-coenzymeA

AChEIs acetylcholinesteraseinhibitors

ACS acutechestsyndrome/acutecoronarysyndromes

ACTH adrenocorticotrophichormone

AD Alzheimer’sdisease

ADH antidiuretichormone

ADP adenosinediphosphate

AED antiepilepticdrug

AF atrial ﬁbrillation

AIDS acquiredimmunedeﬁciencysyndrome

ALL acutelymphoblasticanaemia

ALP alkalinephosphatase

ALT alanineaminotransferase/alaninetransaminase

AMI acutemyocardialinfarction

AMPK adenosinemonophosphate-activatedprotein kinase

AMR antimicrobialresistance

AMD age-relatedmaculardegeneration

anti-dsDNA antibodytodouble-strandedDNA anti-Sm anti-Smithantibody

API activepharmaceuticalingredient

APP amyloidprecursorprotein

APTT activatedpartialthromboplastintime

ARB angiotensinIIreceptorblocker

ARR (absoluteriskreduction)

ART antiretroviraltreatment

ASD autisticspectrumdisorder

AST aspartateaminotransferase/aspartate transaminase

AT-II angiotensinII

ATP adenosinetriphosphate

ATRA all-trans-retinoicacid

AUC areaunderthecurve

b.d. bisdie (twicedaily)

BBB blood–brainbarrier

BCG bacillusCalmette–Guérin

BDNF brain-derivedneurotrophicfactor

BE baseexcess

BHIVA BritishHIVAssociation

BMD bonemineraldensity

BMI bodymassindex

BMR basalmetabolicrate

BNF BritishNationalFormulary

BNP B-typenatriureticprotein

BOPA BritishOncologyPharmacyAssociation

BP bloodpressure

BPH benignprostatichyperplasia

BRB bloodretinalbarrier

BS BritishStandard

BSAC BritishSocietyofAntimicrobialChemotherapy

BTS BritishThoracicSociety

BuChE butyrylcholinestersae

CABG coronaryarterybypassgraft

cAMP adenosinecyclicmonophosphate

CBT cognitive–behaviouraltherapy

CCB calciumchannelblocker

CD56 clusterofdiﬀerentiationantigen56

CDH chronicdailyheadache

CF cystic ﬁbrosis

CFC chloroﬂuorocarbon

CFTR cystic ﬁbrosistransmembraneconductance regulator

CgA chromograninA

cGMP cyclicguanosinemonophosphate

CHF chronicheartfailure

CHM CommissiononHumanMedicines

CHMP CommitteeforMedicinalProductsforHuman Use

CIN cervicalintraepithelialneoplasia

CINV chemotherapy-inducednauseaandvomiting

CKD chronickidneydisease

CMHT communitymentalhealthteam

CNS coagulase-negativestaphylococci

CNS centralnervoussystem

CNV choroidalneovascularisation

CO cardiacoutput

CO 2 carbondioxide

COMT catechol-O-methyltransferase

COPD chronicobstructivepulmonarydisease

COX cyclooxygenaseenzyme

COX-1 cyclooxygenase-1

COX-2 cyclooxygenase-2

CPB cardiopulmonarybypass

CrCl creatinineclearance

CRF chronicrenalfailure

CRH corticotrophin-releasinghormone

CRP C-reactiveprotein

CSCI continuoussubcutaneousinfusion

CSF cerebrospinal ﬂuid

CSII continuoussubcutaneousinsulininjection

CT computedtomography

CTZ chemoreceptortriggerzone

CVD cardiovasculardisease

CVP centralvenouspressure

CVVHD continuousvenovenoushaemodialysis

CVVHF continuousvenovenoushaemoﬁltration

CYP cytochromeP450enzymes

DAFNE doseadjustmentfornormaleating

DALY disability-adjustedlife-year

DAS diseaseactivityscore

DC directcurrent

DDW dose-deﬁningweight

DEHP di-2-ethylhexylphthalate

DES drug-elutingstent

DESMOND DiabetesEducationandSelfManagementin OngoingandNewlyDiagnosed

DXA dual-energyX-rayabsorptiometry

DHFR dihydrofolatereductase

DHP 1,4-dihydropyridine

DHT dihydrotestosterone

DKA diabeticketoacidosis

DLB dementiawithLewybodies

DMARDs disease-modifyinganti-rheumaticdrugs

DNA deoxyribonucleicacid

DNase dornasealpha

dNTP deoxynucleosidetriphosphate

DOT directlyobservedtherapy

DPI drypowderinhaler

DPP-4 dipeptidylpeptidase4

DQLI dermatologyquality-of-lifeindex

DSM-IV DiagnosticandStatisticalManualofMental Disorders,4thedn

DTPA diethylenetriaminepentaaceticacid

DVT deepveinthrombosis

DXA dual-energyx-rayabsorptiometry

EBW excessbodyweight

ECG electrocardiogram

ECoG echocardiogram

ECG-SR electrocardiogram–sinusrhythm

EDSS expandeddisabilitystatusscale

EDTA ethylenediaminetetraaceticacid

EEG electroencephalography

eGFR estimatedglomerular ﬁltrationrate

EGFR-TK epidermalgrowthfactorreceptortyrosinekinase

EMA EuropeanMedicinesAgency

EPO erythropoietin

EPSEs extrapyramidalsideeﬀects

ER endoplasmicreticulum

ESA erythropoietic-stimulatingagent

ESR erythrocytesedimentationrate

ETC electrontransportchain

ETT exercisetolerancetest

EU EuropeanUnion

FBC fullbloodcount

FDA FoodandDrugAdministration

FDG ﬂuorodeoxyglucose

FEV 1 forcedexpiratoryvolumein1second

FT 4 freethyroxine

FTD frontotemporaldementia

FTU ﬁngertipunit

FVC forcedvitalcapacity

GABA g-aminobutyricacid

GAD generalanxietydisorder

GALC galactosylceramidasegene

GARFT glycinamideribonucleotideformyltransferase

GAS GroupAStreptococci

GC guanylylcyclase

GCS GlasgowComaScale

GBL g-butyrolactone

GC gaschromatography

GFR glomerular ﬁltrationrate

GGT g-glutamyltransferase/g-glutamyltranspeptidase

GI gastrointestinal

GIRK G-proteininwardlyrectifyingK+

GISN GlobalInﬂuenzaSurveillanceNetwork

GLP-1 glucagon-likepeptide-1

GMP goodmanufacturingpractice

GORD gastro-oesophagealreﬂuxdisease

Gs stimulatoryG-protein

GP general(medical)practitioner

GSK-3 glycogensynthasekinase-3

GSL generalsaleslist

GTN glyceryltrinitrate

GTP guanosine-50 -triphosphate

HAART highlyactiveantiretroviraltherapy

HAI hospital-acquiredinfection

Hb haemoglobin

HbS sicklehaemoglobin

HbSS haemoglobinsicklecelldisease

HbA1c glycatedhaemoglobin

HbF fetalhaemoglobin

HCAI healthcare-associatedinfection

HCC hepatocellularcarcinoma

HCV hepatitisCvirus

HD haemodialysis

HDF haemodiaﬁltration

HDL high-densitylipoprotein

HF haemoﬁltration

HF heartfailure

HFA hydroﬂuoroalkane

HIV humanimmunodeﬁciencyvirus

HMG-CoA 3-hydroxy-3-methylglutaryl-coenzymeA

HPA HealthProtectionAgency,nowpartofPublic HealthEngland

HPA hypothalamic–pituitary–adrenal

HPC historyofpresentingcomplaint

HPLC high-performanceliquidchromatography

HPMC hydroxypropylmethylcellulose

HPTLC high-performancethinlayerchromatography

HPV humanpapillomavirus

HR heartrate

HRT hormonereplacementtherapy

HSV herpessimplexvirus

HTN hypertension

i.m. intramuscular

i.v. intravenous/intravenously

IBD inﬂammatoryboweldisease

IBW idealbodyweight

ICH intracerebralhaemorrhage

ICU intensivecareunit

IDSA InfectiousDiseasesSocietyofAmerica

IgE immunoglobulinE

IGRA interferon-g releaseassay

IMiD immunomodulatorydrug

INR internationalnormalisedratio

IPSS internationalprostatesymptomscore

iPTH intactparathyroidhormone

IU internationalunit

JIA juvenileidiopathicarthritis

JVP jugularvenouspressure

K ATP ATP-sensitiveK+ channels

K m plasmaconcentrationatwhichtherateisone halfthemaximum

LAD leftanteriordescending(coronaryartery)

LANSS Leedsassessmentofneuropathicpainsymptoms andsigns

LDL low-densitylipoprotein

LFT liverfunctiontest

LMWH low-molecular-weightheparin

LPL lipoproteinlipase

LTBI latenttuberculosisinfection

LUTS lowerurinarytractsymptoms

LV leftventricular

LVF leftventricularfunction

LVH leftventricularhypertrophy

MALA metformin-associatedlacticacidosis

MAOI monoamineoxidaseinhibitor

MAP meanarterialpressure

MAPT microtubule-associatedproteintau

MCP metacarpophalangeal(joints)

MDRD modiﬁcationofdietinrenaldisease(equation)

MELD modelforend-stageliverdisease

MEP medicine,ethicsandpractice

MHRA MedicinesandHealthcareproductsRegulatory Agency

MI myocardialinfarction

MIC minimuminhibitoryconcentration

MMR measles,mumpsandrubella

MMSE Mini-MentalStateExamination

MOH medication-overuseheadache

MR modiﬁedrelease

MRCF medication-relatedconsultationframework

MRI magneticresonanceimaging

MRSA meticillin-resistant Staphylococcusaureus

MS multiplesclerosis

MSH melanocyte-stimulatinghormone

MSSA meticillin-sensitive Staphylococcusaureus

MTX methotrexate

MU millionunits/megaunit

MUPS multipleunitpelletsystem

MUR medicinesusereview

NAAT nucleicacidampliﬁcationtest

NAPQI N-acetyl-p-benzoquinoneimine

NaTHNaC NationalTravelHealthNetworkandCentre

NF-kB nuclearfactor kB

NG nasogastric

NHS NationalHealthService(inBritain)

NICE NationalInstituteforHealthandCare Excellence(formerlyNationalInstitutefor HealthandClinicalExcellence)

NK neurokinin

NKDA noknowndrugallergy

NMDAR N-methyl-D-aspartatereceptor

NMS newmedicinesservice

NNRTI non-nucleosidereversetranscriptioninhibitor

NNT numberneededtotreat

NO nitrousoxide

NPSA NationalPatientSafetyAgency

NRT nicotinereplacementtherapy

NRTI nucleosidereversetranscriptioninhibitor

NSAID non-steroidalanti-inﬂammatorydrug

NSCLC non-smallcelllungcancer

NSTEMI non-ST-segmentelevationmyocardialinfarction

NTS nucleustractussolitarius

NVQ nationalvocationalqualiﬁcation

o.d. omnidie (everyday)

ODU oncologydayunit

OM obtusemarginal(coronaryartery)

o.m. omnimane (everymorning)

o.n. omninocte (everynight)

OGTT oralglucosetolerancetest

OTC overthecounter

p.o. peroral

p.r.n. prorenata (asrequired)

P aCO 2 partialpressureofcarbondioxideinblood

P aO 2 partialpressureofoxygendissolvedinblood

PASI psoriasisareaandseverityindex

PBR paymentbyresults

PCA patient-controlledanalgesia

PCI percutaneouscoronaryintervention

PCR protein(oralbumin):creatinineratio

PCR polymerasechainreaction

PDD Parkinson’sdiseasedementia

PE pulmonaryembolism

PEARL pupilsequalandreactivetolight

PEF peakexpiratory ﬂow

PEFR peakexpiratory ﬂowrate

PEG polyethyleneglycol

PET positronemissiontomography

P-gp P-glycoprotein

PGD patientgroupdirection

PHI primaryHIVinfection

PI proteaseinhibitor

PID pelvicinﬂammatorydisease

PIL patientinformationleaﬂet

PIP proximalinterphalangeal(joints)

PKG cGMP-dependentproteinkinaseG

pMDI pressurisedmetered-doseinhaler

PML progressivemultifocalleukoencephalopathy

PMR patientmedicationrecord

PN parenteralnutrition

POBA plainoldballoonangioplasty

PPAR- g peroxisomeproliferator-activatedreceptor g

PPD p-phenylenediamine

PPD puriﬁedproteinderivative

PPI (protonpumpinhibitor)

PSS portosystemicshunting

PT prothrombintime

PTB pulmonarytuberculosis

PTH parathyroidhormone

PTHrP PTH-relatedpeptide

PTS post-thromboticsyndrome

PUD pepticulcerdisease

PXR pregnaneXreceptor

q.d.s. quaterdiesumendum (fourtimesdaily)

RA rheumatoidarthritis

RAAS renin–angiotensin–aldosteronesystem

RAS renalarterystenosis

RAST radioallergosorbenttest

RBC redbloodcell

RCA rightcoronaryartery

RCT randomisedcontrolledtrial

RDS respiratorydistresssyndrome

REMS rapidlyevolvingmultiplesclerosis

RPS RoyalPharmaceuticalSociety

RNA ribonucleicacid

RR respiratoryrate

RRMS relapsing–remittingmultiplesclerosis

RTA roadtraﬃcaccident

rTPA recombinanttissueplasminogenactivator

s.c. subcutaneously

SA surfacearea

SACT systemicanti-cancertherapy

S aO 2 oxygensaturationofarterialblood

SBP systolicbloodpressure

SCD sicklecelldisease

SCLC smallcelllungcancer

SDS sodiumdodecylsulphate

SERM selectiveestrogen(oestrogen)receptor modulator

SGLT2 sodium–glucoseco-transporter2

SIGN ScottishIntercollegiateGuidelinesNetwork

SLE systemiclupuserythematosus

SLS sodiumlaurylsulphate

SMART singleinhalermaintenanceandrelievertherapy

SmPC SummaryofProductCharacteristics

SNRI serotonin–noradrenalinereuptakeinhibitor

SOB shortnessofbreath

SOBOE shortnessofbreathonexertion

SOP standardoperatingprocedure

SPC SummaryofProductCharacteristics

SPECT singlephotonemissioncomputedtomography

SpO2 bloodoxygensaturation

SSI surgicalsiteinfection

SSRI selectiveserotoninreuptakeinhibitor

SST2 somatostatintype2

STEMI ST-segmentelevationmyocardialinfarction

STI sexuallytransmittedinfection

SV strokevolume

SVR sustainedvirologicalresponse

t.d.s. terdiesumendum (threetimesdaily)

T 3 triiodothyronine

T 4 tetraiodothyronine(thyroxine)

TB tuberculosis

TBA totalbilateraladrenalectomy

TCA tricyclicantidepressant

TDM therapeuticdrugmonitoring

TENS transcutaneouselectricalnervestimulation

THMPD TraditionalHerbalMedicinalProductDirective

THR TraditionalHerbalRegistration

TIA transientischaemicattack

TLC thin-layerchromatography

TNF- a tumournecrosisfactoralpha

TOE transoesophagealechocardiography

TPMT thiopurinemethyltransferase

TPN totalparenteralnutrition

TRD treatment-resistantdepression

TS thymidylatesynthase

TSH thyroid-stimulatinghormone

TST tuberculinskintest

TxA2 thromboxaneA2

U&Es ureaandelectrolytes

UA unstableangina

UKONS UnitedKingdomOncologyNursingSociety

UKPDS UnitedKingdomProspectiveDiabetesStudy

ULN upperlimitofnormal

UPCR urineprotein:creatinineratio

UTI urinarytractinfection

UV ultraviolet

VaD vasculardementia

VCI vascularcognitiveimpairment

V d volumeofdistribution

VEGF vascularendothelialgrowthfactor

VGSC voltage-gatedsodiumchannel

V m maximumrateofmetabolism

VOC vaso-occlusivecrisis

VR venousreturn

VRE vancomycin-resistantenterococcus

VTE venousthromboembolism

WBC whitebloodcells

WCC whitecellcount

WHO WorldHealthOrganization

Introduction

Anintegratedapproachtolearning Withinthehealthcareteam,pharmacistsarethe recognisedmedicinesexperts.Theyhaveabreadth anddepthofunderstandingaboutallaspectsof medicinesthatsetthemapartfromotherhealth professionals.Asaresultoftheirextensive, specialisteducationandtraining,pharmacistscan conceptualiseadrugmolecule,togetherwithits formulationanddelivery,asamedicine,andcan ensureitssafeandeffectiveusebypatients. Pharmacistsalsohaveadeepunderstandingof pharmacologyandtherapeutics,the physicochemicalpropertiesofdrugsand excipients,biopharmacyandpharmacokinetics, sideeffects,contraindicationsanddrug interactions.Thisiscombinedwithknowledgeof thelegalandethicalframeworkinwhich medicinesaresupplied,aswellasbiologicalcauses ofdisease,andthesocialandbehaviouralfactors thatdeterminewhetherapatientwillobtain optimalbene fitfromtheirmedication.Thishugely varied,complex,integrated,expertknowledge allowspharmaciststomakeprofessional judgementsrelatingtomedicines,givingtheman unchallengeablesphereofexpertise,which,when utilisedforpatientbenefit,legitimisespharmacists’ professionalstatus.

Tobeeﬀective,pharmacists’ educationmust preparethemtobescholars,scientists, practitionersandprofessionals – nomeanfeat.A modernundergraduateMasterspharmacy curriculumrecognisestheimportanceofboth pharmaceuticalscienceandpharmacypractice, which,whenseamlesslyintegrated,prepares graduatesforthemanyprofessionalrolesand activitiesthattheywillbecalleduponto undertakenowandinthefuture.Nowadays, pharmacyprogrammesaimtoachievethis integrationduringastudent’sstudies,increasingly incorporatingopportunitiesforworkplacelearning toprovideacontextinwhichtheylearnandapply theirscientiﬁcknowledge.

IntheUK,theGeneralPharmaceuticalCouncil (GPhC)regulatestheeducationandtrainingof pharmacists.TheGPhCisresponsiblefor accreditingpharmacydegreesandensuringthat

theyare ﬁtforpurpose.Ithaspublisheda documentcontainingacomprehensivesetof standardsandoutcomesagainstwhich programmesareaccreditedandreaccredited (GPhC,2011).Thisdocumenthighlights: ‘Curriculamustbeintegrated...thecomponent partsofeducationandtrainingmustbelinkedina coherentway’ and ‘Learningopportunitiesmustbe structuredtoprovideanintegratedexperienceof relevantscienceandpharmacypractice’ .

Theconceptionanddesignofthis book

Integrationofsciencewithpractice,togetherwith itspracticalapplication,isatthecoreofmodern pharmacyprogrammes.Theneedforpharmacy studentstointegratetheirlearninghasbeena guidingprincipleinthedesignandproductionof thisbook.Trueintegrationofalltheelementsthat contributetopharmacists’ knowledgeisdiﬃcult. Thistextaimstopresentthefundamentalaspects ofpharmaceuticalchemistry,pharmacology, pharmaceuticsandtherapeuticswithinapatientcarecontext.Traditionalattemptsatintegration commonlybeginwithsectionsof ‘underpinning’ science,andthenbuildclinicalandprofessional elementsontoit.Thisapproachcanbesuperﬁcial andunderminesthecredibilityofanyresultant learningexercise.Bycontrast,inthistext,withthe helpofmanyexperiencedpractitionercolleagues, eachcasestudyisgroundedinareal-lifeclinical setting,whichhasthenbeenusedasastarting pointtoillustratehowpharmacists’ practiceand decision-makingareinformedbypharmaceutical science.

Thus,thecasestudiesinthisbookwereinitially writtenbypharmacistpractitioners,basedontheir ownpracticeandexperience,withadditional sciencecontentbeingincorporatedlaterthrough collaborationwiththeeditorialteam.Inthisway, thescienceconceptsincludedhaveadirect relevancetocontemporarypractice.Inparticular thescienceisincludedinthecasebecauseithelps informunderstandinganddecision-makingin real-lifepracticesettings:ithasearnedtherightto bethere!

Thecaseshavebeenorganisedintosections, broadlybasedonthe BritishNationalFormulary, themostwidelyusedreferencesourcein pharmacy,wherethechaptersrelatetoparticular systemsofthebody(e.g.thecardiovascular system)ortoaspectsofmedicalcare(e.g. infections).Althoughthishasallowedusto imposesomestructure,ourcasesareverydiverse andreﬂectthefactthatrealpatientsexperience multiplepathologies.Theyincludematerial relevanttothewiderclinicalpicture.

Wehavestriventoincludecasescoveringthe broadestrangeofclinicalconditions,fromboth communityandhospitalpractice.Allthecase studieshaveasimilarstructure.Withineachcase wehaveintegratedasigniﬁcantscience componentfromoneormoreofpharmaceutical chemistry,pharmacologyorpharmaceutics,andin manycasesallthree.Wehaveincludedwhatwe believearethekeyscienceconcepts.However,it wouldbeimpossibletocoverinasinglesetofcase studiesallthepharmaceutical,clinicaland behaviouralsciencethatappearsinan undergraduatepharmacyprogramme.Thegoal hereistodemonstratethepotentialdiversityof clinicalscenariosandtherelevanceofscience acrossall.

Mostcasesdescribetheuseofmanydrugsina particularclinicalsetting.Againithasnotbeen possibletodetailthechemistry,pharmacology, indications,posology,contraindications,side eﬀectsandformulationsforeverydrug.However, thesecasestudiescanbeusedasastartingpoint toexpandlearningandapplicationofknowledge acrossthescienceandpracticedisciplines.Each caseendswithreferences/furtherreadingand extendedlearningpoints,designedtotakethe reader’slearningbeyondthespeciﬁccase; highlightingotherrelevant,tangentialareasof scienceandpractice.

Howtousethisbook

Thisbookhasbeendesignedprimarilyforuseby undergraduatepharmacystudentsandpreregistrationtrainees.However,itmayalsobe usefulforqualiﬁedpharmacists,pharmacy techniciansandotherhealthprofessionals.Itwill alsoprovidearesourcefortutorsandlecturersto plananduseinlearningactivities.

Weintendthisbooktobefreestanding:a learningandteachingaidtopromoteintegration andcontextualisationofmateriallearnedduring

undergraduatestudies.Itisnotatextbook.There areplentyofexcellenttextbooksthatwillprovide adetailedunderstandingofthesubjectsthatare introducedhere.Thecasestudiesprovidedareof varyingcomplexity,independentofeachotherand notintendedtobereadsequentially.

Eachcasebeginswithasetof Learning outcomes whichprovidesanoverviewofwhatis containedinthecasestudyandhighlightswhat thereadershouldbeabletodohavingstudiedthe case.

Each,detailed Casestudy beginswith contextualinformationaboutapatient,including themedicalanddrughistories.Thisequatestothe levelofinformationlikelytobeavailabletoa pharmacistonconsultingmedicalnotes,ortalking withothermembersofthehealthcareteamorto thepatientand/ortheircarer.Thecasesare interspersedwith,andfollowedby,aseriesof questions.Thesearethesortofquestionsthat pharmacistswillaskthemselveswhen encounteringsuchacaseinpractice,orquestions thatmightbeaskedofpharmacistsbypatientsor otherhealthprofessionals.Werecommendthat readersconsidereachquestionbasedinitiallyon theircurrentknowledge,beforeaccessing additionalsourcessuchasthecurrent British NationalFormulary,lecturenotes,NICEguidance, websitesandtextbooks.Attimes,supplementary informationmayberevealedasthecase progresses,whichmaytakereadersinadiﬀerent directionorcausethemtoreﬂectandre-evaluate theirpreviousresponsesandrecommendations.

Thecasesandquestionsarefollowedbya sectionentitled Casediscussion.Wehavechosen nottosupplydiscreteanswersforeachquestion. Suchanapproachgivestheimpressionthata deﬁniteanswerispossible;thatallquestionshave rightandwronganswers.Professionalpractice demonstratesthatreal-lifeissuescannotbe consideredinsuchablack-and-whitemanner,and whatdemarcatestheprofessionalistheir appreciationandacceptanceofuncertaintyand theirabilitytomakejudgementsbasedonthe availableevidence. ‘Answers’ tothequestionscan befoundinthissection,butthereismuchmore besides,becausethecaseisconsideredinits clinical,practiceandsciencecontext.Havingread thissection,referbacktothequestionsposedin thecase,considerhowyoumightanswerthemin lightofthisinformation,andthinkofwhat additionalquestionsyoumightnowaskandwhat

furtherinformationyouwouldlike.Thisisthe spurto Referencesandfurtherreading.Wehave alsoprovidedsome Extendedlearning questions, representingourownthoughtsforhowthiscase mightencourageusefulfurtherstudy.Hopefully, youwillalsohaveformulatedyourownquestions. Finally,althoughallthecasesare ‘practice’ focused,insomeinstanceswehaveincluded Additionalpracticepoints,highlighting supplementarypracticeissuesthatmaybe tangentiallylinkedtothesubstanceofthecase study,oralludingtopertinentdebatesand concernswithinpharmacy.

Thecaseshavebeenwrittenbypractitioners withacademicinput,representingcurrentclinical andscientiﬁcknowledge,andareinformedbythe experience,expertiseandopinionsoftheauthors. Theyshouldnotbetakenasatemplatefor professionalpractice.Readersareremindedthat knowledge,pharmacotherapyandtreatment guidelinesarecontinuallychangingandthat pharmacistsarecalledontomakejudgements basedontheirownknowledgeandexperience.Be prepared,attimes,todisagreewithwhatyouread!

Conventionsusedinthetext

Withthewidelydifferentbackgroundsofthe contributingauthors,therewereinevitably differencesinterminologies,unitsof measurement,etc.,betweencases.Alsoclinical andscienceconventionsoftendiverge.Thus,in thistextweexpressdrugdosesasmg,micrograms (writteninfull),etc.,asisacceptedinclinical practice(tominimisetheriskofprescribing errors),butfollowscientificconventionsfor clinicaldataandothermeasurements,e.g.wehave used mgthroughout(ratherthanmicrogramor mcg)toexpress10-6 grams.

Mostcasesincludemedicinesthatarecurrently beingusedoraretobeusedbyapatient.Note thatalldosesarefortheoralroute(p.o.),unless otherwisestated;dosinginstructionsareindicated asstandardLatinabbreviations,e.g.t.d.s.Wehave ensuredthatthenamesofthemedicinesreferred tointhecasestudiesareasfoundinthemost currentversionofthe BritishNationalFormulary (BNF 68,September2014)atthetimeofwriting. Occasionally,theproprietarynameofaproduct

hasalsobeenincluded,wherethisisappropriate tothecontextofthecase.

Theeditorialteamandthecasestudy authors

Theauthorsofthecaseswerechosenbecauseof theirexperienceaspractisingpharmacists,their uniqueknowledgeofaparticularareaofpractice ortherapeutics,andtheirabilitytocommunicate toearlyyearspharmacists.Thelargemajorityof theauthorscurrentlypractiseaspharmacistsin thecommunityandhospitals,andthecasesreﬂect thatcontemporarypractice.Theirenormous, learnedcontributionstothistextaretestamentto thevastexpertisethatUKclinicalpharmacists nowpossessandusedailyforpatientbene ﬁt.

Theeditorialteam,allwithpharmacydegrees, hasextensiveexperienceinteaching undergraduateandpostgraduatepharmacists,as wellaspharmacytechnicians.Betweenthem,they conductresearchandteachinthecoredisciplines ofpharmacy,namelypharmacypractice, pharmaceutics,chemistryandpharmacology.They haveworkedtogetherbuildingupthecasestudies suppliedbytheauthorstoensurethateachcase integratescurrentscienceandpractice,is coherent,andprovidesatoolforeﬀectivelearning.

Theauthorsandeditorshaveworkedtogether withthesharedbeliefthatthisisavaluableand worthwhileproject.Thecollaborationhasledto aninnovativelearningresource,whichhasdrawn onthecollectiveknowledgeandexperienceofa verydiversegroup.

Thiscollectionofcasestudieshasbeenagreat pleasuretoproduce.Intheprocess,wehave realisedtheenormousrangeofsubjectsofwhich pharmacistsrequireadeepknowledgeand understanding,inordertomaketheirunique contributiontohealthcare.Wehopethatreaders willderivethesameenjoyment,andthatthisbook clearlyillustrateshowthevariousdisciplinesthat comprisepharmacycancomplement,supportand informeachother,suchthatpharmaciststrulyare medicinesexperts.

Reference

GeneralPharmaceuticalCouncil. FuturePharmacists: Standardsfortheinitialeducationandtrainingof pharmacists.London:GPhC,2011.

Gastrointestinal,liverandrenalcases

INTRODUCTION

Thissectioncomprises10casescentredon patientswithgastrointestinal(GI),liverand renaldiseases.TheGIcasesinclude uninvestigateddyspepsia,inﬂammatorybowel diseaseandthreadworminfestation.Liver diseaseisthetopicoffourcases:liverdiseasein anelderlypatient,alcoholiccirrhosis,liver diseasewithascitesandacaseofparacetamol poisoning.Threerenalcasesfocusonchronic kidneydiseaseandhaemoﬁltration/renal replacementtherapy.

Case1

Uninvestigateddyspepsia " 3

Thiscaseconcernsamiddle-agedmanwho presentsinacommunitypharmacywithepigastric discomfortaftereating.Thecaseconsiders approachestoquestioningpatientstogather informationtoenableajudgementtobemade abouttheappropriatecourseofaction.Thecase thenenablesanexaminationoftheadvantagesand disadvantagesofnon-invasivetestsfor H.pylori , interpretationoftestresultsandthetreatmentof H.pylori infection.

Case2

Inflammatoryboweldisease " 7

Thiscaseconcernsapatientwithlong-standing Crohn’sdisease.ThecasedistinguishesCrohn’ s diseasefromulcerativecolitisintermsofits definition,symptoms,signsandcourseofthe disease.Mesalazineisoftencentraltotreatmentof inflammatoryboweldisease.Itsmechanismof actionisdiscussedaswellasitsformulationas modified-releaseoralpreparations,necessitating prescribingbyproprietaryname.Other pharmacologicalagentsarealsoconsidered, includingtheplaceofanti-TNF-a antibody treatment.

Case3

Treatmentofthreadworm " 10

Treatmentofthreadwormtakesplaceina communitypharmacy.Thiscasefocusesonthe signsandsymptomsofinfestation,recommended treatmentsandadditionaladviceforpatients(in thiscasethemotherofyoungchildren). Mebendazoleisthedrugofchoiceanditsmodeof actionisdiscussed.Mebendazoleisavailablein liquidform(oftenpreferableforyoungerchildren). Usingmebendazoleasanexample,thiscase distinguishesdiﬀerentliquidoraldosage formulations:solutions,suspensionsand emulsions.Afurthercomplicationofthecaseis thatonefamilymemberhasepilepsy,sopotential drug–druginteractionsmustbeconsidered.

Case4

Liverdiseaseinanelderlypatient " 13

Thisisthe ﬁrstoffourlivercasesanddescribesan elderlypatientwithliverdisease.Thiscase introducesthebasicstructureandfunctionsofthe liver, ﬁrst-passmetabolism,themainenzymesthat areusedtomonitorliverfunctionandhowliver enzymesareinterpretedtoindicateliverfailure.

Case5

Alcoholiclivercirrhosis " 15

Thiscasedescribesafemalepatientwithalcoholic livercirrhosisadmittedtoanaccidentand emergencydepartment(A&E).Itfocusesonthe interpretationofliverfunctionteststoassess diseaseseverity.Itincludestheoperationand applicationoftheChild–Pughclassiﬁcationof liverinsuﬃciency.Thecaseexaminessome implicationsofliverdiseaseindrughandlingand prescribing.Thecasealsodiscussesthesigns, symptomsandmanagementofacutealcoholic hepatitis.

Case6

Liverdiseasewithascites " 19

Thiscaseinvolvesamalepatientdiagnosedwith alcohol-inducedlivercirrhosis,whoisadmittedto hospitalbecauseofdecompensatedliverdisease. Thiscaseconsiderstheimpactofliverdiseaseon drughandling:pharmacodynamicand pharmacokineticeﬀects.Inparticular,the bioavailabilityofthedrug,drugmetabolismand volumeofdistributionarediscussed.Thecasealso addressesthemanagementofhepatic encephalopathyandthemanagementofascites.

Case7

Managementofparacetamoloverdosewith acetylcysteine " 22

Paracetamolisawidelyusedmildanalgesicand antipyretic,whichwhentakenatrecommended therapeuticdosesissafeandofteneﬀective. However,higherdosesaredangerousand paracetamoloverdoseisoneofthemost frequentlypresenteddrugpoisonings.Thiscase describesthemetabolicpathwaysandmechanisms ofliverdamagethatareaconsequenceof paracetamolpoisoning.Itoutlinesthesigns, symptomsandpresentationofparacetamol overdoseandtheimportanceofestablishingthe numberoftabletsandtimingofingestiontoaid thedevelopmentofatreatmentplan.Thecase discussestheuseandadministrationof acetylcysteineasanantidote.

Case8

Chronickidneydisease " 26

Thiscaseconcernsapatientwithchronickidney diseaseandco-morbidities:type2diabetesand hypertension.Afterthedeﬁnition,causes,signs andsymptomsofchronickidneydiseaseandhow kidneyfunctionisassessedareconsidered;the casethenaddressestherationaleforprescribing drugsforapatientwithchronickidneydisease. Thisinvolvesareviewofthepatient’scurrent medication.Thereisalsoaparticularfocuson furosemide,includingitschemistryand mechanismofaction.

Cases9and10

Cases9and10discusshaemoﬁltration(renal replacementtherapy)withregardtotwopatients whoexperienceanacutedeclineinrenalfunction.

Case9

Haemofiltration " 31

Inthiscase,thepatientundergoescardiacsurgery whichleadstoadeclineincardiacoutputand renalfunction.Therelationshipbetweencardiac andrenaloutputisdiscussed,andtheimpactof medicinesusedtoimprovecardiacfunction. Haemoﬁltrationisstartedtoaddressthedeclinein renalfunction.Thecaseconcludeswitha commentonhowthechemicalpropertiesofa drugcaninﬂuencerenalclearanceanddosing regimens.

Case10

Renalreplacementtherapy " 35

Thiscasedistinguishestheprocessesof haemo filtrationandhaemodialysis,withparticular regardtoimplicationsfortheclearanceof medications.Thispatienthasaviralinfectionthat isresistantto first-andsecond-lineantivirals.A newunlicensedmedication(thathasreached phase2clinicaltrials)isconsidered.Thiscasealso outlinestheclassificationofclinicaltrialsinto phases1–4.

Case1

Uninvestigateddyspepsia

NAVEEDIQBALANDKAYWOOD

LEARNINGOUTCOMES

Attheendofthiscase,youwillbeableto:

. Outlinequestionsyoumayaskapatient aboutuppergastrointestinal(GI)symptoms todecidewhethertotreatover-the-counter (OTC)orrefer

. Discusstheadvantagesanddisadvantages oftheavailablenon-invasivetestsfor H. pylori

. Discusstheterms speciﬁcity and sensitivity inrelationtotestsfor H.pylori

. Recommendappropriatemanagementfor H.pylori.

Casestudy

Youareworkingasacommunitypharmacist.A middle-agedman,MrAS,presentsaskingfor somethingforepigastricdiscomfortaftereating.

. ? WhatquestionswouldyouaskMrASinitially?

MrASsaysthatheisthepatientandthathehas beensuﬀeringfromdiscomfortaftereating,onand oﬀ,forthelast2weeks.Hehasnottriedanything forthisconditionandheisnottakinganyother medicines.Hehasno ‘ALARM’ symptoms.

. ? WhatareALARMsymptoms?

. ? Whenshouldyourefer?

. ? WhatlifestyleadvicewouldyouoﬀerMrAS?

Afterdiscussionwiththepharmacist,thepatient tookranitidine75mgtablets.

" Fourmonthslater... youhaveaphonecall aboutMrASfromyourlocalGP.TheGPoutlines thefollowing:

MrASisa40-year-oldprivatetutorwithdyspepsia. Hehasno ‘ALARM’ symptomsandisbeing managedaccordingtothe ‘uninvestigated dyspepsia’ pathwayintheNICEguidance(NICE, 2004).TheGPhasjudgedthatitisappropriateto testMrASfor H.pylori infection.NICEguidance statesthat H.pylori canbeinitiallydetectedusing eithera 13C-ureabreathtestorastoolantigentest,

orlaboratory-basedserologywhereitsperformance hasbeenlocallyvalidated.

CASENOTES

Historyofpresentingcomplaint

. A4-monthhistoryofintermittentnon-specific epigastricdiscomfortaftereating

Pastmedicalhistory

. Kneearthroscopy(keyholesurgeryusedto investigatekneejointpain)andpartial meniscectomy(kneecartilageremoval)in2002

Medicalhistory

. Dyspepsia

Socialhistory

. Married

. Fourchildren

. Runsaprivatetuitioncentre

. Nohistoryofalcoholconsumption

. Non-smoker

. CametotheUKfromPakistan20yearsago

Drughistory

. Lansoprazole30mgcapsules

. Multivitamins(purchasedwithouta prescription)

. Reportsrashwithpenicillin

TheGPasksforyouradviceonnon-invasivetests availablefor H.pylori

. ? Reviewtheadvantagesanddisadvantagesofkey non-invasivetestingmethodsfor H.pylori.

TheGPhasdecidedthatMrASshouldundertake a 13C-labelledureabreathtest.Hehaschosen HelicobacterTestINFAI – asimpleproprietary breathtestfor H.pylori andadvisesMrASto discontinuetakingthePPIbeforetakingthetest andnottoeatordrinkanything(includingwater) for4hoursbeforehand.

MrASreadinthepatientinformationleaﬂetthat the 13C-labelledureabreathtesthasasensitivityof 97.9%andaspeciﬁcityof98.5%.Heasksyouwhat thismeans.

Onexamination . Weight:89kg . Height:1.80m . BMI:27.4 . BP:138/85mmHg

. ? HowwouldyourespondtoMrAS’squestion?

Thepracticenurseconductsa 13C-labelledurea breathtestonMrAS,andtheresultisnegative. Theprevalenceof H.pylori infectioninmenofMr AS’sageisaround25%(LoganandWalker,2001). TheGPasksyouropiniononthisresultasMrAS hadahighpre-testprobabilityof H.pylori.

. ? Howdoesthetestwork?

. ? Whatcouldhaveledtothenegativetestresult forMrAS?

MrASadmittedthathecontinuedwiththePPI,in spiteofinstructionstothecontrary,ashewas concernedthathissymptomswouldhavehadan eﬀectonhisworkcommitments.MrASstill continuestocomplainofsymptoms.TheGP reassureshimofthereasoningbehind discontinuingPPItherapybeforeundertakingthe Helicobactertestagain.Theretestisissuedasthe previousresultswereinvalid.Theresultsarenow positivefor H.pylori.TheGPasksforyouradvice onthemostsuitableregimenascombinationpacks arenolongeravailable.

. ? WhatadvicewouldyougivetotheGP?

. ? Whywasitnecessarytodiscontinuetakingthe PPIbeforethe H.pylori test?

Casediscussion

Questioningpatientswithupper gastrointestinalsymptoms

On firstmeetingapatient,itisadvisabletohavea systematicapproachtounderstandingapatient’ s problemsanddeterminingwhenitmaybe appropriatetorefertoanotherhealthprofessional. TheWWHAMquestionscanbeusedasaguide toappropriatequestioning(Rutter,2013).This mnemonicshouldbeusedasanaide-memoire;do not firequestionsatpatientsinamannerthatmay affectthe flowoftheconsultation:

Whoisthepatient?

Whatistheproblem?

Howlonghasitbeenaproblem? What Actionhasbeentaken?

Whatother Medicinesarebeingtaken(prescribed ornon-prescription)?

. ! Remember,medicationincludesnon-oral medicinessuchasinhalers,andherbals, homeopathicmedicinesand ‘GSLs’ (general saleslistmedicines).Patients’ perceptionsof whattheyconsidertobemedicationcanbe diﬀerentfromthoseofhealthcareprofessionals.

— ALARMsymptoms

Inadditiontothis,youshouldbeawareof ‘ALARM’ symptoms.Thismnemonicisusedto helpintheassessmentofsymptomsofdyspepsia, andtoidentifycasesthatmaysignifyamore seriousconditionandwarrantfurther investigation.

Anaemia(irondeﬁciency)

Lossofweight

Anorexia

Recentonsetofprogressivesymptoms

Melaena/haematemesis(passageofblacktarry stools/vomitingofblood)

Swallowingdiﬃculty

Referralofpatients

Immediate(sameday) specialistreferralis indicatedforpatientspresentingwithdyspepsia andsigniﬁcantGIbleeding(e.g.vomitinglarge amountsofblood).

Urgent(within2weeks) specialistreferralor endoscopyisindicatedforpatientsofanyageif theypresentwithdyspepsiaandanyofthe following(NICE,2004):

. Chronicgastrointestinal(GI)bleeding(e.g. vomitingsmallamountsofblood,bloodin stools)

. Progressivedysphagia(diﬃcultyswallowing)

. Progressiveunintentionalweightloss

. Persistentvomiting

. Irondeﬁciencyanaemia

. Epigastricmass

. Suspiciousbariummealresult.

Lifestyleadvice

LifestylemodificationmayhelpwithGIsymptoms. Advicecouldbegivenonweightreductionand avoidingprovokingfactors,suchaseatingfattyor spicyfoodsorheavymealsatnight,drinking coffeeoralcohol,andsmoking(NICE,2004).Ifit istobeeffective,questioningshouldelicitthe patient’sperspectivesandtheadviceshouldbe responsivetotheirneedsandsituation.

Testsfor H.pylori

Non-invasivetestingmethodsfor Helicobacterpylori

Thereareseveraldiﬀerentmethodstotestfor H. pylori infection(DeKorwin,2003):

. Ureabreathtest (alsocalledthecarbonisotopeureabreathtest):thepatienttakesaurea productthatcontains 13C-labelledureaasin HelicobacterTestINFAI.If H.pylori ispresent, thebacteriaconvertthe 13C-labelledureato 13C-labelledcarbondioxidewhichisdetected onthepatient’sbreath.Thisisaneﬀectiveand reliabletestforthepresenceof H.pylori infection.Patientsshouldnormallybeadvised toavoidtakingPPIs(atleast2weeksprior)or antibiotics(atleast4weeksprior)to undergoingaureabreathtest.

. Antibodyserology: bloodtestscanmeasure antibodiesto H.pylori.Thus,thesetestswill detectaninfectionifpresent,butantibodies mayremainlongafteraninfectionhascleared.

. Stoolantigentest: thistestdetectsgenetictraces of H.pylori inthefaeces.Itisreliablein diagnosinginfectionandtoconﬁrmeradication.

Sensitivityandspeciﬁcityoftests

Atestwithhigh sensitivity isgoodatcorrectly identifyingpatients whodohaveH.pylori infection.

Atestwithhigh speciﬁcity isgoodatcorrectly identifyingpatients whodonothaveH.pylori infection.

Inthiscase,MrASneedstobeawarethata sensitivity of97.9%indicatesthatthe 13C-labelled ureabreathtestwillcorrectlyidentify,froma cohortof100patients,98%patientswith H.pylori. Thismeansthataround2%patientswhohave H. pylori infectionwillnotbeidentiﬁedbythetestas havingit.Thesepatientswillbelabelled incorrectlyasnothavingtheinfection – asocalled ‘false-negative’ result(NationalPrescribing Centre,2005).

Inturn,a speciﬁcity of98.5%forthe 13C-labelledureabreathtestwillcorrectlyidentify mostpeoplewhodonothave H.pylori infection inacohortof100patients,98.5%patientswillnot have H.pylori infection.Thatmeansthat1.5%of patientswhodonothave H.pylori infectionwill beidentiﬁedbythetestashavingit.These patientswillbelabelledincorrectlyashavingthe

infection – aso-called ‘false-positive’ result (NationalPrescribingCentre,2005).

Theseresultsshouldnotbetheonlyfactorsto beconsideredwhendecidingiftheresultscould beafalsenegativeorpositive.Weneedtotake intoaccounttheprevalenceofthisdiseaseinthe populationtowhichthepatientbelongs(National PrescribingCentre,2005).Youneedtoconsider thepatient’spre-testprobabilityofhaving H. pylori infection.Inthiscase,beawarethatMrAS grewupinPakistan;ratesof H.pylori infectionare higherinless-developedcountries(Loganand Walker,2001).

HelicobactertestINFAI:howitworks

Afteroralingestion, 13C-urealabelledureatablets willrapidlydisintegrateonreachingthestomach. Inthecaseofinfectionwith H.pylori, 13C-labelled ureaismetabolisedbytheureaseenzymepresent in H.pylori.

The 13C-labelledCO2 liberateddiﬀusesintothe bloodvesselsandistransportedasbicarbonateto thelungswhereitisliberatedas 13CO2 inexhaled air,mixedwith 12CO2;thisistheproductof normalrespiration.Infectionwith H.pylori will signiﬁcantlychangetheratio 13C: 12Cinthe exhaledCO2 (Kleinetal.,1996).Therelative abundanceofnaturallyoccurring 13C(sixprotons andsevenneutrons)isaround1%ofallcarbon isotopes;essentiallyalloftheremaining99%is madeupof 12C(sixprotonsandsixneutrons). 12C and 13Caretheonlynon-radioactiveisotopesof carbon.Comparisonofthe 13C: 12Cratioin exhaledCO2 beforeandaftertheingestionof 13Clabelledureacanthereforeindicatethepresence orabsenceof H.pylori ureaseinthe gastrointestinaltract.

Theproportionof 13CO2 inthebreathsamples isdeterminedbyisotope-ratiomassspectrometry (IRMS).Inthisanalyticaltechnique,thebreath sampleisionisedusingapowerfulelectrical currentintheformofabeamofelectrons.As theseelectronscollidewithCO2 moleculesinthe breathsample,theycausetheremovalofelectrons fromtheCO2 molecules,resultinginpositively chargedions.TheCO2 ionsareacceleratedand thendeﬂectedaroundacurvedpath.Heavierions (13CO2 hasarelativemolecularmassof45,

whereas 12CO2 hasarelativemolecularmassof 44)withthesamechargearedeﬂectedlessthan lighterions,allowingseparationandcountingof therelativeamountsof 13CO2 and 12CO2.Ina positivetest,theratio 13CO2 : 12CO2 willbehigher after ingestionof 13C-labelledureathanbefore.

Therate-limitingstepisthe H.pylori urease activity.Theactivityofthisenzymeandits implicationsonscreeningcanhaveahugeimpact onthevalidityoftestresults.

False-negativeresults

Inthiscase,MrASistakinglansoprazole,a protonpumpinhibitor(PPI)thathasadirect antibacterialeﬀecton H.pylori andhasbeen showntoinhibit H.pylori ureaseactivity(Stoschus etal.,1996).PPIcontributiontofalse-negativetest resultshasbeenreportedtooccurinasmanyas 40%ofindividualstakingaPPI(Laineetal.,1998). Themechanismofthiseﬀectstillremainsunclear.

TheTHREEmostcommonhypothesesthat havebeeninvestigatedtoexplainthisoccurrence are:

1PPIshaveaneﬀectonintragastricpH,which couldmaketheintragastricenvironment unfavourablefor H.pylori;thiscouldlead indirectlytoalowerbacterialload(Scottetal. 1998).

2ThehighpHfromPPIconsumptioncould closetheproton-gatedureachannel(HpUreI) thatfacilitatesbacterialcellentryofureaand thereforereduceurea’saccesstocytoplasmic H. pylori urease,whichproducesNH3 andCO2 (Scottetal.,1998).

3Directantibacterialactivityof H.pylori could resultinareductioninbacterialload(Stoschus etal.,1996).

— Advisingonthetreatmentof H.pylori infection

Inthiscase,MrAS’sclaimtohaveanallergyto penicillinshouldbequestionedtodeterminethe likelihoodoftrueallergy,andassesswhetherthe symptomsdescribedareconsistentwithatype1 allergicreaction.Thisquestioningwillalsoensure acorrectrecordingofhisallergystatusandreduce theriskofwithholdingeﬀectivedrugtreatment.A safety ﬁrstapproachwouldexcludetheuseofa penicillinforMrAS.

NICErecommendsa1-weektripletherapy regimenas ﬁrst-line H.pylori eradicationtherapy (NICE,2004).Theoptimumregimenconsistsofa full-dosePPI,witheitheramoxicillin1gand

clarithromycin500mg,ormetronidazole400mg andclarithromycin250mg,allgiventwicedaily. Eradicationiseﬀectivein80–85%ofpatientson tripletherapyusingeithercombination(NICE, 2004).

WeneedtotakeintoaccountMrAS’ s antibiotichistory.ThisispertinenttoMrAS’ s casebecauseeachcourseofclarithromycinor metronidazoleincreasestheriskofresistance (McNultyetal.2012),whichcouldultimatelylead totreatmentfailure.Theimportanceof complianceshouldbestressedtoMrASfor increasingeradicationrates.

AsMrASclaimstohaveanallergytopenicillin theregimenthatwouldbefavouredwillconsistof fulldosePPI,withmetronidazole400mgand clarithromycin250mg,allgiventwicedailyfor1 week.ThisinformationisavailableinChapter1of the BritishNationalFormulary (BNF): Gastrointestinalsystem.

EXTENDEDLEARNING

. Describediﬀerenttypesofallergy/ hypersensitivityreactions

. Howareantibioticsclassiﬁed?Give examplesofeachgroup

. Whatmedicinescancausesymptomsof dyspepsiaasanadverseeﬀect?Howwould youquestionandadvisepatientsabout concurrentuseofthesedrugs?

Referencesandfurtherreading

DeKorwinJD(2003).Advantagesandlimitationsofdiagnostic methodsfor H.pylori infection. GastroenterologyClinBiol 27:380–90. INFAI(2012). 13C-ureabreathtestsfor Helicobacterpylori infection.Availableat:www.infai.com/products/helicobacter. php(accessed20September2012). KleinPD,MalatyHM,MartinRF,GrahamKS,GentaRM, GrahamDY(1996).Noninvasivedetectionof Helicobacter pylori infectioninclinicalpractice:the13Cureabreathtest. AmJGastroenterol 9:690–4. KustersJG,vanVlietAH,KuipersEJ(2006).Pathogenesisof Helicobacterpylori infection. ClinMicrobiolRev 19:449–90. LaineL,EstradaR,TrujilloM,KniggeK,FennertyMB(1998). Eﬀectofproton-pumpinhibitortherapyondiagnostic testingfor Helicobacterpylori. AnnInternMed 29:547–50. LoganRPH,WalkerMM(2001).ABCoftheupper gastrointestinaltract:Epidemiologyanddiagnosisof Helicobacterpylori infection. BMJ 323:920–2. McNultyC,LasseterG,D’ArcyS,LawsonA,ShawI,GlockerE (2012).Is Helicobacterpylori antibioticresistance

surveillanceneededandhowcanitbedelivered? Aliment PharmacolTher 35:1221–30. NationalInstituteforHealthandClinicalExcellence(2004). ManagementofDyspepsiainAdultsinPrimaryCare. ClinicalGuideline17.London:NICE.Availableat:http:// guidance.nice.org.uk/CG17(accessed2October2013). NationalPrescribingCentre(2005).Usingevidencetoguide practice-supplement. MeRecBrieﬁng 30(Suppl).

Case2

Inflammatoryboweldisease PAULBAINS

LEARNINGOUTCOMES

Attheendofthiscase,youwillbeableto:

. Discussthedeﬁnition,signsandsymptoms ofCrohn’sdiseaseandulcerativecolitis

. Describethetreatmentoptionsforrelapses ofCrohn’sdiseaseandulcerativecolitis

. Outlinetheplaceintherapyforanti-TNF- a antibodytreatmentinCrohn’sdisease

. Outlinetheconceptofmodiﬁedreleasefor oraldosageforms

. Describethechemistryandmechanismof actionofaminosalicylates

Casestudy

MrPBisa45-year-oldwhiteman.Hewas diagnosedwithCrohn’sdisease10yearsagoand hassincebeencontrolledonmaintenance mesalazineMR400mgthreetimesdaily.

? Namethetwomainformsofinﬂammatory boweldisease(IBD)

RutterP(2013).Introduction.In: CommunityPharmacy: Symptoms,diagnosisandtreatment. Edinburgh:Churchill Livingstone. ScottDR,WeeksD,HongC,PostiusS,MelchersK,SachsG (1998).Theroleofinternalureaseinacidresistanceof Helicobacterpylori Gastroenterology 114:58–70. StoschusB,Dominguez-MunozJE,KalhoriN,SauerbruchT, MalfertheinerP(1996).Eﬀectofomeprazoleon Helicobacter pylori ureaseactivityinvivo. EurJGastroenterolHepatol 8:811–13.

? Whataretheformulationapproachesthatcan beadoptedtoproducemodiﬁed-releasesolid dosageforms?

MrPBhasbeenadmittedtohospital.Hehasbeen openinghisbowelssixtoseventimesadayand hasconﬁrmedthathisdiarrhoeaisbloody.Hehas afeverandfeelsgenerallyunwell.Itiscleartohis medicalteamthatMrPB’sCrohn’sdiseasehas relapsed.

? Discusstheroleofcorticosteroidsand aminosalicylatesastreatmentsforrelapseof IBD.

MrPBisimprovingonprednisolone40mgeach morning.Hisdoseisslowlyreduced,buthe complainsoffeelingveryunwellwhenhisdoseis reducedtobelow10mgeachmorning.

? Whatisthetreatmentoptiontoavoidtheneed forlong-termprednisolone?

. ? Whatmaybemeasuredbeforestartingthis treatment?

? Whatarethesymptomsofthesetwoforms?

? Whatarethecommonsideeﬀectsof mesalazine/aminosalicylates?Whatarethe importantcounsellingpointsforpatientstaking mesalazine?

. ? Drawthestructureofmesalazine.What structuralfeaturesareimportanttoits pharmacologicalandclinicaluse?

. ? Mesalazinehasbeenprescribedasamodiﬁedreleaseproduct.Whyissuchaproduct appropriateformesalazine?

. ? Whatparametersshouldbemonitoredbefore andduringtherapy?

" Twelvemonthslater... MrPBhasbeen readmittedtohospitalwithanotherrelapse.His Crohn’sdiseaseisnowsevere,asheisopeninghis bowelsonafrequentbasisandhisqualityoflifeis verypoor.Mesalazinehadbeenstoppedsometime ago,becauseithadnoeﬀect.Hisinitialresponseto azathioprinewasgood,butheisnowlosing response.Hehasbeenstartedonprednisolone 40mgeachmorning,buthisdosecannotbe reducedashisCrohn’sdiseaserelapses.

? WhatisthebesttreatmentoptionforMrPB?

Casediscussion

Themainformsofinﬂammatorybowel diseaseandtheirsymptoms

IBDencompassesulcerativecolitisandCrohn’ s disease.Ulcerativecolitisislimitedtothecolon, whereasCrohn’sdiseasemayaﬀectanypartofthe gastrointestinal(GI)tract.Bothconditionsare characterisedbychronicrelapsinginﬂammation.

Ulcerativecolitiscanbedividedintodistalor moreextensivedisease.Distaldiseaseincludes inflammationoftherectumalone(proctitis)orof therectumandsigmoidcolon(proctosigmoiditis). Extensivediseaseincludespancolitis:inflammation ofthewholecolon.Ulcerativecolitisalways involvesinflammationoftherectum.Although Crohn’sdiseasecanaffectanypartoftheGItract, itisusuallylimitedtotheileumandcolon.

ThecausesofulcerativecolitisandCrohn’ s diseaseareunknown.Itisbelievedthata combinationofenvironmentaltriggers(e.g. infection)andgeneticpredispositionleadsto inﬂammationoftheGItract.

Inulcerativecolitis,thesymptomsarelinkedto theareainflamed.Proctitisisassociatedwiththe passageofmucusandblood,butlessoften diarrhoea.Ulcerativecolitisaffectingmoreofthe colonbeyondtherectumisaccompaniedby bloodydiarrhoea.Crohn’sdiseaseisassociated withabdominalpain,whichisoftenthe first symptomofthedisease.Thepainisusually(but notalways)rightsidedandcanmimic appendicitis.Diarrhoeaandweightlossarealso present.Thediarrhoeaisnotalwaysbloody.The abdominalpainofCrohn’sdiseaseisrelatedtothe siteofinflammation.

Structure,chemistryandmechanismof actionofmesalazine

metabolisedtosulfapyridineandtheactive mesalazine.

Themechanismofactionofmesalazine’ s anti-in ﬂammatoryactivityisrelatedtothe mechanismofactionofotherNSAIDssuchas ibuprofen(althoughthereisevidencethat mesalazineactsthroughavarietyofmechanisms). Mesalazinebindsreversiblytotheactivesiteofthe cyclooxygenaseenzymes(COX-1andCOX-2), inhibitingtheproductionofprostaglandins involvedintheinﬂammatoryresponse.Similarto mostNSAIDs,thepresenceofacarboxylgroup (whichisdeprotonatedandnegativelychargedat physiologicalpH)attachedtoahydrophobicgroup (thearomaticringinmesalazine)isimportantfor interactionwiththeCOXactivesite.These featuresmimicthestructureofarachidonicacid, thenormalsubstratefortheCOXenzymes.

— Sideeﬀectsandcounsellingpoints Commonsideeﬀectsincludeheadache,diarrhoea, nausea,vomiting,abdominalpainandrash. Mesalazineistoleratedbetterthensulfasalazine. Patientsreceivingaminosalicylatesshouldbe advisedtoreportanyunexplainedbleeding, bruising,sorethroat,feverormalaisewhileon treatment,duetotheriskofblooddisorders. Treatmentshouldbestoppedifblooddyscrasia (abnormalcellularelements)occurs.

Formulationapproachesformodiﬁed-release, soliddosageformsandtheirapplicationto mesalazine

Mesalazine(alsoknownas5-aminosalicylicacidor mesalamine)isanaminosalicylatenon-steroidal anti-in flammatorydrug(NSAID)usedto treatinflammatoryboweldiseases,suchas ulcerativecolitisandCrohn’sdisease.Mesalazine actslocallyintheGItract,withminimalsystemic sideeffects.Sulfasalazine(anotherNSAID)is

Modified-releaseoralformulationsaimtodeliver drugsatspecificrates,timesorspecific physiologicalsiteswithintheGItract.Production ofamodified-releaseformulationmayresultin extendedrelease(allowingareductioninthe frequencyofdosing),delayedrelease(drugisnot releasedimmediatelyafteradministration)or releaseofdrugataspecificsiteintheGItract(e.g. inthesmallintestineorcolon).Gastroresistant coatings,alsoknownasenteric(pH-controlled) coatings,protectadrugasitpassesthroughthe stomachandcanbeusedfordrugdeliverytothe smallintestineorcolon.Thismaybeemployedto reducetheadverseeffectsofdrugs(suchas NSAIDs)inthestomach,asisthecasehere. Modified-releasecanbeachievedbyusingmatrix polymertablets,polymer-coatedpelletsor osmotic-basedsystems.

Thedrugreleasecharacteristicsoforal mesalazinepreparationsarediﬀerentandthusthe

productsshouldnotbeconsideredas interchangeable.Prescribersmustspecifythe proprietarynameofmesalazinetobedispensed (e.g.Asacol,Pentasa,Salofalk).Patientsshouldbe counselledtoidentifywhichformoforal mesalazinetheytake;thisisdonebestbythe patientrememberingthebrandname.

Corticosteroidsandaminosalicylatesfor treatingrelapseofIBD

Corticosteroidsareindicatedformoderate-tosevererelapsesofCrohn’sdiseaseorIBD.Theyact throughtheinhibitionofseveralinflammatory pathways.Oralglucocorticoidsteroidssuchas prednisoloneorbudesonide,orintravenous hydrocortisone(forsevererelapse)arealloptions. Topicalpreparations(intheformofenemas, foamsorsuppositories)areusefulforrelapsesof ulcerativecolitistocontrolinflammationofthe rectum.Topicalandoralpreparationscanbeused together.Budesonideispoorlyabsorbedand undergoesextensive first-passmetabolism. Prednisoloneisstartedatadoseof40mgeach morning,withhigherdosesbeingnomore effective,whileincreasingtheriskofadverse effects.Oncethepatientisinremission, prednisoloneshouldbewithdrawnslowlyandnot bestoppedabruptly.Toorapidawithdrawalcan leadtoafurtherrelapse.Atypicalwithdrawal regimenwouldinvolveprednisolonebeing reducedby5–10mgevery7–14days.

— Treatmentoptionsavoidingtheneedfor long-termprednisoloneandassociated patientmonitoring ForamildrelapseofulcerativecolitisorCrohn’ s disease,mesalazineatadoseof 4g/daymay induceremission.Topicalrectalpreparationsof aminosalicylatesareeﬀectiveforproctitisordistal ulcerativecolitisandthesecanbecombinedwith oralformsforgreatereﬀect,particularlyin moderateorsevererelapsesofulcerativecolitis.

Thethiopurines,azathioprineand6mercaptopurine,wouldbeindicatedatthisstage. ThemainroleforthiopurinesinIBDissteroid sparing.Thiopurinesshouldbeconsideredforany patientwhorequirestwoormorecoursesof corticosteroidswithinacalendaryear,orthose whosediseaserelapseswhenprednisoloneis reducedto <15mgeachmorningorwithin6 weeksofstoppingprednisolone.Bothazathioprine and6-mercaptopurinearestartedatlowdosesand titratedupwards,aimingfordosesofazathioprine

2–2.5mg/kgperdayor6-mercaptopurine1–1.5mg/kgperday.Themaximumdosewilldiﬀer frompersontopersonandislargelydependenton thedoseatwhichleukopenia(adecreaseinthe numberofwhitebloodcells)develops.

Thiopurinemethyltransferase(TPMT)isan enzymerequiredtometabolisethiopurinedrugs. PatientswithloworabsentlevelsofTPMTareat muchgreaterriskofthiopurine-induced leukopeniaresultingfromaccumulationofthe unmetaboliseddrug.TPMTactivityshouldbe assessedbeforestartingthiopurinetreatment.If activityisveryloworabsent,alternativetreatment shouldbeconsidered.IfTPMTactivityisbelow normalbutnotabsent,bothazathioprineand mercaptopurineshouldbeprescribedatlower doses.

Patientsshouldhaveafullbloodcount(FBC) pre-treatment,andthenweeklyforthe ﬁrst6–8 weeks,followedby3-monthlyifnoproblemsarise. Patientsshouldbeadvisedtoreportany unexplainedbleeding,bruising,sorethroat,fever ormalaisewhileontreatmentbecauseoftherisk ofblooddisorders.Liverfunctiontestsshouldalso beperformedatthesametimeastheFBCdueto thelowriskofhepatotoxicitywiththesedrugs. Liverfunctiontests(LFTs)provideinformation aboutthediagnosisandtreatmentofliverdisease, andmonitoringofliveractivity.Theliverassociatedenzymesthataremeasuredarealanine aminotransferase(ALT),aspartate aminotransferase(AST),alkalinephosphatase (ALP)and g-glutamyltransferase(GGT).In addition,bilirubinandserumalbuminmaybe measured.Thevaluesoftheseparameterswill provideaclinicalpictureofliverfunction,andthe abilityofthelivertometabolisedrugs.

Furthertreatmentoptions

TheNationalInstituteforHealthandCare Excellence(NICE)reviewedthemonoclonal antibodiesagainsttumournecrosisfactor a (TNFa) – inﬂiximabandadalimumab – forthe treatmentofsevereCrohn’sdisease.Bothdrugs areapprovedforsevereactiveCrohn’sdisease wherediseasehasnotrespondedtocorticosteroids and/orimmunosuppressants,orinpatientswho areintolerantof,orhavecontraindicationsto, them.Inﬂiximabisgivenasanintravenous infusionatadoseof5mg/kgatweeks0,2and6, andthenevery8weeksthereafter.Adalimumabis givenbysubcutaneousinjectionatadoseof

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