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Pharmacotherapeutics Theory 1

2016

Example Short Answer Questions - Answers Guidance for Written Answer Questions: Written communication is a critical component of pharmacy practice. For this reason it is a requirement of this course that all written answers are provided in appropriate English. No marks will be awarded for answers containing grammatical errors that require the examiner to interpret the meaning of the answer. Additionally, in pharmacy practice the provision of information that is not required to specifically answer a question can be dangerous; the provision of irrelevant information can lead to misunderstanding. It is expected that answers will specifically address the question in a succinct and logical manner. Answers that contain irrelevant information will be penalised. The magnitude of the penalty will reflect the accuracy, amount and degree of irrelevance of the material. Sufficient time will be allocated in examinations to enable the formulation of acceptable answers. Where it is appropriate to list points, rather than providing a structured answer, this will be clearly indicated in the question.

1.

 Inthemanagementofhypertensionwhichpatientfactorhasthegreatestimpactupondrugtherapyselection? Provideanexplanationastowhythisfactorinfluencesdrugtherapyselection.

ModelAnswer: Comorbidities have the greatest impact upon antihypertensive drug selection (1 mark) as there are no significant differencesinBPloweringbetweenclasses(1mark).DuetoeffectsthatarenotdirectlyrelatedtotheirBPlowering (1mark),somedrugclasseshavespecificbenefitsorrisksinspecificcomorbidities(1mark). (4/4 marks)

PoorAnswer: Comorbidities are the most important determinant of antihypertensive drug therapy selection (1 mark). Comorbiditiesinfluencethebenefitsandrisksofthedrugs(nomarkawarded–Thisstatementisnearlyalwaystrue andinisolationlikethisdoesnotindicateanydepthofunderstanding.Forexample,youneedtoindicatethatthe benefitsarenotrelatedtoBPbutduetootheractionsofthedrug).Factorssuchasageandcostarealsoimportant determinants(nomarkawarded‐technicallycorrectstatementbutitdoesnotaddressthespecificquestion).  (1/4marks)  

Pharmacotherapeutics Theory 1

2.

2016

WhyisratecontroloftenthepreferredmanagementoptionforpatientswithpersistentAFandahistoryof ischaemicheartdisease?

ModelAnswer: Rhythmcontrolis unlikelytobesuccessfulinapatientwith persistent AF(1mark) andsomeofthe drugsthatare usedtoobtainrhythmcontrol,suchasflecainide,haveserious riskswhenusedinpatientswithIHD(1mark).Many ofthedrugsthatareusedtoachieveratecontrolarealsothose thatareusedtocontrolIHDandsothetreatment willbenefitbothconditions(1mark).Incontrast,thedrugsforrhythmcontrolandIHDaredifferentandsopatients wouldneedtobetreatedwithagreaternumberofmedications(1mark). (4/4marks)   PoorAnswer: ItiseasiertocontrolventricularratethanachievenormalrhythminapatientwithpersistentAF(1mark).Thedrugs thatareusedforratecontrolsuchasbetablockersalsohelptocontrolIHD(1mark). (2/4marks)   PoorAnswer: Betablockers,ratelimitingcalciumchannelblockersand digoxinareusedtoslowventricular rateinpatients with AF.Thisisreferredtoasratecontrol(nomarksawarded‐technically correct statements  but they do not answer thespecificquestion).Flecainide,amiodaroneandsotalolareusedforrhythmcontrolwhich iswheretheheart is convertedtothenormalsinusrhythm(nomarksawarded‐technically correct statementsbut they donot answer the specific question). These drugs are dangerous in patients with untreated ischaemic heart disease but can be usedsafelyifithasbeentreated(thisstatementisincorrect–treatmentofIHDdoesnotmakeflecainidesafe). (0/4marks)   

Pharmacotherapeutics Theory 1

3.

2016

Patientswhoaregoingtobeimmobileforaperiodoftimeareatincreasedriskofdevelopingadeepvein thrombosis(DVT). i. WhyisitimportanttopreventthedevelopmentofaDVT?

ModelAnswer: DVTscauselocalsymptomssuchaspainandswelling(1mark), whichmaypersistforalongperiodoftimeafterthe clot itself has resolved (1 mark). DVTs can also dislodge and move to the lungs causing a pulmonary embolus (1 mark) which is a potentially dangerous situation that may result in severe heamodynamic instability or death (1 mark). (4/4marks)  PoorAnswer: DVTs cause pain and swelling in the leg (1 mark) and may cause a pulmonary embolus (1 mark). (Further explanationoftheimportanceoftheseeventsisrequiredtoobtaintheadditionalmarks) (2/4marks)  PoorAnswer: DVTscan cause painandmyocardial infarctionsby spreadingtotheheart.Thisneeds tobepreventedaspatients can die from heart attacks. (It is true that DVTs cause pain but it is unclear from this answer where the pain is occurring.The firstsentencecouldbe interpreted asmeaningthepain isspecificallyassociatedwiththeMI.The linkwithMIistechnicallyincorrect.Thereforenomarksareawarded.) (0/4marks)    ii. DVTscanbepreventedbyusingeitherenoxaparin20mgor40mgdailyorunfractionatedheparin5000 unitsbdortds.Provideabriefdescriptionofthemostclinicallysignificantdifferencesbetweenthese treatmentoptions. ModelAnswer: Enoxaparin is more convenient to administer (1 mark) and is less likely to cause the severe reaction of heparin inducedthromboticthrombocytopenia(1mark).Thedoseofenoxaparin,butnotunfractionatedheparin,needsto beadjustedaccordingtothepatient’s renal function (1 mark)asenoxaparin,butnotheparin,isrenallycleared(1 mark) in order to prevent over‐anticoagulation(1mark). If a patient does experience a bleeding event the effect of unfractionatedheparinismoreeasilyreversedthanenoxaparin(1mark). (6/6marks)  PoorAnswer: Dailyadministrationofenoxaparinismoreconvenientthanbdortdsunfractionatedheparin(1mark).Enoxaparinis lesslikelytocauseadverseeffects(nomarksawarded–thisstatement isnot correct.Enoxparinmaybelesslikely to cause HITTS but if the dose is not appropriately adjusted for renal function it may be more likely to cause bleeding).Theeffectofunfractionatedheparincanbemonitored byAPTT whereasenoxaparin cannot(nomarks awarded–thisis atechnicallycorrectstatementbutit is notimportantforthespecificquestion.The questionis askingaboutDVTprevention.APTTmonitoringisnotrequiredforDVTprophylaxis). (1/6marks)  

Pharmacotherapeutics Theory 1

2016

4. CoronaryarterystentsarethepreferredtreatmentforpatientsexperiencinganSTEMI.Oneofthemajorrisksof stentinsertionistheoccurrenceofstentthrombosis. i. Whichdrugsareusedtopreventstentthrombosis.Provideajustificationfortheuseofthesespecificdrugs.  ModelAnswer: Aspirin and clopidogrel (1 mark). Clot formation on stents is driven predominantly by platelet activation (1 mark) andassuchtwoantiplateletdrugswithdifferentmechanismsofactionareusedtoblockthispathway(1mark–ina pharmacotherapeuticscoursethisisasufficientjustificationforwhytwo drugsarecombinedinthiswayunless you are asked to specifically explain the mechanisms of action, similarly combinations of antibiotics would be justifiedbaseduponspectrumratherthanspecificmechanismsofaction). (3/3marks)  GoodAnswer‐butifyouanswereveryquestionlikethisyouwillrunoutoftime: Dualantiplatelettherapycomprisingaspirinandclopidogrelisusedtopreventstentthrombosis(1mark).Themetal of the stent lining the coronary artery is a strong trigger of platelet activation (1 mark). For this reason two antiplateletdrugsthatact bydifferentmechanismsareused(1mark).Aspirinisanirreversibleinhibitorofplatelet activationbyinhibitingCOX1whichpreventsthe synthesisofTXA2 whichstimulatesplateletactivation. Clopidogrel preventsplateletaggregationbybindingirreversiblytotheP2Y12ADPreceptorwhichpreventstheactivationofthe GPIIb/IIIa receptors which cross link platelet with fibrin. (The information provided in these last sentences is technically correct but it provides far more detail than is required for a question worth only three marks. The questiondoesnotaskforyouto provide a detailedexplanation ofthe pharmacology of thedrugsand assuchno markswouldbeawardedforthesesentences). (3/3marks)  PoorAnswer: Aspirinandclopidogrelareusedtopreventstentthrombosis(1mark).Warfarincanalsobeusedinpatientswhoare highriskofclotformation(‐1mark–warfarinisnotusedtopreventstentthrombosis.It isnow unclearfromthis answeriftherespondentreallyknowswhichdrugsareusedinthissetting). (0/3marks)   ii. Provideanexplanationastohowandwhythistreatmentmaydifferbetweenpatients?  ModelAnswer: Thedurationoftreatment(1mark)isdeterminedbythetype ofstent thatisinserted(1mark).Drugelutingstents require a longer duration of dual antiplatelet (1 mark) therapy as they are more likely to promote thrombosis formationforlongerastheydelayendothelialcellovergrowth(1mark). (4/4marks) Pooranswer: Patient with a bare metal stent are treated for somewhere between 1 and 12 months whilst those with a drug elutingstentaretreatedforatleast12months(2marks –thisdescribesthedifferenceintreatmentbutdoesn’t explainit.SimplystatingthatBMSandDESaredifferentisnotanexplanation). (2/4marks)  

Pharmacotherapeutics Theory 1

2016

5. Theancillaryinstruction ‘takewith food’isrecommendedfor gliclazideMR.Apharmacistdecidestoleavethis labeloffoftheproduct.Provideadetailedexplanationastowhythepharmacistmadethisdecision?  ModelAnswer: The instruction to take with food is intended to protect against hypoglycaemia (1 mark). As this product is a sustainedreleaseformulationthedurationofactionwillbemuchgreaterthantheamountoftimethatthefoodwill protectagainsthypoglycaemia(1mark).Itismoreimportanttocounselabouttheriskof hypoglycaemiashoulda mealbemissedlater inthe dayafterthetabletwastaken(1mark)andthe signs/symptomsofhypoglycaemia and it’smanagement(1mark). (4/4marks)  PoorAnswer: The instruction to take with food is important for drugs that cause gastrointestinal upset. For this reason this instruction is particularly important to use with metformin but less important with the sulphonylureas (no marks awarded–itiscorrectthatthisinstructionisimportantwithmetforminbutthisdoesnotrelatetothisquestion.It is not correct to suggest that this label could be added to sulphonyl ureas on the basis of GI intolerance).  It is importantfor somesulphonylureasbutnot gliclazideasithasalow incidenceofcausinghypoglycaemia(nomark awarded–whilstgliclazidedoeshave arelativelylowerriskofhypoglycaemiathansomeothersulphonylureas it canstillcausehypoglycaemiaandsothiswouldnotbe a sufficientreasontonotaddtheinstruction totakewith food). (0/4marks)  

Pharmacotherapeutics Theory 1

2016

6. ACochraneReviewofrheumatoidarthritis(CochraneDatabase ofSystematicReviews 2007,Issue1‐updated 2009Issue 1)investigatedtheimpactofcorticosteroids onrheumatoidarthritis.Onecomponent of theanalysis wastheinvestigationoflongtermuseoffixedlowdoseprednisolone(7.5mgdaily).Theanalysisconcludedthat;

“Even in the most conservative estimate, the evidence that glucocorticoids given in addition to standard therapy can substantially reduce the rate of erosion progression in rheumatoid arthritis is convincing.” i.

Whatistheimportanceofreducingtherateoferosionprogressioninrheumatoidarthritis?  ModelAnswer: JointdamagefromRAcanbeseverelydisabling(1mark)andcannotberepairedonceithasoccurred(1mark). (2/2marks) PoorAnswer: Joint erosion causes pain and swelling. (no marks awarded – whilst this is true it does not explain the need to reduceerosion.Itispossibletosimplytreatthepain,usingNSAIDs,butinisolationthisisnotan appropriateway tomanageRA) (0/2marks)   ii. Theterm‘standardtherapy’ismostlikelyreferringtowhichdrug(s)‐whereappropriatenamespecific drug(s)orclass(es)?  ModelAnswer: Methotrexate,sulphasalazine,hydroxychloroquine,NSAIDs (2/2marks)   iii. Despite this evidence, corticosteroids are not considered standard therapy to reduce the rate of erosion progression.Provideanexplanationforthis.  ModelAnswer: In order to prevent joint erosion corticosteroids would need to be used longterm (1 mark). The longterm use of corticosteroids may cause many serious side effects (1 mark) some of which, such as osteoporosis and fat redistribution, are highly likely to occur (1mark). (3/3marks)  PoorAnswer: Corticosteriodscauseadverseeffectssuchasosteoporosis,diabetes,skinthinning,moonface,buffalohump,central obesity,infection, immunosuppression,and glaucoma.(nomarksawarded–whilstthisinformationistechnically correctitdoesnotdemonstratethatyoutrulyunderstandtherisksoforalcorticosteroidsanditdoesnotindicate thatyouunderstandhowthesedrugswouldneedtobeusedinRAtopreventjointerosion) (3/3marks) ...