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1、,Polypharmacy and Adverse Drug Reactions(ADR)in the Elderly,Professor Graham DaviesProfessor of Clinical Pharmacy&Therapeutics Kings College London,Content,Statistics and definitionsThe risk of ADRs in the elderlyThe ADR problem the evidenceCausing hospital admissionOccurring in hospitalChallenges P
2、reventabilityManaging the problemSummary&questions,Lecturer,Audience,Time,Level of performance,Lloyd(1968),“One of the greatest hazards is the use of potent drugs is their inherent toxicity.the dangers of the drug appear to be greater now then ever before.”David Barr MD;Hazards of modern diagnosis a
3、nd therapy the price we pay.Frank Billings Memorial Lecture.J Am Med Assoc 1955;159(15):1452-1456,In US:ADR estimated to be between 4th and 6th leading cause of death.Lazarou JAMA 1998,For exampleNSAIDs Blower et al 1997 Aliment Pharmacol Therap,12,000 admissions/yr 20 to GI bleed 2000 deaths/yr cf
4、3500 RTA 400 bed hospital working at capacity Impact greater for 65 yrs:GI bleed,CHF Renal impairment,The statistics,In England:Approx 20%population 60 years of ageConsume 56%of dispensed medicinesCosts around 40%of NHS drug budgetGrowing ageing population,Definitions,Adverse Drug Events(ADEs)any in
5、jury resulting from the use of drugs5 categories of ADEs:1.Adverse drug reactions2.Medication errors3.Therapeutic failures4.Adverse drug withdrawal events5.Overdoses,Nebeker JR,Ann Intern Med.2004;140(10):795-801,Risks from drug treatment,DEFINITION,WHO.International drug monitoring:The role of the
6、hospital.WHO Tech Rep.1969;425:5-24,“ADR is a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis,diagnosis or therapy of disease,or for modification of physiological function”,Classification,Type APredictable from PcologyDose relatedInfluen
7、ced by kientic and dynamic changesAccount for 75%of ADRPreventable,Type BUnrelated to PcologyPoor relationship with doseUncommon and difficult to detect during developmentPatient idiosyncrasy major factorUnavoidable,DEFINITION OF ADR,Edwards 356:1255-59,“An appreciably harmful or unpleasant reaction
8、,resulting from an intervention related to the use of a medicinal product,which predicts hazard from future administration and warrants prevention or specific treatment,or alteration of the dosage regimen,or withdrawal of the product”,DEFINITION,Edwards 356:1255-59,Why are the elderly at risk of ADR
9、s?,Patient,Medicine,Poly-Pharmacy,Pharmaco-genetics,Pharmacokinetic changes in the elderly,Drug distribution changes in body fat/lean ratio phenytoin)Metabolismchanges to liver mass and blood flowdecrease first pass metabolism-increase bioavailability(opiates,nitrates)EliminationDecrease clearance o
10、f renally excreted drugs(digoxin,lithium,antibiotics)active metabolites morphine-6-glucuronide,Patient,Medicine,Poly-Pharmacy,Pharmaco-genetics,Three recent reports:Estimated that between 30-50%medicines prescribed for long term illnesses are not taken as directedIf prescription was appropriate then
11、 this represents a loss for patients,healthcare providers and pharma industriesEffective interventions are elusive(Haynes,et al.1996,2003-series of Cochrane reviews of efficacy of adherence interventions),Non-adherence to medicines,1World Health Organization Report 2003.2Horne et al.Concordance,adhe
12、rence and compliance in medicine taking.NIHR SDO 2006.3NICE.Medicines concordance&adherence:involving adults and carers in decisions about prescribed medicines 2008/9,UNINTENTIONAL Non-adherence,INTENTIONAL Non-adherence,Capacity&resources,Practical barriers,Motivational Beliefs/preferences,Perceptu
13、al barriers,Perceptions&Practicalities Model of Adherence,Horne R,Weinman et al Concordance,Adherence and Compliance in Medicine Taking:A conceptual map and research priorities(2006).National Institute for Health Research Service Delivery and Organisation R&D,London,Patient,Medicine,Poly-Pharmacy,Ph
14、armaco-genetics,ADRs and Age,Incidence of ADR increases with age Elderly receive more medicines Incidence of ADR increases the more prescribed medicines taken(exponentially?)Grymonpre et al(1988)study 50 yrsADR rates 5%for 1 or 2 medicinesIncreased to 20%when 5 medicines,Table:The Prescribing Cascad
15、e,(Source:Adapted from Rochon and Gurwitz,1997),The Evidence,Elderly not extensively studiedUsually part of general data-setHomogeneity of studies a problem,The problem of homogeneity,Primary end points ADE vs ADRDefinitions used Method of identifying ADR(chart review vs direct patient interview)Ass
16、igning causalitySeverity of harmPreventability,Differ in:Algorithms&agreementExpert judgment,MAGNITUDE OF PROBLEM,Published studies relating to ADRADR causing hospital admissionADR during inpatient stay,Systematic Review:ADRs in hospital patients(Wiffen et al 2002),Table:ADR by Clinical Setting(Wiff
17、en et al 2002),ADR by Location(Wiffen et al 2002),Impact of inpatient ADR(Wiffen et al 2002),Cost 380million/year to NHS EnglandConsuming 4%available bed-days,ADR causing hospital admission Beijer 24(2):46-54,Meta-analysis-68 studiesHospitalisation of 6,071 pts ADR related(4.9%)ADR rate varied from
18、0.2%to 41.3%4 fold increase in ADR hospitalisation rate in elderly(65yr)compared to non-elderly88%of the ADR considered preventable in elderly(vs 24%in non-elderly),Landmark UK study6 month Prospective study2 hospital:1 teaching+1 district hospitalMedical and surgical wardsPatients 16 years,More rec
19、ently(Pirmohamed et al BMJ 2004),6.5%of all admissions due to an ADROlder patients more likely to be admitted with ADR 76 yrs(65-83)vs 66(46-79)4%of hospital bed capacity0.15%fatalityDrug-interactions responsible for 1 in 6 ADRs72%were(possibly or definitely)preventableCost to NHS 466 million/year,P
20、irmohamed,M.,et al.Adverse drug reactions as cause of admission to hospital:prospective analysis of 18 820 patients.BMJ,2004.329(7456):15-9.,ADR causing hospital admission,“Older drugs continue to be the most commonly implicated in causing admissions.”,Inpatient Elderly(Tangiisuran et al;Journal of
21、Nutrition Health and Ageing.2009),Prospective,observational design(6/12)ADR in the very elderly(80 years old)Preventability,severity and type of ADR560 pts(mean 85 yrs;63%female)1 in 8 experienced ADRMajority serious(69%)some life-threatening(4%).No deaths.63%preventable,Drugs Causing ADR,Lecturer,A
22、udience,Time,Level of performance,Preventability implies original decisions incorrect?,Rates vary:54%(1998,US;70yr)28%(2003,UK;75 yr)72%(2004,UK;16 yr)56%(2009,UK;16 yr)63%(2009,UK 85 yr),Review Preventability,2 panels(Doctors&Pharmacists)16 preventable cases reviewed,Summary,ADR common admission an
23、d during in-patient stayElderly more at riskRange of factors poly-pharmacyEstablished medicines common cause,Drugs Commonly Implicated,Summary,ADR common admission and during in-patient stayElderly more at riskRange of factors poly-pharmacyEstablished medicines common causeMany preventableIf prevent
24、able strategies for reducing ADRs?,Strategies,Identify patients triggersVitamin K,creatinine changes,plasma concentrationsImprove process of care(NSF stds?)e-prescribing systemsClinical pharmacists on roundsBetter communication across interface&with patients(carers),Strategies(cont.),Predict at risk
25、 patients?GerontoNet Study(NL,Belg,Italy,UK)(Arch Int Med)483pts(mean 80yrs)6 factors score 8 or more=high risk4+Co-morbidities=+1 CCF=+1Liver disease=+1Renal impairment=+1Previous ADR=+2No of medicines=5-7=+1;8=+4,Prescribing to Reduce ADRs,Age,hepatic and renal disease may impair clearance of drug
26、s so smaller doses may be needed.Prescribe as few drugs as possible and give clear instructions to patients and carersIf serious ADRs are liable to occur warn the patientWhere possible use familiar drugs.With new drugs be particularly alert for ADRs and unexpected event.,Poly-pharmacy and Adverse Drug Reactions in the Elderly,Graham Davies,Professor of Clinical Pharmacy&Therapeutics,Kings College,London,
