Polypharmacy and Adverse Drug Reactions (ADR) in the Elderly Professor Graham Davies Professor of Clinical Pharmacy Hazards of modern diagnosis and therapy the price we pay. Frank Billings Memorial Lecture. J Am Med Assoc 1955;159 (15): 1452-1456In US:ADR estimated to be between 4th and 6th leading cause of death. Lazarou JAMA 1998For exampleNSAIDs Blower et al 1997 Aliment Pharmacol Therap12,000 admissions/yr 20 to GI bleed2000 deaths/yr cf 3500 RTA400 bed hospital working at capacityImpact greater for 65 yrs: GI bleed, CHF Renal impairmentThe statisticsIn England:Approx 20% population 60 years of ageConsume 56% of dispensed medicinesCosts around 40% of NHS drug budgetGrowing ageing populationDefinitionsAdverse Drug Events (ADEs) any injury resulting from the use of drugs5 categories of ADEs: 1. Adverse drug reactions 2. Medication errors 3. Therapeutic failures 4. Adverse drug withdrawal events 5. OverdosesNebeker JR, Ann Intern Med. 2004;140(10):795-801Adverse drug eventsMedication errorsRisks from drug treatmentAdverse drug reactionsDEFINITIONWHO. International drug monitoring: The role of the 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”ClassificationType APredictable from PcologyDose relatedInfluenced by kientic and dynamic changesAccount for 75% of ADRPreventableType BUnrelated to PcologyPoor relationship with doseUncommon and difficult to detect during developmentPatient idiosyncrasy major factorUnavoidableDEFINITION OF ADREdwards 356: 1255-59“An appreciably harmful or unpleasant reaction, 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 ”DEFINITIONEdwards 356: 1255-59Why are the elderly at risk of ADRs?PatientMedicineAdverse Drug ReactionPoly- PharmacyCognitive impairment phenytoin)Metabolism changes to liver mass and blood flow decrease first pass metabolism - increase bioavailability (opiates, nitrates) Elimination Decrease clearance of renally excreted drugs (digoxin, lithium, antibiotics) active metabolites morphine-6-glucuronidePatientMedicineAdverse Drug ReactionPoly- PharmacyCognitive impairment 24(2):46-54Meta-analysis - 68 studiesHospitalisation of 6,071 pts ADR related (4.9%)ADR rate varied from 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)16.6%4.1%4.9%Landmark UK study 6 month Prospective study2 hospital: 1 teaching + 1 district hospitalMedical and surgical wardsPatients 16 yearsMore recently(Pirmohamed et al BMJ 2004)1.6.5% of all admissions due to an ADR2.Older patients more likely to be admitted with ADR 76 yrs (65-83) vs 66 (46-79)3.4% of hospital bed capacity4.0.15% fatality5.Drug-interactions responsible for 1 in 6 ADRs6.72% were (possibly or definitely) preventable7.Cost to NHS 466 million/yearPirmohamed, 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.”Low dose aspirin 18% casesInpatient Elderly (Tangiisuran et al; Journal of Nutrition Health and Ageing. 2009)Prospective, observational design (6/12) ADR in the very elderly (80 years old) Preventability, severity and type of ADR 560 pts (mean 85 yrs; 63% female)1 in 8 experienced ADRMajority serious (69%) some life-threatening(4%). No deaths.63% preventableDrugs Causing ADRMost frequent drug class causing ADRN %Cardiovascular active agents Analgesics (opioid mainly) Antibiotics Hypoglycemic agents Psychotropic agents Anticoagulants Others28 15 12 8 6 4 10 34 18 15 10 7 5 12LecturerAudienceTimeLevel of performancePreventability 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 Preventability2 panels (Doctors drug interactions, dynamic changes 8 = +4Prescribing to Reduce ADRsAge, hepatic and renal disease may impair clearance of drugs 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 ElderlyGraham Davies, Professor of Clinical Pharmacy & Therapeutics, Kings College, London