polypharmacy and adverse drug reactions (adr) in the elderly
DESCRIPTION
Polypharmacy and Adverse Drug Reactions (ADR) in the Elderly . Professor Graham Davies Professor of Clinical Pharmacy & Therapeutics King’s College London . Content. Statistics and definitions The risk of ADRs in the elderly The ADR problem – the evidence Causing hospital admission - PowerPoint PPT PresentationTRANSCRIPT
Polypharmacy and Adverse Drug Reactions (ADR) in the Elderly
Professor Graham DaviesProfessor of Clinical Pharmacy & Therapeutics
King’s College London
ContentStatistics and definitionsThe risk of ADRs in the elderlyThe ADR problem – the evidence
• Causing hospital admission• Occurring in hospital
Challenges • Preventability• Managing the problem
Summary & questions
Lecturer
Audience
Time
Leve
l of p
erfo
rman
ce
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 and 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 example…………NSAIDs Blower et al 1997 Aliment Pharmacol Therap
12,000 admissions/yr 20 to GI bleed 2000 deaths/yr cf 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 budget
Growing ageing population
DefinitionsAdverse Drug Events (ADEs)
‘any injury resulting from the use of drugs’
5 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
Adverse drug events
Medication errors
Risks from drug treatment
Adverse drug reactions
DEFINITION
WHO. 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 P’cologyDose relatedInfluenced by kientic and dynamic changesAccount for 75% of ADRPreventable
Type BUnrelated to P’cologyPoor relationship with doseUncommon and difficult to detect during developmentPatient idiosyncrasy major factorUnavoidable
DEFINITION OF ADR
Edwards & Aronson. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 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 ”
DEFINITION
Edwards & Aronson. Lancet. 2000;356: 1255-59
Why are the elderly at risk of ADRs?
Patient Medicine
Adverse DrugReaction
Poly-Pharmacy
Cognitiveimpairment &
adherence
Environment
Pharmaco-genetics
AlteredDrug
Handling
Altered Drug
Response
PhysiologicalDecline Co-morbidities
Recovery, HospitalisationDisabilityDeath
Pharmacokinetic changes in the elderlyDrug distribution
• changes in body fat/lean ratio & protein binding• increase free drug concentrations (warfarin; 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-glucuronide
Patient Medicine
Adverse DrugReaction
Poly-Pharmacy
Cognitiveimpairment &
adherence
Environment
Pharmaco-genetics
AlteredDrug
Handling
Altered Drug
Response
PhysiologicalDecline Co-morbidities
Recovery, HospitalisationDisabilityDeath
Three recent reports:
Estimated that between 30 -50% medicines prescribed for long term illnesses are not taken as directed
If prescription was appropriate then this represents a loss for patients, healthcare providers and pharma industries
Effective 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, adherence and compliance in medicine taking. NIHR SDO 2006. 3NICE. Medicines concordance & adherence:involving adults and carers in decisions about prescribed medicines 2008/9
Patient Medicine
Adverse DrugReaction
Poly-Pharmacy
Cognitiveimpairment &
adherence
Environment
Pharmaco-genetics
AlteredDrug
Handling
Altered Drug
Response
PhysiologicalDecline Co-morbidities
Recovery, HospitalisationDisabilityDeath
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 yrs
• ADR rates – 5% for 1 or 2 medicines• Increased to 20% when >5 medicines
Table: The Prescribing Cascade Initial treatment Adverse effect Subsequent
treatmentSubsequent
adverse effect
NSAIDs Rise in blood pressure
Antihypertensive treatment
Orthostatic hypotension
Thiazide diuretics Hyperuricaemia Allopurinol Hypersensitivity reaction (Skin rashes)
Metoclopramide treatment
Parkinsonian symptoms
Treatment with levodopa
Visual and auditory hallucination
(Source: Adapted from Rochon and Gurwitz, 1997)
The EvidenceElderly 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)Assigning causalitySeverity of harmPreventability
Differ in:•Algorithms & agreement•Expert 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 (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 & de Blaey. Pharm World Sci. 2002; 24(2):46-54•Meta-analysis - 68 studies•Hospitalisation 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-elderly•88% of the ADR considered preventable in elderly (vs 24% in non-elderly)
16.6%
4.1%4.9%
•Landmark UK study•6 month Prospective study•2 hospital: 1 teaching + 1 district hospital•Medical and surgical wards•Patients >16 years
More 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/year
Pirmohamed, 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% cases
Inpatient 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 ADR• Majority serious (69%) some life-threatening(4%). No deaths.
• 63% preventable
Drugs Causing ADRMost frequent drug class causing ADR
N %
Cardiovascular active agents
Analgesics (opioid mainly)AntibioticsHypoglycemic agentsPsychotropic agents AnticoagulantsOthers
28 15 12 8 6 4
10
3418 15107512
Lecturer
Audience
Time
Leve
l of p
erfo
rman
ce
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
Decision Doctors
P’cists
Remove label
5 2
Change decision
11 7
Closer monitoring
0 7
16 16
Summary
ADR common – admission and during in-patient stay
Elderly more at risk• Range of factors – poly-pharmacy• Established medicines common
cause
Drug Common IssuesAntibiotics Allergies & dosage adjustment in renal
dysfunctionAnticoagulants Bleeding; drug interactions, dynamic
changes & environmentCardiac glycosides 1 in 5 experience ADR, NTI & kinetic issues.Diuretics Dehydration, electrolyte imbalanceHypoglycaemic agents (oral & insulin)
Hypoglycaemia, changes to diet, poor monitoring
NSAIDs GI bleed, renal impairmentOpioid analgesia Sedation – dynamic and kinetic changes
Drug’s Commonly Implicated
Summary
ADR common – admission and during in-patient stay
Elderly more at risk• Range of factors – poly-pharmacy• Established medicines common cause• Many preventable
If preventable – strategies for reducing ADRs?
StrategiesIdentify patients – triggers
• Vitamin K, creatinine changes, plasma concentrations
Improve process of care (NSF stds?)• e-prescribing systems• Clinical pharmacists on rounds• Better communication across
interface & with patients (carers)
Strategies (cont.)Predict at risk patients?GerontoNet Study (NL,Belg,Italy,UK) (Arch Int
Med)483pts (mean 80yrs)6 factors – score 8 or more = high risk
• 4+ Co-morbidities = +1 • CCF = +1• Liver disease = +1• Renal impairment = +1• Previous ADR = +2• No of medicines = 5-7 = +1; >8 = +4
Prescribing to Reduce ADRs
Age, 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,King’s College, London