Prescribing in Older People

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Prescribing in Older People What Geriatricians
should know

• Dr Sinead OMahony
• Senior Lecturer in Geriatric Medicine
• Cardiff University

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Critical balance of benefits and risks of
medicines in older people
Disease burden. Under Rx. Health gain.
Drug clearance, Drug dose, Drug choice, ADRs.
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RCTs

• Underrepresentation of older people
  co-morbidities generalisability
• Relatively small patient numbers fail to
  identify harms real world.
• UK 1972 1994, 22 drugs withdrawn post
  licensing, toxicity

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ADRs causing hospital admission prospective
analysis of 18,820 patients

• 1,225 admissions related to ADRs
• 6.5 of all admissions
• Median bed stay 8 days
• 250,000 admissions / year UK
• 466m / year

Pirmohamed BMJ 2004 32915-19
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Drugs causing adverse drug reactions Drugs causing adverse drug reactions
Drug group/drug No () of cases
NSAIDs 363 (29.6)
Diuretics 334 (27.3)
Warfarin 129 (10.5)
ACE inhibitors/ All receptor antagonists 94 (7.7)
Antidepressants 87 (7.1)
Blockers 83 (6.8)
Opiates 73 (6.0)
Digoxin 36 (2.9)
Prednisolone 31 (2.5)
Clopidogrel 29 (2.4)
Pirmohamed BMJ 2004 32915-19
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Independent Risk Factors for Having an Adverse Drug Event Independent Risk Factors for Having an Adverse Drug Event Independent Risk Factors for Having an Adverse Drug Event
Risk Factor Odds Ratio 95 Confidence Interval
Age
65-69 1.0 referent
75-79 1.2 0.94 1.6
gt 80 1.3 1.0 1.7
Female 1.2 1.0 1.5
Charlson Comorbidity Index
0 1.0 referent
gt 5 5.0 3.2 7.9
Number of Scheduled medications
0-1 1.0 referent
2-4 1.8 1.2 2.5
5-7 2.2 1.5 3.2
gt 8 2.9 1.9 4.6
Field TS JAGS 2004 521349-1354
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Risks for ADRs

• Advancing age ?
• Increased number medicines
• Co-morbidities
• Nursing home residents (frail)
• (80 type A, some type B eg augmentin)

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Rates of Adverse Drug Events among 2,916 residents of 18 Nursing Homes Rates of Adverse Drug Events among 2,916 residents of 18 Nursing Homes Rates of Adverse Drug Events among 2,916 residents of 18 Nursing Homes
Type of Drug Related Event Number (Percent) Rate per 100 Resident-Months (95 Confidence Interval)
Adverse drug events 546 1.89 (1.74-2.05)
Preventable 276 (50) 0.96 (0.85 1.07)
Nonpreventable 270 (50) 0.94 (0.83 1.05)
Potential adverse drug events 188 0.65 (0.56 0.75)
Gurwitz JH, AmJ Med 2000 10987-94
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Frequency of Adverse Drug Events by Type Frequency of Adverse Drug Events by Type Frequency of Adverse Drug Events by Type
Type Adverse Drug Event (n 546) Preventable (n 276)
Neuropsychiatric 150 (27) 83 (30)
Falls 67 (12) 55 (20)
Gastrointestinal 65 (12) 30 (11)
Dermatologic/allergic 59 (11) 7 (3)
Hemorrhage 57 (10) 40 (14)
Extrapyramidal symptoms 52 (10) 19 (7)
Infection 34 (6) 1 (0.4)
Metabolic/endocrine 27 (5) 14 (5)
Anorexia/weight loss 20 (4) 14 (5)
Ataxia/difficulty with gait 18 (3) 9 (3)
Gurwitz JH, AmJ Med 2000 10987-94
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Challenge

• Recognise adverse drug reactions

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Case 1

• 83 Year old man, previously fit and well, hx HT,
  AF, TURP, glaucoma
• Presenting symptoms
• Anorexia marked for one month
• Weight loss and wasting
• Severe fatigue and drowsiness
• General Practitioner referred ? Cancer
• Clinical findings tachypnoea, AF 80/min, Added
  HS, ankle oedema

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Medication

• Warfarin as per INR
• GTN spray PRN
• Finasteride 5mg/day
• Domperidone 10 mg tid
• Tamsulosin MR 400 µg/day
• Latanaprost eye drops daily

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• STOP Tamsulosin
• START Frusemide 40 mg/day
• ACEi

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Lessons Learnt

• Immediate benefits of medication changes
• ADRs can develop acutely even when patients have
  been on the same medication for a long time

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Mechanisms of Type A ADRs

• PHARMACODYNAMICS
• The response to a drug at any given
  concentration at its effector site
• What the drug does to the body
• PHARMACOKINETICS
• The factors responsible for producing a given
  concentration at the effector site at any given
  time
• What the body does to the drug

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Pharmacodynamics and age

• Receptor changes
• Density
• Affinity
• Post receptor events
• Homeostasis changes
• Blood pressure control
• Temperature control
• Posture control
• Cognitive function
• Extrapyramidal function

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• HOMEOSTATIC CHANGES IN THE CARDIOVASCULAR SYSTEM
• SUSCEPTIBILITY OF OLDER PEOPLE TO HYPOTENSIVE
• SIDE EFFECTS OF CARDIOVASCULAR DRUGS

Figure 6. The effects of nifedipine 2.5 mg given
intravenously to young (?) and elderly (?)
volunteers. There is no change in the blood
pressure of the young volunteers but a marked
increase in heart rate. By contrast, in the
elderly heart rate is unaffected but there is a
pronounced reduction in systolic blood pressure.
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• Drugs with substantial first pass metabolism have
  greater bioavailability in the elderly
• (e.g. nifedipine, nitrates, propranolol)

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drug metabolism

• Drug metabolism is in 2 phases
• Phase I oxidative metabolism
• oxidation, reduction,
• hydrolysis
• Phase II - conjugative metabolism
• sulphation,
• glucoronidation

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The Ageing Kidney

• Kidneys
• ? Renal mass 400 g early adult life lt 300 g at
  90 years
• ? Number of nephrons halve ages 30 to 70
• Renal blood flow and ?glomerular filtration rate
• Nephrons influenced by BP- hypertensives 700,000
  nephrons/K normotensives 1.4 m. (Keller G, N Eng
  J Med 2003 348 1717-9)

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OXIDATIVE METABOLISM ANTIPYRINE CLEARANCE
Elderly Young
Mean plasma antipyrine half-life 17.4 6.8 hrs 12 3.5 hrs p lt 0.01
(OMalley et al, 1971BMJ) (OMalley et al, 1971BMJ) (OMalley et al, 1971BMJ)
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(Wynne et al. 1990)
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(Williams et al. 1989)
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Plasma Esterases in Delirium
Activity /- (S.E.) Activity /- (S.E.) Mean Difference P Value
Non Delirium Delirium Mean Difference P Value
Acetylcholinesterase (?mol of DTNB transformed per mL of plasma per min) 2.3 (0.05) 1.9 (0.07) 0.4 0.0001
Aspirin Esterase (nmol salicylate formed/mL plasma/min) 80.3 (2.2) 70.4 (2.8) 9.9 0.006
Benzoylcholinesterase (nmol of benzoylcholine iodide utilised/mL plasma/min) 841 (21.6) 689.8 (25.1) 151.2 0.0001
Butyrylcholinesterase (?mol of DTNB transformed per mL of plasma per min) 5.1 (0.1) 4.2 (0.2) 0.9 0.0001
White S OMahony, Age Ageing 2005
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Medicines in Care Home Residents

• High volume prescribing in nursing and
  residential homes
• High use of neuroleptics and benzodiazepines
• High burden of ADRs

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Care Homes Policy agenda

• Care Home Use of Medicines Study. Barber, Quality
  Safety in Health care 2009 18 341-346.
• Prescribing of anti psychotic drugs to people
  with dementia. S Banerjee. Nov 09
• NCD Dementia 2010
• CQC review Care Homes Autumn 2010

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Prescribing Principles

• Avoid unnecessary drug therapy
• Consider alternative treatments
• Appropriate drug choice and awareness of
  co-morbidities
• Use a lower starting dose
• Often use extended dosing interval
• Titrate dose to maximum therapeutic effect
• Potential for ADRs heightened awareness

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Medication Review

• A structured, critical examination of a patients
  medicines with the objective of reaching an
  agreement with the patient about treatment,
  optimising the impact of medicines, minimising
  the number of medication-related problems and
  reducing waste
• Proposed by the Medicines Partnership 2002

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Levels of medication review

• 
  
  
  
  Level 3
• 
  
  Clinical
• 
  Level 2
  Medication
• 
  Treatment
  review
• Level 1
  review
• Prescription
• Level 0 review
• Ad Hoc

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Concordance vs Compliance

• What is Concordance?
• An agreement reached with a patient after
  negotiation that respects the wishes of the
  patient in determining whether and how medicines
  are to be taken.

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Myths vs Reality Survival vs death Myths vs Reality Survival vs death
Myth No point treating - They are living on borrowed time and programmed to die Reality We all have life expectancy left, at any age Life expectancy is continuing to increase
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Getting the most out of medicines How?

• Good prescribing
• Strategies to improve compliance concordance
• Reduce drug errors (including transcription
  errors)
• Regular medication review.

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What the Geriatrician should know

• Knowledge- disease, evidence Rx
• - physiology, older people
• - drugs, ADR profiles
• Skills - diagnostic
• - communication decisions
• Service - Primary/Secondary
• - Care Homes
• - Medication review/ targeted Rx

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Case 3

• 71 Year old man
• PHx DM, TIA, Angina, prostatism, asthma,
  bronchiectasis, DU, Iron deficiency anaemia 2007
  CT abdo pelvis, OGD normal
• Presented Weight loss 2 stone in 6 months
• Low back pain
• Abnormal liver function tests

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Case 3 Results

• Hb 11 g/dl WCC 7.5 Platelets 277
• GGT 674 IU/l (5-48)
• Alk phos 363 IU/l (30-115)
• AST 48 IU/l (5-45)
• Albumin 41 g/l (35-50)
• Bilirubin 6 µmol/l (1-22)
• CRP 14 mg/l (lt6) HbA1c 6.6
• PSA, CEA, Igs, US liver and abdo normal

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Case 3 medicines

• Seretide (Fluticasone/Salmeterol) ii bd
• Tiotropium ii mane
• Salbutamol Inh ii PRN
• Enteric coated Prednisolone 5-7.5 mg/day
• Amlodipine 5 mg/day
• Clopidogrel 75 mg/day
• Atorvastatin 40 mg/day
• Metformin 500 mg tid
• GTN spray PRN
• Bendroflumethiazide 2.5 mg/day
• Finasteride 5mg/day
• Omeprazole 20 mg/day
• Ferrous fumarate 210 mg tid

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Case 3

• STOP
• Metformin
• Atorvastatin
• Finasteride

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Case 3 Lessons Learnt

• Polypharmacy - ?risk of ADRs and drug
  interactions
• Cholestatic liver picture - ?ADR

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MCQ 1

• An 89-year-old female is admitted to the medical
  assessment unit with a 5-day history of
  productive cough and fever,
• PHx AF, HT, OPorosis
• DHx warfarin, digoxin, ramipril, Alendronate,
  Calcichew D3

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• o/e alert, orientated, BP 126/76, RR 18,
• AF 58/min, BMI 17.5, focal signs L Base
• CXR L basal consolidation, creatinine 153, urea
  9.2, Na 136, K 4.9, INR 2.2

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What would you prescribe?

• A) Oral amoxicillin 500mgs tds and oral
  clarithromycin 500mgs bd
• B) iv Ampicillin 500mgs qds and iv clarithromycin
  500mgs bd
• C) Oral amoxicillin 500mgs bd and oral
  clarithromycin 250mg bd
• D) iv augmentin 1.2 gms tds and oral
  clarithromycin 250mg bd
• E) iv cefotaxime 1 gm bd and iv clarithromycin
  500mg bd

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MCQ 2

• An 84 year old gentleman, previously fit and
  independently mobile, is admitted with acute
  confusion, poor mobility and feeling generally
  unwell over a one week period.
• Nausea, anorexia, PHx psychotic depression

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Medications on admission

• Citalopram 20 mg/day
• Mirtazapine 30 mg nocte
• Olanzapine 5mg/day
• Aspirin 75mg/day
• Quinine 200mg nocte

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• Temp 38 C, fluctuating consciousness,
• Disorientated, inattention, agitation.
• ?muscle tone, normal reflexes
• CK 980 IU/L
• CXR clear, Urine dipstik normal, CRP 18mg/l

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Initial management

• A. Trimethoprim 200mg bd for presumed UTI
• B. Lorazepam 0.5mg prn to reduce agitation
• C. Haloperidol 1mg bd to help with delirium
• D. Metoclopromide 10mgs tds - nausea
• E. Stop olanzapine

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