Transcript Pitfalls in Prescribing for Older People

Pitfalls in Prescribing for older
people
Christopher Patterson
McMaster University,
Hamilton, Ontario
Canada
Objectives
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Pharmacokinetic changes with age
Pharmacodynamic changes
Polypharmacy and interactions
Underprescribing
Medication errors
Pharmacokinetics and aging
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Absorption
Distribution
Metabolism
Excretion
• And…therapeutic effect at receptor level
Absorption
• Changes in gastric pH (higher with aging)
• Changes in GI transit time (increased with
aging)
• Changes in intestinal absorptive area
(reduced)
BUT
Very little change in absorption of drugs
Absorption
• Type of preparation often more important
e.g. absorption of phenytoin:
liquid>tablet>capsule
• Interactions important e.g. calcium and
levothyroxine
Distribution
• Chronic illness associated with lower
levels of serum albumin
• Highly protein bound drugs may be
affected by acute displacement eg.
Warfarin and sulphonyureas
• Acid 1 alpha glycoprotein elevated in
acute illness may affect binding
e.g.amitriptyline
Changes in body composition with
aging
Water soluble vs. fat soluble drugs
H2O soluble-hydrophilic
• Atenolol
• Hydrochlorthiazide
• Sotalol
• Theophylline
• Triazolam
• Aminoglycosides
Fat soluble-lipophylic
• Amiodarone
• Diazepam
• Haloperidol
Phenytoin: zero order kinetics
saturation of protein binding sites
Metabolism
• Mostly in liver
• Phase 1
Oxidation, reduction, hydrolysis
Most affected by aging
• Phase 2
Acetylation, glucuronidation, sulfation,
glycine
Mostly unaffected by aging
Metabolism
Changes in hepatic metabolism with age
Serum t ½ (hours) and age
Phase 1 metabolism
Young
Old
Amitriptyline
14.7
27.2
Diltiazem
3.8
4.2
Diazepam
20
75
Warfarin
3.7
4.4
Serum t ½ unchanged:
phase 2 metabolism
Glucuronidation
• Oxazepam
• Temazepam
• Lorazepam
Oxidation
• Metoprolol
Acetylation
• Hydralazine
Elimination
• Elimination represents clearance of drug
from the body
• May be predominantly renal (water soluble
drugs and metabolytes)
• Biliary (e.g. some metabolytes of digoxin)
• Other
Renal function and aging
Drugs predominantly eliminated via
renal route
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Digoxin
Aminoglycoside antibiotics
Lithium
Spironolactone
Vancomycin
Calculation of creatinine clearance
Cockcroft-Galt equation
Pharmacodynamic changes with
aging
Increased receptor sensitivity
• Opioids
• Some benzodiazepines (e.g. nitrazepam)
Reduced response to β adrenergic receptors
• Isuproteronol
Impaired homeostasis
• Antihypertensives (e.g. prazosin)
Adverse Drug Reaction
Idiosyncratic
• Unpredictable
Exaggeration of pharmacological effects
• Predictable
• Start low, go slow!
Incidence of Preventable AEs
(Thomas & Brennan BMJ 2000;320:741)
Event type
Diagnostic
Incidence ages Incidence age
>65
16-64
0.22
0.27
Operative
0.76
0.99
Procedure
0.13
0.69*
Drug
0.17
0.63*
Fall
0.01
0.10*
Drug interactions
Absorption
• Calcium and iron salts
Metabolism
• Warfarin plus metronidazole
Pharmacodynamic
• E.g. Glyceryl trinitrate and sildanefil
Conditions that affect drug
metabolism or action
• Malnutrition
• Heart failure
• Hepatic dysfunction (especially
parenchymal disease cirrhosis)
• Renal impairment or failure
• And many others
Some drugs to be used with
extreme caution in older people
• Anticholinergic drugs (antihistamine H1,
tricyclic antidepressants etc.)
• Long acting benzodiazepines (diazepam,
chlordiazepoxide )
• Theopylline
• NSAIDs (indomethacin, )
• Some opiates (pethidine, meperidine)
• Antipsychotics
Antipsychotics and sudden death
Ray W et al N Engl J Med 2009; 360: 225
SUMMARY
• Changes in pharmacokinetics important
• Especially renal changes (do calculate
Cr/cl)
• Pharmacodynamic changes not always
pedictable
• Watch for drug interactions and side
effects
• Do not overlook effects of illness plus
aging
Serum t ½ (hours) and age
Young
Old
Amitriptyline
14.7
27.2
Diltiazem
3.8
4.2
Sotalol
7.1
11.4
Warfarin
3.7
4.4
Undertreatment
(Grymonpre & Patterson CPS 2006)
Medication class
Percent of optimal
ASA in ischemic heart
disease
Beta blockers after MI
50
Hypertension
50
50
Warfarin for atrial fibrillation
15-44
Antidepressants
10-30
Osteoporosis after hip #
10
Adverse Event
• “An unintended injury or complication
which results in disability, death or
prolonged hospital stay and is caused by
health care management”
• Wilson R et al Med J Aus 1995;163:458
Adverse Events
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Incidence in hospital
Meta analysis of incidence
Adverse drug events
Operative complications
Nosocomial infections
Preventable
2.9-16.6%
6.7%
50%
30%
20%
30-60%
Medication Errors
• Sins of commission: wrong drug, wrong
dose, wrong patient, wrong time, or wrong
route
• Sins of omission: not providing appropriate
medication
• Many errors do not cause adverse events
(we are a very resilient species…)
Detection of Adverse Events
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Voluntary reporting
Computer monitoring
Chart review
Direct observation
Jha K et al J Am Med Informatics Assoc; 5:305
0.7%
9.6%
13.3%
Higher
Why won’t people report errors
or near misses?
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Not aware of error
Not aware of need to report
Patient apparently unharmed
Fear of disciplinary action or litigation
Unfamiliar with reporting mechanisms
Loss of self esteem
Too busy
Lack of feed back when errors are reported
Near Misses: unique
opportunities
• Occur 3-300 times more often than errors
• Fewer barriers to data collection
• Higher incidence allows quantitative
analysis
• Proactive intervention
• Reduces blame
• Hindsight bias reduced
Barach P & Small S BMJ 2000;320:759
Prescribing Problems
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Illegible handwriting
Wrong drug
Wrong dose
Wrong frequency
Wrong route
Wrong patient
Name confusion
Name Confusion
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Losec
amiloride
Fluoxetine
hydralazine
carbamazepine
chlorpropamide
thyroxine
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Lasix
amlodipine
Paroxetine
hydroxyzine
carbimazole
chlorpromazine
thioridazine
Inappropriate Abbreviations
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AZT
CPZ
HCl
HCT
MSO4
MTX
PIT
D/C
SC
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