Pitfalls in Prescribing for older people

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Pitfalls in Prescribing for older people

• Christopher Patterson
• McMaster University,
• Hamilton, Ontario
• Canada

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Objectives

• Pharmacokinetic changes with age
• Pharmacodynamic changes
• Polypharmacy and interactions
• Underprescribing
• Medication errors

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Pharmacokinetics and aging

• Absorption
• Distribution
• Metabolism
• Excretion
• Andtherapeutic effect at receptor level

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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

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Absorption

• Type of preparation often more important e.g.
  absorption of phenytoin
• liquidgttabletgtcapsule
• Interactions important e.g. calcium and
  levothyroxine

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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

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Changes in body composition with aging
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Water soluble vs. fat soluble drugs

• H2O soluble-hydrophilic
• Atenolol
• Hydrochlorthiazide
• Sotalol
• Theophylline
• Triazolam
• Aminoglycosides

• Fat soluble-lipophylic
• Amiodarone
• Diazepam
• Haloperidol

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Phenytoin zero order kinetics saturation of
protein binding sites
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Metabolism

• Mostly in liver
• Phase 1
• Oxidation, reduction, hydrolysis
• Most affected by aging
• Phase 2
• Acetylation, glucuronidation, sulfation,
  glycine
• Mostly unaffected by aging

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Metabolism

• Changes in hepatic metabolism with age

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Serum t ½ (hours) and agePhase 1 metabolism
Young Old
Amitriptyline 14.7 27.2
Diltiazem 3.8 4.2
Diazepam 20 75
Warfarin 3.7 4.4
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Serum t ½ unchangedphase 2 metabolism

• Glucuronidation
• Oxazepam
• Temazepam
• Lorazepam
• Oxidation
• Metoprolol
• Acetylation
• Hydralazine

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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

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Renal function and aging
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Drugs predominantly eliminated via renal route

• Digoxin
• Aminoglycoside antibiotics
• Lithium
• Spironolactone
• Vancomycin

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Calculation of creatinine clearanceCockcroft-Galt
equation
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Pharmacodynamic changes with aging

• Increased receptor sensitivity
• Opioids
• Some benzodiazepines (e.g. nitrazepam)
• Reduced response to ß adrenergic receptors
• Isuproteronol
• Impaired homeostasis
• Antihypertensives (e.g. prazosin)

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Adverse Drug Reaction

• Idiosyncratic
• Unpredictable
• Exaggeration of pharmacological effects
• Predictable
• Start low, go slow!

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Incidence of Preventable AEs(Thomas Brennan
BMJ 2000320741)
Event type Incidence ages 16-64 Incidence age gt65
Diagnostic 0.22 0.27
Operative 0.76 0.99
Procedure 0.13 0.69
Drug 0.17 0.63
Fall 0.01 0.10
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Drug interactions

• Absorption
• Calcium and iron salts
• Metabolism
• Warfarin plus metronidazole
• Pharmacodynamic
• E.g. Glyceryl trinitrate and sildanefil

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Conditions that affect drug metabolism or action

• Malnutrition
• Heart failure
• Hepatic dysfunction (especially parenchymal
  disease cirrhosis)
• Renal impairment or failure
• And many others

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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

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Antipsychotics and sudden death
Ray W et al N Engl J Med 2009 360 225
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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

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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
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Undertreatment (Grymonpre Patterson CPS 2006)
Medication class Percent of optimal
ASA in ischemic heart disease 50
Beta blockers after MI 50
Hypertension 50
Warfarin for atrial fibrillation 15-44
Antidepressants 10-30
Osteoporosis after hip 10
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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 1995163458

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Adverse Events

• Incidence in hospital 2.9-16.6
• Meta analysis of incidence 6.7
• Adverse drug events 50
• Operative complications 30
• Nosocomial infections 20
• Preventable 30-60

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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)

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Detection of Adverse Events

• Voluntary reporting 0.7
• Computer monitoring 9.6
• Chart review 13.3
• Direct observation Higher
• Jha K et al J Am Med Informatics Assoc
  5305

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Why wont people report errors or near misses?

• 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

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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 2000320759

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Prescribing Problems

• Illegible handwriting
• Wrong drug
• Wrong dose
• Wrong frequency
• Wrong route
• Wrong patient
• Name confusion

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Name Confusion

• Losec
• amiloride
• Fluoxetine
• hydralazine
• carbamazepine
• chlorpropamide
• thyroxine

• Lasix
• amlodipine
• Paroxetine
• hydroxyzine
• carbimazole
• chlorpromazine
• thioridazine

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Inappropriate Abbreviations

• AZT
• CPZ
• HCl
• HCT
• MSO4
• MTX
• PIT
• D/C
• SC

• gt,lt
• _at_
• ug
• AU
• HS
• IU
• OS
• OD