Pitfalls in Prescribing for older people Christopher Patterson McMaster University, Hamilton,...
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Transcript of Pitfalls in Prescribing for older people Christopher Patterson McMaster University, Hamilton,...
Pitfalls in Prescribing for older people
Christopher PattersonMcMaster University,
Hamilton, OntarioCanada
Objectives
• Pharmacokinetic changes with age
• Pharmacodynamic changes
• Polypharmacy and interactions
• Underprescribing
• Medication errors
Pharmacokinetics and aging
• 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,
glycineMostly unaffected by aging
Metabolism
Changes in hepatic metabolism with age
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
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
• Digoxin
• Aminoglycoside antibiotics
• Lithium
• Spironolactone
• Vancomycin
Calculation of creatinine clearanceCockcroft-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 Incidence ages
16-64
Incidence age >65
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*
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
50
Beta blockers after MI 50
Hypertension 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
• 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%
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
• Voluntary reporting 0.7%
• Computer monitoring 9.6%
• Chart review 13.3%
• Direct observation Higher
Jha K et al J Am Med Informatics Assoc; 5:305
Why won’t 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
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
• Illegible handwriting
• Wrong drug
• Wrong dose
• Wrong frequency
• Wrong route
• Wrong patient
• Name confusion
Name Confusion
• Losec• amiloride• Fluoxetine• hydralazine• carbamazepine • chlorpropamide • thyroxine
• Lasix• amlodipine• Paroxetine• hydroxyzine• carbimazole• chlorpromazine• thioridazine
Inappropriate Abbreviations
• AZT• CPZ• HCl• HCT• MSO4• MTX• PIT• D/C• SC
• >,<• @• +• ug• AU• HS• IU• OS• OD