1. Pitfalls in Prescribing for older people
Christopher Patterson
McMaster University,
Hamilton, Ontario
Canada

2. Objectives Pharmacokinetic changes with age Pharmacodynamic changes
Polypharmacy and interactions
Underprescribing
Medication errors

4. Pharmacokinetics and aging
Absorption
Distribution
Metabolism
Excretion
And…therapeutic effect at receptor level

5. 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

6. Absorption
Type of preparation often more important e.g. absorption of phenytoin:
liquid>tablet>capsule
Interactions important e.g. calcium and levothyroxine

7. 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

8. Changes in body composition with aging

9. Water soluble vs. fat soluble drugs
H2O soluble-hydrophilic
Atenolol
Hydrochlorthiazide
Sotalol
Theophylline
Triazolam
Aminoglycosides
Fat soluble-lipophylic
Amiodarone
Diazepam
Haloperidol

10. Phenytoin: zero order kinetics saturation of protein binding sites

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

12. Metabolism
Changes in hepatic metabolism with age

13. 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

14. Serum t ½ unchanged: phase 2 metabolism
Glucuronidation
Oxazepam
Temazepam
Lorazepam
Oxidation
Metoprolol
Acetylation
Hydralazine

15. 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

16. Renal function and aging

17. Drugs predominantly eliminated via renal route
Digoxin
Aminoglycoside antibiotics
Lithium
Spironolactone
Vancomycin

18. Calculation of creatinine clearance Cockcroft-Galt equation

19. 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)

21. Adverse Drug Reaction Idiosyncratic Unpredictable
Exaggeration of pharmacological effects
Predictable
Start low, go slow!

22. 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*

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

25. Conditions that affect drug metabolism or action
Malnutrition
Heart failure
Hepatic dysfunction (especially parenchymal disease cirrhosis)
Renal impairment or failure
And many others

26. 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

27. Antipsychotics and sudden death
Ray W et al N Engl J Med 2009; 360: 225

29. 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

30. 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

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

32. 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

33. Adverse Events Incidence in hospital 2.9-16.6%
Meta analysis of incidence %
Adverse drug events %
Operative complications %
Nosocomial infections %
Preventable %

34. 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…)

35. Detection of Adverse Events
Voluntary reporting %
Computer monitoring %
Chart review %
Direct observation Higher
Jha K et al J Am Med Informatics Assoc; 5:305

36. 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

37. Near Misses: unique opportunities
Occur 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

38. Prescribing Problems Illegible handwriting Wrong drug Wrong dose
Wrong frequency
Wrong route
Wrong patient
Name confusion

39. Name Confusion Losec amiloride Fluoxetine hydralazine carbamazepine
chlorpropamide
thyroxine
Lasix
amlodipine
Paroxetine
hydroxyzine
carbimazole
chlorpromazine
thioridazine

40. Inappropriate Abbreviations
AZT
CPZ
HCl
HCT
MSO4
MTX
PIT
D/C SC
>,< @ + ug AU HS IU OS OD