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Pitfalls in Prescribing for older people

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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

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