Pitfalls in Prescribing for older people

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

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 agePhase 1 metabolism

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 clearanceCockcroft-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)

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

31. Undertreatment (Grymonpre & Patterson CPS 2006)

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 6.7% • Adverse drug events 50% • Operative complications 30% • Nosocomial infections 20% • Preventable 30-60%

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 0.7% • Computer monitoring 9.6% • Chart review 13.3% • 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 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

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

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

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