THE AMERICAN GERIATRICS SOCIETY Geriatrics Health Professionals.

1. POLYPHARMACYWendolynGozansky, MD, MPHAssociate ProfessorDivision of Geriatric MedicineUniversity of Colorado Denver AGS THE AMERICAN GERIATRICS SOCIETY Geriatrics Health Professionals. Leading change. Improving care for older adults.

2. CONTENTS • Drugs and the elderly • Pharmacodynamic and pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing

3. 12% of the population is aged 65+ Drug Use in the Elderly

4. 12% of the population is aged 65+ 30% of all prescription drug use is among those aged 65+ Drug Use in the Elderly

5. 12% of the population is age 65+ 30% of all prescription drug use is among those aged 65+ 50% of all OTC drug use is among those aged 65+ Drug Use in the Elderly

6. ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994

7. ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994 • $177 billion in 2000

8. ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994 • $177 billion in 2000 • For every $1 spent on drugs, $1 spent on ADRs

9. ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994 • $177 billion in 2000 • For every $1 spent on drugs, $1 spent on ADRs • 95% of ADRs considered to be predictable

10. ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994 • $177 billion in 2000 • For every $1 spent on drugs, $1 spent on ADRs • 95% of ADRs considered to be predictable • 7-fold increased risk in the elderly • Related to polypharmacy • Changes in pharmacodynamics/pharmacokinetics • Drug-disease interactions

11. Exponential Relation Between Polypharmacy and ADRs JAGS. 1988;36:142-149.

12. CONTENTS • Drugs and the elderly • Pharmacodynamic and pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing

13. Pharmacodynamics Response that occurs when a drug interacts at its receptor

14. Pharmacodynamic Changeswith Aging Increased response (eg, opiates)

15. Pharmacodynamic Changeswith Aging Increased response (eg, opiates) Decreased response (eg, beta-agonists)

16. Pharmacokinetics Drug concentration at the site of action

17. Pharmacokinetics • Drug concentration at the site of action • 4 determinants: • Absorption • Distribution • Metabolism • Elimination

18. PK Changes with Aging: ABSORPTION  gastric pH  gastric emptying  splanchnic blood flow  intestinal motility Minimal clinical importance

19. PK Changes with Aging: DISTRIBUTION  fat mass  muscle mass  total body water  albumin (binds acidic drugs)  alpha-1 glycoprotein (binds basic drugs) Clinically important

20. 20-year-old woman J Nutr. 1997. 127:990-991S.

21. 64-year-old woman 20-year-old woman J Nutr. 1997; 127:990-991S.

22. 64-year-old woman 20-year-old woman J Nutr. 1997. 127:990-991S.

23. 64-year-old woman 20-year-old woman J Nutr. 1997. 127:990-991S.

24. PK Changes with Aging:METABOLISM  hepatic mass  hepatic blood flow  first-pass metabolism Clinically important: Longer half-life of drugs undergoing phase I metabolism (eg, diazepam vs lorazepam)

25. PK Changes with Aging:ELIMINATION  renal mass  renal blood flow  glomerular filtration rate Most clinically important •  concentration of drugs dependent on renal clearance • Serum creatinine alone does not provide adequate information to guide dosing

26. Pharmacokinetic Changeswith Aging What is the best formula for estimating GFR in older adults? • Cockcroft-Gault (CG) • Modification of Diet in Renal Disease (MDRD)

27. CG vERSUS MDRD

28. CG VERSUS MDRD

29. Biology of the Patient • Limited functional reserve

30. Biology of the Patient Disease Compensatory severitymechanisms Symptomatic Asymptomatic Lancet. 1997;350:1157-1158.

31. Biology of the Patient • Limited functional reserve • Drug-disease interactions

32. CONTENTS • Drugs and the elderly • Pharmacodynamic & pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing

33. Do you know what’s in your patient’s medicine cabinet? ~20% of drugs found on home inventory were not revealed by physician interview Most frequently unreported class of drugs?

35. Do you know what’s in your patient’s medicine cabinet? ~20% of drugs found on home inventory were not revealed by physician interview Most frequently unreported class of drugs? BENZODIAZEPINES!!!

36. Altered Compliance • Under-utilization • Over-utilization • Enforced compliance

37. Relation Between Polypharmacyand Number of Prescribers

38. Relation Between Polypharmacyand Compliance

39. Methods to Improve Compliance •  # of drugs, prescribers, and pharmacies • Once-daily or twice-daily dosing • Pill boxes • Medication reminder charts •  frequency of clinic visits

40. CONTENTS • Drugs and the elderly • Pharmacodynamic & pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing

41. Avoid the Prescribing Cascade Drug 1 BMJ. 1997;315:1096-1099.

42. Avoid the Prescribing Cascade Drug 1 Adverse effect misinterpreted as new medical condition BMJ. 1997;315:1096-1099.

43. Avoid the Prescribing Cascade Drug 1 Adverse effect misinterpreted as new medical condition Drug 2 BMJ. 1997;315:1096-1099.

44. Avoid the Prescribing Cascade • HCTZ – Allopurinol • NSAIDs – Antihypertensives • Metoclopramide – Carbidopa/levodopa • Cholinesterase inhibitors – Tolterodine

45. Beware of Drug-Drug Interactions (DDIs) • 100% chance of DDIs with 8 drugs

46. Beware of Drug-Drug Interactions (DDIs) • 100% chance of DDIs with 8 drugs • Nearly 50% of community-dwelling geriatric patients had at least one DDI

47. Beware of Drug-Drug Interactions (DDIs) • 100% chance of DDIs with 8 drugs • Nearly 50% of community-dwelling geriatric patients had at least one DDI • DDIs can result in ADRs or suboptimal dosing

48. Prudent Prescribing Principles • Know your patients and their drug cabinets

49. Prudent Prescribing Principles • Know your patients and their drug cabinets • Educate yourself and your patients

50. Prudent Prescribing Principles • Know your patients and their drug cabinets • Educate yourself and your patients • Understand biases in clinical trials