Pharmacotherapy in Older Adults

1. Pharmacotherapy in Older Adults Janet Cho, PharmD, CGP Clinical Pharmacist, Keck Medical Center of USC Bradley R. Williams, PharmD, FASCP, CGP Professor, Clinical Pharmacy & Clinical Gerontology

2. Prescription Medication Use Gu Q, et al., NCHS Data Brief No. 42, 2010

3. Why Are We Concerned? • Older adults account for 49.8% of hospital admissions due to adverse drug events1 • Rate is greatest for age 85+ years • 87% due to hypoglycemics, anticonvulsants, warfarin, digoxin, theophylline, lithium • Adults age 50+ account for 51.1% of ED admissions for adverse drug events2 • CNS drugs (28.8%), blood modifiers (22.6%), cardiovascular meds (18.1%) are most common 1Budnitz, et al, JAMA, 2006; 2The DAWN Report, 2011

4. Why Are We Concerned? • Medicare hospital readmissions1 • 30 days (19.6%); 60 days (28.2%) • Heart failure, pneumonia, COPD, psychosis are most common discharge diagnoses • Preventable medication errors2 • Renal and hepatic function • Drug interactions • Lack of individualized therapy 1 Jencks, et al., NEJM, 2009; 2 Kohn, et al. Institute of Medicine, 2000

5. Age-associated Issues • Physiologic changes affect both pharmacokinetics and pharmacodynamics • Reduced physiologic reserve narrows the margin for error • Polymedicine increases the risk for adverse reactions and drug interactions • Multiple providers and self-care both increase the risk for inappropriate medication use

6. Physiologic Changes • Body composition • Increase in body fat (% of total body weight) • Women: 33% to 48% • Men: 18% to 36% • Decrease in body water • Reduced serum albumin • Increased α1-acid glycoprotein • Decreased lean body mass

7. Physiologic Changes • Gastrointestinal tract • Increased gastric pH • Reduced intestinal blood flow • Impaired active & passive transport mechanisms • Delayed gastric emptying • Slowed GI motility

8. Physiologic Changes • Liver • Decreased hepatic mass • Reduced hepatic blood flow • Kidney • Loss of functioning nephrons • Reduced renal blood flow • Decreased tubular secretion • Decreased glomerular filtration

9. Drug Absorption • Primarily a passive process that occurs in the small intestine • Rate of absorption may be slowed • Delayed, lower peak serum levels • Increased bioavailability for some hepatically metabolized drugs due to reduced first-pass effect (e.g., verapamil, labetalol, lidocaine) • Transdermal absorption is variable

10. Drug Distribution Factors leading to altered distribution… • Decreased • Lean body mass • Total body water • Serum albumin • Cardiac output • Increased • Total body fat • α1-acid glycoprotein

11. Drugs with Decreased Binding • Benzodiazepines • Diazepam • Lorazepam • Temazepam • Triazolam • Desipramine • Meperidine • NSAIDs • Diflunisal* • Naproxen* • Salicylates* • Phenytoin • Theophylline • Valproate* • Warfarin * >50% decrease

12. Drug Metabolism Factors leading to altered metabolism… • Reduced liver mass and volume • Decreased hepatic blood flow • Altered enzyme activity • Sex and genetic differences • Age-associated declines • Drug interactions • Nutrition and health status

13. Aging & CYP Activity -Cusack. Am J GeriatrPharmacother 2004;2:274-302

14. Other Influences -O’Mahoney & Woodhouse. PharmacolTher 1994;61:279-287

15. Drug Renal Excretion Factors leading to altered excretion… • Reduced kidney mass, number and size of nephrons • Decreased renal blood flow • Decreased glomerular filtration • Reduced tubular secretory mechanisms • Effect of disease

16. CNS Changes • Reduced blood flow and oxygenation • Increased MAO levels • Decreased norepinephrine, dopamine • More sensitive to sedating agents • Greater sensitivity to anticholinergic agents • Increased permeability of the blood-brain barrier

17. Cardiovascular Changes • Decreased response to catecholamines • Primarily affects ß-receptors • Increased circulating norepinephrine • Reduced cardiac output • Increased peripheral resistance • Less responsive baroreceptors

18. Pharmacogenomic Issues • No apparent changes across the adult lifespan • Possibly some decrease in CYP 3A4 and 2A6 • Fast and slow metabolizers • N-acetyltransferase activity • Slow acetylators (autosomal recessive)

19. Medication-related Problems • Dose too high • Dose too low • Improper medication • Contraindication • Allergy • Inappropriate for patient’s age or function • Drug interaction • Adverse drug reaction • Unnecessary medication • Duplicate • No indication • Problem resolved • Untreated indication • Patient not receiving medication

20. Medication Risk Assessment • > 5 medications • > 12 daily doses • Narrow therapeutic index drugs • Multiple prescribers • Taking medicines for at least 3 problems • Uses multiple pharmacies • Someone brings medicines to the home • Complex regimen • At least 4 direction changes in 1 year • Any medicine taken for an unknown reason -Levy HB, Ann Pharmacother, 2003

21. High-risk Patients

22. Summary • Age-associated changes in pharmacokinetics and pharmacodynamics present therapeutic challenges • Interpatient variability makes it difficult to predict clinical effects with certainty • Disease, nutrition, adherence, other drugs complicate the picture • Patients benefit from a “risk management” approach