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… Increased
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. Decreased or Unchanged
Aging & CYP Activity
Decreased
Decreased or Unchanged
Unchanged
CYP 1A2
CYP 2C19
CYP 2A
CYP 2C9
CYP 3A4
CYP 2D6
-Cusack. Am J Geriatr Pharmacother 2004;2:

14. Induction/Inhibition
Other Influences
Factor
Result
Smoking
Induction
Alcohol
Drugs
Induction/Inhibition
Diet
Variable
Malnutrition
Inhibition, if severe
Frailty
Inhibition
-O’Mahoney & Woodhouse. Pharmacol Ther 1994;61:

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

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 Multiple diseases Complex regimens
Drug-disease interactions
Multiple drugs
Adverse effects
Drug-drug interactions
Frail
Risk for overdosage
Depressed
Multiple somatic complaints
Non-adherence
Demented
Unreliable regarding adherence, adverse effects, etc.

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