Medication Use in the Elderly Patient: Physiology, Pharmacology, and Prescribing

1. Medication Use in the Elderly Patient:Physiology, Pharmacology, and Prescribing Anthony J. Caprio, MD Assistant Professor of Medicine University of North Carolina Chapel Hill Division of Geriatric Medicine and Center for Aging and Health

2. Learning Objectives • Identify the physiologic changes associated with normal aging in relation to drug absorption, distribution, metabolism, and excretion • Identify risk factors for Adverse Drug Events in older adults • Recognize Adverse Drug Events • Recognize potentially harmful medications for older adults • Utilize strategies to enhance the safety, effectiveness, and adherence of prescribed medications

3. Challenges of Prescribingfor Older Adults • Multiple chronic medical problems • Multiple medications and prescribers • Different metabolism and responses • Adherence and cost • Supplements, herbals, and OTC drugs Lancet. 1995;346(8966):32–36.

4. Physiologic Changes Associated with Normal Aging • Less Water • More Fat • Less muscle mass • Slowed hepatic metabolism • Decreased renal excretion • Decreased responsiveness and sensitivity of the baroreceptor reflex

5. Absorption • Not affected by the normal aging process • Can be altered by drug interactions • Antacids • Iron • Can be effected by disease • Lack of intrinsic factor (B12 absorption) • Delayed gastric emptying

6. Distribution • Less water = ↓ volume of distribution = higher concentration of water soluble drugs • More fat = ↑ volume of distribution = prolonged action of fat soluble drugs (increased half-life) • Lower serum proteins (like albumin) increases the concentration of unbound (free or active) form of drugs

7. Metabolism • Slowed Phase I, cytochrome P450, reactions • Oxidation, reduction, dealkylation • Warfarin and phenytoin levels may be higher because of altered metabolism • Phase II reactions are essentially unchanged • Conjugation, acetylation, methylation • Drug-drug interactions • Increased risk with increased number of drugs

8. Excretion • Hepatic • Renal • Renal clearance may be reduced • Serum creatinine may not be an accurate reflection of renal clearance in elderly patients (decreased lean body mass). • Active drug metabolites may accumulate • Prolonged therapeutic action • Adverse effects

9. Physiologic Changes Associated with Disease States • Cardiac Disease • Impaired cardiac output (decreased absorption, metabolism, clearance) • Greater susceptibility to cardiac adverse effects • Kidney and Liver Disease • Decreased drug clearance • Neurological Diseases • Diminished neurotransmitter levels • Impaired cerebral bloodflow • Greater sensitivity to neurological effects

10. Lots of Medicationsand Little Evidence • 2/3 of older adults are on regular medications • Adults age >65 account for 1/3 off all prescriptions, but only represent 15% of the US population • Older adults are frequently not included in clinical trials, which makes it difficult to predict drug metabolism or drug effects Health Care Financ Rev. 1990;11:1-41.

11. Dangers of Multiple Medications:“Polypharmacy” • Adverse effects (side effects) • Drug-drug interactions • Duplication of drug therapy • Poor adherence • Cost • Decreased quality of life

12. Adverse Drug Events (ADEs) • Adverse symptoms • Adverse patient outcomes • Doctor visits or hospitalizations • Falls • Functional decline • Changes in cognition (delirium) • Death • ↑ number of medications = ↑ risk of ADEs (even if all the meds are “clinically indicated”)

13. Medications Which Account for Most ADEs in Older Adults • Cardiovascular medications • Psychotropic medications • Antibiotics • Anticoagulants • Non-opioid analgesics (NSAIDS) • Anti-seizure medications (JAGS 2004;52:1349-1354 and NEJM 2003;348:1556-64)

14. Risk Factors for Adverse Drug Events (ADE) • >6 chronic disease • >12 doses/day • ≥ 9 medications • Low BMI (<22kg/m2) • Age >85 years • Creatinine clearance < 50 mL/min • History of prior ADE Consult Pharm 1997;12:1103-11.

15. Prevalence of Prescribing Problems in Primary Care • 35% of community-dwelling older adults experience an ADE annually • 5-28% of inpatient geriatric admissions due to an ADE • 2/3 of nursing home patients experienced an ADE (over a 4-year period) • Between 20-40% of outpatients were prescribed “potentially” inappropriate medications JAGS 1997;45:945-948 JAGS 1996;44:194-197 Am Pharm Assoc 2002;42:847-857

16. Principle 1:“Less is More”(Keep the Medication List Short) • Question the need for new medications • Stop medications, whenever possible • Prioritize treatments • Weigh risks and benefits • But, avoid undertreating older patients • Pain • Systolic hypertension (stroke, renal failure, heart disease) • Anticoagulation and atrial fribrillation (stroke prevention) Drugs Aging 2003; 20 (1): 23-57. Lancet 2000; 355: 865–872. Ann Intern Med 1999;131:492-501. J Gen Intern Med 2005; 20:116–122.

17. Do You Need to prescribe? • Does every condition need a drug? • Is it a benign or self limited condition? • How does this condition bother the patient? • Consider non-drug alternatives • Diet • Exercise • Lifestyle modification • Consider “Over The Counter” (OTC) medications • Not necessarily safer than prescription drugs • Be very careful with herbals and supplements

18. Stopping Medications • Consider interactions with other medications • Is it helping? (Benefit) • Is it harmful? (Risk) • Why was it started? • Is the dose within a therapeutic range? • Consider underlying renal and hepatic insufficiency

19. Clinical Case: Mr. Johnson Mr. Johnson is 83 years old. He has a history of benign prostatic hypertrophy (BPH) and hypertension. After visiting his grandchildren, he developed a viral upper respiratory infection. He took an over-the-counter cold remedy containing a decongestant and diphenhydramine. He now comes to the office because he is unable to urinate. His blood pressure is 190/80. What happened?

20. Urinary Retention and Hypertension • Parasympathetic Nervous System • Mediates detrusor muscle contraction • Blocked by anticholinergic medications like diphenhydramine • Sympathetic Nervous System • α-adrenergic activity causes the urethral sphincter to contract (retaining urine) • α-adrenergic activity increases systemic vascular resistance (raises blood pressure) • Decongestants are alpha-adrenergic agonists (ex. pseudoephedrine and phenylephrine)

21. Clinical Case: Mr. Johnson Since Mr. Johnson has a history of benign prostatic hypertrophy, his physician prescribes terazosin, a peripherally-acting α1-adrenergic antagonist, to help with his urinary retention and to help reduce his blood pressure. Two days later, Mr. Johnson falls in the middle of the night, on the way to the bathroom. He fractures his hip. What happened?

22. Orthostatic Hypotensionand Hip Fracture • Barorecptor sensitivity decreases with age • α-adrenergic blockade can worsen postural hypotension and increase the risk of falls • Falls and Hip fractures are associated with significant morbidity and mortality in older adults

23. Prescribing Cascade:Prescribing a new drug to treat an ADE • Establish the diagnosis • Diphenhydramine and the decongestant precipitated urinary retention in a older male with prostatic enlargement • Urinary retention is an ADE • Stop (or reduce) the offending medications • OTC cold medicine • Need to ask about ALL medications • Avoid prescribing new medications (terazosin)

24. Principle 2Before making a new diagnosis:“Think Drugs” • Consider ADE as etiology of new signs/symptoms • Remember that OTC drugs, supplements, and herbals can cause ADEs • Consider discontinuing or dose-reducing medications rather than treating an ADE with another medication

25. Clinical Case: Mr. Johnson Mr. Johnson arrives in the emergency department and is given meperidine (Demerol) for his pain. He is also very anxious, so he receives diazepam (Valium). A few hours later, Mr. Johnson becomes very confused and somnolent. What happened?

26. Drug-Induced Delirium • Meperidine • Can cause confusion • Active metabolites • Slow renal clearance in older adults • Diazepam • Long-acting benzodiazepine • Lipophilic • Extended half-life in elderly • Increased sensitivity in the elderly • Increased risk of falls and fractures

27. Avoiding Potentially Dangerous Drugs:The Beers Criteria • Consensus-based list of potentially inappropriate medications for older adults • Published 1991, revised 1997, 2002 • Statistical association with ADEs has been documented • Adopted for nursing-home regulation • Does not account for the complexity of the entire medication regimen Arch Intern Med 2003;163:2716-2724. Pharmacotherapy 2005;25(6):831–838

28. Beers Criteria:Anticholinergic Medications • Drug classes • Antihistamines • Tricyclic antidepressants • Antispasmodics and muscle relaxants • Adverse Effects • Dry Mouth • Urinary retention • Constipation • Confusion, delirium

29. Avoiding Potentially Dangerous Drugs:The Beers Criteria • Anticholinergic medications • Decongestants • Hypertension • Bladder outflow obstruction • Meperidine • Benzodiazepines Beers Criteria: Arch Intern Med 2003;163:2721.

30. Clinical Case: Mr. Johnson • Mr. Johnson slowly recovers after his hip fracture. • He continues to have some hip pain, so in addition to acetaminophen, his geriatrician prescribes low-dose opioid analgesics for break-through pain along with laxatives to avoid opioid-induced constipation. • His delirium slowly clears and he is able to participate in physical therapy and is able to return home after rehabilitation. Before he goes home, his medications are carefully reviewed, including OTC medications.

31. Principle 3:“If You Decide to Prescribe,Start Low and Go Slow…” • Start one medication at a time • Start with a low dose and increase gradually • Monitor for response • Monitor and anticipate adverse effects • Assess adherence with regimen

32. Multiple medications Multiple doses Sensory impairments Physical impairments Memory impairment Language and literacy Cost Quality of Life Adverse Effects “Medicalization” Adherence

33. Increasing Adherence • Keep the medication list short • Try to use once daily medications • Encourage use of a pillbox • Review bottles of medications • Write indications for medications on prescriptions • Medication Management programs

34. Things to Remember:Four PRINCPLES • Less is More! (keep the drug list short) • Think Drugs! (before making a new diagnosis) • Start Low and Go Slow • Assess Adherence

35. Things to Remember:Changes with Aging • Absorption usually does not change • Higher concentrations of water soluble and free (unbound) drugs • Longer half-life for lipophilic drugs • Slower phase I metabolism • Impaired excretion • Increased susceptibility to adverse effects