Drugs and the Elderly: Practical Considerations

C. Bree Johnston MD MPH SF VAMC/UCSF Copyright May 2001

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Overview


Scope of the issue  Pharmacokinetics  Pharmacodynamics  Adverse drug reactions and adherence  Underuse of drugs  Nonprescription and alternative therapies  Common sense solutions
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Prescription Drugs


Elderly account for 1/3 of prescription drug use, while only 13% of the population  Ambulatory elderly fill between 9-13 9prescriptions a year (new and refills)  One survey: Average of 5.7 prescription medicines per patient  Average nursing home patient on 7 medicines
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Costs of Drugs
     

Medicare does not pay for prescription drugs Average prescription drug cost for an older person is $500/year, but highly variable Nonprescription drugs and herbals can be quite expensive Many Medicare Managed Care Plans have dropped or severely limited drug coverage Drugs cost more in US than any other country New drugs cost more
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Non-prescription Drugs


Surveys indicate that elders take average of 2-4 2nonprescription drugs daily Laxatives used in about 1/3-1/2 of elders - many 1/3who are not constipated NonNon-steroidal anti-inflammatory medicines, antisedating antihistamines, sedatives, and H2 blockers are all available without a prescription, and all may cause major side effects

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Pharmacokinetics


Decrease in total body water (due to decrease in muscle mass) and increase in total body fat affects volume of distribution Water soluble drugs: lithium, aminoglycosides, alcohol, digoxin


Serum levels may go up due to decreased volume of distribution Half life increased with increase in body fat

Fat soluble: diazepam, thiopental, trazadone



UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Pharmacokinetics
Absorption: Not highly impacted by aging  Variable changes in first pass metabolism due to variable decline in hepatic blood flow (elders may have less first pass effect than younger people, but extremely difficult to predict)


UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Pharmacokinetics and the Liver

Acetylation and conjugation do not change appreciably with age  Oxidative metabolism through cytochrome P450 system does decrease with aging, resulting in a decresed clearance of drugs  Hepatic blood flow extremely variable


UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drugs with Cytochrome P450 Effects

(partial) Inhibitors
Allopurinol Amiodorone Azole antifungals Cimetidine INH SSRIs Tacrine
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Inducers
Metronidazole Quinolones Barbiturates Carbamazepine Phenytoin Rifampin Tobacco

Pharmacokinetics: Excretion and Elimination



GFR generally declines with aging, but is extremely variable

30% have little change  30% have moderate decrease  30% have severe decrease


Serum creatinine is an unreliable marker  If accuracy needed, do Cr Cl


UCSF Division of Geriatrics Primary Care Lecture Series May 2001

The Cockroft and Gault Equation

Cr Cl = 140-age(yrs) X wt (kg) X .85 for women Cr (mg/100ml)X72

May overestimate Cr Cl, especially in frail elders Useful equation, but must be aware of its limitations
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Pharmacodynamics:
What the Drug does to the Body


Some effects are increased

Alcohol causes increase is drowsiness and lateral sway in older people than younger people at same serum levels  Fentanyl, diazepam, morphine, theophylline


Some effects are decreased



Diminished HR response to isoproterenol and beta -blockers

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Mrs. F. is a 92 year old nursing home resident with a history of HTN, heart disease, osteoarthritis, and a stroke. She has been declining recently, with a decreased appetite. Her meds are HCTZ 12.5, ASA 81, digoxin .125, and enalapril 10. She has been on the same meds and dosages for years. On exam, she looks frail BP 130/80 P60 R 16. Other than being thin, her exam is fairly unremarkable. She has no signs of CHF. She has mild left sided weakness and hyper-reflexia, and her MMSE is 27/30, she is not depressed. Her gait is slow with a walker. Labs: Hgb12, Cr 1.3, BUN 20, digoxin level 1.7, others normal. Her EKG is normal except for borderline bradycardia and nonspecific ST changes, which are old. What do you think is wrong?
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Undertreatment


CAD
Beta blockers  ASA


Anticoagulation in AF  HTN, especially systolic HTN  Pain




Particular fear of narcotics in the elderly

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Adverse Drug Reactions



About 15% of hospitalizations in the elderly are related to adverse drug reactions  The more medications a person is on, the higher the risk of drug-drug interactions or drugadverse drug reactions  The more medications a person is on, the higher the risk of non-adherence non-

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drug-Drug Interactions
Common cause of ADEs in elderly  Almost countless good role for pharmacist and computer or on-line programs on Some common examples

   

Statins and erythromycin and other antibiotics TCAs and clonidine or type 1Anti-arrythmics 1AntiWarfarin and multiple drugs ACE inhibitors increase hypoglycemic effect of sulfonylureas

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drug-disease Interactions
    

Patient with PD have increased risk of drug induced confusion NSAIA (and COX-2s) s can exacerbate CHF COXUrinary retention in BPH patients on decongestants or anticholinergics Constipation worsened by calcium, ahticholinergics, calcium channel blockers Neuroleptics and quinolones lower seizure thresholds
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

The Prescribing Cascade



Common cause of polypharmacy in elderly  Some common examples

      

NSAIA ->HTN->antihypertensive therapy >HTNMetoclopromide ->Parkinsonism ->Sinemet Dihydropyridine -> edema ->furosemide NSAIA ->H2 blocker ->delirium ->haldol HCTZ ->gout->NSAIA ->2nd antihypertensive >goutSudafed ->urinary retention ->alpha blocker Antipsychotic ->akithesia ->more meds

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

NSAIDs


Acetaminophen as effective as NSAIDs in mild OA NSAIDs side effects

 

GI hemorrhage (less with COX-2) COXDecline in GFR (COX-2 as well) (COX-

Decreased effectiveness of diuretics, antiantihypertensive agents Indication should justify the increased toxicity of NSAIDs
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drugs and Cognitive Impairment



Common cause of potentially reversible cognitive impairment  Demented patients are particularly prone to delirium from drugs  Anticholinergic drugs are common offenders (TCAs, benadryl and other antihistamines, many others)  Other offenders cimetidine, steroids, NSAIAs
Medical Letter 2000 Drug Safety 1999 Drugs and Aging 1999
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drugs and Falls



  

Biggest risk drugs are long acting benzodiazepines and other sedativesedativehypnotics Both SSRIs and TCAs associated with increased risk of falling Beta blockers NOT associated with increased risk of falling in published literature Mild increase in fall risk from diuretics, type 1A anti-arrythmics, and digoxin antiLeipzig, JAGS
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drug-Food Interactions


Interactions between drugs and food



 

warfarin and Vitamin K containing foods (remember green tea, as well) Phenytoin & vitamin D metabolism Methotrexate and folate metabolism Digoxin may cause anorexia ACE inhibitors may alter taste

Drug impact on appetite

 

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drugs And Dosages to Avoid in Most Instances

  

   

Meperidine Diphenhydramine The most anticholinergic tricyclics: amitryptiline, doxepin, imipramine Long acting benzodiazepines such as diazepam Long acting NSAIAs such as piroxicam High dose thiazides (>25mg) Iron: 325 mg once daily is enough
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Anticipate SEs


Narcotics
 

Begin lactulose or sorbitol and a stimulant laxative Colace is NOT sufficient in most instances Think about osteoporosis prevention Remember steroid induced diabetes Calcium interferes with absorption of levothyroxine

Steroids
 

Levothyroxine


UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Severe ADEs In a Nursing Home



Cardiovascular
 

36%
11% 7%

Digoxin Furosemide Ibuprofen Phenytoin

Analgesics


13%
11%

CNS


19%
9%

ASA

7%

Gerety JAGS 1993

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drug Discrepancies


Difference between medical record and medication bottles in 76% of cases

51% of time medication not recorded  29% medication recorded that patient not taking  20% dosage discrepancy


Risk Factors: Age, number of medications

 UCSF

Bedell et al Arch Intern Med 160, 2000Series May 2001 Division of Geriatrics Primary Care Lecture

Discrepanc Discrepancy P y Present Absent Age 64 56 18 35 56 4.4 <.001 <.001 <.001 <.005 <.001

Cardiologis 82 t Internist 65 >1 MD # meds 80 7.0

Bedell, Arch Inter Med 2000

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

High Risk Situations

Patient seeing multiple providers  Patient on multiple drugs  Patient lives alone and/or has cognitive impairment  Discharge from hospital or any change in venue


UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Hospitalization: A High Risk Time

At hospitalization:  40% of admission medications stopped  45% of discharge medications were started  Serious prescribing problems in 22%  Other prescribing problems in 66%

Beers JAGS 1989, Lipton Medical Care 1992

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Nonadherence


Lack of understanding of how to take



High risk times: Hospital discharge, new meds added, complex regimens

Unable to take  Conscious nonadherence


  

Side effects Lack of understanding of benefits of drug Financial

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Complementary Therapies
     

Very commonly used in the elderly Some common herbs and alternative therapies: AntiAnti-aging DHEA, growth hormone Dementia Gingko biloba BPH Saw palmetto, PC-SPES PCOA Chondroiton sulfate, glucosamine Depression St. John s wort, SAMe
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Adulterants in Products


California Department of Health Services, Food and Drug Branch

  

screened 250 Asian herbal products collected from herbal stores in California assayed products using gas chromatography, mass spectrometry, and atomic-absorption techniques atomicKo, NEJM 1998; 339; 847

32% contained unlabeled medications, 14% mercury, 14% arsenic, 10% lead
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Herbals and Supplements: Regulation



 

Demonstration of safety is NOT required prior to marketing Manufacturing standards are not required Can have health claims, but not claims about treating, preventing, or curing For glucosamine/chondroitin, on third of combinations did not contain listed ingredient www.consumerlabs.com has some drug information
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Herbals and Supplements:Potential interactions with Rx Drugs



SAMe may increase homocysteine levels  St. John s wort and Oral contraceptives  Ginkgo may increase anticoagulant effects of ASA, warfarin, NSAIAs, ticlopidine, and may interact with MAOIs  Bottom line: Try to know what your patient is taking, and ask in a nonjudgmental way
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Use Common Sense in Applying Results to Individual Patients

   

SPAF: 18,000 patients screened, only 7% were enrolled SHEP enrolled 9% of 52,000 patients NNT to benefit one patient may be 20, 30, 50, or 100 in many effective drugs, so Benefit may be marginal in a patient with 8 diseases, dementia, or a life expectancy of six months
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Mr. W. is a 86 year old man with pulmonary HTN, COPD, CRI (creatinine of 2.2), CHF with an ejection fraction of 20%, mild dementia, depression, and severe anemia. He is frequently admitted to the hospital because of severe disease and poor adherence with his medical regimen. His discharge medications on last admission one month ago were aspirin 325mg, 02, enalapril 20mg QD, furosemide 80mg BID, combivent, and sertraline 50mg. The inpatient team decided that he was undertreated, and added metoprolol 12.5mg BID, aldactone, FeSo4 325mg TID, and 3 inhalers. He was readmitted within a week. How might you approach his regimen?
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Principles for Managing Drugs

      

Complete drug history, including herbs and nonprescription drugs Avoid medications if benefit is marginal or if nonnon-pharmacologic alternatives exist Consider the cost Start low, go slow, but get there! Keep regimen as simple as possible Write instructions out clearly Have patient bring in medications at each visit
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Principles (continued)
 

 

Consider medication box or mediset If things don t make sense, consider a home visit Discontinue drugs when possible if benefit unclear or side effects could be due to drug Be cautious with newer drugs Consider if the benefit of the 7th or 8th drug is sufficient to justify the cost, increase in complexity of regimen, and risk of side effects
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Newer drugs


What is unique about this compound?  What clinical data is available?  How does it compare with traditional therapy?  How expensive is it?  With third party payers cover this product?  Does the potential advantage of this new drug justify the risk of using a new drug?
UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Drug Information Sources



www.centerwatch.com/drugs/druglist.htm  www.fda.gov/cder/rdmt/nmecy99.htm  www.fda.gov  www.pslggroup.com/NEWDRUGS.HTM

UCSF Division of Geriatrics Primary Care Lecture Series May 2001

Summary
     

The elderly take more medications than any other age group Pharmacokinetics and pharmacodynamics are altered Adverse drug reactions are common Risks go up with the number of drugs used Nonprescription and herbal therapies are common With care and common sense, we can probably do a better job
UCSF Division of Geriatrics Primary Care Lecture Series May 2001