PMPR 653: Clinical Pharmacotherapeutics III

Michael J. Koronkowski, Pharm.D.

Spring Semester 2002



Goal: To gain an appreciation and understanding of the epidemiology of aging, the physiological changes which occur in aging, their pharmacological impact, pharmacotherapeutic considerations, and the role of a pharmacist practitioner in this process.

Learning Objectives:

  1. Describe the documented and expected changes in demographics as they relate to aging.
  2. Describe and give examples of disease states that are associated with aging and their implications on health care.
  3. In a case scenario, discuss the physiological changes that occur with normal aging and the impact of these changes on the effects and adverse events caused by medication.
  4. Cite examples illustrating the effect that aging has on medication.
  5. Anticipate drug effects, both favorable and adverse, in geriatric patients.
  6. Suggest methods that can be used to overcome age or disease related sensory impairment as they relate to pharmacy practice.
  7. Discuss the risks for adverse drug reactions, non-compliance and other drug related problems as they relate to older patients and suggest optimal pharmacotherapeutic solutions to these identified problems.
  8. Suggest methods of preventing adverse drug reactions and improve medication-taking behavior by older adults.
  9. Communicate information objectively to other clinicians and patients.

Assigned Readings:

  1. Handout materials.
  2. Hanlon JT, Ruby CM, Shelton PS, Pulliam CC. Geriatrics. In: DePiro, JT, Talbert, RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A pathophysiologic approach, 4th edition Stamford CT: Appleton and Lange, 1999, pp. 52-61.
  3. Hanlon JT,Shimp LA, Semla TP. Recent advances in geriatrics: drug-related problems in the elderly. Ann Pharmacother 2000;34:360-5.

Suggested Resource Reading and Textbooks:

1.         Wenger NS, Shekelle P, Davidoff F, Mulrow C. Quality Indicators for Assessing Care of Vulnerable Elders. Ann Intern Med 2001;135 [Number 8 (Part 2) ]:641-758.

2.         Report of the Council on Scientific Affairs. American Medical Association White Paper on Elderly Health. Arch Intern Med 1990;150:2459-72.

3.         Abrams WB, Beers MH, Berkow R, eds. The Merck Manual of Geriatrics, 3rd ed. Whitehouse Station, NJ: Merck & Co.,Inc., 2000. [ available on-line: ]

4.         Bressler R, Katz MD. Geriatric Pharmacology, 2nd edition. New York: McGraw-Hill, Inc., 2001

5.         Delafuente JC, Stewart RB, eds. Therapeutics in the Elderly, 2nd ed. Cincinnati, OH: Harvey Whitney Books Co., 1995.

6.         Evans WE, Schentag JJ, Jusko WJ, eds. Applied Pharmacokinetics, 3rd ed. Vancouver, WA: Applied Therapeutics, Inc., 1992.

7.         Hazzard WR, et al, eds. Principles of Geriatric Medicine and Gerontology, 4th ed. New York: McGraw-Hill, Inc., 1999.

8.    Kane RL, Ouslander JG, Abrass IB. Essentials of Clinical Geriatrics, 4th ed. New York: McGraw-Hill, Inc., 1999.

World Wide Web Resource List on Geriatrics:

  1. Peters R, Sikorski R. Geriatrics resources on the net: A guide to interactive medicine. JAMA 1997;278(Vol.16):1299-1300.
  1. Glowniak J. The internet as an information source for geriatricians. Drugs & Aging 1997;10(3):169-173.
  2. American Geriatric Society
  3. National Institutes on Aging
  4. Gerontological Society of America

Message to Students:

Aging is a universal process to humans.  At present it is an international phenomenon that is occurring across the globe including the third world.  Aging has economic, ethical, lifestyle, political and health care implications to society (to name a few) which over the course of the next century will perhaps dictate society's planning and use of resources more than any other single variable.

It is the intent of this series of lectures to provide an introduction to geriatrics and gerontology.  Some of you may already have a strong background in these fields, while for others the material may be new.  In any case, aging will most certainly impact you professionally and personally.  After all, EVERYONE IS DOING IT!!


I. Aging of America

  1. U.S. Trends

The growth of the population age 65 and older has affected every aspect of our society, presenting challenges as well as opportunities to policymakers, families, businesses, and health care providers.


In 2000, there is an estimated 35 million people age 65 or older in the United States, accounting for almost 13 percent of the total population. The number of older Americans has increased more than ten-fold since 1900, when there were 3 million people age 65 or older (4 percent of the total population).

Despite the growth of the older population, the United States is a relatively young country when compared with other developed nations. In many industrialized countries, older persons account for 15 percent or more of the total population.

In 2011, the "baby boom" generation will begin to turn 65, and by 2030, it is projected that one in five people will be age 65 or older. The size of the older population is projected to double over the next 30 years, growing to 70 million by 2030.

As in most countries of the world, there are more older women than older men in the United States, and the proportion of the population that is female increases with age. In 2000, women are estimated to account for 58 percent of the population age 65 and older and 70 percent of the population age 85 and older.

The population age 85 and older is currently the fastest growing segment of the older population. In 2000, an estimated 2 percent of the population is age 85 and older. By 2050, the percentage in this age group is projected to increase to almost 5 percent of the U.S. population. The size of this age group is especially important for the future of our health care system, because these individuals tend to be in poorer health and require more services than the younger old.

Projections by the U.S. Census Bureau suggest that the population age 85 and older could grow from about 4 million in 2000 to 19 million by 2050. Some researchers predict that death rates at older ages will decline more rapidly than reflected in the Census Bureau’s projections, which could result in faster growth of this population.


  • The proportion of the population age 65 and older varies among states. This proportion is partly affected by the state mortality rate and the number of older persons who migrate to a state. It is also affected by the number of younger persons who move to other states. In 2000, the states with the highest proportions of older persons are Florida, West Virginia, Pennsylvania, Iowa, and North Dakota.
  • There are about 65,000 people age 100 or older in 2000, and the number of centenarians is projected to grow quickly so that there may be as many as 381,000 by 2030.[ Research on the demographics of centenarians, along with clinical, biomedical, and genetic measures, may provide clues to the factors associated with their exceptional longevity.


  • Drug use patterns have also been affected by the changing demographics. In 1968, 10% of the U.S. population was 65 and purchased 25% of all prescription drugs; by 1981 these figures were 12% and 31%, respectively. By the year 2040 it is predicted that 50% of all prescription drugs will be purchased by the 20-25% of the population 65.



Why the increase in the elderly population?

1. Decrease in fertility rate

This affects the percent of the population 65, not the total number.

2. Reduction in mortality

The age-related mortality rates in the U.S. have been decreasing since 1904 when only 25% of the population lived beyond age 65, compared to 70% in 1985.

Why the decrease in mortality?

    • Many would claim that treating hypertension, Medicare and health insurance, fewer people smoking, exercise, and a healthier diet are responsible for the decrease in mortality. In fact, the major impact of these interventions has yet to be realized. The real reason for the decline in mortality is improvements in overall living conditions and sanitation.
    • Over the past 150 years, the major causes of mortality have switched from infectious to chronic disease. For example, tuberculosis was the number one cause of death in the U. S. in 1900, but its incidence had been decreasing since 1856 [Note: tuberculosis is currently on the rise secondary to immigration patterns and immunodeficiency viruses]. In 1984, the four leading causes of death in the U.S. were cardiovascular, cancer, strokes, and pulmonary disease (COPD). Pneumonia and influenza ranked #5 and septicemia ranks #l0.

3. Increase in real numbers and percent primarily due to an increase in the number of annual births before 1920 and after World War II [Baby Boom].

4. Increased life expectancy after age 65

a. Life expectancy - the average number years of life from birth (life span) or some other stated age.

Between 1900 and 1940 the overall life expectancy increased by 14 years, but for those 65 the increase was < 1 year. However, since 1950 the percent gain in life expectancy has favored those 65.


Life Expectancy

  • Life expectancy is a summary measure of the overall health of a population. It represents the average number of years of life remaining to a person at a given age if death rates were to remain constant. In the United States, improvements in health have resulted in increased life expectancy and contributed to the growth of the older population over the past century.


  • Americans are living longer than ever before. In 1900, life expectancy at birth was about 49 years. By 1960, life expectancy had increased to 70 years, and in 1997, life expectancy at birth was 79 years for women and 74 years for men.
  • Life expectancies at ages 65 and 85 have also increased. Under current mortality conditions, people who survive to age 65 can expect to live an average of nearly 18 more years, more than five years longer than persons age 65 in 1900. The life expectancy of persons who survive to age 85 today is about 7 years for women and 6 years for men.
  • Educational attainment is associated with higher life expectancy. The life expectancy of high school graduates at age 65 is approximately one year longer than the life expectancy at that age for persons who did not graduate from high school.
  • Life expectancy varies by race, but the difference decreases with age. In 1997, life expectancy at birth was 6 years higher for white persons than for black persons. At age 65, white persons can expect to live an average of 2 years longer than black persons. Among those who survive to age 85, however, the life expectancy among black persons is slightly higher than among white persons. The declining race differences in life expectancy at older ages are a subject of debate. Some research shows that age misreporting may have artificially increased life expectancy for black persons, particularly when birth certificates were not available. Other research, however, suggests that black persons who survive to the oldest ages may be healthier than white persons and have lower mortality rates.

b. Has the gain in life expectancy been accompanied by a gain in health status?

This is where the question of quality of life becomes an issue. Katz et al. used a longitudinal study of older persons in Massachusetts to address this question. He calculated a person’s active life expectancy (the expected number of years remaining in which the person remains independent in function, i.e., disability free). Katz found that since 1950 only 1.3 of the 4.5 years gained in life expectancy by men was disability free and for women only 1.4 out of 7.5 years gained in life expectancy was disability free. Katz concluded that although women consistently lived longer than men did, the number of years spent disabled is greater and the total non-disabled life expectancy for men and women 65 are similar. (Katz S, et al. NEJM 1983;309:1218-24)

This finding significantly shaped the current philosophy of geriatrics and gerontology so that emphasis is placed on disease prevention and the compression of morbidity in order to increase active life expectancy.


II. Function, Morbidity, Disability, and Mortality

A. Measures of Functional Status

1. Activities of Daily Living (ADL’s)

feeding dressing ambulating

toileting continence   bathing

grooming transfer communication


2. Instrumental Activities of Daily Living (IADL’s)

writing               reading cooking

cleaning             shopping laundry

climb stairs use telephone   manage medications

manage money  ability to travel    ability to work



  • Functioning in later years may be diminished if illness, chronic disease, or injury limits physical and/or mental abilities. Changes in disability rates have important implications for work and retirement policies, health and long-term care needs, and the social well-being of the older population. By monitoring and understanding these trends, policymakers are better able to make informed decisions.





 Examples of projected increase in disabilities

Projected Number of:

Year Hip fractures/yr Persons with dementia

1980 200,000         2 million

2000 350,000        3.7 million

2050 650,000        8.5 million


Cognitive functional status - Tools for Measurement

Orientation x 3 most common measure
in general medicine
limited really
SPMSQ (Pfeiffer) 10 questions, spoken bedside, office, nursing home
MMSE (Folstein) 30 points/tasks,spoken/written office, nursing home, hospital
Other Tests "Confusion" various short tasks bedside, general
Neuropsychological Testing battery of tests and psychologist interview research, hospital

Note: Poor brain (cognitive) function may be the only reason for poor patient performance, (i.e. disability, i.e. loss of independence). It may be reversible.



Memory Impairment

  • Memory skills are important to general cognitive functioning, and declining scores on tests of memory are indicators of general cognitive loss for older adults. Low cognitive functioning (i.e., memory impairment) is a major risk factor for entering a nursing home



Depressive Symptoms

  • Depressive symptoms are an important indicator of general well-being and mental health among older Americans. Higher levels of depressive symptoms are associated with higher rates of physical illness, greater functional disability, and higher health care resource utilization.

  • Women between the ages of 65 and 84 are more likely than men to have severe depressive symptoms. Among persons age 85 or older, men and women have a similar prevalence of severe depressive symptoms.
  • In 1998, about 15 percent of persons ages 65 to 69, 70 to 74, and 75 to 79 had severe symptoms of depression, compared with 21 percent of persons ages 80 to 84, and 23 percent of persons age 85 or older.



B. Morbidity - Chronic Diseases and Co-morbidities

Chronic Health Conditions

  • Chronic diseases are long-term illnesses that are rarely cured. These diseases can become a significant health and financial burden to not only those persons who have them, but also their families and the nation’s health care system. Chronic conditions such as arthritis, diabetes, and heart disease negatively affect quality of life, contributing to declines in functioning and the inability to remain in the community. Five of the six leading causes of death among older Americans are chronic diseases.



C. Mortality Among Older Population


  • Overall, death rates in the U.S. population have declined during the past century. But for some diseases, death rates among older Americans have increased in recent years.


We are approaching an era with a very different age distribution from the present time. Usually, this fact is equated with enormously increased requirements for health care costs and services--but this assumes that society (those with political and financial power) will accept such a burden. At the very least, some extremely hard choices involving limitation of care will be required. More preventative medicine, more efficient and cost-saving curative medicine, and better accountability of cost benefit will be necessary in order to avoid increasing confrontation between a rapidly growing dependent sector of society (ELDERLY) and an increasingly burdened working sector.

Physiology of Aging versus Disease: Implications of Drug Therapy

  1. Aging versus Disease
  1. Disease is abnormal; aging is normal
    1. Aging is heterogeneous
    2. Aging is universal
    3. Aging and chronic disease are independent
    4. a. Four out of five persons 65 has at least one chronic condition

    5. Changes which accompany aging also can lead to morbid or fatal events



    • Impaired Glucose Tolerance (40% of the elderly have altered carbohydrate tolerance) (40% of the elderly have altered carbohydrate tolerance)
    1. changes in glucose tolerance with aging
    1. after age 30-40, there is a 1 to 2mg/dl increase in fasting glucose levels/decade
    2. after age 30-40, the 2 hour post-prandial plasma glucose increases by 8-20mg/dl, per decade


  1. Physiology and Applied Pharmacology of Aging
  1. Organ-Systems and Potential Impact on Drug Response

Central Nervous System

  • Increasing response to CNS depressants
  • Cognitive impairment more likely
  • Weaker homeostatic compensations for primary drug effects


  • Increasing risk of drug induced glaucoma

Endocrine System

  • Increasing resistance to insulin


  • Decreased responsiveness to cardiac stimulants
  • Diminished autonomic compensations for primary drug effects on blood pressure


  • Altered drug metabolism
  • Less protein binding of drugs


  • Decreased renal excretion of drugs
  • Increased susceptibility to nephrotoxic effects of drugs

Alimentary System

  • Decreased passive and active absorption of drugs
  • Delayed gastric emptying slowing onset of drug action
  • Increased susceptibility to drug-induced constipation, inhibition of secretions or mucosal irritation

Reproductive System

  • Increased susceptibility to drug adverse effects affecting sexual function

Musculoskeletal System

  • Increased risk of muscle weakness form drugs


  1. Physiologic Age-Related Changes and their Impact on Drug Response
  1. changes in height
    1. height loss is inevitable with advancing age
    2. onset and rate greatly variable ( 2 inches by 80 years of age)
    3. spinal compression, joint space narrowing, and flatten arches may contribute
  1. changes in weight
    1. exercise and eating habits impact rather than aging process
  1. changes in body composition
    1. fat proportion doubles between 25 and 75 years of age
    2. loss of lean body mass, with some decrease in bone and body organ mass
    3. less water volume
    4. the above results in major drug distribution and disposition changes
  1. changes in renal function
    1. with aging, there is 25-30% decrease in kidney mass, therefore less functional nephrons
    2. renal blood flow decreases significantly with age
    3. creatinine clearance declines on average 8ml/min/1.73m2/decade
    4. creatinine clearance is often overestimated

5. changes in hepatic metabolism

    1. decreased liver mass by 1/3 with advancing age can lead to intrinsic metabolism
    2. pre-synaptic metabolism of some drugs (propranolol, verapamil) declines in older people
    3. drugs metabolized by one-step conjugation preferred over drugs requiring multi-step metabolism (i.e. lorazepam or oxazepam preferred over diazepam or chlordiazepoxide as benzodiazepines)



  1. Pharmacokinetic and Pharmacodynamic Age-Related Changes and their Impact on Drug Response


Pharmacokinetic- factors affecting drug concentrations at the site of action over defined periods of time.


Effects of Aging on Drug Distribution



Physiological Change of Aging

Clinical Significance


Elevated gastric pH

Reduced small bowel surface area

Little change with absorption with age (i.e. no clinical significance)


Reduced total body water; reduced lean body mass; increased total body fat



Reduced serum albumin


Increased a -1-acid glycoprotein

Higher concentration of drugs that distribute in body fluids

Increased distribution and often prolonged elimination half-life of fat soluble drugs

Increased free fraction in plasma of some highly protein bound acidic drugs

Small decreases in free fraction of basic drugs bound to a -1-acid glycoprotein

Hepatic Metabolism


Reduced hepatic mass

Reduced hepatic blood flow

Often decreased first-pass metabolism; decreased rate of biotransformation of some drugs; marked interindividual variation in rate of hepatic metabolism

Renal Elimination

Reduced renal plasma flow

Reduced glomerular filtration rate

Decreased renal elimination of drugs and metabolites; marked interindividual variation

Adapted from Vestal RE: "Aging and pharmacokinetics: Impact of altered physiology in the elderly." Physiology and Cell Biology of Aging. 8:198, 1979.


Pharmacodynamics- end organ responsiveness to a given drug concentration (i.e. "change in function of an end organ (site of action) that results from drug---end organ interaction

  1. General Principles, pharmacodynamic changes are less well defined
    1. dependent upon pharmacokinetic parameters
    2. alteration in receptor site(s), and/or receptor integrity
    3. ( less responsiveness of beta-adrenergic receptors with age)

    4. neurotransmission
    5. (less number of functioning neurons and neurotransmitters or an increase in synaptic gap may attenuate drug-end organ response)

    6. idiosyncratic
    7. unpredictable drug-end organ response

    8. responsiveness

elderly shown more "sensitive" to lower concentrations of some agents (both benzodiazepines and warfarin)


    D. Sensory changes Disease which Impact on Pharmacy Practice

  1. The Older Eye and Vision
    1. decreased accommodation
    2. decreased visual acuity
    3. decreased adaptation to darkness
    4. decreased peripheral vision
    5. decreased glare tolerance
    6. decreased contrast sensitivity
    7. decreased tear secretion

Specific Problems

    • Presbyopia-decreased accommodation of the lens to change shape when focusing on close objects.-decreased accommodation of the lens to change shape when focusing on close objects.
    • Cataracts-affect vision by causing blurring, increased glare, yellowing of vision, streaking of light-affect vision by causing blurring, increased glare, yellowing of vision, streaking of light
    • Primary Open-angle Glaucoma-imbalance between aqueous humor production and outflow.-imbalance between aqueous humor production and outflow.
    • Dry Eyes
    1. patients complain of foreign body sensation, a gritty felling or dryness
    2. Treatment
    1. increase the humidity in the environment
    2. eliminate drugs which may decrease tear production
    3. artificial tear products
    • Age-related macular degeneration-bilateral loss of peripheral vision-bilateral loss of peripheral vision
    1. leading cause of legal blindness in the elderly
    2. no treatment at the present time


Evaluation Tips:

  1. make sure corrective lenses (glasses/contacts) are clean and fit properly
  2. make sure that corrective lenses are the patient’s
  3. make sure lighting is adequate


Low Vision Aids:

  1. increased wattage of light bulb
  2. tinted glasses may decrease glare
  3. magnification devices
  4. night lights
  5. large print on prescription labels, books, etc.


2. The Older Ear and Hearing Loss

( 7-20 million Americans have some hearing impairment; 50% of persons 65)

Specific Problems

  • Presbycusis-bilateral symmetric, sensorineural hearing loss that is associated with aging-bilateral symmetric, sensorineural hearing loss that is associated with aging
    1. secondary to aging
    2. usually high frequency tone is lost first
    3. prolonged noise exposure, decreased blood flow, and athlerosclerosis may contribute

Interviewing a hearing-impaired elder

    1. move to a quiet place
    2. sit them in a corner at eye level
    3. lower the tone of your voice
    4. make sure the area is well lighted
    5. speak slowly and clearly
    6. avoid shouting, it conveys anger and hostility
    7. stay still
    8. use nonverbal gestures
    9. reinforce meaning through touch


3. Age related changes in Taste and Smell

(Schiffman SS. Taste and smell losses in normal aging and disease. JAMA 1997;278:1357-1362.)

    1. dysgeusia-an unpleasant taste in the mouth
    2. dysosmia-an unpleasant smell
    1. age related losses begin in the sixth decade and progress gradually
    2. most commonly due to neural degeneration and atrophy
    3. incidence of hypogeusia and hyposmia in the elderly is 40%
    4. may lead to nutritional deficiencies and impaired detection of hazards


  1. Age related changes in Touch
    1. response to painful stimuli is diminished with aging
    2. pressure touch thresholds on fingers and toes diminish


E. Compliance and its Impact on Drug Response

  • Noncompliance, usually in the form of taking less drug (underadherence), is common; about 40% - 50% of older patients do not take their medications as prescribed
  • 35% of older patients may suffer health problems because of their noncompliance
  • Noncompliance with medication was the cause of 11% of hospitalization admissions in one study


  1. Intentional versus Nonintentional Noncompliance(Cooper, et al. J Am Geriatr Soc 1982;30:329-33.)

Intentional (90%) Unintentional (10%)

52% do not need 60% too expensive

15% adverse effects 15% forgot to take

4% need more         2% misunderstood


    • those patients who were intentionally noncompliant were:
    1. more likely to use 2 prescription medications
    2. more likely to have medications prescribed by 2 prescribers
    3. compliance aids were useful primarily when patients had difficulty remembering to take medication


  1. Dangers of Noncompliance

"Syndrome of relocation stress"- movement of an individual into a controlled health care environment such as admission to a nursing care facility or an acute care setting results in 100% compliance with medication which may result in occult drug toxicity.

  1. Hoarding and Sharing of Medications

  3. Ways to improve medication compliance

    1.  minimizing the number of medicines

    2. simplify medication regimens - chronic medications dosed at most twice daily

    3. increase the user’s knowledge- clear, simple repeated explanation of medication usage

    4. compliance aids- large legible labels, easy-to-remove vial tops, weekly pill boxes, etc.

    5. develop a standard system of promoting compliance


  1. Drug-Related Problems
  1. Multiple Medication Use- Polypharmacy
    1. the use of multiple prescription and OTC medication (Healthy People 2000, 1990.)
    2. the prescription, administration, or use of more medications than are clinically indicated
    3. when a medical drug regimen contains at least one unnecessary medication
    4. the concomitant use of 5 medications

Typical reasons for polypharmacy

  1. multiple prescribers
  2. prescribing practices
  3. multiple pharmacies
  4. lack of a regular, comprehensive medication review
  5. patients’ belief that they need a pill for every illness
  6. lack of patient education by a health care provider or lack of patient knowledge
  7. health care practitioner education ineffective


Methods for preventing polypharmacy

  1. patient education - patient tailored
  2. educate physician, pharmacist, and other health care providers
  3. improve physician prescribing - through both regulatory and non-regulatory means


  1. Medication Errors(Schwartz et al. Am J Pub Health 1962;52:2015-29.)
    • risk for medication errors increased for those living alone, those with poor coping skills, and those individuals mixing medications which includes sharing and hoarding medicines


  1. Practical Solutions and Guidelines to Prevent Drug Related Problems

(adapted from Stewart RB and Cooper JW. Drugs and Aging 1994;4:449-56.)

Prescribing Guidelines to follow

    1. Is the drug necessary?
    2. Assess the benefit to risk ratio
    3. Attempt to make an accurate diagnosis before treatment
    4. Consider and implement all nondrug alternative
    5. Use caution when prescribing for a person who indicates that all previous drugs have failed
    6. Take a comprehensive medication history
    7. Educate and inform patient’s regarding their drug therapy
    8. Communicate with other prescribers and health providers
    9. Avoid treating adverse drug effects with concomitant medication
    10. Try to prescribe a drug that will treat more than one condition
    11. Avoid combination products
    12. Screen for drug-drug and drug-disease interactions
    13. Keep the medication regimen simple
    14. Limit the use of PRN medications
    15. Consider all new medications as a therapeutic trial, re-evaluate therapy continuously


Monitoring Guidelines to follow

    1. Assess if the drug is producing a therapeutic goal
    2. Determine if the drug is still needed, do not be afraid to stop medication with no or unclear indications
    3. Determine if the drug is producing any adverse effects
    4. Assess patients’ complaints or symptoms
    5. Conduct a drug regimen review at least annually


Rules For Dispensing Medication

(Morrow D, Lierer V, Sheikh J. Adherence and Medication Instructions: Review and recommendations, J Am Geriatr Soc 1988;36:1147-60.)

Rule 1: Medication instructions should contain 13 basic components:

    1. Patient’s name
    2. Physician name and phone number
    3. Medication name (both Brand dispensed and chemical name0
    4. Indication
    5. How the medication works
    6. Interaction warnings
    7. Dosage form
    8. Dose
    9. Frequency and times
    10. Duration and refill
    11. Date of issue and expiration date
    12. common adverse effects
    13. Emergency numbers

Rule 2: Medication instructions should be in list format

Rule 3: Begin with the title stating the patient specific goal of the therapy

Rule 4: Use familiar terminology the patient understands

Rule 5: Instruction should be at least 14 point font size or larger

Rule 6: Describe directions with explicit words and phrases

Rule 7: Avoid using ambiguous words and phrases


IV. Adverse Drug Reactions (ADR’s)

  1. Factors Predisposing in the Elderly to ADR’s
    1. multiple medication use
    2. multiple effects of drugs
    3. physiological changes in drug disposition (due to age and disease)
    4. misuse of medication
    5. suboptimal prescribing

Methods of Preventing/Minimizing Adverse Drug Reactions

Limit the number of drugs taken (before a drug is prescribed, ask yourself the following:)

    1. Is this the most effective drug for the disease or condition being treated?
    2. Is the dose appropriate given the patient’s age, renal, and hepatic function?
    3. Is the patient allergic to the drug or similar chemical
    4. Is the patient already taking a drug with pharmacological properties that would duplicate or antagonize the new agent/
    5. Will the addition of the new agent increase the complexity of the patient’s medication regimen such that compliance will be compromised?
    6. Does the patient have another disease that would contradict the use of the drug?
    7. Does the patient understand why the drug is being prescribed and how to take the medicine?
    8. Is the indication for the new drug actually a reaction or secondary to a currently prescribed medication?

Concerning medication already in the patient’s regimen, consider the following questions:

    1. Is the drug still needed?
    2. Is the patient still responding to the regimen?
    3. Is the patient using the drug appropriately with regard to dosing or administration?
    4. Is there a relationship between drugs in the patient’s regimen and signs or symptoms observed?

Impact of Adverse Drug Reactions on Quality of Life and Functional Decline

  1. Physical Functioning (i.e. ADL’s, IADL’s)
  2. Psychological Functioning (i.e. cognitive scales, depression scales)
  3. Social Function (social activities, support systems)
  4. Overall Health (general health perception)
  1. Drug Interactions

1. Drug-disease interactions:

    1. increased prevalence of disease in the older person
    2. difficulty distinguishing subtle reactions from the effects of disease (confounding)

2. Drug-drug interactions:

    1. pharmacokinetic interactions causing differences in drug disposition – often not clinically significant; can be managed
    2. pharmacodynamic interactions causing differences in drug effect – often clinically significant

3. Drug-Nutrient interactions

    1. Drug therapy may alter nutrition, appetite, taste perception
    2. Drug therapy may alter immune system, result in vitamin deficiencies, and enhance physical impairments,


  1. Considerations for effective pharmacotherapy - Effects of specific "high risk" drug classes
  1. Diuretics
    • widely used in the older population for hypertension and heart failure
    • increased risk of hypokalemia
    • lower doses can effectively control conditions
    • careful titration to avoid adverse effects (azotemia, postural hypotension, hypokalemia)
  1. Antihypertensive drugs
    • take into account interracial differences in drug response
    • take into account co-morbid disease states
    • consider drug-drug and drug-disease interactions prior to initiation of therapy
  1. Antiarrhythmic drugs
    • altered pharmacokinetics requires dosage reductions in older persons
    • risk of significant adverse reactions increases with age (i.e. class 1C drugs, mexilitene)
    • clearance of digoxin decreases on average 50% in elderly patients with normal CrCl


  1. Antiparkinsonian drugs
    • drug clearance is reduced in older persons
    • increased susceptibility to postural hypotension and confusion
  1. Psychoactive drugs
    • commonly worsen underlying confusion state therefore limit usage
    • risk of falls increases with dose (i.e. long acting benzodiazepines and antidepressants)
    • using anticholinergics to prevent extrapyramidal effects is not recommended
    • starting doses should be low (1/4 the usual adult dose), increase gradual, re-evaluate, stop as soon as possible


  1. Anticoagulants
    • commonly used in older patients because of high incidence of atrial fibrillation
    • pharmacodynamic sensitivity to anticoagulant effect may increase with age
    • recent studies have NOT confirmed that aging per se increases risk of bleeding
    • age, however does not preclude the use of warfarin provided there are no contraindications
    • older patients may require lower doses


  1. Hypoglycemic drugs
    • incidence of hypoglycemia from oral sulfonylureas may increase with age
    • elderly often have a blunted response, hypoglycemia is more subtle in presentation
    • aging reduces insulin clearance, but dose requirements depend on level of insulin resistance
    • with renal insufficiency, agents cleared by hepatic metabolism (i.e. glipizide) preferred


  1. Analgesics
    • Non-steroidal anti-inflammatory drugs (NSAID’s) are among the most widely used drugs due to prevalence of arthritic disorders
    • mucosal ulceration and GI bleeding are serious consequences of NSAID therapy
    • the risk of NSAID-induced renal impairment may be increased in the older person
    • NSAID use and aging is complicated by high protein binding, hepatic metabolism, sterioisomers, renal insufficiency, and the accumulation of metabolites, which may be hydrolyzed to re-form, parent drug.
    • some evidence indicates decreased clearance of NSAIDs (salicylates, oxaprozin, naproxen) in older patients


   D. Selected Drugs to Avoid in the Elderly Population

    (Source:adapted from Beers MH. Arch Intern Med 1997;157:1531-1536.)



    Potential Problems or Concerns


    Better antiemetics , risk of extrapyramidal effects

    Propoxyphene & Combinations

    Analgesia = APAP but ADR’s = Opiods


    Decreased clearance, neurotoxic


    CNS confusion, hallucinations


    CNS adverse effects more common


    Serious hematological effects

    Antihistamines (chlorpheniramine, diphenhydramine, hydroxyzine, others)

    Anticholinergic effects

    TCA’s (amitriptyline, doxepin)

    Sedating, Anticholinergic , rarely drug of choice in the elderly

    Benzodiazepines (long acting)

    Accumulation, Sedation, risk of falls

    Muscle Relaxants (methocarbamol, carisoprodol,cyclobenzaprine, metoxalone)

    Poorly tolerated, antichlolinergic ADR’s


    Limited proven role, frequently causes orthostatic hypotension


    No more effective than aspirin and more toxic

    All barbiturates (except phenobarbital)

    Highly addictive, many adverse effects

    Iron supplements

    Limit dose to no more than 325mg/day of SO4, constipation offsets absorption

    Ergoloid mesylates

    Ineffective in the treatment of most dementias


    Depression, orthostatic hypotension, impotence, sedation


    Better alternative available, may cause bradycardia and exacerbate depression

    Dicyclomine, hyoscyamine

    Highly anticholinergic, may cause toxicity


    Prolonged half-life may increase risk of hypoglycemia


    Potent negative inotrope and strongly anticholinergic


    Highly addictive and sedating, may suffer withdrawal



E.  Medication Induced Disease or Impairments in the Elderly


Examples of Medication-Induced Disease and Functional Impairment in Older Adults

Type of Impairment

Medications Implicated

Central Nervous System

Cognitive impairment

Benzodiazepines, H2 antagonists, antihypertensives, antipsychotics, analgesics, narcotics, beta blockers, corticosteroids


Anticholinergics, tricyclic antidepressants, low-potency antipsychotics, diphenhydramine, H2 antagonists, narcotics, digoxin, levodopa


Reserpine, methyldopa, beta blockers, digoxin, clonidine, corticosteroids


Tricyclic antidepressants, antipsychotics, benzodiazepines, antihypertensives, anticholinergics , others

Movement disorders

Antipsychotics, metoclopramide, SSRI’s, lithium, anti-Parkinson’s medications, methyldopa, amoxapine


NSAIDs, sympathomimetics, cyclosporine, erythropoietin

Heart Failure

Diuretics, digoxin (diastolic dysfunction), beta blockers, Ca++ blockers (systolic dysfunction), NSAIDs, antiarrhythmics


Levothyroxine, sympathomimetics, theophylline, sulfonyreas, antiarrhythmics, beta blockers, Ca++ blockers, tacrine, tricyclic antidepressants, astemazole, terfenadine, cisapride


Antipsychotics, tricyclic antidepressants, antihypertensives, diuretics, sedative hypnotics, immediate-release nifedipine

Thyroid dysfunction

Amiodarone, lithium, iodinated glycerol, radiocontrast dyes, anticonvulsants


NSAIDs, corticosteroids


Liquid medications (sorbitol), antibiotics, misoprostol, tacrine, others


Anticholinergics, Ca++ blockers, narcotics, calcium/iron supplements, antacids, diuretics



Medication Induced Disease or Impairments in the Elderly (continued)


Examples of Medication-Induced Disease and Functional Impairment in Older Adults


Interstitial pneumonitis/pulmonary fibrosis

Amiodarone, nitrofurantoin, methotrexate, chemotherapeutic agents (busulfan, BCNU, chlorambucil)


ACE inhibitors, beta blockers, narcotics, benzodiazepines, barbiturates

Urinary incontinence

Urge:cholinergic medications, tacrine, bethanechol

Stress:alpha-blockers, antipsychotics

Overflow: nifedipine, narcotics, anticholinergics, alpha-agonists

Functional: sedatives, diuretics


Weight loss

SSRI’s, digoxin, sedatives (impair eating)


Phenothiazines, tricyclic antidepressants, HMG CoA reductase inhibitors, amiodarone, anticholinergics, antibiotics


Animoglycosides, loop diuretics, salicylates, quinidine, quinine, erythromycin, cisplatin

Adapted from: Ann Pharmacother 2000;34:360-5