Michael J. Koronkowski, Pharm.D.
Spring 1998
Michael J. Koronkowski, Pharm.D.
Spring 1998
Introduction to Aging: Demographics & Epidemiology, Aging VS. Disease, and its Implication on Drug Therapy and Pharmacy Practice
Physiology of Aging versus Disease: Implication on Drug Therapy
Assigned Readings:
Suggested Readings:
Learning Objectives:
World Wide Web Resources on Geriatrics
Message to Students:
Aging is an 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 a 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. Global Aging and the Aging of America
In 1900, » 4% of the U.S. population was ³ 65 years old. Today, » 13% of the population is ³ 65 and midway through the next century 20 to 25% of the population will be ³ 65 years. This change in demographics is not unique to the U.S. Countries such as Sweden have already exceeded the 20% mark.
The fastest growing segment of the U.S. population are the old-old or persons ³ 85 years. This segment increased from 0.1% of the population in 1900 to 1% in 1980. Between 1960 and 1980, this portion of the population increased 126% compared to a 26% increase for the rest of the population. Estimates for the year 2050 predict that 5.0% of the population will be ³ 85 years of age.
Drug use patterns have also been affected by the changing demographics. In 1968, 10% of the U.S. population was ³ 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 prescription drugs will be purchased by the 20-25% of the population ³ 65.
B. Why the increase in the elderly population?
1. Decrease in fertility rate
This affects the percent of the population ³ 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, less people smoking, exercise, and a healthier diet are responsible for the decrease in mortality. In fact, the major impact of these interventions have yet to be realized. The real reason for the decline in mortality are 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 increase by 14 years, but for those ³ 65 the increase was < 1 year. However, since 1950 the percent gain in life expectancy has favored those ³ 65.
Country Year 0 1 65 Suriname 1985 63.6 64.8 13.6 USSR 1990 64.2 64.8 12.4 Hungary 1990 65.1 65.2 12.1 USA 1988 71.6 71.4 15.0 UK 1990 73.0 72.6 14.2 Japan 1989 76.2 75.5 16.5 SOURCE: WHO Health Statistics Annual, 1991
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 persons 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, the number of years spent disabled is greater and the total non-disabled life expectancy for men and women ³ 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, and Disability
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
B. Morbidity - Chronic Diseases and Co-morbidities
1. Common chronic conditions and co-morbidities
NUMBER OF SELECTED REPORTED CHRONIC CONDITIONS/1000 PERSONS IN THE USA BY AGE,1982
Types of Conditions Total 65 + yr 65 - 74 yr >= 75 yr Arithritis 495.8 507.8 476.0 Hypertension 390.4 384.3 400.4 Hearing impairment 299.7 262.0 362.2 Heart disease 256.8 224.7 310.0 Deformity or orthopedic impairment 168.5 172.7 161.5 Chronic sinusitis 151.7 159.1 139.6 Visual impairment 101.1 80.7 134.8 Diabetes 88.9 96.6 76.3 Varicose veins 77.7 79.3 75.2 Hernia of abdominal cavity 75.5 87.8 55.2 (Adapted from J. A. Brody, D. B. Brock and T. F. Williams: "Trends in the health of elderly population", in Annual Review of Public Health, Vol. 8, pp. 211-234. 1987. Used with permission)
C. 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
III. Analysis of Demographic Change in the USA
A. Effect of Gender
Currently, women outnumber men in those over 65 years by 3 to 2. Because women live longer and because of the way pensions are generally administered, women living alone tend to be the poorest among the elderly.
B. Effect of Race
The squaring of the population pyramid is more true of whites than of Blacks. Premature black deaths are caused by both a lower mean life span and by greater mortality among the young. Whereas, in 1989, the proportion of Whites over 65 was 13%, the proportion of Blacks and Hispanics was only 8% and 5% respectively.
C. Effect of Fertility
The current rate of increase in the elderly population in the USA largely reflects variations in the birth rate (with a delay of 65 years). Low birth rates during the depression and World War I, together with wartime loss of many young adults, is reflected in the very modest rise in the elderly population projected between now and 2010. This should be followed by a very rapid rise , as the baby boomers age. A different picture of increase emerges with the very old (85+), where an exponential increase began about 1950, and the numbers will grow rapidly through 2050.
D. Geographic Location and Residence
Populations of individual states are governed by 3 factors as any population: fertility, mortality, and migration. Of these the most powerful here is migration. Thus, Florida, in 1989, had an elderly population of 18%, whereas Alaska had one of 4.1%. Curiously, many elderly retire to such places as Florida, many subsequently return to their home states when they become very elderly, probably to gain the support of friends and family.
- In 1989, 1.5 Million or 5% of persons 65+ resided in a nursing home; 93% were white and 45% were 85+.
- Approximately 20% of all people ³ 65 will be in a nursing home at sometime in the future.
- Risks for nursing home placement - living, alone, and widowed
E. Support Ratios
A useful concept is the support ratio, which is the number of persons in a dependency situation (i.e. those over 65 years or those 0-19 years) per 100 persons in a supportive role (those aged between 20-64). This is therefore some measure of societal burden imposed by an elderly population. In terms of the elderly, the ratio has been rising throughout the century (7:100 in 1900, a projected 29:100 in 2020, and 40:100 in 2050)
F. Individual Finances
The elderly, as a group, are a relatively poor segment of the population. If we disregard potential income from home equity about 45% of those over 70, in 1988 had a cash income of between $0 and $10,000. Less than 10% had an income of $35,000 or more. Yet medical expenses are much higher than in any other group.
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 on Drug Therapy
1.Aging is heterogeneous
2.Aging is universal
3. Aging and chronic disease are independent
- Four out of five persons ³ 65 has at least one chronic condition
4. Changes which accompany aging also can lead to morbid or fatal events
Example:
- Impaired Glucose Tolerance (40% of the elderly have altered carbohydrate tolerance0
- 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
II. Physiology and Applied Pharmacology of Aging
1. changes in height
- height loss is inevitable with advancing age
- onset and rate greatly variable (» 2 inches by 80 years of age)
- spinal compression, joint space narrowing, and flatten arches may contribute
2. changes in weight
- exercise and eating habits impact rather than aging process
3. changes in body composition
- fat proportion doubles between 25 and 75 years of age
- loss of lean body mass, with some decrease in bone and body organ mass
- less water volume
- the above results in major drug distribution and disposition changes
4. changes in renal function
- with aging, there is » 25-30% decrease in kidney mass
- renal blood flow decreases significantly with age
- creatinine clearance declines on average 8ml/min/1.73m2/decade
- creatinine clearance is often overestimated
5. changes in hepatic metabolism
- decreased liver mass by 1/3 with advancing age can lead to ¯ intrinsic metabolism
- pre-synaptic metabolism of some drugs (propranolol, verapamil) declines in older people
- 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)
Pharmacokinetic- factors affecting drug concentrations at the site of action over defined periods of time.
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
- dependent upon pharmacokinetic parameters
- alteration in receptor site(s), and/or receptor integrity - (¯ responsiveness of beta-adrenergic receptors with age)
- neurotransmission - (¯ number of functioning neurons and neurotransmitters or an increase in synaptic gap may attenuate drug-end organ response)
- idiosyncratic - unpredictable drug-end organ response
- responsiveness - elderly shown more "sensitive" to lower concentrations of some agents (both benzodiazepines and warfarin)
1. The Older Eye and Vision
- decreased accommodation
- decreased visual acuity
- decreased adaptation to darkness
- decreased peripheral vision
- decreased glare tolerance
- decreased contrast sensitivity
- decreased tear secretion
Specific Problems
- Presbyopia- 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
- Primary Open-angle Glaucoma- imbalance to aqueous humor production and outflow.
- Dry Eyes
1. patients complain of foreign body sensation, a gritty felling or dryness
2. Treatment
- increase the humidity in the environment
- eliminate drugs which may decrease tear production
- artificial tear products
- Age-related macular degeneration- bilateral loss of peripheral vision
1. leading cause of legal blindness in the elderly
2. no treatment at the present time
Evaluation Tips:
- make sure corrective lenses (glasses/contacts) are clean and fit properly
- make sure that corrective lenses are the patient’s
- make sure lighting is adequate
Low Vision Aids:
- increased wattage of light bulb
- tinted glasses may decrease glare
- magnification devices
- night lights
- 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 ³ 65)
Specific Problems:
Presbycusis- bilateral symmetric, sensorineural hearing loss that is associated with aging
- secondary to aging
- usually high frequency tone is lost first
- prolonged noise exposure, decreased blood flow, and athlerosclerosis may contribute
Interviewing a hearing-impaired elder
- move to a quiet place
- sit them in a corner at eye level
- lower the tone of your voice
- make sure the area is well lighted
- speak slowly and clearly
- avoid shouting, it conveys anger and hostility
- stay still
- use nonverbal gestures
- reinforce meaning through touch
3. Age related changes in Taste and Smell
- dysgeusia- an unpleasant taste in the mouth
- dysosmia- an unpleasant smell
- age related losses begin in the sixth decade and progress gradually
- most commonly due to neural degeneration and atrophy
- » incidence of hypogeusia and hyposmia in the elderly is 40%
- may lead to nutritional deficiencies and impaired detection of hazards
4. Age related changes in Touch
- response to painful stimuli is diminished with aging
- pressure touch thresholds on fingers and toes diminish
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% to expensive 15% adverse effects 15% forgot to take 4% need more 2% misunderstood
- those patients who were intentionally noncompliant were:
- more likely to use ³ 2 prescription medications
- more likely to have medications prescribed by ³ 2 prescribers
- compliance aids were useful primarily when patients had difficulty remembering to take medication
2. 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.
3. Hoarding and Sharing of Medications
4. Ways to improve medication compliance
- minimizing the number of medicines
- simplify medication regimens - chronic medications dosed at most twice daily
- increase the user’s knowledge- clear, simple repeated explanation of medication usage
- compliance aids- large legible labels, easy-to-remove vial tops, weekly pill boxes, etc.
- develop a standard system of promoting compliance
Increase compliance Patient's belief that disease is serious Good communication by physician about purpose of medicine Drug calendars and reminder cards Blister-pack packaging of drugs Multicompartment pill boxes Compliance counseling Decrease compliance Multiple drug therapy Complicated drug regimen Long duration of therapy Patient's concern that drug will cause toxicity Patient's belief that drug is unnecessary Cognitive impairment Child-proof pill containers Do not affect compliance Age Patient's sex Ethnicity Educational level Severity of disease Efficacy or toxicity Drug costs(?)
- the use of multiple prescription and OTC medication (Healthy People 200, 1990.)
- the prescription, administration, or use of more medications than are clinically indicated
- when a medical drug regimen contains at least one unnecessary medication
- the concomitant use of ³ 5 medications
Typical reasons for polypharmacy
- multiple prescribers
- prescribing practices
- multiple pharmacies
- lack of a regular, comprehensive medication review
- patients’ belief that they need a pill for every illness
- lack of patient education by a health care provider or lack of patient knowledge
- health care practitioner education ineffective
Methods for preventing polypharmacy
- patient education - patient tailored
- educate physician, pharmacist, and other health care providers
- improve physician prescribing - through both regulatory and non-regulatory means
- 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
Prescribing Guidelines to follow
- Is the drug necessary?
- Assess the benefit to risk ratio
- Attempt to make an accurate diagnosis before treatment
- Consider and implement all nondrug alternative
- Use caution when prescribing for a person who indicates that all previous drugs have failed
- Take a comprehensive medication history
- Educate and inform patient’s regarding their drug therapy
- Communicate with other prescribers and health providers
- Avoid treating adverse drug effects with concomitant medication
- Try to prescribe a drug that will treat more than one condition
- Avoid combination products
- Screen for drug-drug and drug-disease interactions
- Keep the medication regimen simple
- Limit the use of PRN medications
- Consider all new medications as a therapeutic trial, re-evaluate therapy continuously
Monitoring Guidelines to follow
- Assess if the drug is producing a therapeutic goal
- Determine if the drug is still needed, do not be afraid to stop medication with no or unclear indications
- Determine if the drug is producing any adverse effects
- Assess patients’ complaints or symptoms
- 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:
- Patient’s name
- Physician name and phone number
- Medication name (both Brand dispensed and chemical name0
- Indication
- How the medication works
- Interaction warnings
- Dosage form
- Dose
- Frequency and times
- Duration and refill
- Date of issue and expiration date
- common adverse effects
- 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)
- multiple medication use
- multiple effects of drugs
- physiological changes in drug disposition (due to age and disease)
- misuse of medication
Methods of Preventing/Minimizing Adverse Drug Reactions
Limit the number of drugs taken (before a drug is prescribed, ask yourself the following:)
- Is this the most effective drug for the disease or condition being treated?
- Is the dose appropriate given the patient’s age, renal, and hepatic function?
- Is the patient allergic to the drug or similar chemical
- Is the patient already taking a drug with pharmacological properties that would duplicate or antagonize the new agent/
- Will the addition of the new agent increase the complexity of the patient’s medication regimen such that compliance will be compromised?
- Does the patient have another disease that would contradict the use of the drug?
- Does the patient understand why the drug is being prescribed and how to take the medicine?
- 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:
- Is the drug still needed?
- Is the patient still responding to the regimen?
- Is the patient using the drug appropriately with regard to dosing or administration?
- Is there a relationship between drugs in the patients regimen and signs or symptoms observed?
- Activities of Daily Living (ADL’s)
- Cognitive impairment
- Drug-disease interactions:
- increased prevalence of disease in the older person
- difficulty distinguishing subtle reactions from the effects of disease (confounding)
- Drug-drug interactions:
- pharmacokinetic interactions causing differences in drug disposition
- pharmacodynamic interactions causing differences in drug effect
- 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)
- 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
- Antiarrhyhtmic 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
- Antiparkinsonian drugs
- levodopa clearance is reduced in older persons
- increased susceptibility to postural hypotension and confusion
- 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
- Anticoagulants
- commonly used in older patients because of high incidence of atrial fibrillation
- sensitivity to anticoagulant effect may increase with age
- recent studies have 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
- 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
- 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 NBSAID (salicylates, oxaprozin, naproxen) in older patients
Selected References
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