Understanding Geriatric Pharmacology

GERIATRICS
Derese C, B.Pharm,MSc.
1
May,2023

LEARNING OBJECTIVES
 Discuss aspects of aging epidemiology.
 Describe age-related changes in physiology,
especially as they might affect drug
pharmacokinetics.
 List drugs with increased or decreased
pharmacodynamic sensitivity with age.
 Discuss differences in diseases and
syndromes in geriatrics.
 List the types of drug-related problems in older
2

INTRODUCTION
 Pharmacotherapy for older adults can cure or palliate
disease as well as enhance health-related quality of life
(HRQOL).
 HRQOL considerations for older adults include focusing
on improvements in
physical functioning (e.g., activities of daily living),
psychological functioning (e.g., cognition, depression),
social functioning (e.g., social activities, support systems),
and
overall health (e.g., general health perception).
 Despite the benefits of pharmacotherapy, HRQOLcan
be compromised by drug-related problems.
3

EPIDEMIOLOGY OF AGING
 The demographics and health characteristics of persons
aged 65 to 74 years are different from those of persons 85
years of age and older, as are those of persons who are
institutionalized compared with those living in the
community.
 In 2011, the first baby boomers are turning 65 years old;
this will mark a rapid increase in the older population in
the years between 2010 and 2030.
 By 2030, the older population is projected to almost
double in size, resulting in one in five (20%) Americans
older than 65 years.
 This 20% projection for persons aged 65 years and older
will remain relatively stable through 2050. However, the
proportion of the oldest old (>85 years) will continue to
grow. 4

EPIDEMIOLOGY OF AGING….CON’T
 The decline in early death and the better health of older
adults arise from a variety of reasons:
(a) public health measures affecting all age groups (e.g.,
immunizations, prenatal care),
(b) advances in medical technology,
(c) promotion of a healthy lifestyle, and
(d) improvements in living conditions.
 An important factor for healthy aging is regular physical
activity, which has many positive health benefits,
including
disease reduction (e.g., cardiovascular disease),
weight maintenance, and
reduction in physical disability. 5

EPIDEMIOLOGY OF AGING….CON’T(1)
 An important goal in the care of older adults is allowing
them to maintain independence and avoid the need for
institutionalization for as long as possible.
 Functional loss or disability often is a final common
pathway of many clinical problems in older persons,
especially among those older than 75 years.
 Usual definitions of disability include limitations of
activities of daily living (ADLs), instrumental activities
of daily living( IADLs), or significant mobility problems.
 Disability and limitations in physical function increase
with increasing age and are higher in institutionalized
older persons.
6

 Chronic diseases or impairments, such as heart disease,
stroke, and diabetes, are major causes of disability in
older adults.
 An estimated 80% of older adults have at least one
chronic health condition, and more than half have at least
two concomitant conditions.
 Many chronic conditions can be prevented or improved
with behavioral modification, such as diet and physical
activity.
 The prevalence of select common conditions in 2005 to
2006 included hypertension (53%), arthritis (50%), heart
disease (31%), any cancer (21%), diabetes (18%),asthma
(11%), chronic bronchitis/emphysema (10%), and stroke7
(9%).

 Sensory impairments are common in older adults and
pose challenges for maintaining functional independence
and interactions with healthcare providers.
 Chronic diseases are the primary cause of death in older
adults.
 Some important trends have emerged over the past two
decades.
the death rates for heart disease and stroke have decreased.
 secondary to the gains made in the prevention and
treatment of these diseases.
death secondary to Alzheimer disease has increased rapidly
in recent years.
 results from improvements in the diagnosis and awareness
of Alzheimer disease in the medical community
8

Table 1. reviews some common physiologic changes associated
with aging, with an emphasis on those changes that can affect
pharmacotherapy.
TABLE 1-1 .Physiologic Changes with Aging
Organ System Manifestation
Body composition ↓Total body water
↓Lean body mass
↓Body fat
↔or↓ Serum albumin
↑α 1 -Acid glycoprotein (↔ or ↑by several disease
states)
Cardiovascular ↓Myocardial sensitivity to β-adrenergic stimulation
↓Baroreceptor activity
↓ Cardiac output
↑ Total peripheral resistance
Central nervous
system
↓ Weight and volume of the brain
Alterations in several aspects of cognition
Endocrine Thyroid gland atrophies with age
Increased incidence of diabetes mellitus, thyroid9
disease
Menopause

10
TABLE 1-1 Physiologic Changes with Aging…..Con’t(1)
Gastrointestinal ↑Gastric pH
↓Gastrointestinal blood flow
Delayed gastric emptying
Slowed intestinal transit
Genitourinary Atrophy of the vagina because of decreased estrogen
Prostatic hypertrophy because of androgenic
hormonal changes
Age-related changes may predispose to incontinence
Immune ↓Cell-mediated immunity
Liver ↓Hepatic size
↓Hepatic blood flow
Oral Altered dentition
↑Ability to taste sweetness, sourness, bitterness
Pulmonary ↓Respiratory muscle strength
↓Chest wall compliance
↓Total alveolar surface
↓Vital capacity
↓Maximal breathing capacity

TABLE 1-1 Physiologic Changes with Aging……Con’t(2)
Renal ↓Glomerular filtration rate
↓Renal blood flow
↓Filtration fraction
↓Tubular secretory function
↓ Renal mass
Sensory ↓Accommodation of the lens of the eye, causing
farsightedness
Presbycusis (loss of auditory acuity)
↓Conduction velocity
Skeletal Loss of skeletal bone mass (osteopenia)
Skin/hair Skin dryness, wrinkling, changes in pigmentation,
epithelial thinning, loss of dermal thickness
↓Number of hair follicles 11
↓Number of melanocytes in hair bulbs

PHYSIOLOGIC CHANGES WITH AGING
 Age-associated physiologic changes may cause
reductions in functional reserve capacity (i.e., ability
to respond to physiologic challenges or stresses) and
the ability to preserve homeostasis,
thus making the elderly susceptible to decompensation
in stressful situations.
 To deal with physiologic challenges or stresses, older
individuals may require up to 95% of their remaining
reserve capacity.
The cardiovascular, musculoskeletal, and central nervous
systems appear to be most affected.
Examples of homeostatic mechanisms that may become
impaired include postural or gait stability, orthostatic
blood pressure responses, thermoregulation, cognitive
reserve, and bowel and bladder function.
12

TABLE 1-2. Age-Related Changes in Drug Pharmacokinetics
Pharmacokinetic Phase Pharmacokinetic Parameters
Gastrointestinal
absorption
Unchanged passive diffusion and no change
in bioavailability for most drugs
↓Active transport and bioavailability for some
drugs
↓ First-pass extraction and bioavailability for
some drugs
Distribution ↓ Volume of distribution and plasma
concentration of water-soluble drugs
↑Volume of distribution and terminal disposition
half-life (t1/2) for fat-soluble drugs
↑or ↓Free fraction of highly plasma protein-
bound drugs
Hepatic metabolism ↓Clearance and t1/2 for some oxidatively
metabolized drugs
↓Clearance and t1/2 for drugs with high hepatic
extraction ratios
Renal excretion ↓Clearance and t1/2 for renally eliminated drugs
and active metabolites

ALTERED PHARMACOKINETICS
 Absorption
Fortunately, most drugs are absorbed via passive
diffusion, and age-related physiologic changes appear
to have little influence on drug bioavailability.
A few drugs require active transport for absorption,
so their bioavailability may be reduced (e.g., calcium
in the setting of hypochlorhydria).
However, there is evidence for a decreased first-pass
effect on hepatic and/or gut wall metabolism that
results in increased bioavailability and higher
plasma concentrations of drugs such as
propranolol and morphine.
Increased drug bioavailability also may be seen with
the concurrent ingestion of grapefruit juice. 14

ALTERED PHARMACOKINETICS….CON’T(1)
Distribution
 The distribution of medications in the body depends on
factors such as blood flow, plasma protein binding, and
body composition, each of which may be altered with age.
For example, the volume of distribution ofwater-soluble
drugs is decreased, whereas lipophilic drugs exhibit an
increased volume of distribution.
 Changes in the volume of distribution can have a direct
impact on the amount of medication that must be given as
a loading dose.
 The elderly may also exhibit differences in the
distribution of drugs to their sites of action.
For example, for an immunosuppressant that act with T-
lymphocytes, the elderly had a mean 44% increase in the
intracellular (T-lymphocyte)-to-whole blood concentration ratio
of cyclosporine, compared with younger patients.

ALTERED PHARMACOKINETICS…..CON’T(1)
Distribution…..
 P-glycoprotein, a member of the multidrug resistant
(MDR)-associated protein family of efflux transporters,
influences the transport of drugs across the blood—brain
barrier.
 The two major plasma proteins to which medications can
bind are albumin and α1-acid glycoprotein, and
concentrations of these proteins may change with
concurrent pathologies seen with increasing age.
For acidic drugs such as naproxen, phenytoin, tolbutamide, and
warfarin, decreased serum albumin may lead to an increase in
free fraction.
An increase in α1-acid glycoprotein induced by burns, cancer,
inflammatory disease, or trauma may lead to a decreased free
fraction of basic drugs such as lidocaine, propranolol, quinidine,
and imipramine.

Aging Effect Vd Effect Examples
 body water  Vd for
hydrophilic
drugs
ethanol, lithium
 lean body mass  Vd for for
drugs that bind
to muscle
digoxin
 fat stores  Vd for
lipophilic drugs
diazepam, trazodone
 plasma protein
(albumin)
 % of unbound
or free drug
(active)
diazepam, valproic
acid, phenytoin,
warfarin

 Metabolism
Decreased phase I metabolism (e.g., hydroxylation,
dealkylation) producing decreased drug clearance and
increased terminal disposition half-life (t1/2) has been
reported in the elderly for medications such as diazepam,
piroxicam, theophylline, and quinidine.
Phase II metabolism (e.g., glucuronidation, acetylation) of
medications such as lorazepam and oxazepam appears to be
relatively unaffected by advancing age.
Hepatic enzyme induction (e.g., by rifampin, phenytoin) or
inhibition (e.g., by fluoroquinolone and macrolide
antimicrobials, cimetidine) does not appear to be affected1b7y
the aging process.

 Metabolism…….Con’t(1)
Age-related decreases in hepatic blood flow can
decrease significantly the metabolism of drugs with
high hepatic extraction ratios, such as imipramine,
lidocaine, morphine, and propranolol.
The effect of aging on polymorphic drug metabolism
has not been wellstudied.
Advancing age reduces the metabolism of CYP450
isozyme 2D6 substrates by approximately 20%. 18

 Metabolism…….Con’t(2)
Other available data suggest that advancing age has no
significant effect on acetylation or on CYP450 isozymes 2C9-
or 3A4-mediated metabolism.
A single-point blood sampling method for evaluating
CYP450 isoenzyme CYP3A4 activity in older adults has
been described.
A number of potential confounding factors, including race,
gender, frailty, smoking, diet, and drug—drug interactions,
may significantly affect hepatic metabolism in older adults.
19

 Elimination
The effect of aging on the kidney
↓Kidney size
↓Renal blood flow
↓Number of functioning nephrons
renal tubular secretion may not decline in proportion
to other renal processes
►Results lower glomerular filtration rate
 The estimation of creatinine clearance, although not
entirely accurate in individual patients, can serve as a
useful screening approximation.
20

 Elimination
In the future, use of another protein, cystatin C, a
low— molecular-mass protein that is produced by all
nucleated cells, is freely filtered at the glomerulus, and
is not secreted by the renal tubules, may prove to be
superior to the use of creatinine.
This could be the case especially with coexisting
conditions such as cachexia, sedentary lifestyle,
malnutrition, and hepatic disease.
Medications whose excretion is primarily renal and for
which there is evidence of age-related reduction in renal
and total body clearance include
amantadine, aminoglycosides, atenolol, captopril,
cimetidine, digoxin, lithium, and vancomycin. 21

ALTERED PHARMACODYNAMICS
 There is some evidence of altered drug response or
"sensitivity" in older adults.
 Four possible mechanisms have been suggested:
(a) changes in receptor numbers,
(b) changes in receptor affinity,
(c) postreceptor alterations, and
(d) age-related impairment of homeostatic mechanisms.
 For example, muscarinic, parathyroid hormone, β-
adrenergic, α1-adrenergic, and μ-opioid receptors exhibit
reduced density with increasing age.
 Older adults demonstrate an enhanced responsiveness to
anticoagulants such as warfarin and heparin as well as to
thrombolytic therapy
 In contrast, older adults exhibit decreased responsiveness
to certain drugs (e.g., β-agonists/antagonists). 22

CLINICAL GERIATRICS
 Maintenance of independence and prevention of
disability are primary goals in the clinical care of
persons 65 years of age and older.
 To achieve these goals, it is necessary that all healthcare
professionals understand the concept of functional status.
 Functional status is a proxy measure of a patient's
ability to live independently and can be determined in
part by inquiring about an older person's ability to
perform specific tasks.
Examples :-common problems in older adults include
Parkinson disease, falls, hip fractures, benign prostatic
hypertrophy, dementia, glaucoma, postherpetic
neuralgia, and tuberculosis. 23

The Is of Geriatrics: Common Problems in Older Adults
Immobility
Instability
Isolation
Intellectual impairment
Incontinence
Impotence
Infection
Immunodeficiency
Inanition (malnutrition)
 Insomnia
Impaction
Iatrogenesis
Impaired senses

TABLE 1-3. Atypical Disease Presentation in Older Adults
Disease Presentation
Acute myocardial
infarction
Only ~ 50% present with chest pain. In general, older
adults present with weakness, confusion, syncope, and
abdominal pain; however, electrocardiographic findings
are similar to those in younger patients.
Congestive heart
failure
Instead of dyspnea, the older patient may present with
hypoxic symptoms, lethargy, restlessness, and confusion.
Gastrointestinal
bleed
Although the mortality rate is 10%, presenting symptoms
are nonspecific, ranging from altered mental status to
syncope with hemodynamic collapse. Abdominal pain
often is absent.
Upper respiratory
infection
Older patients typically present with lethargy,confusion,
anorexia, and decompensation of a preexisting medical
condition. Fever, chills, and a productive cough may or
may not be present.
Urinary tract
infection
Dysuria, fever, and flank pain may be absent. More
commonly, older adults present with incontinence,
confusion, abdominal pain, nausea/vomiting, and
azotemia.

DRUG-RELATED PROBLEMS IN OLDER ADULTS
 Three important and potentially preventable negative
outcomes caused by drug-related problems that can occur
in older adults are
adverse drug withdrawal events (ADWEs), which are
clinically significant sets of symptoms or signs caused by the
removal of a drug;
therapeutic failure (inadequate or inappropriate drug therap
and not related to the natural progression of disease); and
y
adverse drug reactions (ADRs), defined as reactions that are
noxious and unintended and occur at dosages normally used
in humans for prophylaxis, diagnosis, or therapy.
 ADRs and other drug-related problems are major threats
of healthcare dollars per year.
to the HRQOL of outpatient elders and account for billio25ns

RISK FACTORS OF DRUG-RELATED PROBLEMS IN
OLDER ADULTS
Risk Factors
 Polypharmacy can be defined as either the concomitant us
of multiple drugs or the administration of more
medications than are indicated clinically.
e
 Community-based surveys reveal that older adults take an
average of two to ten prescription and nonprescription
medications each day.
 Drug-use studies that defined polypharmacy as use of one
or more unnecessary medications showed that
polypharmacy occurs in 55% to 59% of older outpatients.
 Polypharmacy also is problematic for older adults because
it may increase the risk of geriatric syndromes (e.g., falls,
cognitive impairment), diminished functional status, and
healthcare costs.

OLDER ADULTS
Risk Factors……
 Polypharmacy also is problematic for older adults
because it may increase the risk of geriatric syndromes
(e.g., falls, cognitive impairment), diminished functional
status, and healthcare costs.
 Causes of Polypharmacy
Aging population „
Complex drug therapies „
Multiple prescribers „
Multiple pharmacies „
Psychosocial factors „
Adverse drug reactions (prescribing cascade)

OLDER ADULTS ……CON’T(1)
 Inappropriate prescribing can be defined as prescribing
medications outside the bounds of accepted medical
standards.
 Studies using explicit drug-use review criteria have found
that between 15% and 24% of community-dwelling older
adults take one or more medications that have a dose,
duration, duplication, or drug-interaction problem.
 Alternatively, inappropriate prescribing can be defined as
prescribing drugs whose use should be avoided because
their risk outweighs their potential benefit.

OLDER ADULTS …….CON’T(2)
Underuse
 It is defined as the omission of drug therapy that is
indicated for treatment or prevention of a disease or
condition.
 The Assessing the Care of Vulnerable Elders (ACOVE)
criteria includes measures for underuse involving
bisphosphonates, anticoagulant/antiplatelet therapy,
angiotensin-converting enzyme inhibitors, and beta-
blockers, highlighting the need for approaches for
improvement.
 Underuse may have an important relationship with
negative health outcomes in older adults, including
functional disability, death, and health services use.

OLDER ADULTS …….CON’T(3)
Medication Nonadherence
 Nonadherence involves patient-related factors, condition-
related factors, therapy-related factors, as well as health
system and social factors.
 In addition, nonadherence could be defined more than one
way, including not filling the prescription, stopping use
of the medication before the entire supply is consumed,
or taking more or less of the medication than stated by
the label.
 Older patients may not adhere to their regimens because o
f
possible adverse effects, an inability to read product labels,
or a lack of full understanding of information about the
prescribed medication.

PROVISION OF COMPREHENSIVE GERIATRIC ASSESSMEN T
 History Taking
Several difficulties may occur while taking medication
histories from older adults. They include
 (a) communication problems (impaired hearing and vision),
 (b) underreporting (e.g., health beliefs, cognitive
impairment),
 (c) reporting of vague or nonspecific symptoms (altered
presentation),
 (d) coexistence of multiple diseases and/or use ofmultiple
medications,
 (e) reliance on a caregiver for the history, and
 (f) lack of medical records to confirm findings.
find value in collecting this vital medication history information.
Despite these potential difficulties, health professionals shou3l1d

COMPREHENSIVE GERIATRIC ASSESSMENT…..CON’T(1)
 Assessing and Monitoring Drug Therapy
The first step in assessing medication appropriateness is t
match the medical problem list with the drug list.
o
If a drug does not have a match with the problem list, or
the drug is not effective or the risks outweigh the benefits
or there is evidence of therapeutic duplication (i.e., two
drugs from the same class), the drug may not be needed.
Table 1–4. lists laboratory monitoring recommendations
for medications used in long-term care facilities and
recommended monitoring parameters.
32

TABLE 1-4. Centers for Medicare and Medicaid Services
Guidelines for Monitoring Medication Use
Monitoring
Interval (in mo)
Drug Monitoring
Acetaminophen (>4 g/d) Hepatic function tests *
Amiodarone Hepatic function tests, thyroid
stimulating hormone level
6
Antiepileptic agents
(carbamazepine,
phenobarbital, phenytoin,
primidone, valproate)
Drug levels 3–6
Angiotensin-converting
enzyme inhibitors or
Angiotensin I receptor
blockers
Potassium levels 6
Antipsychotic agents Extrapyramidal side effects, fasting 6
serum glucose, serum lipid panel
Appetite stimulants Weight, appetite *
Digoxin
Diuretic
Erythropoiesis stimulants
Serum blood urea nitrogen, 6
creatinine, trough drug level
Serum sodium and potassium levels 3
Blood pressure, iron and ferritin 1
levels, complete blood count

TABLE 1-4. Centers for Medicare and Medicaid Services
Guidelines for Monitoring Medication Use…..Con’t(1)
Drug Monitoring Monitoring Interval (in
mo)
Fibrates
Hypoglycemic agents
glycated hemoglobin level
Hepatic function test, 6
complete blood count
Fasting serum glucose level or 6
Iron
Lithium
Iron and ferritin levels, *
complete blood count
Trough serum drug levels 3
Metformin Serum blood urea nitrogen,
creatinine levels
Niacin Blood sugar levels, hepatic 6
function tests
Statins Hepatic function tests 6
Theophylline Trough serum drug levels 3
Thyroid replacement Thyroid stimulating hormone 6
level on tests
Warfarin Prothrombin
time/international normalized
ratio
1

 Documenting Problems and Formulating a
Therapeutic Plan
The clinician must document the problems that have
been detected, develop a therapeutic plan to resolve
them, and establish reasonable therapeutic end points.
Remember that what may be a reasonable end point for
a 40-year-old patient may not be as reasonable for an
80-year-old patient.
A conceptual model is helpful in improving rationale
prescribing.
This model takes into account factors such as remaining
life expectancy, time until benefit, treatment target, and
goals of care to help determine whether certain
medications should be prescribed or continued.
35

 Consulting the Physician Regarding Problems and
Concerns
In most cases, the pharmacist or other healthcare
professional should contact a patient's physician
regarding problems and concerns that have been
detected and documented.
 Counseling and Adherence Aids
Before dispensing medication, consider some general
factors that may enhance adherence by older adults,
such as
 modifying medication schedules to fit patients' lifestyles,
 prescribing generic agents to reduce costs, and
 using easy-to-open bottles, easy-to-swallow dosage forms,
and
 larger type on direction and auxiliary labels.
36

 Counseling and Adherence Aids……
The WHO suggests clinicians consider five dimensions
when assessing medication adherence:
 social/economic factors (e.g., cultural beliefs),
 provider—patient/healthcare system factors (e.g.,
provider—patient relationship),
 condition-related factors (e.g., chronic conditions),
 therapy-related factors (e.g., regimen complexity), and
 patient-related factors (e.g., visual or hearing impairment).
To improve the likelihood of adherence, consider the use
of adherence-enhancing aids (e.g., special packaging, a
medication record, a drug calendar, medication boxes,
magnification for insulin syringes, dose-measuring
devices, and spacers for metered-dose inhalers).
37

 Documenting Interventions and Monitoring Patient
Progress
All interventions must be documented, and the steps
outlined herein must be repeated over time with older
adult patients, especially when patients have made care
transitions .
During follow-up contacts, minimum inquiry should
include asking patients whether they have any questions
or concerns regarding medicines and determining whether
the therapeutic end points previously established have
been achieved.
To assess potential ADRs, ask patients whether they
currently or recently have experienced any side effects,
unwanted reactions, or other problems with their
medications.
38

 Targeting High-Risk Older Adults
In busy practices, the approach outlined may not be
feasible for every patient.
Therefore, practitioners may consider targeting these
activities to patients at high risk for developing drug-
related problems.
Geriatric experts have identified risk factors for
preventable ADRs in older adult nursing home patients.
These include the following medication-related factors:
 (a) polypharmacy (i.e., use of seven or more medications or
more than three cardiac medications), and
 (b) taking specific high-risk drugs (e.g., anticoagulant,
antidepressant, antiinfective, antipsychotic,
anticonvulsant, opioid analgesic, sedative/hypnotic, skel3e9tal
muscle relaxant).

 Targeting High-Risk Older Adults….
Other unique risk factors include
 (a) medication-related issues (i.e., use ofanticholinergics,
benzodiazepines, chlorpropamide, corticosteroids,
nonsteroidal antiinflammatory drugs),
 (b) certain patient characteristics (e.g., multiple
comorbidities, multiple prescribers, age 85 years,
dementia, regular use of alcohol, decreasedrenal
function),
 (c) use of drugs with narrow therapeutic ranges (e.g.,
lithium, theophylline),
 (d) history of an ADR, and
 (e) recent hospitalization.
40

Medication Appropriateness Index
Questions to Ask About Each Individual Medication
1. Is there an indication for the medication?
2. Is the medication effective for the condition?
3. Is the dosage correct?
4
. Are the directions correct?
5. Are the directions practical?
6. Are there clinically significant drug–drug interactions?
7. Are there clinically significant drug–disease or drug–condition
interactions?
8. Is there unnecessary duplication with other medication(s)?
9. Is the duration of therapy acceptable?
10. Is this medication the least expensive alternative compared with
others of equal utility?

CONCLUSION
 The number of people older than 65 years is growing
around the world, and individuals older than 85 years
are the fastest growing segment.
 A number of physiologic changes associated with age,
especially hepatic metabolism and renal excretion, affect
the pharmacokinetics and pharmacodynamicsof drugs.
 Improving and maintaining the patient's functional
status and managing the patient's comorbidities are
hallmarks of clinical geriatrics.
 Certain medical conditions are restricted to older adults,
and drug-related problems represent a major concern for
this group.
41

Understanding Geriatric Pharmacology

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