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Transcript
Stephanie M. Crist, Pharm.D., BCACP, BCGP
Assistant Professor of Pharmacy Practice
Clinical Pharmacist Specialist, Geriatrics
St. Louis College of Pharmacy
March 31, 2017
1.
Learners will understand key aspects of pharmacokinetic and
pharmacodynamic changes in the older adult.
2.
Learners will apply key principles to case examples for
appropriate geriatric prescribing practices.
Preschool or Early
Childhood: 3-6 years
Young Old: 65-74
years
Premature: gestation
<36 weeks
Infant (baby): 1-12
months
Adolescence: 13-18 years
Old Old: ≥85 years
Middle Old: 75-84 years
Middle Childhood: 6-12
Years
Neonate: first postnatal
month of life
Toddler: 1-3 years
Adult: >18 years
Nutritional need
and changes
Pharmacokinetic
changes
Use of evidencebased medicine (EBM)
Counseling and
Education
Pharmacodynamic
changes
Timing of Effect
Lifestyle/prevention
Ethical issues
Severity of condition
Morbidity and Mortality
Patient/Care Partner
involvement
Pharmacokinetic (PK)
Pharmacodynamic (PD)
 How the body affects the
 How the drug affects the
drug
body
 Absorption
 Drug concentration at the site
 Distribution
of action
 Receptor-binding interaction
and capacity
 Metabolism
 Elimination
 ↓ gastric emptying

Longer time to take effect or little
to no absorption
 ↓ parietal cell function

Vitamin B12, calcium, and iron

 Changes in skin turgor
Clinical effect may be small due
to most drugs being absorbed
passively in the small intestine
 AVOID fentanyl (Duragesic,
Actiq®) patches, if possible,
or stay at lowest dose
possible
 Smaller volume of
 ↓ total body water
 ↑ total body fat
 ↓ muscle mass
distribution  higher
concentrations of watersoluble drugs (e.g. ethanol,
digoxin)
 Larger volumes of
distribution of lipophilic drugs
(e.g. diazepam)
 Increase in unbound
 ↓ albumin levels
concentrations of certain
drugs that are more proteinbound (e.g. warfarin,
phenytoin)
 Phase 1 (oxidation,
clearance, half-life) and/or
Phase 2 (conjugation)
affected
 Occurs with age and
possibly with decreased
cardiac output
 Care should be taken
 ↓ hepatic blood flow
 ↓ hepatic mass
when prescribing meds
with narrow therapeutic
windows and pass
through the liver (e.g.
warfarin, theophylline,
phenytoin)
Liver function tests (AST and ALT) do NOT assess the effectiveness
of drug metabolism in the older adult accurately
 Results in:

↓ renal elimination
 Prolonged half-life of drug
 Higher concentrations of drug
metabolites
 As muscle mass decreases,
the serum creatinine can
remain “normal” despite
significant glomerular filtration
rate
 MUST adjust drugs that are
excreted by the kidneys
(e.g. digoxin, gentamycin,
lithium, H2RAs, such as
famotidine (Pepcid)), just to
name a few
 Absorption:
 ↓ gastric emptying
 ↓ parietal cell function
 Distribution:
 ↓ total body water
 ↑ total body fat
 ↓ muscle mass
 ↓ albumin levels
 Metabolism:
 Phase 1 (oxidation, clearance, half-life) and/or Phase 2 (conjugation)
affected
 ↓ hepatic blood flow
 ↓ hepatic mass
 Elimination:
 ↓ renal elimination
 CC: “I’m fine! I just tripped and fell.”
 HPI: Patient is an 82 year old male who resides in a local senior
apartment complex. He is brought in to the emergency
department via ambulance to be evaluated for a fall and
confusion. He recently (10 days ago) completed a course of
antibiotics for a urinary tract infection.
 PMH: Cataracts, COPD, GERD, HTN, CKD, STEMI (2 years
ago), Osteoarthritis
 Allergies: NKDA
 SH: Married 55 years; widowed; has three adult children; retired high
school teacher; (+) tobacco use in past (60 pack-year history), quit in
1999; (+) etoh use in past but not current; (-) illicit drug use; (-)
caffeine use
 FH: Cancer, breast (sister, living); HTN, stroke (mother, deceased
from stroke, 82); DM (father, deceased from MI, 74)
 Vaccinations: influenza (10/2016); PPSV23 (10/2010); tetanus
(10/2009)
 Albuterol 0.09 mg/actuation, inhale two puffs every four hours as needed for shortness of breath
 Advair (fluticasone/salmeterol) diskus 250/50 mcg, inhale one puff every 12 hours
 Spiriva (tiotropium) Handihaler 18 mcg taken inhale two puffs once daily
 Aspirin 81 mg by mouth daily
 Cholecalciferol 2000 units by mouth daily
 Clopidogrel 75 mg by mouth daily
 Clonidine 0.1 mg by mouth three times daily
 Hydrochlorothiazide 25 mg by mouth daily
 Metoprolol tartrate 50 mg by mouth twice daily
 Omeprazole 20 mg by mouth twice daily
 Ranitidine 150 mg by mouth twice daily
 Senna 8.6 mg by mouth daily at bedtime as needed for constipation
 Tramadol 50 mg every four hours as needed for pain
 Acetaminophen 500 mg four times by mouth daily as needed for pain
 Labs: (3/23/17)
Na 141 mEq/L
K 3.8 mEq/L
Cl 106 mEq/L
CO2 22 mEq/L
Gluc 112 mg/dL
BUN 16 mg/dL
Cr 1.1 mg/dL
Ca 9.1 mg/dL
WBC 7.5 K/mm3
Hgb 11.9 g/dL
Hct 37.6%
Plt 191 K/mm3
MCV 85 fL
Alb 3.8 g/dL
T. protein 6.5 TSH 0.827 mIU/L
LDL 81 mg/dL
TG 172 mg/dL
T. chol 190 mg/dL
Mg 1.6 mg/dL
HgA1c 6.2%
25-hydroxyvitamin D 28.7 ng/mL
HDL 42 mg/dL
UA: cloudy urine, negative for nitrite and leukocyte esterase with no bacteria or WBC
 Vitals: (3/23/17)
Ht 68 in
Wt 80.5 kg
BP 134/70 mmHg
IBW 68.4 kg BMI 26.9
P 87 bpm
3-month BP avg 136/72 mmHg
RR 18
T 97.7F
P avg 75 bpm
 What is the clinical difference between GFR and CrCl?
 GFR = process by which the kidneys filter blood to remove excess
fluid and waste products
 Calculated by using the MDRD (Modification of Diet in Renal Disease)
 Does NOT account for body mass
 Differentiates based on race
 Utilization = overall function of kidney; stage level of kidney disease
 CrCl = renal clearance of the substance creatinine
 Calculated by using Cockcroft-Gault equation
 Dependent on age, weight, and sex of the patient
 Affected by protein intake and muscle mass
 Utilization = dosing of medications
1. Adverse Drug Reactions (ADRs)
 5-28% of acute hospital visits within the older adult population
 Suggested that ADRs are the most common type of medication-related
problem in older adults living in nursing homes
 >95% of all ADRs are considered predictable and 50% are considered
preventable
2. Adverse Drug Withdrawal Events (ADWEs)
 Clinically significant sets of signs or symptoms caused by the REMOVAL
of a drug
3. Therapeutic Failure
 Inadequate or inappropriate drug therapy
 Not related to the natural progression of a disease
 Defined as the concomitant use of multiple drugs or the administration
of more medications than are indicated clinically
 Number of minimum medications?
 Usually between more than 3-8 medications would qualify as polypharmacy
 Common/increasing problem of the older adult due to more agents
available on the market and increased co-morbidities
 Can occur in as many as half of outpatient older adult patients
Complications of:
Steps to Avoid:
 ↑ medical expenses
 ↑ incidence of adverse drug events
 ↑ incidence of depression
 ↑ prescribing errors
 ↓ patient adherence
 ↓ social activity
 ↓ cognition
 Weigh benefit vs. risk
 Frequently review list of current
medications
 Simplify regimen
 Suspect a medication for new
symptoms
 Multiple providers and multiple
pharmacies OTC, herbal
products, dietary supplements
 Ask specifically about medications
in a review-of-systems (ROS)
fashion
 Defined as the wrong dose, duration, duplication, and/or drug-
interaction
 Risk outweighs potential benefit
 Avoid the prescribing cascade…
1.
Is there an indication for the drug?
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, drug-disease, and/or
drug-herbal interactions?
7.
Is there unnecessary duplication with other drugs?
8.
Is the duration of therapy acceptable?
9.
Is this drug the least expensive alternative compared to others of
equal utility?
Hanlon et al. J Clin Epidemiology. 1992;45(10):1045
Beers Criteria
 Initially published by Dr.
STOPP/START Criteria
 START criteria was first
Mark Beers, a geriatrician in
1991
published in 2007 and
STOPP in 2009 in Ireland
 Taken over by the American
 Recently updated in 2014
Geriatrics Society (last rev. in
2015)
Must weigh the risks versus the
benefits of all medications taken
by the older adult
(Version 2)
Consider the dose, duration, and
drug-drug, drug-disease, and
drug-herbal interactions before
making a recommendation to the
patient or provider
 Any new symptom should be considered an ADE until proven
otherwise
 A common occurrence, especially in older adults, is to treat an ADE
symptom(s) with another medication to treat the symptom
 Sometimes, this new drug addition can cause a new symptom, which can
again, trigger the addition of another medication; hence, the sequence of
events is known as the “prescribing cascade”
 Examples:
 NSAID users are more likely to be on more antihypertensives
 Metoclopramide (Reglan®) used to treat N/V can have ADRs that mimic
Parkinson disease  carbidopa/levodopa added
 Donepezil (Aricept®) to treat Alzheimer disease  neurogenic bladder is
confused for incontinence  bladder anticholinergic is added
 More medication increases the potential for ADEs (e.g. ADRs), drug
interactions, polypharmacy, nonadherence, cost
 Defined as the omission of an indicated drug
 Example: A diabetic patient with proteinuria on three antihypertensive
medications EXCEPT none of which is an ACEI/ARB which is
indicated
 Increases:
 ADEs
 Disease progression
 Emergency department visits
 Intelligent non-adherence: Doses altered based on the patient’s
perception of disease states/side effects (constipating medications
and diet)
 Cost-related non-adherence: Doses rationed/split/shared to reduce
cost
 Classic non-adherence: Doses forgotten, lost, or otherwise not taken
(not using pill organizer)
 Hyper non-adherence: Taking more of the medication than originally
prescribed (one is good so two must be better, right?; pain meds or
other meds of abuse)
 Increases with perception of being overmedicated, especially during
hospitalization or location of assistive prescribing
 Associated with preventable ADEs and hospital admissions
 Identify non-adherence (e.g. physical pill count, review refill history,
finding missing pills)
Drug / Drug Class
Effects on other Conditions
Acetylcholinesterase inhibitors Incontinence, diarrhea, paradoxical reactions
Alpha-blockers (non-selective) Syncope
Anticholinergics/Antimuscarincs Urinary retention, constipation, glaucoma,
dementia (neurogenic bladder)
Aspirin/NSAIDs GI bleed; CKD/HTN; ↓ effect of diuretic
(+) heart failure
= fluid retention; exacerbation
Benzodiazepines (especially long-acting) Dementia/falls
Bupropion Seizures
Calcium channel blockers Swelling/edema; constipation
Corticosteroids Diabetes
Opioids Constipation
Sedatives/Hypnotics Falls
Adapted from DiPiro, eTable 11-8
 Annual administration recommended in all adults throughout
lifetime
 Fluzone High Dose® (Sanofi Pasteur)
 Patients ≥65 years old eligible to receive
 Greater risk of hospitalization and death due to the flu
 Respond to vaccination with lower antibody titers to influenza hemagglutinin
compared to younger adults
 Contains 60µ of each vaccine antigen compared to the standard dose of 9µ
of each vaccine antigen
 Inactivated, trivalent, standard 0.5 mL intramuscular injection
*ANY product of the flu vaccine is better than NO vaccine annually
 Tdap: one lifetime dose, regardless of last Td administration
 Boostrix® (GlaxoSmithKline Biologicals) is only approved for older
adults
 Adacel® (Sanofi Pasteur) is approved for adults 11-64 years of age
 ACIP recommends the use of Boostrix® in the older adult; however, if
supply is not available or Adacel® is given instead, ACIP considers
this immunogenic and provides protection so no need to also give
Boostrix®
 Td: booster every 10 years recommended to be administered to
all adults throughout lifetime
 PPSV23 (Pneumovax®)
 One lifetime dose for all adults after the age of ≥65 years old
 Some patients may have received 1 or 2 doses of PPSV23 prior to the age of 65 based
on other health conditions (e.g. CKD, heart disease (CHF), chronic lung disease
(asthma, COPD), diabetes, chronic liver disease (including chronic alcoholism),
immunocompromising conditions
 Wait at least 5 years in between PPSV23 administrations
 If have received PPSV23, wait 12 months to administer PCV13
 If have NOT received PCV13, administer PCV13, then wait at least 8 weeks to
administer PPSV23 if immunocompromised, otherwise wait 12 months to administer
PPSV23
 PCV13 (Prevnar®)
 One lifetime dose for all adults after the age of ≥65 years old
 If never have received PPSV23, administer first
 If have received PPSV23, wait 12 months to administer
 If <65 years old, see CDC ACIP recommendations for list of conditions
 Never administer PCV13 and PPSV23 on the same day
 Live vaccine, subcutaneous injection
 All patients ≥60 years old who have had the chicken pox or
chicken pox vaccine
 May administer if the patient has already had shingles to
decrease likelihood of future flares; however, do NOT administer
during an active shingles flare
 Know how to recognize orthostatic hypotension
 Change ≥20 mmHg drop in SBP or change of ≥10 mmHg drop in DBP when
changing positions (lying to sitting or sitting to standing), or symptomatic upon
standing (dizzy, lightheaded, off-balance, falling)
 2014 ACC/AHA JNC 8 goals:
 Adults ≥60 years old, goal = <150/90 mmHg
 Caveat: if already treated with antihypertensive(s), treat BP to goal and SBP <140
mmHg and patient is tolerating well without ADRs or effect of quality of life, treatment
does not need to be adjusted
 If 18-69 years old with CKD, goal = <140/90 mmHg
 Initial or add-on treatment should include an ACEI or ARB to improve kidney outcomes
 No recommendations for patient aged ≥75 years; however, ACEI or ARB will most likely
be beneficial if BP can tolerate and use of a thiazide-like diuretic or CCB could also be
used
 Monitor serum Cr and K+ and reduce dose as necessary (“little is better than none”)
 Diagnostic criteria for CKD does NOT consider age-related decline in kidney function
 If ≥18 years old with DM, goal = <140/90 mmHg
 Endorsed by the ADA and AGS
 Fasting blood glucose goal:
 <150-130 mg/dL but not <100 consistently due to increased risk of hypoglycemic
events as this can lead to falls, decrease in quality of life, and associated ADRs
 Caution on consistently hyperglycemia due to infection rate, vision changes,
confusion, and frequent urination
 Post-prandial blood glucose goal:
 <200 mg/dL
 Hemoglobin A1c goal:
 <7.5-8% for those with life expectancy >5 years with comorbid conditions and
have had the DM for >10 years
 “Tight glycemic control” in the older adult is defined as <7.5% by AGS
 8-9% for those with life expectancy <5 years (typically this is in nursing
home/institutionalized patients)
 An A1c <6.5% linked to all-cause mortality and CV mortality, hypoglycemia, and
weight gain
 Avoid:
 Glyburide (Diabeta®) due to prolonged hypoglycemia
 Chlorpropamide (Diabinese®) due to long half-life and potential for causing SIADH
 Sliding scale insulin regimen, especially when treated in the outpatient setting
 Per American Geriatrics Society 2013 Update on Improving Care of Older
Adults with DM, NO longer recommends aspirin for primary prevention of
CVD, including patients with DM (rationale = insufficient evidence)
 Regardless of age, recommends aspirin 81 mg with DM and known CVD for
secondary prevention unless contraindicated (bleed risk, harms outweigh benefits),
on anticoagulation or life expectancy is poor
 Per US Preventative Service Task Force (USPSTF April 2016) recommendations:

81 mg daily is recommended for primary prevention:
 In any ADULTS 50-59 years with a 10-year ASCVD risk ≥10% (grade B)
 http://cvdrisk.nhlbi.nih.gov/calculator.asp
 Must have a life expectancy of at least 10 years
 Patient is willing to take aspirin for at least 10 years
 In any ADULTS 60-69 years with a 10-year ASCVD risk >10% (grade C)
 Must have a life expectancy of at least 10 years
 Patient is willing to take aspirin for at least 10 years
 Adults over the age of 70 years, evidence is insufficient (grade I), especially for primary
prevention, to assess the balance of benefits and harms for CV prevention and colorectal
cancer
Health Status
A1c* Goal (%)
Healthy (few
comorbidities, intact
cognition and
functional status)
<7.5
Complex/Intermediate
(multiple comorbidities
OR 2+ IADL
impairments or mild to
moderate cognitive
impairment)
<8
Very complex/poor
health (lives in a longterm care facility, endstage chronic illnesses
OR moderate to severe
cognitive impairment
or 2+ ADL
dependencies)
<8.5
Pre- and Postprandial Goal
Glucose
(mg/dL)
Pre: 90-130
Bedtime
Goal
Glucose
(mg/dL)
Blood
Pressure
Goal
(mmHg)
<140/90
Yes, unless
contraindicated or not
tolerated
Longer remaining life
expectancy
100-180
<140/90
Yes, unless
contraindicated or not
tolerated
Intermediate life
expectancy, high
treatment burden,
hypoglycemia
vulnerability, fall risk
110-200
<150/90
Consider likelihood of
benefit (secondary
prevention more than
primary prevention)
Limited remaining life
expectancy makes benefit
uncertain
Post: <200
Pre: 100-180
Rationale
90-150
Post: <180
Pre: 90-150
Statin Use
Post: <200
* “Tight glycemic control” in the older adult is defined as <7.5% by the American Geriatrics Society (AGS); an A1c <6.5% for targeted aggressive treatment in the older
adult has been linked to all-cause mortality and CV mortality, hypoglycemia, and weight gain; per American Diabetes Association (ADA), an A1c goal >8.5% are not
recommended as may expose patient to more frequent higher glucose values and acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar syndrome,
infection rate, confusion, vision changes, and poor wound healing
Adapted from Table 11.1 in American Diabetes Association. Older Adults. Sec. 11. Standards of Medical Care in Diabetes-2017
Diabetes Care 2017;40(Suppl. 1):S99-S104.
 Focus more on the functional status of the patient than on the
number of comorbidities
 At least 3 or presence of a single end-stage chronic illness
 Functional status = marker of overall health and quality of life as well as if
a patient can independently take care of oneself
 The number of comorbidities can affect functional status; therefore
multiple comorbidities increases the potential for a faster rate of decline in
a patient
 The level of control of ANY comorbidity can affect how aggressive a
patient may be treated
 Any change in status, reassessment of goals will be necessary
 Intact cognition = awareness to person, place, and time (AA&O x3);
no functional changes in memory/ability to think and rationalize,
make decisions for self
 If cognitive changes can be reversed, such as caused by medication(s) or
substance-induced, this counts as intact cognition
 2+
IADL (instrumental activities of daily living, more complex than ADLs) impairments* = patient
CANNOT perform, on a consistent basis, at least TWO OR MORE of the following:
Meal preparation (cannot
Shopping (cannot perform
Housework (cannot perform
cook for self)
basic grocery shopping (e.g.
forgets list of items to get or
buys inappropriate items that
does not need)
basic home maintenance (e.g.
cleaning, changing a lightbulb)
Laundry (cannot complete
Able to use phone
task of separating items, placing
in washer and dryer then folding
and putting away clean clothes
properly)
(answer a call or call someone,
even 911)
Managing/taking
medications (e.g. poor or
Transportation (cannot
Keeping track of finances (cannot pay bills on time,
drive self or manipulate public
transportation system safely)
complete taxes, managing funds/budget)
no adherence)
*NOT due access issues, such as not having money for food to cook, to shop, to pay bills, or for a car to drive;
really focusing on a change from what the patient has been able to do in the past; not due to a physical
impairment such as poor vision to drive a car
 2+
ADL (activities of daily living, more basic, simple abilities) impairments = patient CANNOT
perform, on a consistent basis, at least TWO OR MORE of the following:
Bathing (cannot take a
Dressing (cannot get
Grooming (cannot perform
shower or bath to clean oneself
(safely or correctly)
independently)
dressed or undressed properly
independently)
tasks such as brushing teeth,
shaving)
Toileting (cannot go to the
Transfer (cannot get self
Walking (cannot
bathroom by self safely or
correctly; loses ability to know
when to go to the bathroom)
from one place to the next, such
as out of bed to standing
position independently)
independently walk (does not
include use of an assistive
device, such as a walker) from
point A to point B)
Feeding (cannot eat food, drink liquid correctly, sufficiently, or at all independently)
These inabilities to perform tasks is a change from the patient’s normal functioning level. Usually, a person
will lose IADLs before they begin to lose ADLS; therefore that is why ADLs are listed; having the inability to
perform with IADLs and ADLs is NOT considered a normal part of aging
 Mild to moderate to severe cognitive impairment = early to middle
to end stages of dementia
 Click on the link to see examples from the Alzheimer’s Association:
http://www.alz.org/alzheimers_disease_stages_of_alzheimers.asp
 End-stage chronic illnesses = examples include on hemodialysis
for CKD, on hospice or palliative care measures, terminal cancer
diagnosis
 Long-term care (LTC) facility = examples include a nursing home
(NH), skilled nursing facility (SNF) (not necessarily for acute
rehabilitation with the goal to go home),
 Does NOT include an independent living facility (apartment complex)
specifically for older adults
 Could take place in a patient’s home where the patient receives 24/7
care from family and/or a nursing staff
 In general for statin use:
 If between 40 and 75 years, aim for high-intensity statin (lowers LDL by ≥50%)
 Atorvastatin 40-80 mg
 Rosuvastatin 20-40 mg
 Continue a statin if an adult is >75 years and tolerating it well (limited EBM)
 Make sure statin is appropriately renally dosed if CrCl <30 mL/min*
 If a patient has clinical ASCVD, use a moderate-intensity statin (lowers LDL by 30%
to <50%)
 Atorvastatin 10-20 mg
 Rosuvastatin 5-10* mg
 Simvastatin 20-40* mg
 Pravastatin 40*-80 mg
 Lovastatin 40 mg (recommend max of 20 mg*)
 Fluvastatin 40 mg or 80 mg* (recommend max of 40 mg*)
 Pitavastatin 2*-4 mg
 If a patient does not have clinical ASCVD, risk may be overestimated and initiating a statin
requires consideration of other risk factors such as comorbidities, safety (ADRs, drug
interactions), prognosis, and patient preference
 Controversy: If we are no longer monitoring FLPs, how low can the LDL go?
 Prioritize by weighing the risks versus the benefits
 Change minimal amounts of medication at a time
 “Start low, go slow”
 Avoid “one pill for every ill”
 Avoid “newer” or more $$ medications that are NOT superior in
efficacy to less expensive alternatives
 Check renal and hepatic function on EVERY patient at baseline
and intermittently throughout therapy, especially if at risk or during
changes of status

Geriatric Dosage Handbook, Lexicomp

American Society of Consultant Pharmacists (ASCP): http://www.medpass.com/geriatric-medication-handbook.html Geriatric Medication Handbook,
13th ed. ($21.95)

American Geriatrics Society (AGS):
http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clin
ical_guidelines_recommendations/

Geriatrics at your Fingertips by AGS

Gerontological Society of America (GSA): https://www.geron.org/

Merck Manual of Geriatrics:
http://www.merck.com/pubs/mm_geriatrics/contents.htm
 Please email:
[email protected]