Drug Therapy for Older Adults:
Acute Care Considerations
Shelly Gray, PharmD, MS
Acknowledgment: Peggy Odegard, PharmD
Goals




Describe how age-related physiological
changes may affect disposition and
response to drug therapy
Identify drugs that may be associated
with hospitalization
Identify drugs that are associated with
acute care problems such as falls,
confusion, memory impairment, delirium
Discuss strategies for optimizing therapy
Did you know…


28% of hospitalizations for older adults are due to
adverse drug reactions.
Medications are a major cause of hip fractures


Older adults take the bulk of medicines




32,000 seniors affected each year by a fracture
following a medication-related fall.
12.7% of the U.S. population are over 65 years, but
consume approximately 34% of total prescriptions.
individuals 65 to 69 yo take an average 14 Rxs annually
individuals 80 to 84 yo take an average 18 Rxs
annually.
Adverse drug events (ADEs) are among the top five
greatest threats to the health of seniors.
source: ascp.com
Key Considerations


Older persons are a heterogeneous group of
individuals and comprise up to 50% of the
inpatient population
Delirium after surgery has been reported in
9-26% of elderly patients and up to 65% of
patients post hip fx repair


Pain is a complicating factor in post-op delirium
Age is an independent risk for late, postoperative cognitive dysfunction with 9.9% of
patients affected at 3 months in one study
Case Study
Mrs H, an 80 yo woman admitted after a cardiac arrest.
Today she complained to her daughter of nausea and
was somewhat confused prior to her collapse.
PMH: atrial fibrillation, hypertension, osteoarthritis,
insomnia and renal insufficiency.
Medications:
warfarin 2.5 mg mon, wed, fri; 5 mg other days
digoxin 0.125 mg daily (reduced from 0.25 mg
recently)
isosorbide 20 mg TID
aspirin 81 mg daily
lotensin 20 mg daily
oxybutynin 2.5 mg TID
temazepam 15 mg at bedtime
Glucosamine/chondroitin 500/400 TID
PE/Labs: HR 37 on admit, Dig level today 3.4 ng/ml
What do you think might have
caused this admission?
Case Study:History



The medics found duplicate medication
vials for each medication (including
digoxin 0.25). Numerous pills were found
on the floor.
When asked about difficulty in taking
medications as prescribed, she indicated
she doesn’t miss many doses, but can’t
quantify number of missed doses/week;
“don’t like taking so many pills”; “don’t
like the oxybutynin because it causes dry
mouth”.
She has difficulty with ambulation and
reports occasional falls (several/week).
What problems can be prevented
during her admission?
Cardiac Care Standing Orders
I
&
O
Saline lock Flush Q8H
I&O each shift
Aspirin 325mg chewable STAT if not given by medics or ED
 If aspirin not ordered, list contraindication:
M
E
D
I
C
A
T
I
O
N
S
L
A
B
S
R
T
D
/
C
NTG 0.4mg SL Q5MIN X 3 PRN chest pain. Call MD if patient uses 3 doses within 2 hours
NTG Infusion IV. Start at 5mcg/min and titrate to relief of chest pain. Keep SBP between 90 and 130mmHg.
Clopidogrel (Plavix) 300mg PO X 1 dose
Clopidogrel (Plavix) 75mg PO daily
Metoprolol 25mg PO Q12H (hold if HR less than 50 bpm or SBP less than 95mmHg –OR- 2 or 3 heart block)
 If beta-blocker not ordered, list contraindication:
Dalteparin (Fragmin) 120 units per kg subcutaneous Q12H
Diazepam (Valium) 2.5mg IV -OR- 5mg PO Q3H PRN sedation (MR X 1 dose in 30 minutes
if first dose ineffective)
Promethazine (Phenergan) 12.5mg PO or IV Q6H PRN nausea (MR X 1 in 30 minutes)
Zolpidem (Ambien) 5mg at bedtime PRN sleep. (May repeat x1 if ineffective)
Docusate 240mg PO daily (hold for loose stools)
MOM 30ml PO daily PRN constipation
Maalox 30ml PO QID PRN indigestion
Acetaminophen (Tylenol) 650mg PO Q4H PRN fever over 38.5 C or headache
Admit labs (if not done in ED or office): CK, CK-MB, Troponin, BMP, Lipid Panel, CBC, Protime, PTT
CK/CKMB, & Troponin-I draw 6 hours after arrival in ED
EKG routine 12-Lead with Interpretation, 6 hours after admission and PRN chest pain
XR chest 1 view portable on admission (if not done in ED), obtain report for chart
Oxygen 1 to 6 liters per minute by nasal cannula PRN to keep oxygen SaO2 greater than 95%
Initiate Cardiac Discharge education
Consult to Cardiac rehabilitation
Home Meds to be continued
warfarin 2.5 mg mon, wed, fri; 5 mg
other days
digoxin 0.125 mg daily -on hold
isosorbide 20 mg TID
aspirin 81 mg daily
lotensin 20 mg daily
oxybutynin 2.5 mg TID
temazepam 15 mg at bedtime
Glucosamine/chondroitin (?- P&T not
quite sure)
Inpatient vs. home meds
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Aspirin 325 mg QD
NTG 0.4 SL prn
Nitro drip
Clopidogrel 75 mg QD
Metoprolol 25 mg BID
dalteparin 120 units/kg q12
Diazepam 5 mg po q3hr prn
sedation
Promethazine 12.5 mg po/IV
q hrs prn nausea
Zolpidem 5 mg HS prn
DOSS 250 mg HS prn
Maalox prn heartburn
MOM 30 cc prn constipation
APAP 650 mg 1-2 q4 prn
pain/fever
1.
2.
3.
4.
5.
6.
7.
8.
warfarin 2.5 mg mon,
wed, fri; 5 mg other days
digoxin 0.125 mg daily
(on hold)
isosorbide 20 mg TID
aspirin 81 mg daily
lotensin 20 mg daily
oxybutynin 2.5 mg TID
temazepam 15 mg at
bedtime
Glucosamine/chondroitin
Case Study Intervention


Concerns: cognition and medication
adherence resulting in cardiac arrest;
standing orders
Inpatient Actions:





change diazepam to lorazepam for anxiety
minimize promethazine use; falls precautions
Hold home aspirin tx
? need for isosorbide during ntg drip
Either zolpidem or temazepam prn sleep, address
sleep hygiene in planning for d/c
Case Study Intervention

Discharge Planning:






remove all old med bottles to minimize risk of
dosing error
? Need or change isosorbide TID to once daily
product
oxybutynin was not very effective so
discontinue
not able to simplify the warfarin regimen
? Need for aspirin
taper temazepam
How it looks on discharge!
Medical Problems: htn, atrial fibrillation, s/p
recent AMI, insomnia, osteoarthritis, renal
insufficiency
Meds:
 lotensin 20 mg daily
 warfarin 2.5 mg mon, wed, fri; 5 mg other
days
 Aspirin 81 mg daily
 Metoprolol 50 mg BID (hold if pulse <60 bpm,
call if pulse >100 bpm)
 Acetaminophen 500 mg TID prn knee pain
 Glucosamine/chondroitin 500/400 TID for
osteoarthritis
 Chamomille tea for sleep (her preference)
Most Common Prescription Drugs
Therapeutic Class
Cardiovascular
CNS
Endocrine/Metabolic
Analgesic
Respiratory
Duke EPESE 1986-1987
%
47
13
11
10
7
Most Common OTC Drugs
EPESE(%) MoVIES (%)
Analgesic
42
66
Nutritional
23
38
Gastrointestinal
21
38
Respiratory
3
5
Frequency of Drug Use
MoVIES Ann Pharmacother 1996:30:589
30
% (n=1360)
25
20
15
10
5
0
0
1
2
3
4
Number of Medications
5-7
8+
Incidence of ADEs in Older
Persons in Ambulatory Setting


Cohort of 27,617 Medicare enrollees
1523 ADEs

28% preventable


Error occurred at prescribing and
monitoring phases
38% were serious, life-threatening or
fatal

42% of these were preventable
JAMA 2003;289:1107
Which Drugs Cause Serious ADEs?
Ambulatory
 Diuretics
 Nonopioid
analgesics
 Anticoagulants
 Antiepileptics
Nursing Home
 Opioids
 Antipsychotics
 Antiinfectives
 Antiepileptics
 Antidepressants
JAMA 2003;289:1107
Arch Intern Med
2001;161:1629
How does aging influence drug
therapy?
Goal #1

Describe how age-related
physiological changes may affect
disposition and response to drug
therapy
Consideration #1

Pharmacokinetic changes do occur
with age





Absorption
Distribution
Hepatic Metabolism
Renal Elimination
These changes may result in the need
for adjustment of drug dosing and
require careful monitoring for effects.
Absorption:
The chemistry of the GI track changes with aging.


These changes do not have any major impact on
medication dosing or use!
Drug absorption in the gastrointestinal (GI)
system is not impaired despite many age-related
changes in the GI tract with age



decreased GI blood flow
increased gastric pH
diminished GI motility
The most significant effect on absorption is other
illnesses…Effects on cardiac output (e.g. CHF) or
gut rest are considerations in the acute care
setting
Drug Distribution:
The makeup of the body changes with aging.

Age-related increased
body fat and
decreased lean body
mass may predispose
to

retention of more fatsoluble drugs


Example, Valium™
and some
anesthetic agents
over-dose of drugs
distributed to lean
tissue or body water

Example, ethanol
or aminoglycosides
Metabolism:
Liver performance is somewhat reduced with aging.

The liver’s system for activating
medications or performing metabolism is
not as efficient with aging.

With aging, the liver’s size and blood flow are
reduced which results in some reduction in
the ability for the liver to metabolize
(inactivate) drugs

Recommendation: If used, use medicines that
have shorter half-lives or don’t require
extensive metabolism.
Renal Elimination

Age-related decline in kidney
function by about 1% per year after
the age of 50 years

Can lead to excess or over-dose of
drugs cleared by the kidney if dose not
adjusted (e.g. many antibiotics,
ranitidine or Zantac™, lithium)
Creatinine Clearance
creatinine =
clearance
(140-age) weight in kg
72 (serum creatinine)
*multiply by 0.85 if female
** use IBW unless >20% over
***estimate based on stable renal function so may
not apply in acutely ill patients
Is it an issue?
“Young”
“Old”
Cr Cl =
(140 - 40) 72
72 (1.0)
Cr Cl = 100 ml/min
Cr Cl =
(140-80) 72
72 (1.0)
Cr Cl = 60 ml/min
Yes: <60 ml/min is a cutoff for adjustment of
many drug doses
Case
80 yr old female with
hypertension & DJD
Started on ranitidine 150
mg BID for GERD
Estimated renal function
(140-80) 65 kg (0.85)
1.5 * 72
CrCl= 31 ml/min
Meds: Tylenol 1 gm QID,
Enalapril 10 mg BID
65 kg, Scr=1.5 mg/dl
Effect of reduced renal function?
Can lower ranitidine dose to QD.
General Principles of Drug
Clearance


Steady state concentration
Css= F * Dose
Cl
Half life (t1/2)=0.693*Vd/Cl


Factors that reduce clearance will result in an
increased plasma concentration and may
increase toxicity
Factors that increase Vd may result in increase
T ½ if clearance doesn’t change
Consideration #2
Pharmacokinetic and pharmacodynamic
parameters may be altered more by
concomitant diseases, medications and
nutritional status than by aging alone.
New drugs should be avoided/ used
cautiously until their full effects in older
persons are known.
PK Action Item!

Toxicity due to an age-related
pharmacokinetic change can often be
anticipated and prevented with
appropriate dose adjustments and close
monitoring for adverse events
 Screen for appropriate dosing on
admission and adjust whenever needed
(keep in mind, some doses may have
been so for years- it’s never to late to
change them!)
Pharmacodynamics

Sensitivity to certain drugs
increases with age

especially drugs that work at receptors
or in the central nervous system
Propranolol (Inderal™)
 Diazepam (Valium™) and valium-like
drugs
 Narcotics (e.g. Vicodin™ or morphine)

Why does this happen?
Altered homeostatic mechanisms

physiological reserve capacity to respond to stress
beyond energy needed for daily activities

gradual reduction occurs with aging

more susceptible to decompensation under stress
(infections, trauma, drug effects).

more difficult to maintain homeostasis (regulate
blood pressure, pH, etc).
Specifically
Changes in water/sodium regulation
Decrease in balance control
Prolongation in CNS reaction time
Reduced responsiveness to
hypoglycemia
1.
2.
3.
4.
•
Altered beta receptor sensitivity to
glucagon
Inability to recover quickly from
orthostasis
5.
•
altered baroreceptor response
How do these Pharmacodynamic
Changes Affect Medication Use?
Altered receptor sensitivity may
affect efficacy or toxicity of certain
drugs:


Beta agonists (e.g. albuterol)
Beta antagonists (e.g. metoprolol)
How do these Pharmacodynamic
Changes Affect Medication Use?
Risk of orthostatic hypotension greater





Vasodilators (e.g. hydralazine)
ACE inhibitors
beta antagonists
nitrates
calcium channel antagonists
How do these Pharmacodynamic
Changes Affect Medication Use?
Altered sensitivity to drugs
affecting neurotransmitters

Dopaminergic system


decrease in dopamine2 receptors in
striatum
Cholinergic system
loss of cholinergic cells
 decrease in choline acetyltransferase

How do these Pharmacodynamic
Changes Affect Medication Use?
Increased sensitivity to drugs with
effects on neuroendocrine system




Anaesthetics
Opioids
Anticonvulsants
Psychotropic agents
PD Action Item!

Toxicity due to an age-related
pharmacodynamic change may be
hard to predict, however careful
monitoring for desired effects and
taking actions to avoid unwanted
effects is key to preventing
problems.
Goal #2
Identify drugs that may be
associated with hospitalization
Case
Anne is an 88 year old women who
was just admitted for a GI bleed.
She has a h/o stomach upset x3
weeks (burning pain) for which she
was taking ranitidine OTC.
What are your initial thoughts?

Could a medication have caused
this problem?
The answer: YES

Four weeks prior to hospitalization, she…



began using ibuprofen 400 mg every 4 hours
while awake for dental pain.
scheduled a DDS visit, however, needed to
reschedule so delayed the visit by 20 days.
did not report the regular ibuprofen use to her
PCP because she didn’t think it was important
since she would see her DDS about the dental
pain.

Ouch!




Regular use of NSAIDs is a leading cause of GI
bleeding and gastritis in older adults!
1/3 of regular NSAID users have GI ulceration
(gastric or duodenal) on endoscopy
OR 5.36 for serious gastric complications
Gut protection is essential for regular NSAID
users to prevent problems
Becker JA. Br J Clin Pharmacol.
2004; 58(6): 587–600
Costs of this ADE








Hospitalization (via ED)
Two office visits to PCP
GI consultation
Endoscopy
Rxs
Cancellation of social activities
Frustration and fear
3 plane flights for family
How does this happen?
The Prescribing Cascade
BMJ 1997;315:1096-1099
Drug-related Causes of Admission
Key Players

Drug
1.
2.
3.
4.

NSAIDs
Narcotics
Digoxin
CNS active drugs
like
benzodiazepines,
sleepers, some BP
meds
Non-adherence

Problem
1.
2.
3.
4.
GI bleed
GI obstruction
Arrhythmia
Falls
Poor illness control
Always consider medication use in the differential
diagnosis

A direct drug effect?


Age-related pharmacokinetic
change?


Change the dose
Age-related pharmacodynamic
change?


Stop the drug
Stop the drug? Change the dose?
Drug-related needs
Case
SR, a 75 year old healthy female,
visits her MD with a 1 month history
of sleep complaints. She “just can’t
fall asleep at night” and would like
something to help. Her MD
prescribes zolpidem (Ambien ™ ) 10
mg at bedtime as needed (#30).
ADEs Can Lead to Hospitalization
1 week later, SR is rushed to the ER
after suffering a fall down a flight of
stairs. A fracture of the right femur is
seen on x-ray. While she tolerates the
surgery well, she has poor endurance
with therapeutic exercises and
therefore is sent to a local skilled
nursing facility. 1yr later, she still
requires use of a walker.
Pertinent History about SR




Drinks ½ pot of coffee daily
Takes a mid-morning and early
evening nap daily – just does not
have any energy
Does not exercise
Lost her husband 1 year ago. Is
still very quick to tears and is
having difficulty enjoying
pleasurable activities
Goal #3

Identify drugs that are associated
with acute care problems.
The primary concern…

Some medicines cause changes in the
body that might seem like a normal part
of aging so are unrecognized as
problematic therapies.






confusion
falling
constipation
feeling sad or depressed
poor memory
Heartburn
Medications that may increase risk of
falls











Blood pressure medicines
Antidepressants
Antihistamines
Parkinsons medicines
Anti-psychotics
Benzodiazepines
Decongestants
Opioids
Muscle relaxers
Sleep medicines
Urinary anticholinergics
Drugs and Falls/Hip Fractures
Leipzig R JAGS 1999:47:40, JAGS 1999:47:30

Consistent evidence




Benzodiazepines
Antidepressants
Antipsychotics
Weak/inconsistent evidence


Analgesics (NSAIDS, narcotics)
Cardiovascular agents

thiazides, antiarrhythmics, digoxin
BZD and Hip Fractures:
Does Duration of Action Matter?

Several studies have found that
both short-and long-acting
benzodiazepines increase risk ~2
fold for falls/hip fractures



Short acting: oxazepam, alprazolam
Long acting: diazepam, flurazepam
Dose probably more important than
half-life
Herings R Arch Intern Med 1995, Neutel Age Aging 1996
Medications cause constipation

Narcotics


Require stimulant laxative, at the
minimum, to promote GI motility with
ongoing use (e.g. Senna). A stool
softener can be added but is
inadequate as sole therapy.
Other products associated with
constipation include
anticholinergics, CCBs, calcium, iron
Medications cause cognitive dysfunction, memory
impairment, and delirium

Some Culprit
Drugs







Narcotics
Hypnotics
Benzos
Anesthetics
Phenothiazines
Corticosteroids
anticholinergics

Possible Problems



All may cause falls,
confusion, delirium,
or other cognitive
dysfunction
BZDs may cause
memory
impairment
Phenothiazines
may cause dystonic
rxns
Drug Effects on Cognition




307 outpatients with dementia
12% (n=36) had an ADE impairing
cognition
Discontinuation/modification
improved cognition
16 were using benzodiazepines
Larson Ann Intern Med 1987
Delirium



Delirium is not an uncommon problem in
the operative period for older adults
Delirium associated with surgery may
occur early (post op day 2-7 interval) or
late (3 mos)
Pain increases risk for delirium and may
compromise a weakened CV system




Pre-operatively
Peri-operatively
Post-operatively
Age increases risk for delirium
How should delirium be managed?
1.
2.
3.
4.
Remove or correct the cause!
Low dose haloperidol (0.5 mg IV/PO)
may be used for its sedative qualities
(IV faster acting)
Low dose, oral atypical antipsychotics
(e.g. risperidone 0.25 mg) are used,
however, action is not immediate due to
oral absorption. Some concern with
association with stroke.
Management is acute! Remember,
these meds may be confused for chronic
meds if sent home at discharge!
Medications to avoid using in older
adults unless absolutely needed





Meperidine
(Demerol)
Propoxyphene
(Darvon™)
Pentazocine (Talwin)
Trimethobenzamide
(Tigan)
Muscle relaxants like
Robaxin, Soma,
Flexeril




Disopyramide
(Norpace)
Methyldopa
(Aldomet)
Long acting benzos
(Dalmane, Valium,
Librium)
Amitriptyline
Geriatrics Consultation

In a small RCT (n=126), a
structured geriatrics consultation
resulted in reduced risk of delirium
(RR 0.64) for older adults (mean
age 79) admitted for surgical repair
of hip fx.
Volume 49 Issue 5 Page 516-522,
MAY 2001
Content of Structured Geri
Consultation






CNS oxygen
delivery
Fluid/electrolytes
Severe pain mgmt
Eliminate
unnecessary meds
Regulate bowel
and bladder fn
Adequate nutrition




Early mobilization
& rehab
Px, early
detection, and tx
of major post-op
complications
Appropriate
environmental
stimuli
Tx agitated
delirium
Volume 49 Issue 5 Page 516-522,
MAY 2001
Optimizing Drug Use in the Elderly
1.
2.
3.
4.
Consider whether drug therapy is
necessary
Use least number of drugs to treat
common problems
Adjust dosing to match pk/pd needs
Establish reasonable therapeutic
endpoints and monitor for desired
outcome


5.
Watch for ADRs and for effects on
functional status
Monitor and encourage persistence with
therapy
Consider possibility of drug-induced
illness for any symptom or problem