Download Medication Use in the Elderly: Presentation and Speaker`s

Medication Use in the
Elderly Patient:
Physiology, Pharmacology, and Prescribing
Anthony J. Caprio, MD
Assistant Professor of Medicine
University of North Carolina Chapel Hill
Division of Geriatric Medicine and Center for Aging and Health
Learning Objectives

Identify the physiologic changes associated with normal
aging in relation to drug absorption, distribution, metabolism,
and excretion

Identify risk factors for Adverse Drug Events in older adults

Recognize Adverse Drug Events

Recognize potentially harmful medications for older adults

Utilize strategies to enhance the safety, effectiveness, and
adherence of prescribed medications
2
Challenges of Prescribing
for Older Adults
•
Multiple chronic medical problems
•
Multiple medications and prescribers
•
Different metabolism and responses
•
Adherence and cost
•
Supplements, herbals, and OTC drugs
Lancet. 1995;346(8966):32–36.
3
Physiologic Changes Associated
with Normal Aging
• Less Water
• More Fat
• Less muscle mass
• Slowed hepatic metabolism
• Decreased renal excretion
• Decreased responsiveness and sensitivity of the
baroreceptor reflex
4
Absorption
 Not
affected by the normal aging process
 Can be altered by drug interactions


Antacids
Iron
 Can


be effected by disease
Lack of intrinsic factor (B12 absorption)
Delayed gastric emptying
5
Distribution

Less water = ↓ volume of distribution = higher
concentration of water soluble drugs

More fat = ↑ volume of distribution = prolonged
action of fat soluble drugs (increased half-life)

Lower serum proteins (like albumin) increases
the concentration of unbound (free or active)
form of drugs
6
Metabolism

Slowed Phase I, cytochrome P450, reactions



Phase II reactions are essentially unchanged


Oxidation, reduction, dealkylation
Warfarin and phenytoin levels may be higher because
of altered metabolism
Conjugation, acetylation, methylation
Drug-drug interactions

Increased risk with increased number of drugs
7
Excretion

Hepatic

Renal



Renal clearance may be reduced
Serum creatinine may not be an accurate reflection of
renal clearance in elderly patients (decreased lean
body mass).
Active drug metabolites may accumulate


Prolonged therapeutic action
Adverse effects
8
Physiologic Changes Associated
with Disease States

Cardiac Disease



Kidney and Liver Disease


Impaired cardiac output (decreased absorption,
metabolism, clearance)
Greater susceptibility to cardiac adverse effects
Decreased drug clearance
Neurological Diseases



Diminished neurotransmitter levels
Impaired cerebral bloodflow
Greater sensitivity to neurological effects
9
Lots of Medications
and Little Evidence
•
2/3 of older adults are on regular medications
•
Adults age >65 account for 1/3 off all
prescriptions, but only represent 15% of the US
population
•
Older adults are frequently not included in
clinical trials, which makes it difficult to predict
drug metabolism or drug effects
Health Care Financ Rev. 1990;11:1-41.
10
Dangers of Multiple Medications:
“Polypharmacy”
• Adverse effects (side effects)
• Drug-drug interactions
• Duplication of drug therapy
• Poor adherence
• Cost
• Decreased quality of life
11
Adverse Drug Events (ADEs)

Adverse symptoms

Adverse patient outcomes






Doctor visits or hospitalizations
Falls
Functional decline
Changes in cognition (delirium)
Death
↑ number of medications = ↑ risk of ADEs
(even if all the meds are “clinically indicated”)
12
Medications Which Account for
Most ADEs in Older Adults
 Cardiovascular
 Psychotropic
medications
medications
 Antibiotics
 Anticoagulants
 Non-opioid
analgesics (NSAIDS)
 Anti-seizure
medications
(JAGS 2004;52:1349-1354 and NEJM 2003;348:1556-64)
13
Risk Factors for
Adverse Drug Events (ADE)

>6 chronic disease

>12 doses/day

≥ 9 medications

Low BMI (<22kg/m2)

Age >85 years

Creatinine clearance < 50 mL/min

History of prior ADE
Consult Pharm 1997;12:1103-11.
14
Prevalence of Prescribing
Problems in Primary Care
•
35% of community-dwelling older adults experience an
ADE annually
•
5-28% of inpatient geriatric admissions due to an ADE
•
2/3 of nursing home patients experienced an ADE (over
a 4-year period)
•
Between 20-40% of outpatients were prescribed
“potentially” inappropriate medications
JAGS 1997;45:945-948
JAGS 1996;44:194-197
Am Pharm Assoc 2002;42:847-857
15
Principle 1:
“Less is More”
(Keep the Medication List Short)
• Question the need for new medications
• Stop medications, whenever possible
• Prioritize treatments
• Weigh risks and benefits
• But, avoid undertreating older patients

Pain

Systolic hypertension (stroke, renal failure, heart disease)

Anticoagulation and atrial fribrillation (stroke prevention)
Drugs Aging 2003; 20 (1): 23-57.
Lancet 2000; 355: 865–872.
Ann Intern Med 1999;131:492-501.
J Gen Intern Med 2005; 20:116–122.
16
Do You Need to prescribe?
• Does every condition need a drug?
• Is it a benign or self limited condition?
• How does this condition bother the patient?
• Consider non-drug alternatives
• Diet
• Exercise
• Lifestyle modification
• Consider “Over The Counter” (OTC) medications
• Not necessarily safer than prescription drugs
• Be very careful with herbals and supplements
17
Stopping Medications
•
Consider interactions with other medications
•
Is it helping? (Benefit)
•
Is it harmful? (Risk)
•
Why was it started?
•
Is the dose within a therapeutic range?
•
Consider underlying renal and hepatic insufficiency
18
Clinical Case: Mr. Johnson
Mr. Johnson is 83 years old. He has a history of benign
prostatic hypertrophy (BPH) and hypertension. After
visiting his grandchildren, he developed a viral upper
respiratory infection. He took an over-the-counter cold
remedy containing a decongestant and
diphenhydramine. He now comes to the office because
he is unable to urinate. His blood pressure is 190/80.
What happened?
19
Urinary Retention and Hypertension

Parasympathetic Nervous System



Mediates detrusor muscle contraction
Blocked by anticholinergic medications like
diphenhydramine
Sympathetic Nervous System



α-adrenergic activity causes the urethral sphincter to
contract (retaining urine)
α-adrenergic activity increases systemic vascular
resistance (raises blood pressure)
Decongestants are alpha-adrenergic agonists (ex.
pseudoephedrine and phenylephrine)
20
Clinical Case: Mr. Johnson
Since Mr. Johnson has a history of benign
prostatic hypertrophy, his physician prescribes
terazosin, a peripherally-acting α1-adrenergic
antagonist, to help with his urinary retention and
to help reduce his blood pressure.
Two days later, Mr. Johnson falls in the middle of
the night, on the way to the bathroom. He
fractures his hip.
What happened?
21
Orthostatic Hypotension
and Hip Fracture
 Barorecptor
sensitivity decreases with age
 α-adrenergic
blockade can worsen
postural hypotension and increase the risk
of falls
 Falls
and Hip fractures are associated with
significant morbidity and mortality in older
adults
22
Prescribing Cascade:
Prescribing a new drug to treat an ADE
• Establish the diagnosis
• Diphenhydramine and the decongestant precipitated urinary
retention in a older male with prostatic enlargement
• Urinary retention is an ADE
• Stop (or reduce) the offending medications
• OTC cold medicine
• Need to ask about ALL medications
• Avoid prescribing new medications (terazosin)
23
Principle 2
Before making a new diagnosis:
“Think Drugs”
•
Consider ADE as etiology of new signs/symptoms
•
Remember that OTC drugs, supplements, and herbals
can cause ADEs
•
Consider discontinuing or dose-reducing medications
rather than treating an ADE with another medication
24
Clinical Case: Mr. Johnson
Mr. Johnson arrives in the emergency department
and is given meperidine (Demerol) for his pain.
He is also very anxious, so he receives diazepam
(Valium).
A few hours later, Mr. Johnson becomes very
confused and somnolent.
What happened?
25
Drug-Induced Delirium

Meperidine




Can cause confusion
Active metabolites
Slow renal clearance in older adults
Diazepam





Long-acting benzodiazepine
Lipophilic
Extended half-life in elderly
Increased sensitivity in the elderly
Increased risk of falls and fractures
26
Avoiding Potentially Dangerous Drugs:
The Beers Criteria
•
Consensus-based list of potentially inappropriate
medications for older adults
•
Published 1991, revised 1997, 2002
•
Statistical association with ADEs has been documented
•
Adopted for nursing-home regulation
•
Does not account for the complexity of the entire
medication regimen
Arch Intern Med 2003;163:2716-2724.
Pharmacotherapy 2005;25(6):831–838
27
Beers Criteria:
Anticholinergic Medications
• Drug classes
• Antihistamines
• Tricyclic antidepressants
• Antispasmodics and muscle
relaxants
• Adverse Effects
• Dry Mouth
• Urinary retention
• Constipation
• Confusion, delirium
28
Avoiding Potentially Dangerous Drugs:
The Beers Criteria
• Anticholinergic medications
• Decongestants
• Hypertension
• Bladder outflow obstruction
• Meperidine
• Benzodiazepines
Beers Criteria: Arch Intern Med 2003;163:2721.
29
Clinical Case: Mr. Johnson
•
Mr. Johnson slowly recovers after his hip fracture.
•
He continues to have some hip pain, so in addition to
acetaminophen, his geriatrician prescribes low-dose
opioid analgesics for break-through pain along with
laxatives to avoid opioid-induced constipation.
•
His delirium slowly clears and he is able to participate in
physical therapy and is able to return home after
rehabilitation. Before he goes home, his medications are
carefully reviewed, including OTC medications.
30
Principle 3:
“If You Decide to Prescribe,
Start Low and Go Slow…”
•
Start one medication at a time
•
Start with a low dose and increase gradually
•
Monitor for response
•
Monitor and anticipate adverse effects
•
Assess adherence with regimen
31
Adherence

Multiple medications

Language and literacy

Multiple doses

Cost

Sensory impairments

Quality of Life

Physical impairments


Adverse Effects

“Medicalization”
Memory impairment
32
Increasing Adherence

Keep the medication list short

Try to use once daily medications

Encourage use of a pillbox

Review bottles of medications

Write indications for medications on prescriptions

Medication Management programs
33
Things to Remember:
Four PRINCPLES
1.
Less is More! (keep the drug list short)
2.
Think Drugs! (before making a new diagnosis)
3.
Start Low and Go Slow
4.
Assess Adherence
34
Things to Remember:
Changes with Aging

Absorption usually does not change

Higher concentrations of water soluble and free
(unbound) drugs

Longer half-life for lipophilic drugs

Slower phase I metabolism

Impaired excretion

Increased susceptibility to adverse effects
35