Download Pharmacotherapy - Geriatrics Care Online

PHARMACOTHERAPY
OBJECTIVES
Know and understand:
• Key issues in geriatric pharmacology
• Effects of age on pharmacokinetics and
pharmacodynamics
• Risk factors for adverse drug events for older
patients and ways to mitigate them
• Principles of prescribing for older patients
Slide 2
TOPICS COVERED
• Challenges of Geriatric Pharmacology
• Aging and Pharmacokinetics
• Aging and Pharmacodynamics
• Adverse Drug Events
• Drug-drug & Drug-disease Interactions
• Principles of Prescribing for Older Adults
• Nonadherence
Slide 3
WHY GERIATRIC
PHARMACOTHERAPY IS IMPORTANT
People 65+
People <65
65+ share of prescriptions
<65 share of presciptions
100
90
80
70
60
50
40
30
20
10
0
Present
2040
Now, people age 65+ are 13% of US population, buy 33% of prescription drugs
By 2040, will be 25% of population, will buy 50% of prescription drugs
Slide 4
WHY GERIATRIC PHARMACOTHERAPY
IS CHALLENGING
• More drugs are available each year
• FDA and off-label indications are expanding
• Formularies change frequently
• Knowledge of drug-drug interactions advances
• Drugs change from prescription to OTC
• “Nutraceuticals” (herbal preparations, nutritional
supplements) are booming
Slide 5
PHARMACOKINETICS
Absorption
Distribution
Metabolism
Elimination
Slide 6
AGING AND ABSORPTION
• Amount absorbed (bioavailability) is not changed
• Peak serum concentrations may be lower and
delayed
• Exceptions: drugs with extensive first-pass effect
(bioavailability may increase and serum
concentrations may be higher because less drug
is extracted by the liver, which is smaller with
reduced blood flow)
Slide 7
FACTORS THAT AFFECT
DRUG ABSORPTION (1 of 2)
• Route of administration
• What is taken with the drug
• Comorbid illnesses
Slide 8
FACTORS THAT AFFECT
DRUG ABSORPTION (2 of 2)
• Divalent cations (calcium, magnesium, iron) can
affect absorption of many fluoroquinolones (eg,
ciprofloxacin)
• Enteral feedings interfere with absorption of some
drugs (eg, phenytoin)
• Increased gastric pH may increase or decrease
absorption of some drugs
• Drugs that affect GI motility can affect absorption
Slide 9
EFFECTS OF AGING ON
VOLUME OF DISTRIBUTION (VD)
• Age-associated changes in body composition can
alter drug distribution
•  body water  lower VD for hydrophilic drugs
•  lean body mass  lower VD for drugs that bind
to muscle
•  fat stores  higher VD for lipophilic drugs
•  plasma protein (albumin)  higher percentage
of drug that is unbound (active)
Slide 10
AGING AND METABOLISM
Metabolic clearance of a drug by the liver
may be reduced because:
• Aging decreases liver blood flow, size
and mass
• The liver is the most common site of
drug metabolism
Slide 11
WHY THE METABOLIC
PATHWAY MATTERS
• Phase I pathways (eg, hydroxylation,
oxidation, dealkylation, and reduction)
convert drugs to metabolites with <, =, or >
pharmacologic effect than parent compound
• Phase II pathways convert drugs to inactive
metabolites that do not accumulate
 With few exceptions, drugs metabolized by
phase II pathways are preferred for older
patients
Slide 12
OTHER FACTORS THAT AFFECT
DRUG METABOLISM
• Age and gender (eg, oxazepam is metabolized
faster in older men than in older women;
nefazodone concentrations are 50% higher in
older women than in younger women)
• Hepatic congestion from heart failure (eg, reduces
metabolism of warfarin)
• Smoking (eg, increases clearance of theophylline)
Slide 13
KEY CONCEPTS ABOUT
DRUG ELIMINATION
• Half-life: time for serum concentration of drug
to decline by 50%
• Clearance: volume of serum from which the
drug is removed per unit of time (eg, L/hour
or mL/minute)
Slide 14
KIDNEY FUNCTION IS CRITICAL
FOR DRUG ELIMINATION
• Most drugs exit the body via the kidney
• Reduced elimination  drug accumulation
and toxicity
• Aging and common geriatric disorders can
impair kidney function
Slide 15
THE EFFECTS OF AGING
ON THE KIDNEY
 kidney size
 renal blood flow
 number of functioning nephrons
 renal tubular secretion
Result: Lower glomerular filtration rate
Slide 16
SERUM CREATININE DOES NOT
REFLECT CREATININE CLEARANCE
 lean body mass  lower creatinine production
and
 glomerular filtration rate (GFR)
Result: In older persons, serum creatinine stays in
normal range, masking change in creatinine
clearance (CrCl)
Slide 17
TWO WAYS TO DETERMINE
CREATININE CLEARANCE
Measure
• Time-consuming
• Requires 24-h urine collection
• 8-h collection may be accurate but not
widely accepted
Estimate
• Usually done with the Cockroft-Gault
equation (see next slide)
Slide 18
COCKROFT-GAULT EQUATION
(Ideal weight in kg) (140 – age)
_________________________ x (0.85 if female)
(72) (serum creatinine in mg/dL)
Slide 19
LIMITATIONS OF THE
COCKROFT-GAULT EQUATION
• In patients without a significant age-related decline in
renal function, the equation underestimates CrCl
• In patients with muscle mass reduced beyond normal
aging, the equation overestimates CrCl
• Modification of Diet in Renal Disease (MDRD) is
another method for estimating GFR
 Not validated in adults ≥70 years old or in racial or
ethnic groups other than white and black Americans
Slide 20
PHARMACODYNAMICS
• Definition: Time course and intensity of the
pharmacologic effect of a drug
• May change with aging, eg:
 Benzodiazepines may cause more sedation
and poorer psychomotor performance in older
adults (likely cause: reduced clearance of the
drug and resultant higher plasma levels)
 Older patients may experience longer pain
relief with morphine
Slide 21
SUCCESSFUL PHARMACOTHERAPY
• Uses the correct drug
• Prescribes the correct dosage
• Targets the correct condition
• Is appropriate for the patient
Failure in any one of these can result in
adverse drug events (ADEs)
Slide 22
THE BURDEN OF INJURIES
FROM MEDICATIONS (1 of 3)
ADEs are responsible for 5% to 28% of
acute geriatric hospital admissions
Slide 23
THE BURDEN OF INJURIES
FROM MEDICATIONS (2 of 3)
Incidence of ADEs:
26/1000 hospital beds
(2.6%)
ADEs occur in 35% of
community-dwelling
elderly persons
Slide 24
THE BURDEN OF INJURIES
FROM MEDICATIONS (3 of 3)
1.4
1.2
1
0.8
0.6
0.4
0.2
0
In nursing homes, $1.33 is spent on ADEs for
every $1.00 spent on medications
Slide 25
MOST COMMON MEDICATIONS
INVOLVED IN ADEs
• Cardiovascular drugs, diuretics, NSAIDs,
hypoglycemics and anticoagulants
• Medications with a narrow margin of
safety
Slide 26
OPTIMIZING PRESCRIBING
• Achieve balance between over- and underprescribing
of beneficial therapies
• >20% of ambulatory older adults receive at least one
potentially inappropriate medication
• Nearly 4% of office visits and 10% of hospital
admissions result in prescription of medications
classified as never or rarely appropriate
• Underprescribing can result from thinking older adults
will not benefit from medications intended as primary
or secondary prevention or from aggressive
treatment of chronic conditions
Slide 27
COMMONLY OVERPRESCRIBED AND
INAPPROPRIATELY USED DRUGS
• Anti-infective agents
• Anticholinergic agents
• Urinary & GI
antispasmodics
• Antipsychotics
• Benzodiazepines
• Digoxin for diastolic
dysfunction
• Dipyridamole
•
•
•
•
•
•
•
•
H2 receptor antagonists
Laxatives & fecal softeners
NSAIDs
Propoxyphene
Proton-pump inhibitors
Sedating antihistamines
Tricyclic antidepressants
Vitamins and minerals
Slide 28
COMMONLY
UNDERPRESCRIBED DRUGS
•
•
•
•
•
•
•
ACE inhibitors for patients with diabetes and proteinuria
Angiotensin-receptor blockers
Anticoagulants
Antihypertensives and diuretics for uncontrolled hypertension
β-blockers for patients after MI or with heart failure
Bronchodilators
Proton-pump inhibitors or misoprostol for GI protection from
NSAIDs
• Statins
• Vitamin D and calcium for patients with or at risk of osteoporosis
Slide 29
RISK FACTORS FOR ADEs
• 6 or more concurrent chronic conditions
• 12 or more doses of drugs/day
• 9 or more medications
• Prior adverse drug event
• Low body weight or low BMI
• Age 85 or older
• Estimated CrCl < 50 mL/min
Slide 30
ADE PRESCRIBING CASCADE
DRUG 1
Adverse drug effect—
misinterpreted as a new medical condition
DRUG 2
Adverse drug effect—
misinterpreted as a new medical condition
Slide 31
DRUG-DRUG INTERACTIONS
• May lead to ADEs
• Likelihood  as number of medications 
• Most common: cardiovascular and
psychotropic drugs
Slide 32
KEY FACTS ABOUT
DRUG-DRUG INTERACTIONS
• Absorption can be  or 
• Use of drugs with similar or opposite effects
can result in exaggerated or diminished effects
• Drug metabolism may be inhibited or induced
• Herbal preparations may also interact
Slide 33
CYTOCHROME P-450 AND
DRUG INTERACTIONS
• Effects of aging and clinical implications are still
being researched
• CYP3A4 is involved in more than 50% of drugs on
the market
• CYP3A4 is induced by rifampin, phenytoin, and
carbamazepine and is inhibited by macrolide
antibiotics, nefazodone, itraconazole, ketoconazole,
and grapefruit juice
Slide 34
MOST COMMON ADVERSE EFFECTS
OF DRUG-DRUG INTERACTIONS
• Confusion/delirium
• Cognitive impairment
• Hypotension
• Acute renal failure
Slide 35
COMMON DRUG-DRUG INTERACTIONS
Combination
ACE inhibitor + diuretic
ACE inhibitor + potassium
Antiarrhythmic + diuretic
Risk
Hypotension, hyperkalemia
Hyperkalemia
Electrolyte imbalance, arrhythmias
Benzodiazepine + antidepressant,
antipsychotic, or benzodiazepine
Confusion, sedation, falls
Calcium channel blocker + diuretic
or nitrate
Hypotension
Digitalis + diuretic
Arrhythmias
Slide 36
COMMON DRUG-DISEASE
INTERACTIONS
• Obesity alters VD of lipophilic drugs
• Ascites alters VD of hydrophilic drugs
• Dementia may  sensitivity, induce paradoxical
reactions to drugs with CNS or anticholinergic
activity
• Renal or hepatic impairment may impair
detoxification and excretion of drugs
Slide 37
PRINCIPLES OF PRESCRIBING
FOR OLDER PATIENTS: THE BASICS
• Start with a low dose
• Titrate upward slowly, as tolerated by
the patient
• Avoid starting 2 drugs at the same time
Slide 38
BEFORE PRESCRIBING
A NEW DRUG, CONSIDER:
• Is this medication necessary?
• What are the therapeutic end points?
• Do the benefits outweigh the risks?
• Is it used to treat effects of another drug?
• Could 1 drug be used to treat 2 conditions?
• Could it interact with diseases, other drugs?
• Does patient know what it’s for, how to take it,
and what ADEs to look for?
Slide 39
PRINCIPLES OF PRESCRIBING
ANNUALLY
• Ask patient to bring in all medications (prescribed,
OTC, supplements) for review
• Ask about side effects and screen for drug and
disease interactions
• Look for duplicate therapies or pharmacologic
effect
• Eliminate unnecessary medications and simplify
dosing regimens
Slide 40
NONADHERENCE
• May be as high as 50% among older patients
• May result from clinician’s failure to consider
patient’s financial, cognitive, functional status
• May result from patient’s beliefs and
understanding of drugs and diseases
Slide 41
SUMMARY
• Successful prescribing means choosing the correct
dosage of the correct drug for the condition and
individual patient
• Age alters pharmacokinetics (drug absorption,
distribution, metabolism, and elimination)
• ADEs are common but can be minimized with strict
attention to risk factors, drug-drug interactions, and
drug-disease interactions
Slide 42
CASE 1 (1 of 3)
• A 75-year-old man comes to the office because he has
increased pain related to osteoarthritis. At his last
office visit 2 weeks earlier, his pain level was 3 of 10; it
is now 5 of 10.
• In addition to osteoarthritis, he has type 2 diabetes
mellitus, chronic kidney disease, and major depressive
disorder, which was diagnosed at his last office visit.
• His current medications include codeine 30 mg/
acetaminophen 300 mg, 2 tablets q6h; glipizide 10 mg
q12h; NPH insulin 20 U at bedtime; aspirin 81 mg/d;
and most recently, paroxetine 20 mg/d.
Slide 43
CASE 1 (2 of 3)
Which of the following is the best option for
managing this patient’s pain?
(A) Increase codeine/acetaminophen dose.
(B) Change codeine/acetaminophen to oxycodone/
acetaminophen.
(C) Change codeine/acetaminophen to propoxyphene/
acetaminophen.
(D) Add ibuprofen 200 mg q6h.
(E) Discontinue paroxetine.
Slide 44
CASE 1 (3 of 3)
Which of the following is the best option for
managing this patient’s pain?
(A) Increase codeine/acetaminophen dose.
(B) Change codeine/acetaminophen to oxycodone/
acetaminophen.
(C) Change codeine/acetaminophen to propoxyphene/
acetaminophen.
(D) Add ibuprofen 200 mg q6h.
(E) Discontinue paroxetine.
Slide 45
CASE 2 (1 of 3)
• A 79-year-old woman comes to the office to establish
care. She reports that she often feels sleepy.
• History includes osteoporosis, hip fracture, systolic heart
failure, hypertension, frequent falls, chronic kidney
disease, and post-herpetic neuralgia.
• Medications include extended-release metoprolol 100
mg/d, gabapentin 600 mg q8h, alendronate 35 mg/wk,
vitamin D 800 IU/d, calcium carbonate 500 mg q8h, and
aspirin 81 mg/d.
• Serum creatinine is 1.5 mg/dL, with estimated creatinine
clearance of 30 mL/min.
Slide 46
CASE 2 (2 of 3)
Which of the following would be most likely to
relieve this patient’s sleepiness?
(A) Reduce gabapentin dosage to 600 mg q12h.
(B) Start lisinopril 2.5 mg/d.
(C) Discontinue alendronate.
(D) Increase vitamin D to 1200 IU/d.
(E) Switch extended-release metoprolol to metoprolol
50 mg q12h.
Slide 47
CASE 2 (3 of 3)
Which of the following would be most likely to
relieve this patient’s sleepiness?
(A) Reduce gabapentin dosage to 600 mg q12h.
(B) Start lisinopril 2.5 mg/d.
(C) Discontinue alendronate.
(D) Increase vitamin D to 1200 IU/d.
(E) Switch extended-release metoprolol to metoprolol
50 mg q12h.
Slide 48
CASE 3 (1 of 4)
• A 79-year-old woman comes for a follow-up office
visit 2 weeks after hospital discharge. She had been
admitted for exacerbation of heart failure.
• She has atrial fibrillation, hypertension, systolic
heart failure (New York Heart Association class III),
and coronary artery disease.
• Medications include furosemide 20 mg q12h,
potassium 10 mEq/d, lisinopril 10 mg/d, warfarin 2
mg/d, metoprolol 25 mg q12h, and, since hospital
discharge, spironolactone 12.5 mg/d.
• On examination, the patient’s weight is stable and
she has returned to baseline function.
Slide 49
CASE 3 (2 of 4)
• Laboratory tests:
On
discharge
Today
Sodium (mEq/L)
137
139
Potassium (mEq/L)
4.7
5.3
BUN (mg/dL)
20
21
Creatinine (mg/dL)
1.1
1.3
Slide 50
CASE 3 (3 of 4)
Which of the following is the most appropriate next step?
(A) Discontinue spironolactone.
(B) Discontinue potassium supplement.
(C) Decrease lisinopril dosage.
(D) Increase lisinopril dosage.
(E) Change furosemide schedule to a single daily dose.
Slide 51
CASE 3 (4 of 4)
Which of the following is the most appropriate next step?
(A) Discontinue spironolactone.
(B) Discontinue potassium supplement.
(C) Decrease lisinopril dosage.
(D) Increase lisinopril dosage.
(E) Change furosemide schedule to a single daily dose.
Slide 52
ACKNOWLEDGMENTS
Editor:
Annette Medina-Walpole, MD
GRS7 Chapter Author:
Todd P. Semla, MS, PharmD
GRS7 Question Writer:
Shelly L. Gray, PharmD, MS
Medical Writers:
Beverly A. Caley
Faith Reidenbach
Managing Editor:
Andrea N. Sherman, MS
Copyright © 2010 American Geriatrics Society
Slide 53