Transcript Principles of Geriatric Drug Therapy

Principles of Geriatric
Drug Therapy
Beata Ineck, Pharm.D, BCPS, CDE
University of Nebraska Medical Center
College of Pharmacy
Omaha VA
Objectives
1. Review predictors for adverse drug events
in the elderly.
2. Discuss pharmacokinetic changes in the
elderly and how they alter medications.
3. Discuss pharmacodynamics and the
effects of aging.
4. Review criteria for appropriate prescribing
in the elderly.
• 30% of admissions due to drug related
problems
• 2/3 of nursing facility residents have
ADE over 4 years
• 106,000 deaths and $85 billion for
medication related problems in 2000
• 5th cause of death
Arch Intern Med 2003;163:2716-2724
Predictors of Adverse Drug Events
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> 4 prescription medications
Length of stay in hospital > 14 days
> 4 active medical problems
Admission to general medical unit
History of alcohol use
Lower mean MMSE score
2-4 new medications added during
hospitalization
Clin Geriatr Med 1998;14:681.
J Gerontol 1998;53A9A):M59
JAMA 2003;289:1107
AGE RELATED CHANGES
Geriatric Brain Function
• Brain mass and cerebral blood flow 
• BBB may become more permeable
• Secondary memory may be diminished
• Short term memory difficulties 2° to decline in
– Learning
– Information retrieval
– Processing speed
Pharmacokinetics and Aging
• Behavior of drugs in the body
• Absorption, distribution, metabolism,
elimination
• Removal of drugs from the body is slowed
Absorption
• Increased GI pH
– Calcium carbonate, “azoles”, iron
• Slower gastric motility/emptying
• Increased fat/decreased muscle
– Transdermal, IM, SQ
• Dysphagia may potentially alter absorption
Overall, extent or rate of absorption not significantly altered
Distribution
• Increased Vd for water soluble drugs
•  in body fat
•  in serum proteins
Pharmacokinetics and Aging
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Identify the drug below that is
metabolized more slowly in elderly
adults than in young adults.
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Amlodopine
Atorvastatin
Metoclopramide
Morphine
Pharmacokinetics and Aging
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Identify the drug below that is
metabolized more slowly in elderly
adults than in young adults.
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Amlodopine
Atorvastatin
Metoclopramide
Morphine
Metabolism
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Drugs with a high extraction ratio (ER)
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Decreased clearance:
• reduced hepatic blood flow
• reduced liver mass
High Extraction
• Examples of high ER drugs with decreased
clearance:
– Meperidine, morphine
– Metoprolol, propranolol
– Amitriptyline, nortriptyline
– Verapamil
Metabolism
• Decreased oxidative (phase I, P-450)
metabolism due to reduced liver
volume and perfusion.
– Diazepam, piroxicam, theophylline,
quinidine
– Confounded by smoking, diet, drug
interactions, race, sex, and frailty
Patient Case
An 82 year old white woman has been
having anxiety due to the anniversary of her
husband’s death. Which one of the
following would be the safest pharmacologic
treatment for her anxiety?
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Alprazolam
Chlordiazepoxide
Diazepam
Lorazepam
An 82 year old white woman has been
having anxiety due to the anniversary of her
husband’s death. Which one of the
following would be the safest pharmacologic
treatment for her anxiety?
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Alprazolam
Chlordiazepoxide
Diazepam
Lorazepam
Metabolism
• No change in phase 2 metabolism
– Lorazepam, oxazepam, temazepam
Renal Elimination
• Identify the drug below that is renally
excreted more slowly in elderly adults
than in young adults.
Celecoxib
Gabapentin
Morphine
Sertraline
Renal Elimination
• Identify the drug below that is renally
excreted more slowly in elderly adults
than in young adults.
Celecoxib
Gabapentin
Morphine
Sertraline
Renal Elimination
Decrease in:
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Kidney mass
Nephron size and number
Renal blood flow
Tubular secretion
Glomerular filtration rate
Examples of Renally Eliminated
Drugs
– Metoclopramide, H2-blockers, digoxin,
gabapentin, atenolol, nadolol, allopurinol,
magnesium laxatives, chlorpropamide
– Aminoglycosides, cephalosporins,
penicillins, quinolones, vancomycin
Renally-Eliminated Active
Metabolites
• Meperidine (normeperidine)
• Morphine (M3G and M6G)
• Propoxyphene (norpropoxyphene)
• Venlafaxine (O-desmethylvenlafaxine)
• Carbamazepine (Carbamazepine-10,11epoxide)
Drug Dosing and Measures of
Renal Function
• Use creatinine clearance
– Calculated or measured
Estimated CrCl (ml/min) = (140-age) x (IBW) * 0.85 for females
72 x SCr
– If SCr < 1, use SCr = 1 to adjust for  muscle mass
• Serum creatinine (used alone)
– An unreliable marker in elderly
Example: Creatinine Clearance
vs. Age in a 5’5”, 55 kg Woman
Age
Scr
CrCl
30
1.1
65
50
1.1
53
70
1.1
41
90
1.1
30
Pharmacodynamics and Aging
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Some effects are increased
– alcohol increases drowsiness and lateral
sway
– e.g. diazepam, morphine, theophylline
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Some effects are decreased
– diminished HR response to -blockers
Pharmacodynamics: Acetylcholine
Blockers
• Decreased tolerance to adverse effects
• Constipation, urinary retention
• Dry mouth, dry eyes, dry skin
• Memory impairment
• Delirium
Pharmacodynamics: Digoxin
• Pattern of toxicity – young vs. elderly
• Increased cardiac sensitivity to digoxin
due to:
– Hypokalemia, hypothyroidism,
hypomagnesemia, hypercalcemia, acute
hypoxia
Pharmacodynamics: Dopamine
Blockers
• CNS dopamine decline
• Adverse drug effects from antipsychotic
agents, metoclopramide
– Extrapyramidal effects
– Parkinsonism
– Tardive dyskinesia
Risk Factors for Drug Related
Problems in the Elderly
• Suboptimal prescribing
• Medication Errors
• Medication nonadherence
Medication Appropriateness Index
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Is there an indication?
Is the medication effective for the condition?
Is the dosage correct?
Are the directions correct?
Are the directions practical?
Are there clinically significant drug-drug
interactions?
Are there clinically significant drug-disease
interactions?
Is there unnecessary duplication?
Is the duration of therapy acceptable?
Is this drug the least expensive alternative?
Additional Criteria for Drug Use
• Compatible safety and side effect profile
• Low risk of drug/nutrient interactions
• T1/2 < 24h with no active metabolites
• No adjustments for renal/hepatic function
• Strength/dosage form match
recommendations for older adults
Newer Drugs
• What is unique about the new drug?
• Is clinical data available?
• How does it compare with traditional
therapy?
• Cost?
• Coverage by third party payers?
• Does potential advantage justify risk of
new drug?
How to Prescribe Appropriately
1. Obtain complete drug history
2. Avoid prescribing prior to diagnosis
3. Review medications regularly
4. Know actions, adverse effects, toxicity
5. Start at low dose and titrate
6. Try not to start two drugs at the same time
7. Reach therapeutic dose before
switching/adding
8. Consider non-pharmacological alternatives
How to Prescribe Appropriately
7. Educate patient/caregiver
8. Use one drug to treat two conditions
9. Keep regimen as simple as possible
10. Caution with combination products
11. Communicate with other prescribers
12. Avoid drugs from same class/similar actions
13. Avoid one drug to treat side effect of another
Drug 1
Adverse drug effect
misinterpreted as
new medical
condition
Drug 2
Adverse
Drug Effect
Prescribing Cascade
BMJ. 1997;315:1097
Underprescribing
Overprescribing
Optimize Drug
Therapy
Patient Case
A 78 year old African American man has a hx of
falls. He also has a hx of DM, HTN, depression
and insomnia. He is currently taking glipizide
5mg qd, HCTZ 25mg qd, sertraline 25mg qd,
and diazepam 2mg prn insomnia. His BP is
126/62, HR 68, RR 18, CBC WNL, BUN/SCr
28/1.2, HbA1c 7.2%, Chol 109, TG 58, HDL 41,
LDL 56. Which one of the following
medications is underutilized?
a.
b.
c.
d.
Aspirin
Beta blocker
HMG CoA reductase inhibitor
Warfarin
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b.
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Aspirin
Beta blocker
HMG CoA reductase inhibitor
Warfarin
Undertreatment
• CAD
– -blockers
– Aspirin
• Anticoagulation for A Fib
• HTN
• Pain
Drug-Food Interactions
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Warfarin and vitamin K
Methotrexate and folate
Phenytoin and vitamin D metabolism
Impact on appetite
– taste alteration
– decreased saliva production
Drug-Disease Interactions
• Decongestants and anticholinergics  BPH
• CCB’s and anticholinergics  constipation
• NSAIDs  Heart Failure
NSAIDs
• Side effects
– GI hemorrhage
– Decline in GFR
• Decreased effectiveness of diuretics
and antihypertensives
• For mild OA, use acetaminophen
Anticipate Side Effects
• Narcotics
– begin stimulant laxative
– docusate not sufficient
• Steroids
– osteoporosis prevention
– hyperglycemia
Drug-Induced Osteoporosis
• Identify the drug listed below that has
been associated with osteoporosis in
elderly adults.
a.Alprazolam
b.Divalproex
c.Fluoxetine
d.Risperidone
Drug-Induced Osteoporosis
• Identify the drug listed below that has
been associated with osteoporosis in
elderly adults.
a.Alprazolam
b.Divalproex
c.Fluoxetine
d.Risperidone
Drug-Induced Osteoporosis
• Glucocorticoids
• Anticonvulsants
• Excessive thyroid replacement
• Gonadotropin-releasing hormone
analogues
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Potential Barriers to
Improving Adherence
Poor attitude
Memory deficits
Language
Literacy
Cultural beliefs
Alternative health
beliefs
• Poor support
• Pride
• Denial
• Fear or
embarrassment
• Side effects
• Religious beliefs
• Unable to “see”
results of drug
therapy
• Lack of choices
• Cost
Vermiere E, et al. J Clin Pharm Ther. 2001;26:331-342.
Factors Influencing Ability to Comply
•  3 chronic conditions
• > 5 prescription medications
•  12 medication dosages per day
• Regimen changed  4 times in past 12 months
•  3 prescribers
• Significant cognitive or physical impairment
• Living alone in community
• Recently discharged from hospital
• Reliance on caregiver
• Low literacy Medication cost
• Demonstrated poor compliance history
Med Care 1991;29:989
Brown Bag
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Rx, OTC, Herbal, Vitamins, Supplements
Ask what each medication for
Ask how it is taken
Discontinue unnecessary medications
Patterns of Herbal Therapy Use
Among Men and Women 65+
Year Old
• Men
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Garlic
Glucosamine
Saw palmetto
Ginkgo biloba
Lecithin
Chondroitin
Ginseng
• Women
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Ginkgo biloba
Glucosamine
Garlic
Ginseng
Chondroitin
St. John’s wort
Echinacea
Kaufman DW et al, JAMA 2002.
OTC’s
• Elderly take average of 2-4 OTC’s qd
• Laxatives used in 1/3 to 1/2
• NSAIDs, antihistamines, H2 blockers
ALL CAN CAUSE SIDE EFFECTS!
Strategies to Ensure Adherence
• Find out about patient/family expectations;
explain why some may not be met
• Provide information on illness / consequences
of nonadherence
• Use a behavioral contract
• Increase motivation by enlisting patient/family
in decision-making process
Haynes RB, et al. Patient Education and Counseling. 1987;10:155-166
Use Adherence Enhancing Aids
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Medication record
Drug calendar
Medication boxes
Magnification for insulin syringes
Spacers for MDI’s
Strategies to Ensure Adherence
• Ask patient/family to repeat instructions
• Keep directions / labels simple,use lay terms
• Give clear instructions on drug regimen,
preferably in writing
• Emphasize importance of adherence at each
visit
• Involve patient’s spouse or partner
Haynes RB, et al. Patient Education and Counseling. 1987;10:155-166
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Questions?