Prescribing in Geriatrics

Objectives
1. Understand key issues in geriatric
pharmacotherapy
2. Understand the effect age on
pharmacokinetics and
pharmacodynamics
3. Discuss risk factors for adverse drug
events and ways to mitigate them
4. Understand the principles of drug
prescribing for older patients
Prescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
2

Challenges of Geriatric
Pharmacotherapy
 New drugs available each year
 FDA approved and off-label indications are expanding
 Changing managed-care formularies
 Advanced understanding of drug-drug interactions
 Increasing popularity of “nutriceuticals”
 Multiple co-morbid states
 Polypharmacy
 Medication compliance
 Effects of aging physiology on drug therapy
 Medication cost
3

Why is guideline required for Geriatric
Prescription?
➢ Elderly patients are at higher risk of adverse
events.
➢ ADRs are 2 to 3 times greater compared to
younger patients.
➢ Studies shows that 1/5 of all patients above 65
years experiences an ADR.
4

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
5

Predictors of Adverse Drug Events
> 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
6

7

8

9

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
10

Pharmacokinetics (PK)
Absorption
 bioavailability: the fraction of a drug dose reaching the systemic
circulation
Distribution
 locations in the body a drug penetrates expressed as volume per
weight (e.g. L/kg)
Metabolism
 drug conversion to alternate compounds which may be
pharmacologically active or inactive
Elimination
 a drug’s final route(s) of exit from the body expressed in terms of half-
life or clearancePrescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
11

Effects of Aging on Absorption
Rate of absorption may be delayed
Lower peak concentration
Delayed time to peak concentration
Overall amount absorbed (bioavailability)
is unchanged
12

Hepatic First-Pass Metabolism
For drugs with extensive first-pass
metabolism, bioavailability may increase
because less drug is extracted by the liver
Decreased liver mass
Decreased liver blood flow
13

Factors Affecting Absorption
Route of administration
What it taken with the drug
Divalent cations (Ca, Mg, Fe)
Food, enteral feedings
Drugs that influence gastric pH
Drugs that promote or delay GI motility
Comorbid conditions
Increased GI pH
Decreased gastric emptying
DysphagiaPrescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
14

Effects of Aging on Volume of Distribution (Vd)
Aging Effect Vd Effect Examples
 body water  Vd for hydrophilic
drugs
ethanol, lithium
 lean body mass  Vd for for drugs
that bind to muscle
digoxin
 fat stores  Vd for lipophilic
drugs
diazepam, trazodone
 plasma protein
(albumin)
 % of unbound or
free drug (active)
diazepam, valproic acid,
phenytoin, warfarin
 plasma protein
(1-acid glycoprotein)
 % of unbound or
free drug (active)
quinidine, propranolol,
erythromycin, amitriptyline
Prescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD 15

Aging Effects on Hepatic
Metabolism
Metabolic clearance of drugs by the liver may be
reduced due to:
decreased hepatic blood flow
decreased liver size and mass
Examples: morphine, meperidine, metoprolol,
propranolol, verapamil, amitryptyline, nortriptyline
16

Metabolic Pathways
Pathway Effect Examples
Phase I: oxidation,
hydroxylation,
dealkylation, reduction
Conversion to
metabolites of lesser,
equal, or greater
diazepam, quinidine,
piroxicam,
theophylline
Phase II:
glucuronidation,
conjugation, or
acetylation
Conversion to inactive
metabolites
lorazepam, oxazepam,
temazepam
** NOTE: Medications undergoing Phase II hepatic metabolism
are generally preferred in the elderly due to inactive metabolites
(no accumulation)

High Extraction
Examples of high ER drugs with decreased
clearance:
Meperidine, morphine
Metoprolol, propranolol
Amitriptyline, nortriptyline
Verapamil
18

Other Factors Affecting Drug
Metabolism
Gender
Comorbid conditions
Smoking
Diet
Drug interactions
Race
Frailty
19

Concepts in Drug Elimination
Half-life
time for serum concentration of drug to decline by
50% (expressed in hours)
Clearance
volume of serum from which the drug is removed per
unit of time (mL/min or L/hr)
Reduced elimination  drug accumulation and
toxicity
20

Effects of Aging on the Kidney-Renal
Elimination
Decreased kidney size
Decreased renal blood flow
Decreased number of functional nephrons
Decreased tubular secretion
Result:  glomerular filtration rate (GFR)
Decreased drug clearance: atenolol,
gabapentin, H2 blockers, digoxin,
allopurinol, quinolones
21

Examples of Renally Eliminated
Drugs
Metoclopramide, H2-blockers, digoxin,
gabapentin, atenolol, nadolol, allopurinol,
magnesium laxatives, chlorpropamide
Aminoglycosides, cephalosporins, penicillins,
quinolones, vancomycin
22

Renally-Eliminated Active Metabolites
Meperidine (normeperidine)
Morphine (M3G and M6G)
Propoxyphene (norpropoxyphene)
Venlafaxine (O-desmethylvenlafaxine)
Carbamazepine (Carbamazepine-10,11-epoxide)
23

Estimating GFR in the Elderly
Creatinine clearance (CrCl) is used to
estimate glomerular rate
Serum creatinine alone not accurate in the
elderly
 lean body mass  lower creatinine production
 glomerular filtration rate
Serum creatinine stays in normal range,
masking change in creatinine clearance
24

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
**Formula for IBW(Ideal Body Weight)
For males: IBW=50kg+2.3kg * each inch over over 5 feet
For females: IBW=45.5kg+2.3kg * each inch over 5 feetPrescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
25

Example: Creatinine Clearance vs.
Age in a 5’5”, 55 kg Woman
301.190
411.170
531.150
651.130
CrClScrAge
26

Limitations in Estimating CrCl
Not all persons experience significant age-related
decline in renal function
Some patient’s muscle mass is reduced beyond that of
normal aging
Suggest using 1 mg/dL if serum creatinine is less than normal
(<0.7 mg/dL)
Not precise, may underestimate actual CrCl
27

Pharmacodynamics (PD)
Definition: the time course and intensity of
pharmacologic effect of a drug
Age-related changes:
 sensitivity to sedation and psychomotor
impairment with benzodiazepines
 level and duration of pain relief with narcotic
agents
 drowsiness and lateral sway with alcohol
 HR response to beta-blockers
 sensitivity to anti-cholinergic agents
 cardiac sensitivity to digoxinPrescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
28

Pharmacodynamics and Aging
 Some effects are increased
 alcohol increases drowsiness and lateral
sway
 e.g. diazepam, morphine, theophylline
 Some effects are decreased
 diminished HR response to -blockers
29

PK and PD Summary
PK and PD changes generally result in decreased
clearance and increased sensitivity to medications
in older adults
Use of lower doses, longer intervals, slower titration
are helpful in decreasing the risk of drug
intolerance and toxicity
Careful monitoring is necessary to ensure successful
outcomes
30

Risk Factors for Drug Related
Problems in the Elderly
Suboptimal prescribing
Medication Errors
Medication nonadherence
31

Optimal Pharmacotherapy
Balance between overprescribing and
underprescribing
Correct drug
Correct dose
Targets appropriate condition
Is appropriate for the patient
Avoid “a pill for every ill”
Always consider non-pharmacologic therapy
32

Medication Appropriateness Index
1. Is there an indication?
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 interactions?
7. Are there clinically significant drug-disease
interactions?
8. Is there unnecessary duplication?
9. Is the duration of therapy acceptable?
10. Is this drug the least expensive alternative?Prescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
33

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
34

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?
35

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
36

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
37

Optimize Drug
Therapy
Overprescribing
Under
prescribing
38

Consequences of Overprescribing
Adverse drug events (ADEs)
Drug interactions
Duplication of drug therapy
Decreased quality of life
Unnecessary cost
Medication non-adherence
39

Adverse Drug Events (ADEs)
Responsible for 5-28% of acute
geriatric hospital admissions
Greater than 95% of ADEs in the
elderly are considered
predictable and approximately
50% are considered preventable
Most errors occur at the ordering
and monitoring stages
40

Most Common Medications
Associated with ADEs in the Elderly
Opioid analgesics
NSAIDs
Anticholinergics
Benzodiazepines
Also: cardiovascular agents, CNS agents, and
musculoskeletal agents
41

The Beers Criteria
High Potential for
Severe ADE
High Potential for
Less Severe ADE
amitriptyline
chlorpropamide
digoxin >0.125mg/d
disopyramide
GI antispasmodics
meperidine
methyldopa
pentazocine
ticlopidine
antihistamines
diphenhydramine
dipyridamole
ergot mesyloids
indomethacin
muscle relaxants

Patient Risk Factors for ADEs
Polypharmacy
Multiple co-morbid conditions
Prior adverse drug event
Low body weight or body mass
index
Age > 85 years
Estimated CrCl <50 mL/minPrescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
43

Prescribing Cascade
Drug 1
Adverse drug effect
misinterpreted as new
medical condition
Drug 2
Adverse Drug
Effect
Drug 3
44

Drug-Drug Interactions (DDIs)
May lead to adverse drug events
Likelihood  as number of medications 
Most common DDIs:
cardiovascular drugs
psychotropic drugs
Most common drug interaction effects:
confusion
cognitive impairment
hypotension
acute renal failure
45

Concepts in Drug-Drug Interactions
Absorption may be  or 
Drugs with similar effects can result additive
effects
Drugs with opposite effects can antagonize
each other
Drug metabolism may be inhibited or induced
46

Common Drug-Drug Interactions
Combination Risk
ACE inhibitor + potassium Hyperkalemia
ACE inhibitor + K sparing diuretic Hyperkalemia, hypotension
Digoxin + antiarrhythmic Bradycardia, arrhythmia
Digoxin + diuretic
Antiarrhythmic + diuretic
Electrolyte imbalance; arrhythmia
Diuretic + diuretic Electrolyte imbalance; dehydration
Benzodiazepine + antidepressant
Benzodiazepine + antipsychotic
Sedation; confusion; falls
CCB/nitrate/vasodilator/diuretic Hypotension

Common Drug-Disease Interactions
Combination Risk
NSAIDs + CHF
Thiazolidinediones + CHF
Fluid retention; CHF exacerbation
BPH + anticholinergics Urinary retention
CCB + constipation
Narcotics + constipation
Anticholinergics + constipation
Exacerbation of constipation
Metformin + CHF Hypoxia; increased risk of lactic
acidosis
NSAIDs + gastropathy Increased ulcer and bleeding risk
NSAIDs + HTN Fluid retention; decreased
effectiveness of diuretics

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 metabolism
and excretions of drugs
Drugs may exacerbate a medical condition
49

Drug-Disease Interactions
Decongestants and anticholinergics → BPH
CCB’s and anticholinergics → constipation
NSAIDs → Heart Failure
50

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
51

Identify the drug listed below that has been
associated with osteoporosis in elderly adults.
a.Alprazolam
b.Divalproex
c.Fluoxetine
d.Risperidone
52

 Glucocorticoids
 Anticonvulsants
 Excessive thyroid replacement
 Gonadotropin-releasing hormone analogues
53

GENERAL PRINCIPLES
1. Start with a low dose, & titrate the medication
dose slowly.
2. Half life of many drugs are prolonged due to
reduced hepatic and renal function.
3. Optimal therapeutic response is not obtained
with rapid dose escalation because steady
state conc. of the drug is not reached.
4. Fewest no: of drugs should be used to treat pts.
5. Always evaluate possible drug toxicity.
54

Prescribing Appropriately
 Determine therapeutic endpoints and plan for assessment
 Consider risk vs. benefit
 Avoid prescribing to treat side effect of another drug
 Use 1 medication to treat 2 conditions
 Consider drug-drug and drug-disease interactions
 Use simplest regimen possible
 Adjust doses for renal and hepatic impairment
 Avoid therapeutic duplication
 Use least expensive alternative
55

Preventing Polypharmacy
Review medications regularly and each
time a new medication started or dose is
changed
Maintain accurate medication records
(include vitamins, OTCs, and herbals)
“Brown-bag”
56

Brown Bag
Rx, OTC, Herbal, Vitamins, Supplements
Ask what each medication for
Ask how it is taken
Discontinue unnecessary medications
57

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!
58

Medication Adherence is big
problem??
59

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
60

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
• CostPrescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
61

Strategies to Ensure Adherence
 Find out about patient/family expectations; explain why
some may not be met
 Provide information on illness / consequences of non-
adherence
 Use a behavioral contract
 Increase motivation by enlisting patient/family in
decision-making process
62

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
63

Use Adherence Enhancing Aids
 Medication record
 Drug calendar
 Medication boxes
 Magnification for insulin syringes
 Spacers for MDI’s
64

Summary
Successful pharmacotherapy means using
the correct drug at the correct dose for
the correct indication in an individual
patient
Age alters PK and PD
ADEs are common among the elderly
Risk of ADEs can be minimized by
appropriate prescribing
65

Case Study
66

Patient A is 82 years of age with a history of congestive heart
failure, glaucoma, hypertension, and osteoarthritis. Her
current medications are furosemide, potassium, lisinopril,
metoprolol, aspirin, timolol maleate opthamic solution
(Timoptic), acetaminophen (as needed), multivitamin,
and a calcium/vitamin D supplement (800 IU daily). She
has an appointment with a new orthopedic physician.
During the appointment, the patient complains of
persistent arthritic pain in her knee. The physician
prescribes the NSAID meloxicam (7.5 mg per day) for pain
and inflammation.
Case 1:
67

Case 1: Comments and Discussion
 From the orthopedic standpoint, prescription of meloxicam is good
practice, as it should help to ameliorate patient A's symptoms.
However, from a cardiac standpoint, this is a risky approach due to
the potential side effect of fluid retention and its effect on the heart. In
general, NSAIDs can be dangerous for an individual of Patient A's age.
NSAIDs (including meloxicam, but also over-the-counter options like
ibuprofen) have been issued "black box" warnings by the U.S. Food
and Drug Administration for the increased risk of:
 Serious and potentially fatal cardiovascular and thrombotic events,
including myocardial infarction and stroke
 Serious adverse gastrointestinal events such as bleeding, ulcer, and
intestinal perforation (higher in elderly patients)
68

 Patient A has a good working relationship with her primary care
provider, who has instructed her to contact him regarding any
changes in her medication regimen. She calls her physician prior to
taking the medication, and he advises her not to take the NSAID.
Instead, he devises a pain management plan that minimizes the
potential risks. Previously, Patient A was taking acetaminophen as
needed, averaging up to one dose daily. This is increased to twice
daily extended-release acetaminophen (650 mg). For breakthrough
pain, tramadol 25 mg every four hours (as needed) is prescribed.
Another option considered was the topical anti-inflammatory
diclofenac sodium 1% topical gel, which would have fewer side
effects than systemic agents. Aside from pharmacotherapy, the
patient is scheduled with a physical therapist to create a safe exercise
plan, including strengthening and range-of-motion exercises.
69

Case 2:
 Patient B is a man, 78 years of age, who resides in a nursing facility. One
year ago, he fell and fractured his left hip and underwent surgical repair.
He returned to the nursing facility, completed rehabilitation, and
regained most of his prior function. After the surgery, Patient B was
prescribed warfarin to prevent deep vein thrombosis (DVT) after surgery.
During a routine survey, a state surveyor discovers that Patient B is still
being administered warfarin. After further investigation, it is discovered
that the warfarin was never discontinued after the appropriate duration
after the hip fracture repair. The surveyor considers warfarin an
unnecessary drug, and a citation (F-Tag 329) is issued. After contacting
the attending physician, the warfarin is promptly discontinued.
70

Case 2: Comments and Discussion
 Patient B's case is an example of using the right drug but not using it for the correct
duration. After orthopedic surgery, warfarin is usually indicated for approximately two
to three months or until activity/ambulation has increased to a point that the risk of DVT
is reduced. There is a substantial burden of treatment with warfarin, including weekly
evaluations of prothrombin time/international normalized ratio (PT/INR), adverse
reactions, interactions, and increased risk of bleeding and brain hemorrhage,
especially for patients with a history of falls.
 There is shared responsibility for this error between the prescriber/healthcare provider
and the facility. The provider did not follow through and discontinue the medication
when it was no longer needed, and the facility nursing staff should have realized that
the drug was no longer necessary and approached the provider for an order to
discontinue. The nursing facility could have called the orthopedic physician for orders
and duration of warfarin treatment after surgery. When a medication is started, the
stop date for that medication should be considered and established. The consultant
pharmacist could have intervened as well.
71

All ill don’t have pill…!!
72

References
 Clin Geriatr Med 1998;14:681
 J Gerontol 1998;(53A9A):M59
 JAMA 2003;289:1107
 Arch Intern Med 2003;163:2716-2724
 Haynes RB, et al. Patient Education and Counseling; 1987;10:155-166
 Better prescribing in the elderly; CGS Journal of CME; volume 2, issue 3,
2012
 Prescribing for older people; James C Milton, Ian Hill-Smith and Stephen H
D Jackson; BMJ 2008;336;606-609
 Doucet J, Chassagne P, Trivalle C, et al. Drug-drug interactions
related to hospital admissions in older adults: a prospective study of
1000 patients. J Am Geriatr Soc 1996;44(9):944-948.Prescribing Guidelines for Geriatrics: Dr. Asish Kumar Saha, PharmD
73

Don’t forget:
If no Accident ;
Every one will
become a Geriatric
We don’t need your “Money” or
“Property”….
What we need is “Love”, “Care” &
“Affection”….!!
74

Prescribing in Geriatrics

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