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1. GERIATRIC PHARMACOLOGY
Ravish Yadav

3.  20% of hospitalizations for those >65 are due
to medications they’re taking
Adults >65 years old

4.  Alzheimer`s disease
 Parkinsonism
 Stroke
 Vascular dementia
 Visual impairment specially cataracts and macular degeneration
 Atherosclerosis
 Arthritis
 Heart failure
 Fractures
 Cancer
 Diabetes
 Heart failure
Diseases with increased
incidence in elderly

5.  Physiologic change
◦ Decreased gastric acidity
◦ Decreased gastrointestinal blood flow
◦ Delayed gastric emptying
◦ Slowed intestinal transit time
 General clinical effect
◦ None on passive diffusion or bioavailability for most
drugs
◦ Decreased active transport: Decreased bioavailability
for some drugs
◦ Decreased first-pass effect: Increased bioavailability
for some drugs
Physiologic Changes of Aging Affecting Absorption

6.  Decreased Total body water
◦ Increased Plasma Conc. of water soluble drugs
◦ Lower doses are required: Lithium, digoxin, ethanol, etc
 Decreased Lean body mass
◦ Increased Volume Distribution, Longer (t½) of water soluble
drugs
◦ Accumulation into fat of lipid soluble drugs: Benzos, etc
 Decreased Serum Albumin
◦ Increased unbound fraction of highly protein bound drugs
◦ Binds acidic drugs: warfarin, phenytoin, digitalis, etc
 Decreased Alpha1 Acid glycoprotein
◦ Increased unbound fraction of highly protein bound drugs
◦ -Binds basic drugs: lidocaine and propranolol, etc
Physiologic Changes of Aging
Affecting Distribution

7.  Difficult to predict, depends on
General health & nutritional status
 Use of alcohol, medications
Long term exposure to environmental toxins/pollutants
 Aging causes decreased liver mass/ hepatic blood
flow
Delayed/reduced metabolism of drugs
Higher plasma levels
Greatest changes in phase 1 reaction those carry out
microsomal p450 enzyme system
Decline in liver ability to recover from injury
 Lower serum protein levels
Loss of protein binding
 Idiosyncratic reactions
Physiological changes of
aging affecting metabolism

8.  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
Aging Effects on Hepatic
Metabolism

9.  Determined
◦ Primarily by renal function
◦ Declines with age and is worsened by co-morbidities
◦ Decline is not reflected in an equivalent rise in
serum creatinine since creatinine production is
reduced due to lower muscle mass
Physiological changes of aging
affecting elimination

10.  Physiologic change
◦ Decreased GFR
◦ Decreased renal blood flow
◦ Decreased renal mass
 General clinical effect
◦ Decreased clearance, Increased (t½) of renally
eliminated drugs
Physiologic Changes of Aging
Affecting Elimination

11.  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
Estimating GFR in the Elderly

12.  Measure
◦ Time consuming
◦ Requires 24 hr urine collection
 Estimate
◦ Cockroft Gault equation
(IBW in kg) x (140-age)
------------------------------ x (0.85 for
females)
72 x (Scr in mg/dL)
Determining Creatinine
Clearance

13.  Pharmacodynamic changes in the elderly have
been less extensively studied
 Evidence of enhanced end-organ responsiveness
or “sensitivity” to medications with aging
 Enhanced “sensitivity” may be due
◦ Changes in receptor affinity
◦ Changes in receptor number
◦ Post-receptor alteration
◦ Age-related impairment of homeostatic mechanisms
Example: decreased baroreceptor reflexes
Pharmacodynamic changes in
elderly

14.  Age-related changes:
◦  sensitivity to sedation and psychomotor
impairment with benzodiazepines
◦  level and duration of pain relief with narcotic
agents
◦  drowsiness with alcohol
◦  sensitivity to anti-cholinergic agents
◦  cardiac sensitivity to digoxin

15.  Cognitive changes associated with vascular
and other pathology
 Economic stresses with greatly associated
with reduced income or due increased
expenses due to illness
 Loss of spouse
Behavioral and lifestyle
changes

16.  Positive relationship between number of drugs
taken and incidence
 Overall incidence is estimated to be at least twice
that in the younger population
 Prescribing errors
◦ Polypharmacy
◦ Drug interactions with other prescriptions
◦ Unawareness of age related physiologic changes
 Drug usage errors
◦ “Hidden ingredients”: OTCs
Major Reasons for Adverse Drug
Reactions in the Elderly

17. Factors contributing to adverse drug reactions
in elderly patients
Polypharmacy
How many prescription medications are too many? >4 or >6
Many elderly people receive 12 medications per day
Heart, kidney, liver,
thyroid

18.  Economic factors
◦ May have to choose between food and medications
 OTCs instead of expensive doctor visits
 Use of outdated medications
 Use of home remedies
 Share medications
 Nutritional status may affect how body metabolizes
medications

19.  Concurrent use of multiple medications
◦ >65 = 12% of population
◦ Consume 30% of all prescription drugs [average
person takes 4-5 prescription meds]
◦ Consume 40% of OTCs
 Excessive use of drugs
 Overdose of a drug
Polypharmacy

20.  Risks of problems:
◦ Medication errors
 Wrong drug, time, route
◦ Adverse effects from each drug
 Polypharmacy primary reason for adverse reactions
◦ Adverse interactions between drugs
Polypharmacy

21.  CNS drugs
◦ Sedative-hypnotics: Benzodiazepines and barbiturates
◦ Analgesics: Opioids
◦ Antipsychotic, antidepressants: Haloperidol, lithium, TCAs
 Cardiovascular drugs
◦ Antihypertensives: Thiazides, beta-blockers
 Antiarrhythmic drugs
◦ Quinidine and procainamide:  clearance and  (t½)
 Antimicrobial drugs
◦ Beta-lactams and aminoglycosides:  clearance
 Anti-inflammatory drugs
◦ NSAIDs: GI bleed and irritation
Major Drug Groups Requiring Monitoring

22.  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
Optimal Pharmacotherapy

23.  Polypharmacy
 Multiple co-morbid conditions
 Prior adverse drug event
 Low body weight or body mass index
 Age > 85 years
 Estimated CrCl <50 mL/min
Patient Risk Factors for ADEs

24. 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

25. 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

26.  Avoid prescribing prior to diagnosis
 Start with a low dose
 Avoid starting 2 agents at the same time
 Reach therapeutic dose before switching or
adding agents
 Consider non-pharmacologic agents
Principles of Prescribing in the
Elderly

27.  Review medications regularly and each time a
new medication started or dose is changed
 Maintain accurate medication records (include
vitamins, OTCs, and herbals)
Preventing Polypharmacy

28.  Suggest physician prescribe combination
drugs or long-acting forms
◦ Fewer pills to remember
 Suggest re-evaluation of medications
periodically
 Encourage client to use one pharmacy
 New medications
◦ Good information
◦ Encourage follow up
If client taking > five meds
regularly

29.  There are several practical obstacles to
compliance that the prescriber must recognize
◦ Forgetfulness
◦ Prior experience
◦ Physical disabilities
 Recommendations to improve compliance
◦ Take careful drug history
◦ Prescribe only for a specific and rational indication
◦ Define goal of drug therapy
◦ High index of suspicion regarding drug reactions and
interactions
◦ Simplify drug regimen
Compliance

30.  Avoid newer, more expensive medications
that are not shown to be superior to less
expensive generic alternatives
 Simplify the regimen
 Utilize pill organizers or drug calendars
 Educate patient on medication purpose,
benefits, safety, and potential ADEs
Enhancing Medication
Adherence

31.  Basic and Clinical Pharmacology by Bertram
G. Katzung Susan B. Master
References