GERONTOLOGICAL
PHARMACOLOGY UPDATE
Thomas W. Barkley, Jr., DSN, ACNP-BC, FAANP
Professor of Nursing
CONSIDERATIONS
Drug use in the older population
Polypharmacy and inappropriate prescribing
 Senior health considerations
 Drugs for common indications
 Drug dosing in the older patient


◦ Drugs most prone to cause adverse drug reactions
◦ Dosage reduction of commonly prescribed drugs
Director of Nurse Practitioner Programs
California State University, Los Angeles
and
President

Drug of abuse
Barkley & Associates
Pharmacotherapeutics in the Geriatric
Patient
Older adults (age>65) are the fastest growing
segment of the population.
 Most Americans will suffer from at least 3
chronic illnesses.
 Adults over 65 consume over 30% of all
prescription meds; 86% have a chronic health
problem requiring meds.
 Elderly also consume the greatest number of
over-the-counter meds.

Pharmacotherapeutics in the Older
Patient
Male Medicare patients are prescribed over 13
medications/year.
 Female Medicare patients are prescribed over
16 medications/year.

Pharmacotherapeutics in the Older
Patient
Over 20% of hospitalizations in adults over 65
are due to effects of prescription drugs.
 Polypharmacy and inappropriate prescribing
are major contributors to these
hospitalizations.

WHAT PREDISPOSES
THE OLDER PATIENT
TO ADVERSE DRUG
REACTIONS?
Facts About Adverse
Drug Effects in the Elderly
Predisposing Factors for
Drug Toxicity in the Older Patient
Elderly have more ADEs than any other group
due to greater number of medications and
concurrent disease states.
 ADEs rank 5th after congestive heart failure,
breast cancer, hypertension, and pneumonia
among leading preventable threats to health of
older Americans.
 Increased number and potency of drugs
contributes.
 Elderly population is increasing.

ENVIRONMENTAL FACTORS
COMPLICATING THE PROBLEM
Predisposing Factors for Drug Toxicity in
the Older Patient
Gastrointestinal tract: Altered gastric pH
(more alkaline) and altered GI transit time due
to the use of stimulant laxatives.
 Dietary factors: Such as grapefruit juice,
vitamins, alcohol use.
 Smoking: Affects the metabolism of tricyclic
antidepressants, propranolol, neuroleptics,
theophylline and warfarin.



Metabolism and Polypharmacy
Use of medications that interfere with drug
metabolism at the same cytochrome P450
enzyme also elevates risk of cognitive adverse
effects (e.g. CYP3A inhibitor, fluoxetine with
alprazolam can increase risk of oversedation).
 Consider pharmacogenetics as well.

Increased prevalence of chronic disease(s).
Adverse drug effects may go unnoticed or
unreported.
 Decreased drug absorption with increasing age.

Physiological changes which affect drug
metabolism and excretion
◦ Decreased hepatic blood flow
◦ Decreased liver enzyme activity and synthesis
◦ Decreased renal blood flow
 Use creatinine clearance, not serum creatinine, as a
measure.
◦ Decreased renal excretion of drugs
 ALL OF THESE TEND TO INCREASE THE DURATION OF
THE DRUG IN THE BODY.
Gerontological Pharmacology:
Implications For All Prescribers
Effects of Aging on Pharmacokinetics
Absorption
Distribution
 Elimination


EFFECTS OF AGING ON
PHARMACOKINETICS:
DRUG ABSORPTION
Photo by rubberpaw
Effects of Aging on Pharmacokinetics:
Drug Absorption

Effects of Aging on Pharmacokinetics:
Drug Absorption

Elderly may have:
◦ Decreased gastrointestinal motility
◦ Decreased blood flow
◦ Increased gastric pH
• These changes are expected to decrease
gastrointestinal blood absorption, but decreased
motility results in a longer drug absorption time.
• As a result, alternate administration routes for drugs
should be considered.
Effects of Aging on Pharmacokinetics:
Drug Distribution

Volume distribution
◦ Not an actual physiological measurement but
important nonetheless
◦ Volume of distribution (Vd) =
Amount of Drug in the Body
Concentration of Drug in the Blood or Plasma
per Kilogram of Body Weight
Gastrointestinal
conditions may further
complicate drug
absorption
• Little information regarding absorption of:
–
–
–
–
Delayed release formulation
Transdermal administration
Transbuccal administration
Transbronchial administration
Effects of Aging on Pharmacokinetics:
Drug Distribution

The volume of distribution determines the
loading dose of a drug
◦ Loading dose (mg/kg) =
Desired Blood Concentration (mg/L)
Volume of distribution (L/kg)
Effects of Aging on Pharmacokinetics:
Drug Distribution

Aged have lean body mass and body water, thus
decreasing Vd
◦ Decreased Vd will cause drugs that distribute into body
water or muscle will have higher initial plasma
concentration following administration.
◦ Water soluble drugs distributed less effectively in elderly
patients
 Cardiovascular (CV) disease can further complicate this
distribution
◦ Ethanol is thought to be affected by reduced Vd, causing
a higher blood concentration for any quantity Cw4
of ethanol
consumed
Effects of Aging on Pharmacokinetics:
Drug Distribution
More adipose tissue in elderly person increases
the Vd of lipophilic drugs because fat is a depot
for these agents
 The effect and duration of action of some drugs
are increased as both liver size and hepatic
blood flow decrease along with subsequent
hepatic inactivation.
 Renal function in the aged is also decreased,
resulting in higher plasma levels of free drug.

◦ More free drug concentration = more potent effect
Photo by Biggishben
Effects of Aging on Pharmacokinetics:
Drug Distribution

Orosomucoid or alpha-1 glycoprotein binding
is not altered with aging
◦ Neutral pH, basic drugs not affected, as these
typically bind to orosomucoid

However, most drugs are acidic and bound by
serum albumin
◦ Serum albumin and, subsequently, the drug-binding
capacity of most drugs are decreased approximately
12% in the aged, thereby increasing free drug
concentration.
Effects of Aging on Pharmacokinetics:
Drug Distribution
Drug-drug interactions can increase in free
drug concentration when one drug displaces
another from albumin.
 Notable drug-drug interaction occur only if:

◦ Drug is highly bound to plasma albumin
◦ The free drug has a narrow concentration range
between therapeutic and toxic concentration
◦ Drug has small Vd

One such example of drug-drug interaction is
between warfarin and acetylsalicylic acid.
Warfarin
Effects of Aging on Pharmacokinetics:
Drug Distribution

Conditions in which drug-drug interactions can
occur include:
◦
◦
◦
◦
◦
◦
Inhibition of drug absorption
Decreased Hepatic blood flow
Inhibition of renal excretion
Inhibition or stimulation of drug metabolism
Displacement from albumin binding
Pharmacodynamic effects of drugs on tissue
Acetylsalicylic acid
Effects of Aging on Pharmacokinetics:
Drug Distribution

Narcotic analgesics also affected by decreased
protein binding
◦ Meperidine study indicated a correlation between
aged patients and higher free drug fractions

Renal disease
◦ Frequent acidosis also results and further decreases
binding
Effects of Aging on Pharmacokinetics:
Drug Elimination

EFFECTS OF AGING ON
PHARMACOKINETICS:
DRUG ELIMINATION
Effects of Aging on Pharmacokinetics:
Drug Elimination: Clearance

Clearance is the amount of blood flow completely
extracted of the drug per unit of time
◦ Not how much drug is removed but how much blood
must be cleared to eliminate the drug
◦ Measured as milliliters per minute per kilogram

◦ Clearance
◦ Half-life
Effects of Aging on Pharmacokinetics:
Drug Elimination: Clearance

Must maintaining plasma-drug concentration
steady state (Css) over time

The absolute rate of drug elimination is
essentially a linear function of the plasma
concentration of the drug.
◦ Use wide range of doses to maintain
Total clearance is the sum of drug clearances of all
organs
◦ For most drugs, a constant fraction of the drug in
plasma is eliminated per unit time.
◦ Liver and kidneys are two major sites

Studies indicate changes in drug clearance are
primarily due to the combination of decreased
blood flow and liver size.
Effects of Aging on Pharmacokinetics:
Drug Elimination: Half-life
Half life = time it takes for drug concentration
in plasma to decrease by ½  Clinical half‐life accounts for volume distribution and clearance
Half-life(t½) = 0.693 x Vd

Clearance
Where effect and duration of drug relate to
levels of the drug in the blood, the processes
that eliminate the drug must also be
considered.

Clearance determines what dose must be
administered per unit of time
Effects of Aging on Pharmacokinetics:
Drug Elimination: Half-life

Rule of thumb for obtaining over 90% Css
is that four doses of the drug are needed,
administered at every half life; thus four
half-lives are needed to remove over 90%
of the drug from the body
◦ Half-lives dictate dosing intervals
◦ Half-lives dictate time necessary for
stabilization or reduction in effects of the
drug in terms of drug concentration
Effects of Aging on Pharmacokinetics:
Drug Elimination: Half-life

Half lives may increase in the aged; not all drugs
are known, but some are.
HEPATIC DRUG
METABOLISM OR P450?
◦ Possibly due to decrease drug clearance or increase
in drug distribution
Hepatic drug metabolism or P450?
Hepatic drug metabolism or P450?
The effect and duration of action of some drugs
are increased, as both liver size and hepatic
blood flow decrease along with subsequent
hepatic inactivation.
 In general, age-related decreases in liver mass,
hepatic enzyme activity, and hepatic blood flow
result in a decrease in the overall metabolic
capacity of the liver in the elderly population.

Hepatic drug metabolism or P450?
Hepatic drug metabolism or P450?
Most studies support an age-related decline in
phase I drug metabolism in elderly persons.
 Age-related decreases in hepatic
biotransformation are associated generally with
the CYP monooxygenase system (CYP450)



◦ Alternate metabolic pathways do not appear to be
markedly affected by age.
◦ Benzodiazepines subject to both phase I and II
metabolism have longer elimination times
Phase I reaction transform parent molecule
◦ Oxidations
◦ Reductions
◦ Hydrolytic reactions

Phase I reactions usually inactivate a bioactive
molecule
Phase II reactions
◦ Glucuronide conjugation
◦ N-acetylation
◦ Sulfate group
The range of capacity between individuals is
greater than changes reported to occur in
individuals as they age.
 Phase II is unchanged in the elderly population

◦ Evidenced by the elimination of sedative-hypnotics such
as oxazepam, a drug subject to only phase II metabolism,
is unchanged in the aged
Oxazepam
Hepatic drug metabolism or P450?

For a drug to undergo substantial first-pass
metabolism by the liver, it must be efficiently
extracted from the blood.
Hepatic drug metabolism or P450?

◦ Hepatic blood flow decreased from 12% to 14% in
the aged, thus decreasing extraction efficiency.
◦ Drugs that have low hepatic clearance (≤0.3) are
substantially bound to plasma proteins with limited
free-drug concentrations, and have relatively little
first-pass metabolism.
Hepatic drug metabolism or P450?
At certain concentrations, ability of liver to
extract and metabolize some drugs will be
insufficient
◦ Proportionately small increase in total drug dose will
result in a large increase in systemic drug
concentration as the kinetics become dose
dependent.
Hepatic drug metabolism or P450?

Increased systemic bioavailability has been shown
for several highly extracted drugs in elderly
persons.
 Decreased rates of gastrointestinal absorption may
reduce bioavailability of highly extracted drugs
because a greater fraction of the drug is
metabolized in the first pass through the liver.

◦ Duration of action for such drugs may be prolonged
because of slow absorption and/or release from depots
or because in situ, a longed-lived drug is derived from a
short-lived prodrug
Decreases in the hepatic
biotransformation of drugs with a
high hepatic extraction ratio in
elderly persons are predicted
from the decrease in liver blood
flow,
◦ There is significant variability
between individuals, though.

Photo by Joxemai
Age-related decreases in hepatic
biotransformation are associated
generally with the CYP
monooxygenase system (CYP450)
◦ Alternate metabolic pathways do
not appear to be markedly affected
by age.
Hepatic drug metabolism or P450?
Hepatic drug metabolism or P450?
The CYP enzymes, a superfamily of heme proteins,
are found in all living species and are involved in
metabolism of a wide variety of chemically diverse
endogenous and exogenous compounds.
 Biotransformation of drugs in the elderly
population is more likely to be the basis of an
adverse drug reaction when the hepatic P-450
family of enzymes is involved.


◦ In the normal healthy population, 6-fold differences in
rates of cytochrome P-450 (CYP) drug metabolism are
observed.
The situation is further complicated because
multiple reactions may occur for a given drug that
involves CYP enzymes; many drugs are known to
be inducers of selective CYP enzymes that may or
may not be involved in their own metabolism.
 Therefore, hypothetically, even a drug that a patient
has tolerated well may have cause an adverse drug
reaction after a second drug that alters the hepatic
metabolism is added or discontinued.
Hepatic drug metabolism or P450?

Grapefruit juice, taken proximally to the
administration of selected drugs, increases
serum levels of numerous drugs known to be
metabolized by CYP3A4.
Hepatic drug metabolism or P450?

◦ Elderly patients have liver disease associated many
conditions.
◦ Adverse drug reactions may suggest liver
dysfunction.
◦ Numerous drugs have had reports of increased
bioavailability due to grapefruit juice.
Renal Excretion of Drugs in the Elderly

Similar to hepatic blood flow in the elderly,
renal blood flow is also reduced.
◦ Occurs in the absence of nephropathy
◦ Approximately 1% decrease per year after age of 50
◦ Reduction affects the many drugs that are excreted
by the kidneys
 Assuming that more than 60% of the drug is excreted by
kidney
 Higher drug concentration in blood of primarily renal
excreted drugs typically found when glomerular filtration
rate decreases
Renal Excretion of Drugs in the Elderly

Overall, elderly typically have:
◦
◦
◦
◦
Declining renal function
Decreased renal blood flow
Decreased renal mass
Decreased creatinine clearance
Any impairment of normal liver function
potentially will alter hepatic biotransformation.
Renal Excretion of Drugs in the Elderly

Insufficient to measure renal function by serum
creatinine alone
◦ Normal levels may be seem even though the
reduction in creatine clearance or glomerular
filtration is substantial

Differences in creatinine clearance correlate
with about a two-fold increase in the half-life of
penicillin in the elderly
Classes of Cyp450
Hepatic drug metabolism or P450?

Cytochrome P450 enzyme system
Hepatic drug metabolism or P450?

◦ Oxidation by the cytochrome P450 system which is a family of
drug-metabolizing enzymes in the liver. The major function of this
enzyme system is to add an oxygen atom to the drug substrate.
◦ drug + O2 --------> drug-OH
◦ nonpolar, lipid-soluble) (polar, water-soluble)
◦ CYP1, CYP2, CYP3
◦ Families of enzymes that metabolize drugs
◦ 9 other CYPs that metabolize endogenous
compounds in the body
◦ Divided further into subclasses designating isoforms
that metabolize specific drugs/drug families
Phase 1 Metabolism
Phase I (nonsynthetic) - major types
Hepatic drug metabolism or P450?

Phase II (synthetic) reactions occur in the liver
and gut wall. The products of Phase II reactions are
called conjugated metabolites, and are virtually always
inactive, very polar and/or ionized, and easily excreted.
Several types of conjugation may occur:
 i. glucuronide conjugation – liver
 ii. N-acetylation - liver, gut wall; addition of an
acetate group to a nitrogen atom. Individuals are
classified as either slow or fast acetylators depending
on genetic factors, e.g., sulfonamides, isoniazid,
procainamide.
Acetaminophen Glucuronidation
Considerations of Metabolism
Age
 Induction
 Inhibition
 First-pass effect
 Nutritional status
 Disease state
 Enterohepatic circulation

Effects of Aging on Pharmacodynamics

◦ Altered sensitivity
◦ Modified response to a given stimulus
◦ How homeostatic mechanisms contribute to altered
response
EFFECTS OF AGING ON
PHARMACODYNAMICS
Effects of Aging on Pharmacodynamics:
Altered sensitivity
Because of the changes in renal drug elimination,
hepatic drug clearance, pharmacodynamics, and
homeostatic mechanisms in elderly persons, discerning
the role of intrinsic sensitivity is difficult.
 Studies have shown elderly are more sensitive to:

◦ Warfarin
◦ Sedative-hypnotics
◦ Narcotic analgesics
Effects of Aging on Pharmacodynamics:
Decreased Homeostatic Response

Elderly patients with decreased plasma volume,
diminished vasomotor regulation, impaired
glucose tolerance, greater morbidity from
infections, and other limitations may be more
susceptible to adverse effects of drugs.
Pharmacodynamics
Effects of Aging on Pharmacodynamics:
Pharmacodynamic Changes
As people age, responses to certain stimulant
agents change.
 Elderly patients have decreased variation of heart
rate in the course of β-adrenergic blockade,
indicating a decrease of parasympathetic function.
 Decreased baroreceptor function.
 Drug sensitivity in elderly patients has been shown
to be reduced to both isoproterenol stimulation
and β-adrenergic blockade.
 Observations confirm decreased beta-adrenergic
responses in elderly

ADRs and Why?

Adverse drug reactions in aged populations are
typically not idiosyncratic
◦ More likely extensions of the usual effects of the
drugs
ADRs and Why?


COMMON SIGNS OF ADVERSE DRUG
REACTIONS IN THE OLDER PATIENT
Frequent adverse drug reactions identified the
elderly

◦ Bleeding due to oral anticoagulants
◦ Hypoglycemia from diabetes treatment
◦ Gastropathy associated with non-steroidal antiinflammatory drugs

Because polypharmacy is common, the
potential for adverse drug reactions has
increased with every class

WHICH PRESCRIPTION DRUGS ARE
MOST LIKELY TO CAUSE AN ADR?
Cardiovascular drugs
Central nervous system (CNS)-active drugs
 Long-acting or sedating drugs
 Non-steroidal anti-inflammatory drugs
(NSAIDS) and other “blood thinners”
 Muscle relaxants






The Latest “Bad Guys”



MAIN ADRs SEEN
◦
◦
◦
◦

GI bleeds secondary to NSAID use
Falls resulting in fracture
Low fasting blood sugar
Dehydration
CAUSES OF ADRs
◦
◦
◦
◦
Polypharmacy
Failure to recognize renal impairment
Prior GI problems
Use of long-acting benzodiazepines, antipsychotics,
antidiabetic drugs, NSAIDS, narcotics
A recent study linked almost 50% of adverse
drug events in elderly outpatients to:
◦
◦
◦
◦
◦

PATIENT ADVERSE EFFECTS IN THE
LONG TERM CARE FACILITY
Restlessness
Falls
Depression
Confusion
Loss of memory
Constipation
Incontinence
Extrapyramidal symptoms
Warfarin
Aspirin
Insulin
Clopidogrel
Digoxin
Inappropriate use of these drugs was the main
reason for the adverse event…
DRUG ERRORS IN THE ELDERLY
Frequency of Inappropriate Prescribing

Factors Contributing to
Inappropriate Prescribing
Community-Dwelling Elderly
◦ Inappropriate drugs used by 23.5%.


Patients who had been referred

Had a number of prescriptions

Were prescribed an antianxiety agent, sedative,
antidepressant, analgesic, platelet inhibitor,
antispasmodic

Medication was prescribed by a provider in a
nonmetropolitan area.
◦ Increased rate by 73%
Board and Care Home Elderly
◦ Increased rate by 22% for each med
◦ 20.2-27.4% had inappropriate prescriptions.

Outpatient Elderly
◦ 4.45% outpatient visits resulted in an inappropriate
prescription.
◦ Increased rate by 6-284-fold!
Patient Characteristics
That Contribute
Number of active chronic medical diagnoses (>6)
Nine or more medications
 Number of doses of medication per day (>12)
 Low body weight or body mass index (< 22 kg/sq
m)
 Recent transfer from hospital
 Advanced age (>85)
 Prior adverse drug reaction


Beers List
Updated by Fick, et al., in
2003
 Includes drugs that are
dangerous “as is”
 Includes drugs that are
dangerous dependent on
diagnosis
 Link to this list is
http://archinte.amaassn.org/c
gi/reprint/163/22/2716

Patient Characteristics
That Contribute
Cancer
 Depression
 Cognitive impairment
including dementia
 Decreased renal
function (estimated
creatinine clearance
< 50 mL/min)

Drugs from Beers List Causing a High
Degree of Bad Outcomes
Pentazocine
 Indomethacin
 Trimethobenzamide
 Muscle relaxants
 Flurazepam
 Amitriptyline
 Doxepin
 Meprobamate

Trimethobenzamide
Drugs from Beers List Causing a High
Degree of Bad Outcomes
Drugs from Beers List Causing a High
Degree of Bad Outcomes
Short- and long-acting BZDs
 Disopyramide
 Methyldopa
 Chlorpropamide
BZDs
 Gastrointestinal antispasmodics
 Anticholinergics
 Diphenhydramine
 All barbiturates except phenobarbital and those
used for seizures

Drugs from Beers List Causing a High
Degree of Bad Outcomes
Drugs from Beers List Causing a High
Degree of Bad Outcomes

Orphenadrine
Guanethidine
 Guanadrel
 Nitrofurantoin
 Methyltestosterone
 Thioridazine
 Mesoridazine




Photo by Josumiselunico
Drugs With Anticholinergic Activity
Meperidine
Ticlopidine
 Ketorolac
 Amphetamines and anorexic agents
 Long-acting NSAIDs
 Daily fluoxetine
 Long-term use of stimulant laxatives
 Amiodarone

Short-acting nifedipine
Mineral oil
 Desiccated thyroid
 Several more drugs cause a “low severity
rating” of bad outcomes and should also be
avoided in the elderly patient.
POLYPHARMACY
DEFINITION: Concomitant use of many drugs.
Excessive use of prescriptive medications.
 Actual number of drugs varies in the literature.
Ranges from 2,4,5,6,10 drugs used
concomitantly.
 Controversial as to whether this definition
should also include OTC meds, herbal meds,
alternative meds and pro re nata meds.

POLYPHARMACY

THE USE OF MORE PRESCRIBED MEDICINES
THAN ARE CLINICALLY INDICATED.
FACTORS THAT INFLUENCE THE
DEVELOPMENT OF POLYPHARMACY IN
THE OLDER PATIENT






Increasing number of chronic illnesses
Use of multiple medications
Concept of a “pill for every ill”
Susceptibility to product
advertisements
Availability of nonprescription drugs
Tendency toward self-treatment
Photo by BrokenSphere
FACTORS THAT INFLUENCE THE
DEVELOPMENT OF POLYPHARMACY IN
THE OLDER PATIENT
OUTCOMES OF POLYPHARMACY
Decreased compliance
Increased adverse drug effects
 Decreased social activity, increased depression
 Increased risk for nursing home placement
 Increased risk of prescribing errors


Hoarding of old medications
Prohibitive cost of prescription products
 Use of multiple prescribers
 Use of different sources for medications
 Lack of knowledge about medications and
medical condition


Photo by Thomas Bjørkan
OUTCOMES OF POLYPHARMACY

Increased morbidity (Increased mortality?)
 Increased incidence of iatrogenic illness

Graphic by Keith Evans
Increased cost
Culprits that complicate the
polypharmacy problem:
• OTCs
• Herbal medications
OVER-THE-COUNTER MEDICATIONS TO
WATCH IN THE OLDER PATIENT






Cimetidine and other H2 blockers
NSAIDs
Decongestants
Antihistamines
Laxatives
Antacids
OTC AGENTS THAT COMPLICATE THE
POLYPHARMACY PROBLEM
Cimetidine (Tagamet): Inhibits enzymes in the liver,
thereby prolonging the duration of other drugs in the
body.
 Decongestants: Cause increased blood pressure.
These also have anticholinergic effects.
 NSAIDs: May decrease renal blood flow thereby
reducing elimination of drugs from the body; cause GI
bleeds.

OTC AGENTS THAT COMPLICATE THE
POLYPHARMACY PROBLEM
HERBAL PREPARATIONS TO WATCH
IN THE OLDER PATIENT
Antihistamines: Certain OTC preps (e.g.,
Diphenhydramine) are highly sedating and have
pronounced anticholinergic effects.
 Antacids: May adsorb to other drugs if taken at the
same time, decreasing their absorbance.
 Laxatives: May decrease GI transit time for drugs,
decreasing their absorbance.









HERBAL PREPARATIONS TO WATCH IN
THE OLDER PATIENT

Hawthorn: Interacts with digoxin and cardiovascular meds.

Kava: Interacts with sedatives and CNS depressants.

Licorice: Acts as a steroid.

Ma huang: Interacts with monoamine oxidase inhibitors, theophylline,
decongestants, methyldopa and caffeine.

Mistletoe: Interacts with BP meds, antidepressants.

St. John’s Wort: Interacts with just about everything.

Saw palmetto: Do not take with meds for benign prostatic hypertrophy.

Yohimbe: Interacts with decongestants, antidepressants, and mood-altering
drugs.
Aloe vera: Interacts with digoxin and diuretics.
Black cohosh: Interacts with sedatives and blood pressure
meds.
Ephedra: Interacts BP meds, antidepressants.
Feverfew: Interacts with warfarin, NSAIDS
Garlic: Interacts with anticoagulants and glucose-lowering
agents.
Ginger: Interacts with warfarin and heart meds.
Ginkgo: Interacts with anticoagulants.
Ginseng: Interacts with digoxin, furosemide, and blood glucoselowering agents.
Drugs For Cardiovascular Problems
Lipid-lowering agents
 Antihypertensives
 Anticoagulants
 Drugs for heart failure

The Prevalence of Statins

In 2004, CV disease killed 870,000 people.
Mechanism of Action of Statins

Complex MOA
◦ The inhibit HMGCoA reductase. This decreases
cholesterol synthesis.
◦ They increase the number of LDL receptors on
hepatocytes causing a removal of LDLs from blood.
◦ They decrease apolipoprotein B-100 synthesis; a
decrease in VLDLs is seen.
◦ 1.6 X that of cancer deaths
◦ 8 X higher than accidental deaths
◦ 55 X more deaths than those due to HIV/AIDS
Congenital heart disease is the single leading cause of
death in the US today.
 Each year, 310,000 people die in an ER or without ever
being hospitalized due to a heart attack.
 16 million people alive today have a history of a
myocardial infarction (MI).
 Each year, 1.2 million Americans have a new or recurrent
MI.

Graphic by Jatlas2
Other Statin Benefits
Statins
They promote plaque stability by cholesterol
removal and decreased calcification.
 Decreased inflammation.
 Improvement of endothelial function.
 Decreased risk of atrial fibrillation.
 Decreased risk of thrombosis by decreasing
platelet aggregation and thrombin formation.

Statins
“Are these drugs too dangerous to use?”
Statins
“Are these drugs too dangerous to use?”



Risks associated with use include:
◦ Myositis and rhabdomyolysis
 Mild injury may present as muscle weakness or tenderness, local
or diffuse. This is seen in 1 to 5% of cases.
 Rarely, this may progress to myositis with elevated creatinine
kinase. Check for CK levels 10 times the ULN—if >10, d/c the
statin.
◦ Men over 50 and women over 60.
◦ + Elevated C reactive protein levels.
◦ + Another CV risk factor such as HTN, low HDL,
smoking, family history.

**Note: High LDLs are not on the list…
◦ Half of all heart attacks and strokes happen in
people with low or normal LDLs.
◦ Not sure if all statins will work the same…
Risks associated with use include:
◦ Diabetes (especially in patients over 60)
 CV benefit is greater than risk of diabetes.
 Check patient’s blood glucose regularly.

Liver injury
◦ If serum transaminase stays at 3X the ULN with
monitoring, d/c the statin.
◦ Safe and BENEFICIAL to use in patients with nonalcoholic fatty liver disease.
◦ Fatal rhabdo seen less than 0.15 cases in 1 million
prescriptions.
 Rosuvastatin has the highest risk.
◦ RISK BENEFIT RATIO STILL SWINGS IN FAVOR OF
USING A STATIN!!
◦
In February, 2010, the FDA approved statins
(Crestor) for:

A possible benefit—do statins increase bone
formation?
Statin $$ Comparison

Atorvastatin generic
Statin News

◦ 100 10 mg tabs $75 (dose 10 mg at bedtime to
start)

Simvastatin generic

Rosuvastatin generic
High-dose simvastatin recently relegated to
restricted use.
◦ 80-mg dose associated with increased risk of
myopathy.
◦ Patients taking this dose for more than a year with
no symptoms of muscle pain or weakness may stay
on it; do not escalate to this dose.
◦ Higher risk in females.
◦ 120 10 mg $199 (dose 20 mg at bedtime to start)
◦ 90 10 mg $74 (dose 20 mg at bedtime to start)
More Statin News
Anything New?

Do not use simvastatin with ketoconazole
(Nizoral), itraconazole (Sporanox), or
posaconazole (Noxafil). Do not use with
clarithromycin, erythromycin or telithromycin
(Ketek); HIV protease inhibitors, nefazodone,
gemfibrozil, cyclosporine, and danazol.
 Do not exceed 10 mg dose with amiodarone,
verapamil, and diltiazem, and the 20-mg dose
should not be exceeded with amlodipine
(Norvasc) and ranolazine (Ranexa).

Blood Pressure Meds
Diuretics--HCTZ
Much to consider here!
 Quality of life.
 Look at reducing BP especially in the face of
compelling indications.
 Start low and slow.
 Consider combination drugs.


Recently approved combination of simvastatin
and sitagliptin (Januvia).
 Combination is called Juvisync.
 Gives good glucose control plus lipid-lowering
benefits in the type 2 patient.
 Watch for hypoglycemia, headache, URI, rhinitis,
muscle pain.
 Convenient, may help compliance.
 Dosed as 50/10, 50/20, 50/40 mg.
Cheapest, most effective way to lower elevated
BP
◦ Should be an initial drug of choice for most patients
with hypertension
◦ Preferred in isolated systolic hypertension
◦ Preferred in African Americans
Diuretics--HCTZ
Diuretics - Furosemide
Hydrochlorothiazide is preferred for mobilizing
fluid in mild to moderate heart failure.
 Lower blood pressure by decreasing blood
volume and reducing arteriolar resistance.


Furosemide lowers BP by causing a loss of fluid
volume and by relaxing venous smooth muscle.
 Used for CHF, edema of cardiac or renal origin,
hypertension.
◦ Monitor electrolytes, monitor for hypokalemia, can
increase LDLs, total cholesterol, triglycerides,
hyperglycemia in diabetic patients.
◦ Monitor for hypotension, hypokalemia, transient
ototoxicity.
Hydrochlorothiazide
Diuretics - Furosemide
BP Medications with No Compelling
Indications…..
Reserved for patients who need greater
diuresis than thiazides can offer.
 Used for patients with low glomerular filtration
rate.
 Avoid in diabetes, gout, hypokalemia.

With Compelling Indications
With Compelling Indications


◦ SBP 140-159 mm Hg or DBP 90-99 mm Hg
◦ ACE inhibitors, angiotensin receptor blockers,
calcium channel blockers, diuretic or combination.

Stage 2 Hypertension
◦ SBP > 160 mm Hg or DBP > 100 mm Hg
◦ Consider combinations from the start; amlodipine
plus renin angiotensin aldosterone system blocker;
or diuretic plus…
Heart Failure

Aortopathy/Aortic aneurysm
◦ Thiazide, beta blocker, CCB, ACEI, ARB, aldosterone
antagonist.

Diabetes

Chronic kidney disease

Stroke prophylaxis

Early Dementia

Post-MI

CAD or high CVD risk
◦ Beta blocker, ACEI, aldosterone antagonist, ARB
◦ Thiazide, beta blocker, ACEI, CCB

Stage 1 Hypertension
Angina pectoris
◦ Beta blocker, CCB
◦ Beta blocker, ARB, ACEI, thiazide, CCB
◦ ACEI, ARB, CCB, thiazide, beta blocker
◦ ACEI, ARB
◦ Thiazide, ACEI, ARB, CCB
◦ ACEI, ARB, thiazides, CCBs
Combination Therapy for Hypertension
Heart Failure in the Older Patient
More likely than unlikely in this patient
population
 Additive or synergistic effects
 Better compliance
 Decreased adverse events
 Prolonged duration of action
 More target organ protection


Beta-Blockers: Atenolol & Metoprolol
Both are beta-1 blockers with no intrinsic
sympathomimetic activity.
 When used in patients undergoing ST-elevation MI
(STEMI), they reduce pain, infarct pain, and short-term
mortality.

◦ Beta-receptor blockade reduces cardiac work and oxygen
demand; BP is lowered; risk of dysrhythmia is reduced.
ACEI, ARBs, beta blockers and aldosterone
antagonists reduce mortality.
◦ If patient cannot tolerate ACEI/ARBs, vasodilator Tx
with hydralazine and nitrates.

Digoxin and diuretics are good for symptom
control but require monitoring.
◦ Orthostatic hypotension, renal function, electrolyte
imbalances, drug interactions, worsening of
comorbid diseases.
Beta-Blocker Use
PO dosing should begin within 24 hours of STEMI and
continue for at least 2-3 years thereafter.
 Contraindications to use include overt HF, heart block
>1st degree, pronounced bradycardia or persistent
hypotension, and cardiogenic shock. Watch in patients
with chronic obstructive pulmonary disease (COPD).

If the patient continues to use these PO, long-term
survival increases.
 Metoprolol: Toprol is XL, Lopressor is IR.

Beta-Blocker Use
Other Uses for Beta Blockers
These drugs will potentiate the blood pressurelowering and cardiac effects of
antihypertensives, calcium channel blockers,
antithyroid medications.
 They may cause cold extremities and exercise
intolerance or sedation.
 Do not discontinue abruptly!


Ventricular arrhythmias, atrial ectopy
 Migraine prophylaxis
 Essential tremor
 Aggressive behavior (not in dementia)
 Prevention of MI, atrial fibrillation/flutter,
hypertrophic obstructive cardiomyopathy
Anticoagulants


Dabigatran
Warfarin still a mainstay.

◦ Benefits outweigh risks in patients at risk for stroke
following atrial fibrillation.
◦ Is risk of bleeds due to falls greater in the elderly?
Not really—benefits are STILL greater.

Newer anticoagulants offer some advantages.
◦ Dabigatran
◦ Rivaroxaban
Direct thrombin inhibitor.
Avoid use in patients taking NSAIDs or other
agents that promote bleeds.
◦ Watch in history of GI bleeds; give with proton
pump inhibitor (PPI).
Do not need to do monitoring, but check liver
enzymes at baseline and regularly.
 Expensive!

Rivaroxaban
Newer Anticoagulants
Factor Xa inhibitor.
Does not require monitoring, but has no reversing
agent, so must not be used in a patient with history of
bleeds or with active bleeding.
 Do not use in patient on other anticoagulants or
NSAIDs.
 Has drug interactions with CYP3A4 substrates.
 Expensive!!



When / Who to Treat With An
Anticoagulant?
Compare risk/benefit.
 Complicated here by many things…
 Use assessment tools for stroke risk, bleeding
risk, consider gender, history, use your
pharmacist or an antithrombotic risk
assessment Tool.
 Review the order frequently; review
risk/benefit; review response and QOL.

Apixaban, Edoxaban, Betrixaban are all in trials
and development.
 Cost may be prohibitive
 Warfarin will continue to be a mainstay.
Drugs for Benign Prostatic Hyperplasia
Affects 80% of men > 80 years old
 Increased urinary frequency
 Linked to QOL issues
 Linked to falls?

Drugs for BPH









Mechanisms of Drugs for BPH
Finasteride (Proscar)—5-alpha-reductase inhibitors
Dutasteride (Avodart)
Dutasteride plus tamsulosin (Jalyn)
Terazosin (Hytrin)—alpha blockers
Doxazosin (Cardura)
Tamsulosin (Flomax)
Alfuzosin (Uroxatral)
Silodosin (Rapaflo)
Often taking both types of drugs in combination is
the best.

5-alpha reductase inhibitors
◦ Inhibit the conversion of testosterone to
dihydrotestosterone (DHT), lowering serum levels
of DHT. Since this hormone is trophic for the
prostate, the gland no longer grows when DHT is
decreased.
 Takes 6 to 12 months to work; works best in very enlarged
prostate.
 Decreased ejaculate volume and libido in 5-10%.
 Rarely, gynecomastia.
Dihydrotestosterone
Mechanisms of Drugs for BPH

Alpha blockers
What’s New for BPH??

 These give relatively rapid improvement even in mild
enlargement; require lifelong use.
◦ Silodosin and tamsulosin are selective for alpha-1
receptors on the prostate; the others are not, and
will lower BP as well.
◦ Use caution with other BP-lowering drugs and with
phosphodiesterase inhibitors.
Tadalafil (Cialis)
◦ A phosphodiesterase inhibitor used for ED.
◦ Prescribed for BPH because it helps with urinary
urgency, weak urine stream, frequent urination especially
at night.
◦ Not for men who also take nitrates.
◦ Not for concomitant use with alpha-blockers due to
significant drop in BP.
◦ Blockade of alpha receptors in the smooth muscle
of the bladder neck decreases dynamic obstruction
of the urethra

Botulinum Toxin
◦ A single injection into the prostate may decrease
symptoms for up to a year.
Drugs for Osteoarthritis
Osteoarthritis Treatment
NSAIDs
 Disease-modifying antirheumatic drugs
(DMARDs)
 Drugs for neuromuscular pain


Non-pharmacologic means first
 Acetaminophen
 NSAIDs in combination with acetaminophen
 Low potency opioids
 Adjunctive analgesics
◦ TCAs, anticonvulsants, serotonin-norepinephrine
reuptake inhibitors
Photo by Drahreg01
Phenylbutazone, a NSAID
Osteoarthritis


Osteoarthritis Treatment
Acetaminophen is drug of first choice.

◦ No renal impairment at normal doses.
◦ No GI bleed risk at normal doses.
◦ May cause hepatic toxicity in patients with hepatic
impairment or alcohol use.

Acetaminophen
Opiates
◦
◦
◦
◦
Dose at 4 g or less per day for osteoarthritis,
back pain, dental pain, arthralgia, myalgia.
Use when other therapies fail.
SE include constipation, sedation, addictive potential.
Avoid codeine.
Consider tramadol (non-opiate).
Acetaminophen
Morphine, an opiate
NSAIDs for Osteoarthritis


Concern about cardiovascular risk.
COX-2 inhibitors are associated with highest risk.
Osteoarthritis Treatment

◦ Capsaicin, methyl salicylate, diclofenac gel
◦ Reduce systemic SE of NSAIDs.
◦ Celecoxib (Celebrex)
Of the COX-1 COX-2 inhibitors, naproxen has the
lowest CV risk but causes more GI bleeds.
 Diclofenac causes more CV effects due to greater
COX-2 inhibition.

Medications for Arthritis/DMARDs



Topical agents

Anticonvulsants
◦ Carbamazepine, phenytoin, valproic acid, gabapentin,
pregabalin
◦ May help with neuropathic pain.
◦ Watch for allergies/rashes, sedation.
Other Drugs for Osteoarthritis
Daily supplementation with chondroitin sulfate
has been useful for hand osteoarthritis.

Hyaluronic Acid
◦ Incidence greater than 50% in people over 60.

Topical diclofenac (Voltaren) gel
Takes several months for effects to develop.
May be taken with NSAIDs.
◦ Causes some improvement in knee OA.
◦ Avoids GI, CV, renal risks of NSAIDs.
◦ Watch for dermatitis.
◦ Apply to affected joints 4 times/day.
Osteoarthritis Treatment

Chronic Neuromuscular Pain
Antidepressants

◦
◦
◦
◦

Used when pain is associated with sleep disorders.
Used in cases of fibromyalgia.
May modulate nerve impulses.
TCAs, SSRIs, serotonin-norepinephrine reuptake
inhibitors.
Consider mechanism.
Duloxetine (Cymbalta) modulates neurogenic
mechanisms in neuromuscular pain.
 Also has an impact in osteoarthritis in some
patients.
GI Drugs
Proton Pump Inhibitors
GERD
Ulcer
 GI upset due to medications



◦ NSAIDs
Up to 44% of adults have heartburn at least
once/month; 14% once a week; 7% every day.
 Less than 50% of patients with GERD have the
erosive form.
◦ Most have NERD.
◦ PPIs can work for both—daily for erosive GERD,
PRN for NERD.
Proton Pump Inhibitors
Mechanism of Action of PPIs

These drugs irreversibly inhibit the H/K-ATPase
on the parietal cell.

Reduce acid production by almost 100% within
2 hours after a single dose.
◦ Inhibit both basal and stimulated acid production.
◦ Once pumps are inhibited, the effect lasts for days;
recovery may take weeks.
Nexium and Prevacid Vs. Prilosec

Nexium and Prevacid are the S-isomers only of
Omeprazole.
◦ They are metabolized more slowly and maintain
blood levels longer.
◦ Cost:
 90 Nexium (20 mg): $50
 84 Prevacid (30 mg): $48
 100 Prilosec (20 mg): $38
Nexium
PPIs—The Downsides

Treatment for over 1 year in a patient over 50 is
associated with a 44% increase in hip fracture (and
higher in patients over 60)—this study now being
questioned, though warning still in place for Rx PPIs.
◦ Make sure patient takes 1000-1500 mg calcium and 400-800
IU Vitamin D.
◦ Monitor bone density.

May cause rebound GERD if discontinued.
◦ Seen even in healthy volunteers.
PPIs—The News
PPIs and clopidogrel—there was concern about
an increase risk of GI bleeds. This seems
unfounded, but research finds an
overprescribing of PPIs to cardiac patients for
extended periods.
 Omeprazole has many drug-drug interactions
due to its metabolic profile; lansoprazole may
be a safer choice.

CNS-Active Drugs
Dementia
Drugs for dementia
Drugs for sleep/insomnia
 Drugs for depression
 Drugs for psychosis



Tremendous problem worldwide—35 million
sufferers.
 This number will double every 20 years to 66 million
in 2030 and 115 million in 2050.
 Dementia currently has a price tag of $315
billion/year.
◦ $422-604 when all social/caregiver/family costs are factored
in.

7th leading cause of death in the US.
Photo by Digimint
Memantine ER
Antidepressants in Dementia
N-methyl-D-aspartate blocker
Recently approved by the FDA
 Once-a-day dosing
 Benefits for cognition, assessment, behavior, and
caregiver burden but not function
 Reserved for moderate-to-severe AD



◦ Off-label for mild symptoms

Good for patients who suffer from
neuropsychiatric or behavioral symptoms
Should they be used?
 Newer research seems to indicate little, if any
data.
 Commonly prescribed meds include sertraline,
mirtazapine.
 Side effect incidence is higher in the dementia
patient.
In Women With Post-Menopausal
Dementia…
NSAIDs and AD
Heavy use of NSAIDs increases risk of AD by
as much as 66%.
 Heavy use defined as 500 standard daily doses
over a 2-year period.
 This seems to negate earlier data about a
protective effect of NSAIDs.
Conjugated equine estrogen has been shown to
have negative cognitive effects on the brain,
made worse in patients with a history of
impairment or familial risk.
 17-beta-estradiol has positive or neutral effects.
 Helps especially with verbal memory
performance.


Compelling Old Drug for AD?
Polypharmacy as a Contributor to
Dementia
Low-dose lithium
Early studies show benefit in a cohort who
took lithium at a low dose.
 These patients with amnestic mild cognitive
impairment (aMCI) had better cognitive
response than placebo group. They had less
phosphorylated tau (P-tau) protein in CSF after
low-dose lithium treatment.





In the U.S., polypharmacy is found in 40% of those older than
65 years.
Residents of long-term care facilities are a small but important
group of patients who ingest many daily medications, taking an
average of six to eight drugs daily.
Use of multiple medications with anticholinergic effects can
increase patients' total anticholinergic burden as evidenced by
clinical signs such as dry mouth, sedation, confusion and even
hallucinations and delirium.
Any Bright News for Dementia?
Future Directions in Treatment for AD
Certain drugs for blood pressure management
have shown some improvement in cognition in
patients with dementia.
 Dihydropyridine CCBs decrease cognitive
impairment .


◦ Nifedipine, nicardipine, amlodipine, isradipine,
felodipine, nisoldipine
ACEI (Captopril, Perindopril), ARBs, diuretics
do, too.
 NOT beta blockers.

Dihydropyridine
Anti-amyloid drugs to reduce the production of
beta-amyloid (tau)
◦ Beta- and gamma-secretase inhibitors, beta amyloid
antibodies

Drugs that block the phosphorylation of tau

Drugs that block the formation of
neurofibrillary tangles
◦ Protein kinase inhibitors
Drugs for Sleep
Options include OTC drugs and prescription.
 OTC

◦ Antihistamines—not recommended because of long
half-lives, can cause dizziness, tolerance may develop
within 3 days of consistent use.
◦ Melatonin—variable success; lack of standardized
preps problematic. Helps with sleep initiation but
not maintenance.
Drugs for Sleep



Prescription options
Ramalteon (Rozerem)—melatonin agonist; lasts for about 4
hours
Benzodiazepines may be used, but short-term only; rebound
insomnia
◦ Triazolam (Halcion), Estazolam (ProSom), Temazepam (Restoril),
Flurazepam (Dalmane)*, Quazepam (Doral)*

Non-Benzodiazepines—watch for sleep-eating, walking, driving;
must be discontinued if sleep-driving occurs. Do not use longacting or sustained-release preparations*
◦ Zolpidem (Ambien)*, Zalaplon (Sonata), Eszopiclone (Lunesta)
Drugs for Sleep

Occasionally, antidepressants may be used.
◦ In patients with refractory insomnia.
◦ In patients with a history of substance abuse.
◦ Along with stimulant daytime antidepressants.

Consider trazodone (Desyrel), nefazodone
(Serzone), amitriptyline and nortriptyline
(Aventil).
Benzodiazepines in the Elderly
Use is associated with episodic memory
problems, poor concentration, disinhibition,
drowsiness, dysarthria, motor incoordination,
and falls.
 Risks associated with use include slowed
reaction time, visuospatial deficits, impaired
driving skills, and increased MVA.
 On Beers’ list for these risks!

Antipsychotics in the Older Adult
Antipsychotics in the Older Adult
In 2001, more than 70% of US atypical
antipsychotic prescriptions were written for
off-label indications such as dementia.
 In 2002, however, growing safety concerns,
including reported increases in diabetes and
stroke risk, began to emerge. These concerns
eventually culminated in an FDA black box
warning in 2005.


Why were they prescribed?
◦ Crying, wandering, agitation.
◦ These are NOT indications for use.

Overt aggression, true psychosis, risk of harm
to self or others
◦ Consider risk/benefit.

Do we have anything else for these patients?
◦ Not really….make the environment the best
possible!
Antipsychotics in the Older Adult

Linked to increase risk of CVAs.
◦ Especially in patients with dementia.

Opioid Use

First-generation antipsychotics are highest risk
drugs to use.
◦ Thioridazine, prochlorperazine, haloperidol.
◦ Risk is reduced if drug is discontinued.

Chronic and acute use are associated with
deficits in executive functions, attention,
concentration, recall, visuospatial skills, and
psychomotor speed.
Second-generation antipsychotics most often
prescribed in this population are risperidone
and olanzapine.
◦ Also associated with CVAs, but risk is less.
Conditions That May be Treated with
OTC Medications in the Older Adult
Allergy
Common cold
 Osteoarthritis
 Heartburn
 Insomnia

Allergy

Consider inhaled cromolyn sodium drugs.
◦ Local effects only so no drug interactions.
◦ No adjustment in dose for renal, hepatic disease.


Ketotifen
◦ OTC antihistamine for ocular conjunctivitis.
◦ Conjunctive congestion, headache, rhinitis may be SE,
but no drug interactions.

Loratidine (Claritin)
◦ Does not penetrate the BBB well so not as sedating.
◦ No anticholinergic SE.
Photo by Wolfgang Ihloff
Common Cold
Most systemic medications interact with Rx
drugs the older patient may be taking for HTN,
CV ailments or diabetes.
 Consider Oxymetazoline spray decongestant
for short-term use (3-5 days).

◦ No systemic effects due to lack of absorption.
◦ Promotes drainage, improves breathing.
◦ Rebound stuffiness WILL occur.
Heartburn
Famotidine and nizatidine are recommended H2
receptor blockers.
 Main drug interactions are related to acid-lowering
effects.

◦ Dosage adjustments needed for patients with renal
impairment.

Omeprazole is a PPI that may be used but consider…
◦ Takes up to 4 days before relief is felt.
◦ Interacts with Cyp450 enzymes so drug-drug interactions are
common.
 Lansoprazole may be a safer choice??
◦ Patient should not take for longer than 14 days—rebound
reflux common!
Constipation

Bulk-forming laxatives are among the safest.
◦ Psyllium, methylcellulose

Emollient laxatives (e.g., Docusate)
◦ Should be reserved for the patient who should not
strain during defecation. Patient with MI,
hemorrhoids, following rectal surgery.

Polyethylene glycol 3550 is osmotic, but does
not cause electrolyte disturbances.

Glycerin suppositories
Insomnia
Most OTC products for insomnia contain
antihistamines and should be AVOIDED in the
elderly.
 Some promising studies with melatonin.

◦ May improve sundowning in patients with dementia.

Check sleep hygiene before initiating Rx
therapy.
◦ Safe to use in the cardiac patient, in renal failure.
Photo by Chad fitz
What About Illicit Drugs?


35 million people are 65 or older.
Substance abuse affects about 17% of this
population.
◦ This is expected to double by 2020.
◦ Includes abuse of prescription drugs: opioids,
benzodiazepines.
Cannabis Use in the Elderly
May cause a protracted impairment even after
discontinuance and years of abstinence.
 Attention and short-term memory may be
especially affected.

◦ These are most affected acutely as well, as is
executive function.
Regional Differences Affecting Drug of
Abuse Use
Socioeconomic factors influence access to
healthcare, overall health, drug of abuse use,
education level, etc.
 Lifestyle factors—healthy choices with respect
to alcohol, tobacco, recreational drugs, diet
 Areas of concern….

Where Does Marijuana Work in the
Brain?
Effects of Marijuana are DoseDependent
Causes three effects on the brain: euphoria,
sedation, and hallucinations.
 Low-Moderate dose: euphoria, relaxation,
appetite stimulation, impairment of short-term
memory, impairment of driving skills,
depersonalization.
 High dose: hallucinations, paranoia, delusions.

Alcohol Use in the Older Population
Alcohol is the most commonly used
recreational drug in older adults. Among
40,556 U.S. adults age 60 years and older, 52.8%
of men and 37.2% of women were current
drinkers.
 A safe amount of alcohol intake for individuals
over age 65 would be no more than seven
drinks per week and no more than four at one
sitting for both men and women.

Photo by Fiona Shields
The J-Curve
Deaths Due to Alcohol by County
Alcohol Plus…..
Alcohol-Related Dementia

In a survey of 83,321 older outpatients, 19% of
those taking prescription medications known to
adversely interact with alcohol reported
concomitant alcohol use.

Deficits in abstracting abilities, short-term
memory, executive control.
◦ This is in contrast to AD, where word-finding ability
is hampered, there is profound memory loss, and
recognition and recall are affected.

With abstinence, physical and mental function
do NOT continue to deteriorate (as they do in
AD).
◦ However, ARD may contribute to worsening of AD.
•
Photo by Tim “Avatar” Bartel
Non-Medical Use of Pain Relievers in
Persons Aged 12 and Older
Other Drugs of Abuse
Which Drugs are the Worst?
Medication Adherence
Drugs of abuse are problematic.
Sometimes the prescription drugs may become
the drugs of abuse.
 The most-prescribed have issues of their own,
including “black box” warnings that have to be
taken into account.



40% or more of the elderly fail to take drugs as
prescribed.
◦ May not fill or refill prescriptions.
◦ May not follow dosing directions.
Outcomes of non-adherence may be toxicity or
therapeutic failure (90%).
 Much of the time non-adherence is intentional.

◦ “I don’t need this drug.”
GUIDELINES FOR PRESCRIBING IN THE
ELDERLY--SAIL PROTOCOL
Steps for Reducing Medication Errors in
the Elderly
S Simplify regimens (q day drugs)
 A Adverse effects, both side effects and
interactions
 I Indications for drug use must be well-defined
 L List all current meds, including OTC drugs,
herbal and alternative medicines


Consider a “brown bag” session.
Reduce medications wherever possible.
 Check indications--are all meds necessary?
 Communicate with other caregivers.
 Check OTC and herbal use.
 Ascertain compliance.
 EDUCATE!

PREVENTION OF POLYPHARMACY

Recognition of polypharmacy is key.
REVIEW MEDICATION REGIMENS

 “Brown bag” approach is useful.

Educate patients with respect to medication
use.

Communication between prescribers is key.
Review drug regimens regularly.
 Is drug being taken as prescribed?
 Are all agents still needed?
 Can the regimen be simplified?
 Clinical pharmacist consult may be useful.
 “Essential medication only” approach may prevent
polypharmacy.
WHAT CAN BE DONE TO LIMIT ADVERSE
DRUG REACTIONS IN OLDER PATIENTS?
Anticipate more side effects, and maybe more
toxicity.
 Recognize that many drugs may be effective in
doses LOWER than what the manufacturer
recommends.
 ALWAYS communicate side effects or a desire
to change a dose with the prescriber.
DRUGS SHOWN TO BE EFFECTIVE AT DOSES
LOWER THAN THE MANUFACTURER
RECOMMENDS








DRUGS SHOWN TO BE EFFECTIVE AT DOSES
LOWER THAN THE MANUFACTURER
RECOMMENDS






Fexofenadine (20 tid vs 60 mg bid)
Fluoxetine (2.5-10 mg/d vs 20 mg/d)
Flurazepam (15 mg qhs vs 30 mg qhs)
Hydrochlorothiazide (12.5 mg/d vs 25-50 mg/d)
Ibuprofen (200 mg tid-qid vs 400 mg tid-qid)
Lisinopril (5 mg/d vs 10 mg/d)
Amlodipine (2.5 mg/d vs 5 mg/d)
Atenolol (25 mg/d vs 50 mg/d)
Atorvastatin (2.5-5 mg/d vs 10 mg/d)
Bupropion (50 mg bid vs 100 mg bid)
Captopril (12.5 mg qd or bid vs 50-75 mg/d)
Diclofenac (75 mg /d vs 100-200 mg/d)
Enalapril (2.5 mg/d vs 5 mg/d)
DRUGS SHOWN TO BE EFFECTIVE AT DOSES
LOWER THAN THE MANUFACTURER
RECOMMENDS






Lovastatin (10 mg/d vs 20 mg/d)
Metaprolol (50 mg/d vs 100 mg/d)
Misoprostol (50-100 mcg qid vs 200 mcg qid)
Nefazodone (50 mg/d or bid vs 100 mg bid)
Nizatidine (25-50 mg bid or 100 mg qhs vs 150
mg bid or 300 mg qhs)
Omeprazole (10 mg/d vs 20 mg/d)
DRUGS SHOWN TO BE EFFECTIVE AT DOSES
LOWER THAN THE MANUFACTURER
RECOMMENDS
WHAT IS A PATIENT TO DO?








Ondansetron (1-4 mg tid vs 8 mg bid-tid)
Pravastatin (5-10 mg/d vs 20 mg/d)
Ranitidine (100 mg bid vs 150 mg bid)
Simvastatin (2.5-5 mg/d vs 10 mg/d)
Trazodone (25-100 mg/d vs 150 mg/d)
Zolpidem 5-7.5 mg qhs vs 10 mg qhs




Be aware of polypharmacy and learn steps to reduce it.
Be aware that many drugs are effective in lower dosages than
prescribed (but ALWAYS consult a physician before altering
your dose).
Be aware of drugs that should be avoided in the older patient.
Remember drugs should make one feel better, not worse.
Communicate with all prescribers.
Check drug name against prescription!
Some Final Rules
Your Enemy, Your Friend
Dose reduction is likely (start low!).
An increased incidence of toxicity is likely.
 Avoid poly-clinic, poly-prescriber situations.
 Avoid treating non-medical problems with
drugs.



The self-empowered patient
◦
◦
◦
◦
◦
“My friend tells me…”
“My other HCP said…”
“I read in a magazine that…”
“I saw on TV that…”
“I saw on the INTERNET….”