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Pharmacological Considerations in Treating Geriatric Patients
April 25, 2007
Kathryn McMahon
Learning Objectives
After reading this text the participant should be able to:
1. Explain how aging-related decline in organ function impacts pharmacokinetics with
specific emphasis on the kidneys, liver, blood volume and skeletal muscle.
2. Describe aging-related concerns for the use of digoxin, warfarin, NSAIDS,
sedative/hyponotics, and drugs with anticholinergics effects.
3. Explain how poly-pharmacology impacts on adverse effects in geriatric populations.
4. Describe how the pathologies commonly seen in the geriatric population are
expected to alter pharmacological properties and lead to predictable complications.
5. Discuss measures that a physician can take to avoid over-medication of the elderly.
I. Introduction
A. Definitions
1. Geriatric – 65 y or older.
2. Homeostenosis - the progressive constriction of homeostatic reserve of
organs
II. “Rules of Thumb” for drug therapy in geriatric and elderly
1. Take a careful drug history.
 The disease to be treated could be drug-induced.
 Drugs being taken could lead to predictable adverse effects of the drug(s) to
be prescribed.
2. Prescribe only for specific and rational indications.
3. “Start low and go slow.”
 Define the response goal of all drug therapy.
 Initiate the therapy with small doses and titrate toward that desired response
goal.
 Wait at least 3 half lives (adjusted for age) before increasing the dose.
 If “normal” adult dosage does not result in expected response, check blood
levels.
 If expected response does not occur at the appropriate blood level of drug,
switch to a different drug.
4. Always be alert for and suspicious for drug reactions and interactions.
 Check what drugs (prescription, OTC, herbals, recreational) the person is
taking.
5. Simplify the drug regime as much as possible.
 Try to use drugs that can be taken at the same time of day.
 Reduce the number of drugs taken whenever possible, i.e. “Stop more drugs
than you start.”
III. Predictions of the Affect of Aging on Pharmacology
Differences affecting GI absorption - GI function including gastric acidity, gastric
emptying, and GI motility are expected to be decreased. Overall though, GI absorption
of most drugs is minimally altered in the absence of pathology of the GI tract.
Differences affecting drug distribution Increased fat mass and decreased muscle mass, leading to an increased fat to lean
ratio and decreased lean body mass, are predicted in the elderly. These changes
predict decreased volumes of distribution of hydrophilic drugs and increased volumes of
distribution of lipophilic drugs.
Because of homeostenotic decreases of liver function, albumin production is
predicted to be decrease in the elderly and, on average, albumin levels are decreased
by about 12.5% of the elderly. This predicts that drugs which have a high affinity to
albumin, such as warfarin, would have increased free drug concentrations in the
blood.
Differences affecting drug metabolism - Blood flow to organs is predicted to be
decreased. Blood flow to liver is decreased by 40 to 45%. Liver mass is also expected
to be decreased. These two predictions suggest that drugs metabolized by the liver
would be expected to be less rapidly metabolized in elderly. Within the liver cell itself,
metabolism of drugs can also be changed. Unfortunately some drug metabolism is
decreased while some is increased in elderly.
As a first approximation, one should predict that a drug is metabolized less,
and this will potentially lead to higher blood levels and/or more long-lasting
effects.
Differences affecting drug elimination - Blood flow to the kidneys is predicted to
be decreased in the elderly and glomerular filtration rate is also predicted to be
decreased. As a general rule the glomerular filtration rate is decreased by 1%/year after
age 50.
Also remember that blood creatine levels are not accurate estimates of renal
function in the elderly because of the loss of muscle mass due to aging-related atrophy.
Instead, creatine clearance (CC) should be used for an approximation of renal function.
Table I
Creatine Clearance Estimates in Adults
Age
CC (ml/min/m2)
20 y
140
50 y
127
80 y
97
The net result of the cumulative aging-related changes to the kidney is predicted to be
decreased elimination of drugs by the kidney.
Pharmacodynamic differences - Aging-related changes in target organ response
to drugs can be seen but they can be increased or decreased responsiveness that are
specific to the drug. This leads to a situation where it is difficult to predict how an elderly
individual will respond to a drug. This pharmacodynamic unpredictability in conjunction
with the potential alterations in pharmacokinetic properties of a drug leads to the
recommendation that drug therapy be started at low dose and titrated on the
basis of tolerability and response in the elderly (“start low and go slow”).
IV. Responses to co-morbidity & poly-pharmacy (including OTCs) of note in
geriatric population
Affecting absorption - The most significant of these are due to drugs having
anticholinergic effects altering absorption of other drugs.
Affecting drug distribution – Many pathologies (i.e. heart failure, dehydration,
edema, ascites, renal disease/failure, malnutrition, hepatic cirrhosis & some cancers)
and poly-pharmacies affect drug distribution.
Affecting metabolism - The liver’s ability to recover from injury decreases with age
and so recent history of liver disease should trigger a cautionary note for therapies
involving drugs metabolized to inactive products by the liver. Congestive heart failure
can decrease both the blood flow to liver and metabolic rates within liver leading to
predictions of decreased drug metabolism.
Poly-pharmacy, as in any age group, often causes changes in drug metabolism.
There are few aging-specific examples of drug-drug interactions that affect metabolism.
Titrating drugs in elderly to identify the minimal effective dose is generally wise
to avoid adverse effects due to unpredictable changes in drug metabolism.
V. Specific drugs that warrant special note in elderly
Drug Affected
Digoxin
Drugs of Concern for Drug-Drug Interactions
Interaction
Interacting Drugs
Increased digoxin
Quinidine, indomethacin, verapamil
concentration or effect
nifedipine, dilitiazem, esmolol,
(symptoms: arrhythmias,
flecainide, hydroxychloroquine,
GI disturbances, & CNS)
ibuprofen, quinine, tolbutamide,
amiodarone, erythromycin, tetracycline
& spironolactone
Decreased digoxin
Antacids, pysllium, kaolin-pectin,
concentration or effect
aminosalicyclic acid, colestipol,
(symptoms: progression of sulfasalazine, antineoplastics,
or reappearance of heart
cholestyramine & metoclopramide
failure or atrial fibrillation)
Warfarin
Increased probability of
NSAIDs
gastric erosion & bleeding
Drugs that slow warfarin
Sulph antibiotics (e.g. sulfamethoxazole,
metabolism - Reduction of
Bactrim®)
intestinal flora responsible Macrolides (e.g. erythromycin)
for vitamin K production
Quinolines (e.g. ciprofloxacin, Cipro®)
by antibiotics is probable Phenytoin
as well as decreased
metabolism and clearance of warfarin. (symptoms: excess
anticoagulation)
Drug-Disease Interactions
Disease
Benign prostatic hyperplasia
Drugs
Adverse Effect
Decongestants
Acute urinary retention
with  adrenergic agonist
or mimetic activity
Cardiac conduction
Verapamil, atenolol
Heart block
Chronic Obstructive
Pulmonary Disease (COPD)
β adrenergic blockers
Bronchoconstriction
& Respiratory depression
Dementia
Benzodiazepines,
Opiates
Delirium
Diabetes
Corticosteriods
Hyperglycemia
Hypertension
NSAIDS
Increased blood pressure
Hyponatremia
Diuretics
Decreased serum Na
Postural hypotension
Diuretics, vasodilators
& Ca channel blockers
Syncope, falls, hip
fractures
Commonly Used Drugs with High Potential for Severe Adverse Drug Reactions
Considered “High Severity” by HCFA for Nursing Home Residents who are > 65 y
Class or Drug
Amitriptyline (Elavil®)
Risk
Anticholinergic effects (blurred vision, constipation,
urinary hesitancy, confusion)
Digoxin (Lanoxin®)
Cardiac arrthymias due to digoxin intoxication
Anticholinergics
Dicyclomine (Bentyl®)
Adverse anticholinergic effects (blurred vision,
constipation, urinary hesitancy, confusion)
Sedative/hypnotics
Excessive sedation including respiratory depression
and ataxia and other motor impairment leading to falls
and accidents.
NSAIDs
Gastric bleeding
Metoclopramide (Reglan®)
Depression, dystonic reactions, Parkinsonism and
tardive dyskinesia