Geriatric Medicine

Polypharmacy and Drug

Reactions in the
Elderly

Erbil, November 2022

Assistant prof. Ali D. Dauod
CLINICAL
OBJECTIVES:
• Describe the varying needs for preventing both mortality and
morbidity of an elderly population.
• List types of ADRs and common drugs associated with ADRs in elderly
(one of the “vulnerable” groups)
• List Primary, Secondary, Drug withdrawal syndromes, and Tertiary ADR
in chronically ill people and older adults.
• To improve the care of older adults by decreasing exposure to
potentially inappropriate medications.
 CASE STUDY
A 75-Year-Old Woman with a Bag full of Pills
 CLINICAL CASE PROBLEM 1:
A 75-Year-Old Woman with a Bag full of Pills

• A 75-year-old woman comes to your office for the first time with her daughter.
Her daughter describes her mother as having undergone “a marked personality
change.” she began seeing people floating down into her field of vision.
• The mother’s previous physician visited 1 week ago. At that time, the physician
prescribed a number of medications, including pills for her stomach, anxiety,
depression, and insomnia in addition to her existing pills for HTN, IHD, and
arthritis.
• On further questioning, the daughter states that the mother had been fairly
well before the physician’s visit. In response to the patient’s complaints, the
physician prescribed HCTZ, propranolol, nifedipine, digoxin, ibuprofen,
cimetidine, Maalox, amitriptyline, and triazolam.
• On examination, the patient is agitated and confused. Her BP is 100/70 mm Hg,
and her PR is 54 beats per minute and regular. She has a bruise on her head
from a fall 3 days ago. Examination of the CVS reveals a normal S1 and S2 with
a grade 6 systolic murmur heard along the left sternal edge. There are no
other abnormalities.
Adverse drug events

Note: Medical errors and ADR are a common cause of death worldwide
• ~770,000 people are injured or die annually
• Spend 8-12 days longer in the hospital
• Costs $16,000-$24,000 +
• 9.7% of ADEs result in permanent disability (note: e.g., becoming
crippled after fall and fracture, severe hypotension causing ischemic
CVA, etc.)
Summary
1) Prevalence: Drug reactions are common, especially in the elderly, who are taking an
average of 13 medications. ADRs are at least twice as common in elderly patients as in
younger patients. Multimorbidity and polypharmacy were both associated with admission
due to ADRs. Those with an ADR were taking on average 35% more medicines than those
without (10.5 vs 7.8, p<0.001), which is an established risk factor for ADRs.
2) Types of ADRs:
• Side effects
• Drug toxicity
• Drug-disease interaction
• Drug-drug interaction (note: cimetidine is a non-selective cytochrome P450 enzyme inhibitor
and interferes with the metabolism of many other drugs, hence producing many drug
reactions)
3) Most common drugs associated with ADRs:
• Cardiovascular drugs (note: e.g., Ionotropic, antihypertensives, vasodilators, blood thinners,
etc.)
• Psychotropic drugs
• Analgesics.
Note: Therapeutic and toxic doses of
medications[1][2]
• Minimum effective concentration (MEC) is the minimum plasma
concentration of a drug needed to achieve sufficient drug concentration at
the receptors to produce the desired pharmacologic response.
• Maximum Safe Concentration (MSC) or Minimum Toxic Concentration
(MTC): The concentration of drug in plasma above which toxic effects are
produced. A concentration of drug above MSC is said to be a toxic level.
• The drug concentration between MEC and MSC represents the therapeutic
range.
• Side effect and toxic effect are two subclasses of adverse drug effects. The
side effect is defined as the therapeutically undesired but often
unavoidable effect that occurs at the normal therapeutic doses of a drug.
Side effects can be unrelated to dose. On the other hand, the toxic effect
occurs due to overdose or the repeated dose of a drug (it’s dose related)
4) Categories of ADRs
A. Primary ADR (one drug with one side reaction): (i) cimetidine causes psychosis and (ii)
propranolol induces depression.
B. Secondary ADR (requires at least two drugs to cause an interaction): statin medications
and azithromycin may cause elevated creatine kinase.
C. Drug withdrawal syndromes: (i) beta blocker withdrawal leads to angina or tachycardia;
(ii) addictive drugs cause withdrawal syndromes (benzodiazepines).
D. Tertiary ADR: benzodiazepines result in a higher incidence of falls.
• Dr: Karwan: Tertiary ADR involves more serious consequences – it leads to a
“disease” rather than just a side effect. Other examples include an NSAID leading
to a severe new-onset peptic ulcer disease, and heparin use leading to
osteoporosis.
5) Physician factors implicated in ADRs
E. Physician gives a high-risk drug to a vulnerable host (NSAID for a patient with peptic
ulcer disease).
F. The physician gives a highly interactive drug to a pharmacologically vulnerable patient
(i.e., captopril given to a patient taking a potassium-sparing agent).
G. The physician prescribes an inappropriate drug to treat an unrecognized drug side
effect
(i.e., an antidepressant given to treat beta-blocker depression).
6) Ensure appropriate follow-up.
7) Obtain a complete drug history and medication compromise with any transition to
hospitals, assisted living facilities, nursing homes, or homes.
8) Avoid prescribing before a diagnosis is made.
9) Review medications regularly and before adding a new medication.
10) Know the actions, adverse effects, and toxicity of the medications you prescribe.
11) Start at a low dose and titrate according to tolerability and response.
12) Attempt to maximize the dose before switching to another.
13) Avoid using one drug to treat the side effects of another.
14) Set of reasonable rules: Follow the set of rules listed in the Clinical Case Management
Solution.
 Rules that will minimize ADRs in the
elderly.
The following is a good set of rules for prescribing medication in geriatric
patients.
1) Recognize that there is no drug to treat aging. 9) Select the dose carefully: start very low and go
very slow.
2) Recognize that more prolongation of life is not a
valid reason to use medications that decrease the 10) Anticipate and minimize ADRs by considering
quality of life. side effect profiles.
3) Make sure that the effects of treatment outweigh 11) Determine whether the patient needs help using
the risks. the medication.
4) Establish a priority order for treatment. 12) Educate the patient and family. Continually re-
evaluate whether your patient needs a specific
5) Keep the number of drugs administered concurrently
drug.
to a minimum (note: This is in contrast to younger
patients, in whom using combinations at lower 13) Perform a drug review every 3 months for every
doses that act synergistically is better than using a elder taking more than one medication.
single drug at higher doses [Dr. Karwan])
14) Check serum levels when indicated.
6) Know your patient well. Consider renal and hepatic
15) Destroy old medications.
impairment. Consider what else (including over-the-
counter medications) is being taken and who else is 16) Use medication cards.
prescribing drugs.
17) The Beers criteria identify medications that are
7) Always begin with nonpharmacologic therapy first, if usually considered inappropriate when they are
possible. given to the elderly.
8) If you decide to prescribe a drug, know it well.
Consider using a few drugs often rather than many
drugs infrequently.
What are the Beers Criteria and why are they important
for reducing adverse drug events in geriatric patients?
1) Older adult population, defined as individuals over the age of 65.
2) ADEs are a major problem in older adults and can lead to hospitalization, disability, and even
death.
3) The Beers Criteria, first created in 1991 by Dr. Mark Beers, MD, is a set of tools that can be
used to reduce the risk of adverse drug events in the older adult population (note: it gives
guidance on which medications are inappropriate for and should be avoided in the elderly).
4) There are Four categories in the Beers List:
1) Types of medications that are “potentially inappropriate” for older people (anticholinergic
medications [note: elderly patients are more liable to anticholinergic side effects [1] such as
urinary retention, glaucoma, constipation, etc.[1]], benzodiazepines, sedative-hypnotics,
etc.)
2) Types of medications that should be used with caution in older adults (certain blood
pressure medications, “blood thinners”, etc.)
3) Combinations of drugs that may result in harmful drug-drug interactions (taking tizanidine,
a common muscle relaxant with ciprofloxacin, an antibiotic, etc.)
4) Medications that should be avoided or have their doses appropriately adjusted in people
with poor kidney function (valium, metformin, famotidine, etc., and many, many other
drugs!)
(extra)
 CLINICAL CASE PROBLEM 1:
A 75-Year-Old Woman with a Bag full of Pills
• A 75-year-old woman comes to your office for the first time with her daughter.
Her daughter describes her mother as having undergone “a marked personality
change.” she began seeing people floating down into her field of vision.
• The mother’s previous physician visited 1 week ago. At that time, the physician
prescribed a number of medications, including pills for her stomach, anxiety,
depression, and insomnia in addition to her existing pills for HTN, IHD, and
arthritis.
• On further questioning, the daughter states that the mother had been fairly well
before the physician’s visit. In response to the patient’s complaints, the
physician prescribed HCTZ, propranolol, nifedipine, digoxin, ibuprofen,
cimetidine, Maalox, amitriptyline, and triazolam.
• On examination, the patient is agitated and confused. Her BP is 100/70 mm Hg,
and her PR is 54 beats per minute and regular. She has a bruise on her head
from a fall 3 days ago. Examination of the CVS reveals a normal S1 and S2 with a
grade 6 systolic murmur heard along the left sternal edge. There are no other
abnormalities.
Notes:
• Maalox is a balanced mixture of two antacids; aluminum hydroxide is a slow-acting
antacid and magnesium hydroxide is a quick-acting one
• Cimetidine can cause psychosis and hallucinations
• Propranolol is lipophilic and can hence cross the blood brain barrier. Hence, it can
cause central side effects, e.g., depression. Propranolol is also one of the more
useful beta blockers for migraine prophylaxis because of its lipophilic nature. Some
other beta blockers such as sotalol, nadolol, atenolol and bisoprolol are hydrophilic
and cant cross the blood brain barrier.
• The hallucinations may also be a tertiary ADR; fall resulting from benzodiazepine
use.
• Digoxin has a very narrow therapeutic index, which means that there is only a small
difference between the minimum effective concentrations and the minimum toxic
concentrations in the blood. With such drugs, small increases in dose or in
blood/serum concentrations could lead to toxic effects. Digoxin toxicity can lead to
death, even producing arrhythmias despite being used for arrhythmia itself. In
states of hypokalemia, or low potassium, digoxin toxicity is actually worsened
because digoxin normally binds to the ATPase pump on the same site as potassium.
When potassium levels are low, digoxin can more easily bind to the ATPase pump,
exerting the inhibitory effects. Hypokalemia can be caused by hydrochlorothiazide,
which this patient is taking.
 CASE STUDY
An 85-Year-Old Female Patient with Dangerously High Blood
Pressure
CLINICAL CASE
PROBLEM 2:
An 85-Year-Old Female Patient with Dangerously High Blood Pressure

An 85-year-old female patient of yours was prescribed a combination of

hydrochlorothiazide and clonidine because of a “dangerously high” blood pressure of
190/105 mm Hg. When you hear this story, you are concerned about possible adverse
side effects. Your worst fear comes true when you find yourself attending her in the
emergency department with a serious adverse event you believe is directly related to
the medications she was prescribed.
SELECT THE BEST ANSWER TO THE FOLLOWING QUESTIONS

• Which of the following statements regarding this patient's acute medical problem is true?
A. This patient's problem is unlikely to be related to her medications
B. This patient's presentation is unusual after the initiation of medications in the elderly
C. This patient's problem is unlikely to lead to hospitalization
D. This patient's problem is likely to be transient
E. none of the above statements is true
This patient's problem can be characterized in the following manner:
• it is likely to be related to the beginning of medications she was prescribed;
• it is common after the initiation of medication in the elderly, especially multiple
medications;
• it is very unlikely to be transient unless some or all of the medications are discontinued;
and
• it will commonly lead to hospitalization. It is thought that up to 20% of hospitalizations,
and perhaps significantly more in the elderly, are a result of iatrogenic disease. Iatrogenic
disease is almost always associated with multiple medication use.
SELECT THE BEST ANSWER TO THE FOLLOWING QUESTIONS

Which of the following statements regarding the use of drugs In the elderly Is true?
A. Elderly patients should be treated in the same way as younger patients are with respect to drug initiation
B. Elderly patients generally need the same dose of medications as younger patients do
C. Psychotropic drugs are unlikely to produce significant side effects in elderly patients
D. elderly patients taking multiple medications should be reassessed on a yearly basis
E. none of the above statements Is true

The following are some helpful guidelines on the initiation of drugs in the elderly:
• Drug initiation in the elderly should be done cautiously. The general rule should be to start very low and go
very slow.
• The elderly patient usually needs a considerably lower dose of drug than does the young adult. The general
rule on drug initiation in elderly patients is "no more than 50% of the usual adult dose; no more than one
drug at a time. Increases should not be made any more quickly than once a week."
• Psychotropic drugs should be used with special caution. Psychotropic medications are frequently misused
in the elderly, and dosing should be monitored closely.
• All elderly patients should have a formal drug review performed at least every 3 months. At that time, all
drugs and the drug doses should be seriously considered for reduction or discontinuation, especially (ADR).
SELECT THE BEST ANSWER TO THE
FOLLOWING QUESTIONS
What is the most likely medication causing the pink rats and the people from outer
space in the patient?
A. propranolol
B. Hydrochlorothiazide
C. Ibuprofen
D. Cimetidine
E. digoxin

• The most common medication-induced cause of hallucinations in elderly

patients is propranolol.
• Many elderly patients who are prescribed propranolol develop visual or auditory
hallucinations.
• Unfortunately, rather than having an evaluation of their medication list, many of
these patients are then prescribed antipsychotic medications to treat the
hallucinations.
SELECT THE BEST ANSWER TO THE
FOLLOWING QUESTIONS
Of the drug combinations listed, which is the most likely to result in a drug-drug
interaction in the elderly?
A. cimetidine and propranolol
B. digoxin and hydrochlorothiazide
C. ibuprofen and captopril
D. triazolam and amitriptyline
E. haloperidol

• Patients who develop ADRs are more likely than those who do not develop an ADR
to be taking six or more drugs.
• The most commonly identified combination likely to result in a drug-drug interaction
is digoxin with a diuretic. In this case, the most likely ADR would be hypokalemia
from the diuretic, which may lead to digoxin toxicity in the susceptible elder.
• These combinations are considered secondary drug reactions, which require at least
two drugs to cause an interaction.