Drug
Interactions in the
Elderly
Summarized
by Robert W. Griffith, MD
September
28, 2007
Summary
The
need to identify, manage,
and prevent drug
interactions is
particularly important for
older patients. They may
be taking a number of
medications, and often
have several chronic
disorders. A holistic,
multiprofessional,
team-based approach is
recommended, assisted by
computerized prescribing
software with appropriate
alerts.
Introduction
Elderly
patients are more likely
to experience drug
interactions than younger
people. They take more
medications, they have
more co-existing diseases,
and they may not have an
adequate nutritional
status. Moreover, there
are more of them who have
survived severe health
challenges - e.g. organ
transplants or HIV
infections - than younger
folk. Fortunately, health
professionals' knowledge
of the risks of
interactions in the
elderly has improved,
which mitigates the
problem somewhat. However,
there is room for
improvement, as shown in a
recent article in the
Lancet. Here are some
points taken from this
article.
The
types of drug interactions
It's
not enough to examine the
effect of one drug on
another - a so-called
drug-drug interaction.
There are drug-disease,
drug-food, drug-alcohol,
drug-herb, and
drug-nutrition
interactions. One can also
include drug-patient
interactions, where the
specific genetic make-up
in the patient affects
their individual response
to a drug.
Drug-drug
interactions can be
pharmacokinetic or
pharmacodynamic. In a
pharmacokinetic
interaction, one drug can
influence the other's
absorption into the body
or the rate of its
breakdown, changing the
amount of the dose of the
second drug that's
available to do its work
(or produce an overdose or
toxic effect). A
pharmacodynamic
interaction occurs when
one drug affects the way
another drug produces its
effect on the target
tissue in the body, either
inhibiting or enhancing
the effect.
An
example of a
pharmacokinetic
interaction is when
ciprofloxacin (an
antibiotic) is given with
olanzapine (used for
mental disorders); the
antibiotic blocks the
liver enzyme that breaks
down olanzapine, producing
blood levels that cause
muscle spasms and falls. A
pharmacodynamic drug
interaction is exemplified
when ciprofloxacin is
given together with
glibenclamide (an
antidiabetic);
ciprofloxacin reinforces
gibenclamide's effect on
the blood sugar, producing
profound hypoglycemia.
Drug-disease
interactions are
likely with chronic
disorders of the liver
(responsible for breaking
down drugs) or the kidneys
(responsible for excreting
drugs and their breakdown
products). Patients with
such conditions may
require lower-than-usual
doses of many drugs. More
rarely, a disease can
affect the tissues where a
drug has an effect; an
example of this is the
administration of
metaclopramide (used to
treat an inactive stomach)
in Parkinson's disease
patients, which can worsen
the Parkinsonian symptoms.
Australian researchers
have reported that actual
drug-disease interactions
are two to three times
more frequent than actual
drug-drug interactions.
Drug-nutrition
interactions can
occur when inadequacies in
the diet can allow
deficiencies to develop.
For instance, too little
protein can result in a
low serum albumin level;
drugs that are large
carried bound closely to
protein would then be
present in greater amounts
of their 'free' or
immediately active form,
producing overdose
effects. An example is
when the anti-epileptic
phenytoin is given to a
patient with a low albumin
level, causing confusion,
insomnia, and staggering.
Overweight
and obesity, perhaps
related to nutrition, can
also affect the dose of
drug required for a
desired effect. A small
thin elderly person often
requires a lower dose than
a large, overweight
patient; ignoring this may
result in side effects in
the small subject, or a
lack of effect in the
overweight patient.
Drug-herb
interactions are
increasingly common,
because patients have
turned to alternative
medicines more often in
recent years, and they
don't inform their doctors
of the herbs and
supplements that they are
taking. This is
particularly the case with
older patients. For
example, taking gingko
along with aspirin causes
a decrease in the function
of the blood platelets, so
that there's an increased
risk of bleeding. People
often believe that
alternate medications are,
by nature, harmless and
unable to produce or
precipitate side effects.
Drug-alcohol
interactions are usually
an example of drug
synergy; the soporific
effects of alcohol
potentiate the sedative
action of bromazepam and
other minor tranquilizers
(see link below).
Inadvertent
Drug-Drug Interactions
The
risk of drug interactions
increases with the number
of drugs taken. Physicians
are often unaware of all
the drugs their patients
are taking; sometimes a
patient will visit two
doctors, each of who
prescribe medications.
Patients may visit
different pharmacies,
rendering the pharmacy
software-generated
warnings virtually
useless. And older people
are notorious hoarders -
they may keep unused
medications for years, and
turn to them when they
feel symptoms warrant
their use.
An
Approach to the Problem
The
authors of the article
suggest that physicians
should consider the
following:
1.
Concentrate on potential
drug-drug interactions
that are common, which
involve drugs with a
narrow dose range - e.g.
digoxin, phenytoin, or
warfarin (a blood thinner)
- and where lab monitoring
tests are usually
available. Such
interactions are detected
by computer software
systems.
2.
Think carefully before
prescribing a drug to
someone who is already
taking nine or more drugs,
or has 5 or more
comorbidities (co-existing
medical conditions) -
these are 'exposure'
levels at which a new
drug-drug or drug-disease
interaction is highly
likely.
3.
Avoid, if possible cascade
interactions. This is when
an adverse drug reaction
is interpreted as a new
medical disorder, and a
new drug is prescribed to
treat the symptoms. A
study has provided a good
example. Patients with
Alzheimer's disease who
are prescribed a
cholinesterase inhibitor,
such as Donepezil (Aricept®)
or Rivastigmine (Exelon®),
may develop urinary
incontinence; this may
lead to a prescription for
an anti-cholinergic drug,
which would not have been
necessary if the first
drug had been correctly
selected or dosed.
If
an interaction is
diagnosed
This
is what the doctor may do
in such circumstances:
1.
If possible, discontinue
one or other of the drugs
at fault. Otherwise, try
changing the dose or the
time of administration.
2.
Review all the drugs the
patient is taking for
their appropriateness, and
to ensure the lowest
effective dose is being
used.
3.
Consider substituting the
suspect drug with another
of similar efficacy but a
lower chance of
interaction.
4.
Order monitoring of drug
serum levels, if such
tests are available.
5.
Be ready to discontinue
drugs if a cascade
interaction is suspected.
Prevention
is better than cure
One
of the best preventive
steps is achieved by
computer systems that
screen for interactions at
the time of electronic
prescribing, and show
alerts before the
prescription is filled.
This should be done
consistently and
continuously, and linked
to a source for
intelligent
recommendations about
alternative therapies.
There is a risk that
health professionals may
ignore or over-ride such
alerts, but, with better
education, such instances
will become fewer.
The
optimum health management
team for geriatric
patients should consist of
a physician (preferably a
geriatrician), nurse, and
pharmacist. Working
together they should be
able to avoid most drug
interactions.
Source
- The
challenge of managing
drug interactions in
elderly people. L. Mallet
, A. Spinewine ,
A. Huang, Lancet,
2007, vol. 370,
pp. 185--191
