PHARMACOLOGY

Pharmacology is one area of the health sciences which is of particular

importance to gerontologists (= health care professionals who specialize in
the field of aging related dimensions of change over the lifespan).
Appropriately used, drugs will increase quality of life.
However, drugs can be responsible for serious side effects which may
result in hospitalisation and even death.

We live in a society where drug use is widespread.

However, we often don't think of the potential adverse consequences of
drugs we are given.
The aged are at particular risk, because few drugs are tested in the aged,
and most dosing schedules are determined for young people.
We need to be aware that drugs may improve quality of life, or decrease
it.
By understanding the principles of drug use which relate specifically to the
aged, you will be better able to assess the quality of treatment and
benefits your patients are receiving from the drugs they use.

In order to address the biological aspects of ageing which are particularly

relevant to pharmacology, we must begin with a basic overview of general
pharmacological principles.

1 PHARMACOKINETICS

There are several important steps in the movement of the drug through
the body:
absorption
bioavailability
distribution
biotransformation
elimination

Absorption, distribution, metabolism and excretion of drugs are all

affected by the ageing process.
Absorption is the process by which a drug, once administered, enters the
blood.
It is thought to be affected by changes in the motility (=contraction of the
muscles that mix and propel contents in the gastrointestinal tract) of the
stomach and intestines which occur as people age.
Diseases such as congestive heart failure which alter blood flow to the gut
will also affect absorption.
Absorption becomes less important when drugs are taken chronically.

Distribution is affected by:

increased body fat and decreased body water.
Drugs which are soluble in water will be distributed in a smaller
volume, and will therefore reach higher plasma concentrations (=The
liquid part of the blood and lymphatic fluid, which makes up about
half of the volume of blood)
Fat soluble drugs will be stored in the fat reserves in the body and
consequently persist for a longer time.

plasma protein binding.

Plasma protein levels in the blood fall as people age.
Hence, less of an administered dose is in the bound form, and more
is in the active, unbound form.
Immobility and chronic disease further decrease the plasma protein
levels and drug binding
because the binding capacity of the plasma proteins is decreased,
displacement of drugs occurs more easily, increasing the dangers
from the use of multiple drugs.

Metabolism is often slower in the aged as the result of decreased liver

function.
The normal doses are determined on the results of tests on people in the
18 - 40 age group, and therefore do not allow for the slower metabolism
of drugs in the aged.
In general, the clearance rate of drugs in the aged is about 66% of that in
younger people.
The dose should be adjusted accordingly (i.e. 66% of the recommended
dose), or the dosing interval increased.

Excretion is the aspect of pharmacokinetics most affected by ageing.

This is due to changes in kidney function.
Renal blood flow falls with age - by 60 it is about 50% of the blood flow in
a young adult.
If less blood is flowing to the kidney, there is less chance for drugs to be
removed from the blood.

How do changes in other body systems affect the use of drugs in the
aged?

Changes in the gastrointestinal system can affect the absorption of

orally administered drugs.
However, when a drug is being used for a prolonged period of time,
these changes may be unimportant.
Changes in the cardiovascular system can affect the distribution of
drugs around the body.
Changes in the blood, particularly plasma protein levels, can affect
drug transport (plasma protein levels can be affected by changes in
other body systems, diseases or by malnutrition or immobility).
Changes in enzyme systems, particularly in the liver, can affect
biotransformation.
Changes in renal and gastrointestinal function can affect
elimination.
Cognitive decline can affect a person's capacity to self medicate (= an
individual uses a substance to self-administer treatment for ailments)
and use drugs safely.
Changes in the musculoskeletal system may limit a person's ability to
self medicate (for example they may find it more difficult to open
packaging).

2. DRUG USE IN THE AGED

Drug used in the aged is widespread.

A study conducted in the United Kingdom found that 75% of people over
75 years of age took a prescription drug.
66% of these people received between 1 and 3 drugs, 25% received
between 4 and 6 drugs.
The use of multiple drugs is known as polypharmacy.

Another survey found that 12.5% of hospital admissions in the aged were
in part due to treatment with drugs, and that in 7.7% of cases, adverse
reactions to drugs were the only factor leading to admission.

2.1 ADVERSE REACTIONS

A recent study in Australia showed that approximately 6% of admissions of

aged people to an intensive care ward were due to interactions between
medications they had been prescribed. 1
Approximately 1 in 4 older patients admitted to hospitals are prescribed at
least 1 inappropriate medication, and up to 20% of all inpatient deaths are
attributable to potentially preventable adverse drug reactions.2
An adverse reaction is an undesired consequence of drug treatment.
While patients of any age can suffer an adverse reaction, the incidence
increases as people age.
Patients aged between 60 and 70 years have twice the incidence of
adverse reactions compared with people under 50.

A previous history of an adverse reaction increases the risk of further

reactions occurring.
It is therefore useful to know whether people under your care have a
history of adverse reactions.
The second factor which increases the risk of adverse reactions is an
increase in the number of drugs being taken.

Adverse reactions may manifest themselves in a number of ways.

1 Betteridge TM. Frampton CM. Jardine DL. (2012) Polypharmacy--we make it worse! A cross-sectional study from an
acute admissions unit. Internal Medicine Journal. 42(2):208-11.
2 Scott IA. Gray LC. Martin JH. Mitchell CA. (2012) Minimizing inappropriate medications in older populations: a 10-step

conceptual framework. American Journal of Medicine. 125(6):529-37.e4.

 They often contribute to falls, which are the sixth leading cause of death.
In the aged population living in the community, the use of psychoactive
(=affecting the mind) drugs is the most important risk factor for falls.
Users are 28 times more likely to suffer falls than non users, and the
impairment of motor and cognitive skills continues for a period of time
after drug use is halted.

2.1.1 DRUGS LIKELY TO CAUSE ADVERSE REACTIONS

benzodiazepines (e.g. valium)
non-steroidal antiinflammatories (e.g. aspirin, naproxen, ibuprofen)
opiate analgesics (e.g. codeine)
major tranquillisers
diuretics

2.1.2 HOW TO DEAL WITH ADVERSE REACTIONS

One of the greatest difficulties encountered in dealing with adverse drug

reactions is their identification.
The clearest indication that an adverse reaction has occurred is a temporal
(=connected with or limited by time) association between the onset of
symptoms and the addition of a new drug or change in the dosing
schedule.

If you suspect that an adverse reaction has occurred, the patient's medical
practitioner should be consulted.

BODY SYSTEM POTENTIAL ADVERSE REACTIONS

CENTRAL NERVOUS SYSTEM mental compromise
depression
excitation
cognitive defects
Amnesia (=partly or completely loses their memory)
Ataxia (=loss of full control of the bodys
movements)
CARDIOVASCULAR SYSTEM hypotension
orthostatic hypotension (=postural hypotension)
 hypertension
Dysrhythmias (=arrhythmia)
angina
GASTROINTESTINAL SYSTEM Gastritis (=stomach lining is inflamed)
gastro oesophageal reflux
constipation
diarrhoea
ulceration

One approach suggested to minimise the risk of adverse reactions is:

1) ascertain (=find out the true or correct information about something) all
current medications;
2) identify patients at high risk of or experiencing adverse drug reactions;
3) estimate life expectancy in high-risk patients;
4) define overall care goals in the context of life expectancy;
5) define and confirm current indications for ongoing treatment;

6) determine the time until benefit for disease-modifying medications;

7) estimate the magnitude of benefit versus harm in relation to each
medication;
8) review the relative utility of different drugs;
9) identify drugs that may be discontinued; and
10) implement and monitor a drug minimization plan with ongoing
reappraisal (=reassessment) of drug utility and patient adherence by a
single nominated clinician.3

As stated previously, the incidence of adverse reactions increases as the

number of drugs being taken by a patient increases.
Over-prescribing is one factor which may contribute to the incidence of
adverse reactions.

Over-prescribing is a particular problem in residential settings, where

psychotropic drugs (=Any drug capable of affecting the mind, emotions,
and behaviour), analgesics (=relieve pain) and laxatives (=treat and
prevent constipation) are commonly prescribed.
The psychotrophics are frequently prescribed agitation, sleeplessness and
pain rather than for a diagnosed condition.

A study conducted in England found that 18% of patients in the care of

community nurses had received psychotropic drugs in the last 24 hours,
compared with 78% of those in nursing homes.
One potential area of criticism of this study is that it is comparing different
populations.
Perhaps the conditions which have resulted in the patients being placed in
nursing homes are best treated using these drugs.
The home care patients may have different conditions, which do not
require drugs from this class.
However, the survey did report that the most active and least impaired of
the nursing home patients were receiving the most psychotropic drugs.

Should we be concerned about the use of psychotropic drugs?

The answer is yes.
The most common iatrogenic illnesses (=illness caused by medical
examination or treatment) in the aged are associated with the build up of
metabolites (=a substance formed in or necessary for metabolism) of
psychotropic drugs.
These conditions include:
parkinsonism (=any condition that causes a combination of the
movement abnormalities seen in Parkinson's disease such as tremor,
slow movement, impaired speech or muscle stiffness)
postural hypotension
drowsiness
confusion
rashes
jaundice.

The use of psychotropic drugs presents a particular problem for managing

care.
There may be a conflict between optimal care for an individual, (who may
be best served by avoiding psychotropic drugs), and the demands of
running the residential care establishment, which may necessitate the use
of such drugs in difficult patients.
This is a situation where theory and practice are often incompatible, and
serving the best interests of the individual may not serve the best interests
of the vast majority of patients. 4

2.3 COMPLIANCE

Compliance refers to how well a patient follows the instructions relating to

drug use.
Proper compliance is essential if the patient is to get maximum benefit
from a drug, and poor compliance is the single biggest problem in drug
treatment of any age group.
The good news is that the elderly have the best compliance of any age
group.

Compliance decreases as the number of drugs being taken increases, and

the duration of treatment increases.

You need to know whether your patient will comply with their drug
therapy.
There are two important issues to consider when assessing compliance.
Firstly, the patient must be mentally and physically able to comply with
the treatment programme, and second, the patient must want to comply.
Generally, patients will comply if they understand the treatment is
beneficial, and if the benefits outweigh the costs and inconveniences.

The most common reason why a patient will stop taking drugs is that the
drugs are having no beneficial effect.
Therefore, lack of compliance may be sending an important clinical
message regarding the treatment.
A patient who stops taking a drug cannot be assumed to be being difficult.
The issue of physical capacity to comply is addressed in part by the
principles of dispensing (=prepare medicine and give it to people, as a
job).
Patients should receive drugs in containers that are well labelled and easy
to open.
Colour coding of the bottles is a good idea.
Blister packs and child proof containers are more difficult to use than
screw caps.

= Blister packs = difficult for children to open

The patient must also be clearly told the directions for use.
Non-comprehension is in general a more serious cause of non compliance
than the patient deliberately halting the treatment.
Giving a specific time interval between doses or stating specific times for
administration results in far better compliance than instructions such as
use twice daily (which means every 12 hours).
The best understood directions are:
take once daily
take at (a specific time)
take 30 minutes before meals on an empty stomach
take during meals

The worst understood directions are:

take three / four times daily
take with meals
take as directed

Where possible, the drugs should be administered at the same time.

This can be achieved if the patient's medical practitioner is made aware of
the dosing schedule the patient is on.
It is often possible to select a formulation (=creating or preparing
something carefully) of a drug which allows for 12 hourly dosage to match
the other drugs being used, rather than eight hourly dosage.
This makes a huge difference to the ease of drug use:
with 12 hourly dosage for drugs A and B both are administered at 7
am and 7 pm
with 12 hourly dosage for A and 8 hourly dosage for B the
administration schedule is: A and B at 7 am, B at 3 pm, A at 7 pm, B
at 11 pm.

Although once daily administration of drugs is easiest, it is associated with

increased toxicity and adverse effects as a result of the high plasma
concentrations which occur soon after administration, and the potential
for a build up of metabolites.

2.4 SPECIFIC ASPECTS OF THE CAREGIVER'S ROLE

As a caregiver, there are four main areas in which you can make a
contribution to better drug use in the aged.
Ensuring that there is good compliance, by educating patients about the
specifics of their drug use requirements, checking on their drug use and, if
necessary, supervising.
Be alert for the possibility of adverse reactions, monitoring the patient
whenever there is a change in medication or in the use of existing
medication.
Guard against self-medication and the use of over the counter drugs.
Ensure that the medications taken by a patient are reviewed regularly
and that all medical practitioners treating the patient are fully informed of
all drugs used.

WORLD HEALTH ORGANISATION DRUG USE RECOMMENDATIONS

1. Drugs should not be used for longer than necessary and should be
reviewed at periodic intervals.
2. Drug treatment should not be regarded as a substitute for advice or
adjustments to daily living.
3. The margin between the therapeutic effect and the toxic dose is in
many cases small, and drugs suitable for young people may not be suitable
for aged people with the same condition.
4. The smallest number of drugs should be used and the regime (=a set of
rules about medical treatment that you follow in order to stay healthy or
to improve your health) should be easy to follow.

5. Touch and colour vision are well preserved in the aged making size,
shape and colour of the drugs very important.
Liquid preparations are usually acceptable.
Large tablets may be difficult to swallow.
6. Clear packaging which is easily opened is essential.
7. The patient should be educated about their drugs.
8. A friend or relative may need to be involved to ensure compliance.
9. There must be regular reviews of treatment.

The seven deadly sins of prescribing are:5

1. A drug is prescribed to treat a disease or ailment that is actually caused
by an adverse reaction to another drug.
2. A drug is prescribed to treat a problem that should be treated initially
with non-pharmacologic therapy.
3. Attempt to treat a medical problem that may be either self-limited
(=running a definite and limited course) or unresponsive to pharmacologic
treatment.

4. A drug is prescribed for a problem, but instead of the safest, most

effective treatment, the healthcare provider recommends an agent (=a
chemical or a substance that produces an effect or a change) that is
inappropriate for a geriatric patient.
5. Two drugs are prescribed appropriately, but they interact to cause
serious injury or death, and there was no monitoring plan in place for the
interaction.
6. Two or more drugs in the same drug class are used to treat separate
problems.
The drugs do not improve efficacy, but rather have additive effects that
could harm the patient.
7. The correct drug is selected to treat a problem, but the dosage is much
too high for the patient.

What are the common issues surrounding the use of drugs in the aged?

The main problem associated with drugs in the aged is polypharmacy, or

overuse, and the associated increased risk of adverse reactions.
Adverse reactions can manifest themselves in a variety of ways and can
affect many different body systems.
It is possible that an adverse drug reaction will be attributed to a disease,
resulting in even more drugs being taken.
Comorbidities (=1 or more additional diseases co-occurring with a primary
disease) which are common in the aged, complicate the safe use of drugs.
Over-the-counter medications may interact with prescribed drugs a
person is taking.
Medications often have an adverse effect on appetite and can contribute
to nutritional deficiencies.
Compliance may also be a problem, requiring a well-designed system to
ensure that medications are used safely.

ADVERSE REACTIONS AND OVERPRESCRIBING CASE STUDY

An elderly woman is living with her son, one of her seven children.
Her daughter in law feels that her husband is unfairly burdened with
responsibility for looking after his mother, and resents her presence in the
house.
The tension between the married couple is obvious, and a cause of great
concern to the mother in law.
Recently, the situation has been made worse by nocturnal incontinence
suffered by the elderly woman.
She has tried to conceal this from her son and daughter in law, but her
attempts to change the bed in the middle of the night have disturbed the
sleep of the family.
Increasingly, the elderly woman is suffering from insomnia.
This is yet another cause for concern, and she decides to consult with her
doctor.
On arrival at the practice, she finds the GP has taken a holiday, and
employed a locum to cover her absence.
The elderly woman discusses the problem of insomnia with the locum, and
is prescribed valium to help her sleep.
Three months later, she is admitted to a nursing home.

QUESTIONS
Make a comprehensive list of all the factors which may have contributed
to the elderly woman's admission to the nursing home.
In creating the list, try to work back from the obvious signs to identify the
possible root causes of the problems.

Identify how the treatment of this woman may have been changed to
produce a different outcome (a hint - is drug therapy the best option for
insomnia? Are the symptoms being treated or the cause?)

Review the Adverse Reactions and Overprescribing Case Study,

answering the questions and considering creating a concept map to
illustrate the issues.

It is best to begin at the end of the case, when the woman is admitted to a
nursing home.
Incontinence is one of the most common problems associated with nursing
home admission.

The woman was prescribed Valium in order to treat insomnia.

Valium is a symptomatic treatment only - meaning that it treats a
symptom without treating the underlying cause.
Unless the cause is identified and treated, the problem will re-occur as
soon as treatment with Valium finishes.

Valium is a particularly dangerous drug in the age, because it has a very

long half life.
The normal dosing schedule for younger people is likely to result in
excessive blood levels of the drug in the aged.
This can result in drowsiness or apparent cognitive decline, and
significantly increases the risk of falls.
If it has the desired effect produces sleep at night, it increases the risk of
incontinence.
Fear of incontinence may become an additional risk factor for insomnia.

Given the family situation, it is quite likely that this woman is depressed.
The underlying causes of the problems this woman is experiencing are
likely to be psychological and social.
Incontinence may be underlying (=be the basis or cause of sth) these
factors.
Because this woman has been attended by a locum it is unlikely that the
prescribing doctor will know their social and family background.