C H A P T E R 3 2
Cholinergic agonists
497
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Myasthenia gravis is an autoimmune disease
characterised by antibodies to the ACh receptors.
This results in a loss of ACh receptors and eventual
loss of response at the neuromuscular junction.
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Acetylcholinesterase inhibitors are used to
treat myasthenia gravis because they allow the
accumulation of ACh in the synaptic cleft, prolonging
stimulation of any ACh sites that remain.
KEY POINTS
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Alzheimer’s disease is a progressive dementia
characterised by a loss of ACh-producing neurons
and ACh receptor sites in the neurocortex.
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Acetylcholinesterase inhibitors that cross the blood–
brain barrier are used to manage Alzheimer’s disease
by increasing ACh levels in the brain and slowing the
progression of the disease.
CRITICAL THINKING SCENARIO
Indirect-acting cholinergic agonists
THE SITUATION
A.J., a 75-year-old man with an unremarkable medical
history, is seen in the clinic for evaluation of memory loss
and confusion. Three years ago, his wife began to notice
memory gaps and confusion when A.J. was driving around
town. He would get lost only a few blocks from home. The
problem has become steadily worse. He was diagnosed
with Alzheimer’s disease after neurological tests and
medical evaluation ruled out other causes for his problem.
He did not want to take any drugs, but when he heard the
diagnosis, he became quite frightened and agreed to try
medication. His wife states that she is somewhat concerned
about giving him medication because he has sometimes
had trouble swallowing and chokes on his food. She
excitedly tells A.J. that once he starts the medication, his
memory will return and things will be normal again. A.J. is
placed on rivastigmine.
CRITICAL THINKING
What could be responsible for A.J.’s symptoms?
What modifications can be made to the prescription to
ensure A.J.’s safety if he is having trouble swallowing?
What important information about the disease and the
effectiveness of drug therapy needs to be discussed
with A.J. and his wife
? Will things return to normal?
What potential adverse effects can be anticipated with
rivastigmine, and how might these effects complicate
the situation for A.J. and his wife?
DISCUSSION
Alzheimer’s disease is a chronic, progressive disease that
involves the loss of neurons in the cortex of the brain that
are responsible for making connections between different
memories. A.J. has had the problem for at least 3 years, and
his loss of memory and confusion have become worse over
that period of time. Unfortunately, there is nothing available
at this time that can stop the loss of neurons or restore the
function that has already been lost.
One of the problems that occur with Alzheimer’s
disease is difficulty swallowing. Swallowing is a complex
CNS reflex that requires coordination of impulses, and with
this disease, the ability to swallow in a coordinated manner
is often lost. This can lead to aspiration and pneumonia,
which are often the underlying causes of death with
Alzheimer’s disease. Since A.J. already has some difficulty
swallowing, it would be important to look into the forms
in which rivastigmine is provided. In this case, the drug is
available in capsule form and as an oral solution. The oral
solution might be suggested because it could be much
easier to swallow. As the disease progresses, this drug
is also available as a transdermal system, which would
eliminate the need to swallow the drug. The status of A.J.’s
swallowing should be evaluated before starting therapy
and periodically as time goes on to determine how safe the
dosage form of the drug is for his particular situation.
A.J. and his wife should receive information on
Alzheimer’s disease and its progression. The drugs available
at this time do not reverse the memory loss and they do
not cure the disease. A.J.’s wife may be encouraged to
monitor A.J.’s behaviour, ability to perform activities of daily
living and other significant markers of importance to them.
The drug should slow the progression of the disease and it
might be helpful to monitor progress to see if the drug is
being effective. She might also want to become involved in
an Alzheimer’s support group or organisation, which could
provide valuable support, educational materials and access
to community resources. This is an overwhelming diagnosis
and it might be necessary to approach these individuals
over several visits to give them both time to adjust. It is
important to always include a family member and provide
information in writing for later reference when doing
teaching with a person with Alzheimer’s disease.
Many of the adverse effects associated with the
indirect-acting cholinergic agonists are a result of the
parasym-pathetic stimulation caused by these drugs and
may complicate A.J.’s care as his disease progresses. GI
effects can include increased salivation, which may further
