C H A P T E R 3 2
Cholinergic agonists
493
Alzheimer’s disease. This drug works in a unique way to
slow the effects of this disease and is the only drug of its
class that is available (Box 32.5).
Therapeutic actions and indications
The indirect-acting cholinergic agonists work by revers-
ibly blocking acetylcholinesterase at the synaptic cleft.
This blocking allows the accumulation of ACh released
from the nerve endings and leads to increased and pro-
longed stimulation of ACh receptor sites at all of the
postsynaptic cholinergic sites. Indirect-acting cholin-
ergic agonists work to relieve the signs and symptoms
of myasthenia gravis and increase muscle strength by
allowing ACh to accumulate in the synaptic cleft at
neuromuscular junctions. Indirect-acting choliner-
gic agonists that more readily cross the blood–brain
barrier and seem to affect mostly the cells in the cortex
to increase ACh concentration in the area of the brain
where ACh-producing cells are dying, affecting memory
and the ability to access and link different memories, are
used in the treatment of Alzheimer’s disease. In addition
to usual indications, pyridostigmine has also recently
been approved for military personnel to increase survival
after exposure to particular
nerve gases
—irreversible
acetylcholinesterase inhibitors used in warfare to cause
paralysis and death by prolonged muscle contraction
Safe medication administration
Myasthenic crisis versus cholinergic crisis
Myasthenia gravis is an autoimmune disease that runs an
unpredictable course throughout the person’s life. Often, the
disease goes through an intense phase called a myasthenic
crisis, marked by extreme muscle weakness and respiratory
difficulty.
Because of the variability of the disease and the tendency
to have crises and periods of remission, management of the
drug dose for a person with myasthenia gravis is a challenge.
If a person goes into remission, a smaller dose is needed.
If a person has a crisis, an increased dose is needed. To
further complicate the clinical picture, the presentation
of a cholinergic overdose or cholinergic crisis is similar
to the presentation of a myasthenic crisis. The individual
with a cholinergic crisis presents with progressive muscle
weakness and respiratory difficulty as the accumulation of
ACh at the cholinergic receptor site leads to reduced impulse
transmission and muscle weakness. This is a crisis when the
respiratory muscles are involved.
For a myasthenic crisis, the correct treatment is increased
cholinergic drug. However, treatment of a cholinergic crisis
requires withdrawal of the drug. The person’s respiratory
difficulty usually necessitates acute medical attention.
At this point, the drug edrophonium can be used as a
diagnostic agent to distinguish the two conditions. If the
person improves immediately after the edrophonium
injection, the problem is a myasthenic crisis, which is
improved by administration of the cholinergic drug. If the
person gets worse, the problem is probably a cholinergic
crisis, and withdrawal of the person’s cholinergic drug along
with intense medical support is indicated. Atropine helps
to alleviate some of the parasympathetic reactions to the
cholinergic drug. However, because atropine is not effective
at the neuromuscular junction, only time will reverse the drug
toxicity.
The person and significant others will need support,
teaching and encouragement to deal with the tricky
regulation of the cholinergic medication throughout the
course of the disease. Health professionals in the acute care
setting need to be mindful of the difficulty in distinguishing
drug toxicity from the need for more drug—and be prepared
to respond appropriately.
The drugs used to help people with this progressive
disease are several indirect-acting cholinergic agonists
that do not cross the blood–brain barrier and do not effect
ACh transmission in the brain (see Table 32.2). These drugs
include edrophonium (generic), neostigmine (generic) and
pyridostigmine (Mestinon).
Alzheimer’s disease
Alzheimer’s disease is a chronic, progressive disease
on the brain’s cortex. Eventually it results in memory
loss so severe that the person may not remember how
to perform basic activities of daily living and may not
recognise close family members. Although Alzheimer’s
disease primarily strikes the elderly, it has a tremendous
impact on family members of all ages. For example, adult
children of Alzheimer’s sufferers, many of whom are
busy raising children of their own, may find themselves
in the role of caregivers—in essence, becoming parents
of their parent.This new role can put tremendous stress
on individuals who are trying to struggle with work,
family and issues related to their parent’s care.
When caring for an Alzheimer’s sufferer and family,
the health professional must remember that the person’s
cultural background can affect how the family copes. For
instance, those who tend to have solid extended families
or who are part of communities that offer strong social
support and interdependence may be better equipped
to deal with caring for the person as the disease
progresses. In contrast, families that are more goal and
achievement oriented and who value autonomy and
independence may find themselves overwhelmed by
the person’s needs and may require more support and
referrals to community resources.
The health professional is in the best position to
evaluate the family situation. By approaching each
situation as unique and striving to incorporate cultural
and social norms into the considerations for care, the
health professional can help to ease the family’s burden
while also maintaining the dignity of the person and the
family through this difficult experience.
Cultural considerations
BOX 32.4
