490
P A R T 5
Drugs acting on the autonomic nervous system
The drugs carbachol and pilocarpine are available
as ophthalmic agents. They are used to induce
miosis
,
or pupil constriction; to relieve the increased intraocular
pressure of glaucoma; and to allow surgeons to perform
certain surgical procedures.
Pilocarpine, which binds to muscarinic receptors
throughout the system, is used to increase secretions
in the mouth and GI tract and relieve the symptoms of
dry mouth that are in seen in Sjögren’s syndrome. It is
approved for use in adults and is given three times a day,
often with meals.
Pharmacokinetics
The direct-acting cholinergic agonists are generally well
absorbed after oral administration and have relatively
short half-lives, ranging from 1 to 6 hours. The meta
bolism and excretion of these drugs is not known but
is believed to occur at the synaptic level using normal
processes similar to the way that ACh is handled. Drugs
used topically are not generally absorbed systemically.
Contraindications and cautions
These drugs are used sparingly
because of the potential
undesirable systemic effects of parasympathetic stimu-
lation.
They are contraindicated with hypersensitivity
to any component of the drug
to avoid hypersensitiv-
ity reaction
and in the presence of any condition that
would be exacerbated by parasympathetic effects, such
as bradycardia, hypotension, vasomotor instability and
coronary artery disease,
which could be made worse
by the cardiac- and cardiovascular-suppressing effects
of the parasympathetic system.
Peptic ulcer, intestinal
obstruction or recent GI surgery
could be negatively
affected by the GI stimulating effects of the parasym-
pathetic nervous system.
Asthma
could be exacerbated
by the increased parasympathetic effect, overriding
the protective sympathetic bronchodilation.
Bladder
obstruction or impaired healing of sites from recent
bladder surgery
could be aggravated by the stimulatory
effects on the bladder.
Epilepsy and parkinsonism
could
be affected by the stimulation of ACh receptors in the
brain.
Caution should be used during pregnancy and
breastfeeding
because of the potential adverse effects on
the fetus or neonate.
Adverse effects
Individuals should be cautioned about the potential
adverse effects of these drugs. Even if the drug is being
given as a topical ophthalmic agent, there is always a
possibility that it can be absorbed systemically. The
adverse effects associated with these drugs are related
to parasympathetic nervous system stimulation. Cardio
vascular effects can include bradycardia, heart block,
hypotension and even cardiac arrest related to the
cardiac-suppressing effects of the parasympathetic
nervous system. GI effects can include nausea, vomiting,
cramps, diarrhoea, increased salivation and involuntary
defaecation related to the increase in GI secretions and
activity. Dehydration is possible due to the increase in GI
motility and resultant diarrhoea. Urinary tract effects
can include a sense of urgency related to the stimulation
of the bladder muscles and sphincter relaxation. Other
effects may include flushing and increased sweating sec-
ondary to stimulation of the cholinergic receptors in the
sympathetic nervous system.
Clinically important drug–drug interactions
There is an increased risk of cholinergic effects if these
drugs are combined or given with acetylcholinesterase
inhibitors, such as neostigmine or tacrine. The person
should be monitored and appropriate dose adjustments
made.
Prototype summary: Bethanechol
Indications:
Acute postoperative or postpartum
non-obstructive urinary retention; neurogenic atony
of the bladder with retention.
Actions:
Acts directly on cholinergic receptors to
mimic the effects of ACh; increases tone of detrusor
muscles and causes emptying of the bladder.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
30–90 mins 60–90 mins 1–6 hours
T
1/2
:
Metabolism and excretion unknown; thought
to be synaptic.
Adverse effects:
Abdominal discomfort, salivation,
nausea, vomiting, sweating, flushing.
Care considerations for people receiving
direct-acting cholinergic agonists
Assessment: History and examination
■
■
Assess for contraindications or cautions: known
allergies to these drugs
to avoid hypersensitivity
reactions
; bradycardia, vasomotor instability,
peptic ulcer, obstructive urinary or GI diseases;
recent GI or genitourinary surgery; asthma;
parkinsonism or epilepsy,
which could be
exacerbated or complicated by parasympathetic
stimulation
; and current status of pregnancy and
breastfeeding
because of the potential for adverse
effects to the fetus or neonate.
■
■
Perform a physical assessment
to establish
a baseline status before beginning therapy,
