380
P A R T 4
Drugs acting on the central and peripheral nervous systems
affinity for cholinergic receptor sites in the CNS than for
those in the peripheral nervous system. However, they
still block, to some extent, the cholinergic receptors that
are responsible for stimulation of the parasympathetic
nervous system’s postganglionic effectors. This blockage
is associated with the adverse effects (see Chapter 33),
including slowed gastrointestinal (GI) motility and
secretions, with dry mouth and constipation, urinary
retention, blurred vision and dilated pupils.
Anticholinergic drugs are indicated for the treatment
of parkinsonism, whether idiopathic, atherosclerotic or
postencephalitic, and for the relief of symptoms
of extrapyramidal disorders associated with the use of
some drugs, including phenothiazines. Although these
drugs are not as effective as levodopa in the treatment
of advancing cases of the disease, they may be useful as
adjunctive therapy and for people who no longer respond
to levodopa. See Table 24.2 for usual indications.
Pharmacokinetics
The anticholinergic drugs are variably absorbed from
the GI tract, reaching peak levels in 1 to 4 hours. They
are metabolised in the liver and excreted by cellular
pathways. All of them cross the placenta and enter breast
milk (see Contraindications and cautions). Benztropine
and biperiden are available in oral and intramuscular/
intravenous forms. Benzhexol is only available in an oral
form.
Contraindications and cautions
Anticholinergics are contraindicated in the presence of
allergy to any of these agents
to avoid hypersensitivity
reactions
. Inaddition, they are contraindicated innarrow-
angle glaucoma, GI obstruction, genitourinary (GU)
obstruction and prostatic hypertrophy,
all of which
could be exacerbated by the peripheral anticholin-
ergic effects of these drugs
, and in myasthenia gravis,
which could be exacerbated by the blocking of acetyl-
choline-receptor sites at neuromuscular synapses.
The
safety and efficacy for use in children have not been
established.
Administer these agents cautiously in the following
conditions: tachycardia and other dysrhythmias and
hypertension or hypotension
because the blocking of
the parasympathetic system may cause a dominance
of sympathetic stimulatory activity
, and hepatic dys-
function,
which could interfere with the metabolism of
the drugs and lead to toxic levels.
They should be used
during pregnancy and breastfeeding only if the benefit
to the mother clearly outweighs the potential risk to the
fetus or neonate. In addition, use caution in individuals
who work in hot environments
because reflex sweating
may be blocked, placing the individuals at risk for heat
prostration.
Adverse effects
The use of anticholinergics for Parkinson’s disease and
parkinsonism is associated with CNS effects that relate
to the blocking of central acetylcholine receptors, such
as disorientation, confusion and memory loss. Agita-
tion, nervousness, delirium, dizziness, light-headedness
and weakness may also occur.
Anticipated peripheral anticholinergic effects include
dry mouth, nausea, vomiting, paralytic ileus and consti-
pation related to decreased GI secretions and motility.
In addition, other adverse effects may occur, includ-
ing tachycardia, palpitations and hypotension related
to the blocking of the suppressive cardiac effects of
the parasympathetic nervous system; urinary retention
and hesitancy related to a blocking of bladder muscle
activity and sphincter relaxation; blurred vision and
photophobia related to pupil dilation and blocking of
lens accommodation; and flushing and reduced sweating
related to a blocking of the cholinergic sites that stimu-
late sweating and blood vessel dilation in the skin.
Clinically important drug–drug interactions
When these anticholinergic drugs are used with other
drugs that have anticholinergic properties, including
the tricyclics antidepressants and the phenothiazines,
there is a risk of potentially fatal paralytic ileus and an
increased risk of toxic psychoses. If such combinations
must be given, monitor people closely and implement
supportive measures. Dose adjustments are often neces-
sary. In addition, when antipsychotic drugs are combined
Prototype summary: Biperiden
Indications:
Adjunctive therapy for Parkinson’s
disease; relief of symptoms of extrapyramidal
disorders (parkinsonism).
Actions:
Acts as an anticholinergic, principally in
the CNS, returning balance to the basal ganglia
and reducing the severity of rigidity, akinesia and
tremors; peripheral anticholinergic effects help
to reduce drooling and other secondary effects of
parkinsonism.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
1 hours
1–1.5 hours 6–12 hours
IM 15 mins
Unknown Unknown
T
1/2
:
18.4 to 24.3 hours; metabolised in the liver.
Adverse effects:
Disorientation, confusion, memory
loss, nervousness, light-headedness, dizziness,
depression, blurred vision, mydriasis, dry mouth,
constipation, urinary retention, urinary hesitation,
flushing, decreased sweating.
