488
P A R T 5
Drugs acting on the autonomic nervous system
C
holinergic agonists
act at the same site as the neuro-
transmitter acetylcholine (ACh) and increase the activity
of the ACh receptor sites throughout the body. Because
these sites are found extensively throughout the para-
sympathetic nervous system, their stimulation produces
a response similar to what is seen when the parasym-
pathetic system is activated. As a result, these drugs
are often called
parasympathomimetic
because their
action mimics the action of the parasympathetic nervous
system. Because the action of these drugs cannot be
limited to a specific site, their effects can be widespread
throughout the body, and they are usually associated
with many undesirable systemic effects.
Cholinergic agonists work either directly or indi-
rectly. Direct-acting cholinergic agonists occupy receptor
sites for ACh on the membranes of the effector cells of
the postganglionic cholinergic nerves, causing increased
stimulation of the cholinergic receptor. In contrast,
indirect-acting cholinergic agonists cause increased
stimulation of the ACh receptor sites by reacting with
the enzyme
acetylcholinesterase
and preventing it from
breaking down the ACh that was released from the
nerve. These drugs produce their effects indirectly by
producing an increase in the level of ACh in the synaptic
cleft, leading to increased stimulation of the cholinergic
receptor site (Figure 32.1). See Box 32.1 for use of these
drugs across the lifespan.
DIRECT-ACTING CHOLINERGIC AGONISTS
The direct-acting cholinergic agonists are similar to
ACh and react directly with receptor sites to cause the
same reaction as if ACh had stimulated the receptor
sites. These drugs usually stimulate muscarinic recep-
tors within the parasympathetic system. They are used
as systemic agents to increase bladder tone, urinary
excretion and GI secretions, and as ophthalmic agents
to induce miosis to relieve the increased intraocular
pressure of glaucoma (see Table 32.1). Systemic absorp-
tion usually does not occur when these drugs are used
ophthalmically.
Direct-acting cholinergic agonists include bethane-
chol (
Urocarb
), carbachol (
Isopto Carbachol
,
Miostat
)
and pilocarpine (
Isopto Carpine
). These agents are used
infrequently today because of their widespread para-
sympathetic activity. More-specific and less-toxic drugs
are now available and preferred.
Lens accommodation
Pupil constriction
lacrimal secretions
and salivation
synaptate effect
Effects of cholinergic drugs
Pharmacodynamics of
cholinergic drugs
ACh
ACh
Acetylcholinesterase
Acetyl CoA + Choline (from diet)
Choline
+
Acetic
acid
Enzyme
Muscarinic
or nicotinic
cholinergic
receptor
Nerve
terminal
Neuron or
effector cell
Neuromuscular junction;
causes muscle contraction
Ca
+
Ca
+
Direct-acting
cholinergic
drugs stimulate
receptor
directly
Indirect-acting
cholinergic drugs
block acetylcholin-
esterase leading to
increased ACh in
synapse
secretions
rate
contractility
conduction
secretions
motility
Muscle contraction
Sphincter relaxation
Vasodilation
Oculomotor n.
Facial n.
Glossopharygeal n.
Vagus n.
Pelvic n.
sphincter
constriction
1
2
2
3
3
4
1
4
5
5
FIGURE 32.1
Pharmacodynamics of cholinergic drugs and associated physiological responses.
