6
Cholinergic Agonists and Muscarinic
Receptor Antagonists
Frank J. Dowd
K E Y I N F O R M AT I O N
Cholinergic Agonists
• Acetylcholine stimulates both muscarinic and nicotinic receptors.
• Agonists at cholinergic receptors are either directly acting or
indirectly acting.
• Muscarine, pilocarpine, and cevimeline are directly acting at
muscarinic agonists.
• Carbachol is directly acting and nonselective but used for its
muscarinic effects.
• A number of tissues respond to muscarinic receptor agonists.
• Indirectly acting cholinergic agonists are drugs that inhibit
acetylcholinesterase.
• Neostigmine and physostigmine are reversible inhibitors of
acetylcholinesterase.
• Organophosphates are irreversible inhibitors of
acetylcholinesterase.
• Drugs that inhibit acetylcholinesterase increase acetylcholine at
both muscarinic and nicotinic sites.
Antagonists at Muscarinic Receptors
• Atropine and atropine-like drugs (antimuscarinic drugs) (e.g.,
benztropine, ipratropium, solifenacin) block muscarinic receptors.
• The therapeutic and adverse effects of antimuscarinic drugs are
the result of inhibition of the effect of acetylcholine, or other
agents that stimulate muscarinic receptors, in various tissues and
organs.
CASE
Mrs. C is your 65-year-old dental patient. It has been one year since
her last dental appointment. Nine months ago, her physician prescribed
solifenacin (VESIcare) for her overactive bladder. After starting at a dose
of 5 mg/day, the dose was increased to 10 mg/day, and the medication
has been effective in reducing her urinary urgency. She reports that she
can tolerate solifenacin reasonably well; however, she occasionally has
dry eyes and especially notices xerostomia that is most evident at night.
She sometimes has to keep a glass of water on her nightstand at night
to relieve the dry mouth. Mrs. C has had good oral health in the past and
has not had active caries in the last several years. At this appointment,
her oral soft tissue looks dry but, otherwise, normal. Incipient root sur-
face carious lesions are observed on the facial surfaces of tooth num-
bers 4, 5, and 11. You deduce that the xerostomia may be contributing to
the increase in caries. Would you include a drug sialogogue in managing
Mrs. C’s oral condition?
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• Common effects of antimuscarinic drugs include (roughly in
order of occurrence or magnitude and depending on route
of administration) the following: xerostomia, dry eyes, lack
of sweating, urinary retention, reduced overall GI activity,
antiparkinsonian effects in CNS, mydriasis, cycloplegia,
bronchodilation, and cardiac effects including tachycardia. (These
effects are opposite of those from muscarinic receptor agonists.)
• Atropine-like drugs are used for their effects on the respiratory
system, GI tract, genitourinary tract, central nervous system, and
to block excessive stimulation of muscarinic receptors.
• The indications for atropine-like drugs are the following: to
produce mydriasis, overactive bladder, chronic obstructive
pulmonary disease, to reduce salivary secretion, sinus node
tachycardia, as a preanesthetic medication, to reduce parkinsonian
tremors, to reduce bowel activity, to prevent motion sickness,
and to reduce the effects of substances that stimulate muscarinic
receptors, namely: cholinesterase inhibitors, drugs that directly
stimulate muscarinic receptors, and poisoning from certain types
of mushrooms.
• Contraindications for the use of antimuscarinic drugs include
prostate hypertrophy and atony of either the urinary bladder or GI
tract.
CHOLINERGIC AGONISTS
Cholinergic drugs (also called cholinomimetic drugs) are agents that
mimic the actions of the endogenous neurotransmitter acetylcholine
(ACh). They are directly acting cholinergic drugs because they bind to
and stimulate cholinergic receptors. As described in Chapter 5, ACh is
the primary neurotransmitter released from the nerve terminals of (1)
the preganglionic fibers of the parasympathetic and sympathetic nervous
systems, (2) the postganglionic fibers of the parasympathetic nervous sys-
tem (which include most of the postganglionic cholinergic neurons), and
(3) some postganglionic fibers of the sympathetic nervous system (mostly
fibers to the sweat glands). ACh is also the primary neurotransmitter
released at somatic efferent nerves innervating skeletal muscle. The major
cholinergic receptors for acetylcholine at these sites are nicotinic recep-
tors. Therefore, Figure 6-1 shows that peripheral cholinergic nerves may
be linked to either muscarinic or nicotinic receptors. Review Figures 5-1
and 5-2 for important information on the anatomy and physiology of
the autonomic nervous system and somatic nerves to skeletal muscles.