BMD 308: PHARMACOLOGY

ANS – Cholinergic Pharmacology

AMA KYERAA THOMFORD (PhD)

DEPARTMENT OF BIOMEDICAL SCIENCES
UNIVERSITY OF CAPE COAST
Learning Objectives:
Students should be able to List and describe the mechanism of
action, therapeutic indications, and adverse effects of the
following:

1. Cholinergic agonists and cholinesterase inhibitors

2. Direct, indirect, and mixed acting cholinergic agonists
3. Muscarinic and nicotinic receptor antagonists

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 PARASYMPATHOMIMETICS
(CHOLINOMIMETICS):
Drugs that facilitate or mimic some or all of the actions of
the parasympathetic nervous system.

Direct Acting Indirect Acting

Muscarinic Nicotinic Anticholinesterases

receptor receptor
agonists agonists
Reversible Irreversible
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 Direct Acting Cholinergic Agonists
• Acetylcholine *not used therapeutically – N/M
• Carbachol * (Miostat) – N/M
• Bethanechol * (Urecholine) – M
• Pilocarpine (Pilocar, Ocusert) – M

• Indications – Urinary retention after surgery or postpartum,

Glaucoma
• Adverse effects –
• Muscarinic (M): salivation, flushing, bronchospasm, sweating,
nausea, abdominal pain – acid indigestion and GI cramping,
diarrhea, and possibly, decreased blood pressure.
• Nicotinic (N)- Fasciculations, respiratory arrest
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 Direct Acting Cholinergic Nicotinic Agonists

• Nicotine
• MOA**- Low doses – ganglionic stimulation causing euphoria and arousal.
CNS effects cause relaxation and improves attention (Acute)
• Indications – None
• Adverse effects – Vomiting, convulsions, hypertension, cardiac arrhythmias,
Respiratory arrest – (depolarizing blockade), Muscarinic effects - PNS ganglia
stimulation.

• Succinylcholine *:
• MOA - Overstimulation results in depolarizing blockade
• Indications – muscle relaxation/paralysis associated with intubation, other
procedures
• Adverse effects – Fasciculations, respiratory arrest, malignant hyperthermia

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Indirect Acting Cholinergic Agonists – Reversible

• Neostigmine *
• Pyridostigmine* (Mestinon,)
• Physostigmine
• MOA - Prolongs duration of acetylcholine by binding with and
blocking acetylcholinesterase.
• Therefore both Nicotinic(N) and Muscarinic(M) effects!
• Indications – Myasthenia Gravis, Glaucoma, Atropine Poisoning
• Adverse effects –salivation, flushing, bradycardia,
bronchospasm, sweating, nausea, abdominal pain, diarrhea,
decreased blood pressure, muscle fasciculations (N), and
respiratory arrest (N).
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Indirect Acting Cholinergic Agonists – Reversible - CNS

• Used in Alzheimer’s :

• Donepezil (Aricept, Aricept ODT)

• Galantamine (Razadyne, Razadyne ER)
• Rivastigmine (Exelon) – tertiary amine

• MOA– Increase cerebral concentrations of acetylcholine by

inhibiting acetylcholinesterase
• Adverse effects –Same as other reversible ACHase Inhibitors

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Indirect Acting Cholinergic Agonists – Irreversible

• Echothiophate* (Phospholine)

• MOA- Prolongs duration of acetylcholine by permanently

inactivating acetylcholinesterase.
• Therefore both Nicotinic(N) and Muscarinic(M) effects!
• Indications – Glaucoma
• Adverse effects –salivation, flushing, bradycardia, bronchospasm,
sweating, nausea, abdominal pain, diarrhea, decreased blood
pressure, muscle fasciculations (N), and respiratory arrest (N).

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“SLUDWARMF”
• Sweating
• Lacrimation
• Urination
• Diarrhea
Muscarinic
• Wheezing
• Accommodation
• Rhinorrhea
• Miosis

• Fasciculations Nicotinic
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 PARASYMPATHOLYTICS
(ANTICHOLINERGICS):
Drugs that reduce or inhibit some or all of the actions of
the parasympathetic nervous system.

Muscarinic Nicotinic
receptor receptor
antagonists antagonists

Ganglionic Neuromuscular
blocking drugs blocking drugs
(Nn) (Nm)
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Parasympatholytics
Muscarinic receptor antagonists
• MOA- Block muscarinic receptors on the effector organs of
the parasympathetic nervous system and on the sweat glands
• Indications – Varied - specificity for muscarinic receptors is a
key reason behind their usefulness.
• Adverse effects –
• Autonomic
• PNS - dry mouth, blurred vision, tachycardia, urinary retention,
and constipation
• SAS - Inhibition of sweating
• CNS - restlessness, confusion, and hallucinations
• Common mnemonic : “hot as a hare, blind as a bat, dry as
a bone, red as a beet, and mad as a hatter"

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Parasympatholytics
Muscarinic receptor antagonists
• Atropine Sulfate – Cholinesterase poisoning
• ACLS: Bradycardia, Pulseless Electrical Activity and Asystole
• Benztropine (Cogentin) – Parkinsonism
• Dicyclomine (Bentyl) – Irritable Bowel Syndrome
• Ipratropium *(Atrovent) – COPD, Rhinorrhea
• Tiotropium * (Spiriva) – COPD, Rhinorrhea
• Oxybutynin (Ditropan) – Overactive bladder
• Tolterodine (Detrol) – Overactive bladder
• Tropicamide (Mydriacyl) - Mydriasis (short duration)
• Scopolamine - Motion Sickness, Amnesia
* Advanced cardiac life support (ACLS) is a group of procedures and techniques that treat immediately life-threatening
conditions, including cardiac arrest, shock, stroke, and trauma.

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Parasympatholytics
Nicotinic receptor antagonists- Ganglionic Blockers (NN)

• Mecamylamine – Non-depolarizing, competitive blocker

• Nicotine – Depolarizing blocker
• High doses – ganglionic blockade causing respiratory paralysis and
hypotension
• No selectivity - block receptors on both the parasympathetic
and sympathetic ganglia
• Adverse Effects – Intolerable
• Hypotension, Orthostatic Hypotension, atony of bladder and GI Tract,
cycloplegia, xerostomia, sexual dysfunction, hyperthermia
• Rarely used therapeutically

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Parasympatholytics
Nicotinic receptor antagonists- Neuromuscular Blockers (NM)

• Tubocurarine* - Prototype
• Pancuronium *
• Vecuronium*
• Indications – muscle relaxation/paralysis associated with
intubation, other procedures
• MOA - Competitive blocker - action can be reversed by
increasing concentration of Ach**
• Adverse Effects – Respiratory arrest

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