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Cholinergic Receptors
Antagonists
59-291 Section 2, lecture 3
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• Muscarinic Receptor Antagonists
– Belladonna alkaloids
• Derived from plants; Atropa belladonna (the deadly night
shade)
• Atropine, scopolamine
• Well absorbed from the gut and distributed to CNS
• Systemic administration, short half life of ~ 2h
• Topical ocular admin, longer half life.
– Bind to iris pigments and are released over days ,darker irises
bind more
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Pharmacologic effects- muscarinic receptor antagonists inhibit
parasympathetic nerve stimulation
relax smooth muscle
increase heart rate
Increase conductivity in the heart
Inhibit exocrine gland secretion
These effects are dose dependent
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Cardiac effect
• Standard dose
– Blocks the effect of vagus nerve
• Increases heart rate
• Increases AV conduction velocity
• Low dose
– When delivered by IV, at low dose slows heart
rate
• by stimulating vagal motor nucleus in the brain
• Used to treat sinus bradycardia which can
lead to hypotension, ischemia if left
untreated
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Central Nervous System
• Atropine, scopolamine;
– Block muscarinic receptors
• Sedation
• Excitement
• Scopolamine
– More sedating than atropine
– Used as an adjunct to anesthesia
• Atropine
– Mild stimulation followed by a slower and
longer-lasting sedative effect
– Higher dose>> deliruim, hallucination
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Nicotinic Receptor Antagonists
• Ganglionic blocking agents (e.g.
Trimethaphan)
– Block NN receptors at sympathetic and parasy.
– Effect on a tissue: depends on sympathetic or
parasy. system is dominant
– No longer are used to treat chronic
hypertension
– Trimethaphan is occasionally used in cases of
hypertensive emergency, when extremely high
blood pressure must be lowered rapidly
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Nicotinic Receptor Antagonists
•
Neuromuscular blocking agents
–
–
1.
2.
Inhibit neurotransmission at skeletal muscle
Causing muscle weakness and paralysis
Non-depolarizing blockers
Depolarizing blockers
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Nondeporolarizing Neuromuscular
blocking agents (Curariform drugs)
• Positively charged, e.g.
Pancuronium, Tubocurarine
• Are not well absorbed from
the gut, hence they do not
cause poisoning when
ingested with contaminated
meat
• Do not cross blood-brain
barrier (BBB)
• Competitive antagonists of
Ach at NM receptors
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Nondeporolarizing Neuromuscular
blocking agents
• Paralyze small fast moving muscles of eyes
and face> larger muscles of the limbs and
trunk > finally the intercostal muscles and
the diaphragm
• Is used for relaxation of abdominal muscles
for surgical procedures without producing
apnea
• Side effects: stimulate mast cells to release
histamine> tachycardia, hypotension and
bronchospasm
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Depolarizing Neuromuscular
Blocking Agents
• Succinylcholine; two molecules of Ach
• Binds to NM receptors and depolarizes the
motor end plate
• First transient muscle contraction
(fasciculation) followed by a sustained
muscle paralysis
• Ultra-short duration action (5-10 min) due
to the effect of plasma cholinesterase
• Is used to produce muscle relaxation before
and during surgery
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Adrenergic Receptor Agonists
• Diverse pharmacological effect: treatment
of a wide spectrum of clinical conditions
• Cardiovascular emergencies to common
cold
• Sympathetic Stimulation> release of NE, E
> Adrenergic receptors> physiological
effects
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Inhibits NE
release
Contract vascular
smooth muscle, iris,
bladder sphincter
muscle
Relaxes
bronchial,
uterine, and
vascular
smooth
muscle
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b-Adrenergic Receptors
• Activation of b1 adrenergic receptors
– Positive chronotropic effect ( heart rate)
– Positive inotropic effect ( contractility)
– Positive dromotropic effect ( impulse conduction
velocity)
• Activation of b2 adrenergic receptors
– Relaxation of bronchial, uterine, vascular smooth
muscle cells
– Potassuim uptake in skeletal muscles
– Glycogenolysis
• Activation of b3 adrenergic receptors
– lipolysis
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Dopamine Receptors
• Dopamine receptors only activated by
dopamine and not by any other adrenergic
receptor agonist
– D1: Muscle relaxation in vascular smooth
muscles
– D2: modulate neurotransmitter release
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Imidazoline Receptors
• Activated by adrenergic receptor agonists
and other substances that contain
imidazoline structure
• Found in CNS and PNS
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Signal transduction
• Adrenergic, dopamine and imidazoline receptors
are G-protien binding receptors
 a1 Activate phospholipase C, which catalyzes the
release of IP3 and DAG from membrane
phospholipid
• IP3 releases Ca2+ from sarcoplasmic reticulum in
a1
SM cells and muscle contraction>
vasoconstriction> increase BP
 a2 activation> inhibition of adenylate cyclase>
cAMP
 b and D1 receptor activation > stimulation of
adenylate cyclase > cAMP
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Practice Questions
• Determine the location and function of the
following adrenergic receptors
 a1 receptors
– Postjunctional smooth muscles;
– Contraction of vascular SM, iris dilator muscle, bladder
sphincter muscle
 a2 receptors
– Presynaptic neurons postganglionic neurons
– Feedback inhibition of NE release
 b1 receptors
– Cardiac cells
– Positive chronotropic, inotropic, dromotropic effects
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• What is succinylcholine? What is the effect
and structure of this drug?
• Nicotinic receptor antagonist
• Depolarizing blocking agent
• Two molecules of Ach
• Binds to nicotinic receptors and causes
persistent depolarization of motor end plate
• Fasciculation followed by sustained
paralysis
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