Cholinergic receptor stimulants & antagonists

Question 1

choline ester that acts on M1-M3 receptors in all peripheral tissues
Contracts bladder wall (M3), relaxes the sphincter (M3)
Major application is for urinary retention or treat post op ileus
Tox: cyclospasm, diarrhea, urinary urgency, vasodilation, reflex tachycardia, sweating

Answer 1

bethanechol

Question 2

AChE inhibitor that acts on both muscarinic and nicotinic receptors
used IV to reverse severe atropine poisoning
Used topically to treat glaucoma
Tox: increased parasymp effects: nausea, vomiting, diarrhea, urinary urgency

Answer 2

physostigmine

Question 3

What are the effects of a cholinergic activator at M2 receptors?

Answer 3

inhibition of cAMP production and activation of potassium channels

• decreases HR and contractility
• M2 receptors are on heart, nerves and smooth muscle

Question 4

What are the effects of cholinergic activators at M3 receptors?

Answer 4

IP3 and DAG cascade
bronchoconstriction
vasoconstriction
vasodilation (by release of NO)
M3 receptors are located on glands, smooth muscle and endothelium

Question 5

What are the effects of nicotine on the heart?

Answer 5

sympathomimetic effects include tachycardia & HTN

Question 6

What are the direct effects of muscarinic agonists on the heart?

Answer 6

-increases the potassium current at the SA and AV nodes, purkinje cells and ventricular muscle cells
-decreases slow inward movement of calcium current
-reduces funny current
Note: parasympathetic innervation is much higher in the atria than in the ventricles

Question 7

What are the direct actions of muscarinic agonists on arteries and veins?

Answer 7

dilation (M3) and reduction of peripheral vascular resistance

(release of NO = EDRF from endothelial cells)
Note: due to baroreceptor reflex, tachycardia follows the vasodilation

Question 8

Why does muscarinic activation in atherosclerosis cause vasoconstriction?

Answer 8

In atherosclerosis, the endothelium is not intact and release of NO does not occur from stimulation of M3 receptors. Instead, interaction with smooth muscle causes vasoconstriction

Question 9

inverse agonist of muscarinic receptor that reduces PR interval by blocking M2 receptors of AV node
causes bronchodilation and reduction of secretions
children are sensitive to its hyperthermic effects (inhibition of sweating causes ___ fever)

Answer 9

atropine

Question 10

inverse agonist of muscarinic receptor, used for motion sickness and management of secretions during surgery

Answer 10

scopalamine

Question 11

nicotinic antagonist used to treat HTN
-decreased arteriolar & venomotor tone
-sits on or near the nicotinic channel and occludes or closes it
Adverse: orthostatic hypotension

Answer 11

hexomethonium

Question 12

competitive inhibitor for ACh at nicotinic receptor
reduces arterioloar & venomotor tone
causes markedly decreased bp -> orthostatic hypotension

Answer 12

trimethaphan

Question 13

synthetic analog of atropine used to treat COPD
inverse agonist of muscarinic receptor (M3) -> causes bronchodilation
Do not use in glaucoma

Answer 13

ipratropium

Question 14

Why would a ganglion blocker be used to treat HTN?

Answer 14

These block the nicotinic receptor and cause arteriolar and venomotor tone to be decreased. Note: since these drugs are specific to nicotinic receptors, drugs that block muscarinic receptors will still be effective. Giving atropine can cause tachycardia (wouldn’t that be exacerbated by baroreceptor response to profound hypotension caused by the drug? -> yes)

Question 15

nicotinic ganglion blocker that is a competitive inhibitor of ACh
-decreases arteriolar and venomotor tone -> markedly decreases bp-> orthostatic hypotension

Answer 15

trimethaphan

Question 16

Describe the effects of acetylcholine release by the vagus at the SA node.

Answer 16

• decreases cAMP which causes voltage-dependent pacemaker channels (If) to shift more negative
• reduces phosphorylation and availability of L-type calcium channels (ICa)

Question 17

AChE inhibitor

prodrug insecticide that is absorbed by all routes

Answer 17

malathion

Question 18

AchE inhibitor used as nerve gas

undergoes aging in 10 minutes, making the enzyme-inhibitor complex more difficult to break

Answer 18

Soman

Question 19

activates muscarinic receptors in the heart to increase potassium flux across cardiac cell membranes and decrease potassium flux in ganglion and smooth muscle cells

Answer 19

muscarine

Question 20

What is the direct effect of ACh on vascular smooth muscle?

Answer 20

contraction (M3) -> most vascular beds do not have cholinergic innervation, except the coronary vasculature

Question 21

What would the effect of physostigmine on vascular smooth muscle? on the heart?

Answer 21

none
-no synapse there so no ACh release
on the heart?: decrease HR (M2)