Cardiovascular Effects of Cholinergic Agonists & Antagonists (Sweatman)

Question 1

Agonism of M2 receptors in the heart have what effect?

Answer 1

Deceleration of SA node and Decreased atrial contractility

Question 2

Agonism of M3 and M5 receptors on BVs has what effect?

Answer 2

Causes NO release –> peripheral vasoDilation –> Decreased BP

Question 3

Describe the effects of M2 agonism on the Heart, Smooth muscle, and peripheral nerves.

Answer 3

Via G1/Go signaling, inhibition of adenylate cyclase, decreased cAMP:
SA node: Decreased HR
AV node: Decreased conduction velocity
Atrium: increased refractory period, Decreased contraction
Ventricle: slight Decreased contraction
Smooth muscle: Contraction
Peripheral nerves: Decreased ganglionic transmission

Question 4

Describe the effects of M3 agonism.

Answer 4

Couples by Gq/11–> activation of PLC –> Increased IP3 –> Increased DAG –> Increased Ca2+ and PKC –> depolarization/excitation –> Increased EPSPs
Release of NO
Vasodilation in periphery
“M3 lets NO free”

Question 5

What is the ONE muscarinic antagonist we need to know and what does it do?

Answer 5

Atropine

Increases HR, dilates pupils (sympathetic action), decreases salivation/other secretions

Question 6

Explain the effects of atropine upon the heart and vasculature and define the clinical utility of atropine administration.

Answer 6

Increased resting HR
Increased peripheral tone (minimal)
In high doses, atropine flush, to offset increased temp due to decreased sweating.
Utility:
Abolishes reflex vagal cardiac slowing or asystole
Prevents or abolishes bradycardia or asystole from parasympatheticomimetic drugs as well as cardiac arrest from electrical stimulation of the vagus (parasympathetic overdrive).
Facilitates AV conduction by shortening refractory period of AV node. Also, improves pts with inferior or posterior wall MI by relieving severe sinus or nodal bradycardia or AV block.

Question 7

What effect do cholinergic nerve products (Ach) have on adrenergic activity (NE) at the neuromuscular junction on the heart?

Answer 7

Inhibition via M2 Ach receptors on SA node cells.
Hyperpolarization due to more K+ influx –> inhibited cAMP synth. –> reduced phosphorylation by PKA –> decreased ATP for Ca2+ channel, Decreased contractile Rate & Force.
The alpha-2A autoreceptor on the adrenergic nerve terminal also acts to provide negative feedback.

Question 8

Describe the effects of Ach on the CV system.

Answer 8

Vasodilation
Decreased HR
Decreased AV node conduction velocity
Decreased force of atrial contraction
*Responses may be obscured by CV reflexive effects

Question 9

What effect does Ach have on each of these:

SA node, atrial contractility, and AV node?

Answer 9

SA node: Decreased HR primarily by decreasing rate of spontaneous depolarization Decreased NE release –> decreased atrial contractility
AV node: Decreased conduction and Increased refractory period by inhibiting Ca+ influx. (drug induced complete heart block)

Question 10

You give your pt IV ACh. What’s going to happen?

Answer 10

Transient drop in BP (due to M3 receptor stimulation –> vasodilation) & reflex tachycardia
Large dose –> bradycardia or AV nodal conduction block
*remember, vascular tone does not receive direct parasympathetic innervation, but will respond to exogenous muscarinic agonists/antagonists (Ach/Atropine).

Question 11

What effect does atropine have on the heart?

Answer 11

Transient decrease in HR (4-8 BPM) with low dose

Increased resting HR with high dose

Question 12

Atropine has what effect on peripheral vasculature?

Answer 12

Increased SM tone (vasoConstriction) [MINIMAL bc very little parasympathetic influence on peripheral vasculature]