Cholinergic Antagonists

Question 1

IV ACh results in what?

Answer 1

transient decrease in BP and reflex Tachycardia via stimulation of M3 receptors in vascular endothelium to produce vasodilation (NO)

*large doses lead to bradycardia or AV nodal conduction block

**If endothelium of vessel is damaged (pathological), IV ACh will act diectly on M3 receptors in the underlying smooth muscle causing contraction (Vasoconstriction)

Question 2

Stimulation of M2 couples by Gi/Go which leads to

Answer 2

Inhibition of Adenylate cyclase and decrease in cAMP

leads to the activation of inward potassium channels and inhibition of voltage gates calcium channels leading to hyper-polarization and inhibited neuronal activity

Question 3

T or F: Vasculature recieves parasympathetic innervation?

Answer 3

False!

But, the vasculature WILL respond to exogenous muscarinic agonists/antagonists

Question 4

What are the ACh effects on the AV node?

Answer 4

Decreased conduction
Increased refractory period

-via inhibiting calcium current
(this is responsible for drug-induced complete heart block)

Question 5

What are the ACh effects on the atria?

Answer 5

Hyperpolarization and decreased action potential duration by increasing K+ current

-also decreasing cAMP formation leads to decreased NorEPI release, which decreases atrial contractility

Question 6

M3 receptors couples through Gq to release….

Answer 6

Inositol triphosphate and diacylglycerol which leads to increased calcium and protein kinase C

*excitatory and leads to synthesis of NO

Question 7

what are the 4 primary effects of ACh on the CV system?

Answer 7

1. Vasodilation
2. Decreased HR
3. Decreased AV node conduction velocity
4. decrease force of atrial contraction

• these may effects may be obscured due to CV reflex effects

Question 8

In vasculature, stimulation of muscarinic M3 and M5 receptors leads the synthesis and release of…

Answer 8

Endothelin-derived relaxing factor, Nitric oxide (NO)

-vasodilator

Question 9

Atropine uses:

Answer 9

• Anticholinergic (anti-muscarinic)
  1. Inhibits temporary over-activity of vagal tone on the heart

2. Prevents/Stops bradycardia
   - cased by parasympathomimetic drugs in the circulation and cardiac arrest from stim of the vagus

Question 10

Atropine’s effect on circulation?

Answer 10

direct effects minimal (vascular beds lack significant cholinergic innervation)

High doses -> dilation of cutaneous blood vessels (especially in blush areas = Atropine flush)

-atropine flush is a compensatory rxn permitting the radition of heat to off-set the effect of the atropine-induced rise in temp (atropine inhibits sweating)

Question 11

ACh effects on the ventricular tissue?

Answer 11

ACh effects are much smaller than on the SA and AV nodes

Question 12

Atropine’s effect on the heart?

Answer 12

Main effect: Alter (resting*) HR
-max HR uneffected
Decreases with low doses (4-8bpm)
- via inhibited Presynaptic M1 receptors

Progressive tachycardia with higher doses
- via inhibited M2 receptors on SA nodal pacemaker cells (Vagal tone antagonized)

Question 13

What are the direct cholinergic effects on the SA node?

Answer 13

• Activation of K channels
• Inhibition of Calcium channels

*Inhibition of pacemaker (SA node) activity

results in less spontaneous depolarization

Question 14

Stimulation of the muscarinic M2 receptors….

Answer 14

decreases neuronal activity in the SA and AV nodes and decreases contractility in atrial tissue

=> decreased HR and contraction