Lecture 18

Question 1

Where, by what enzyme, and from what components is acetycholine (ACh) synthesized?

Answer 1

Sythensized in presynaptic nerve terminals by choline acetyl transferase (CAT) using choline and acetylene-CoA.

Question 2

What are the 2 main ACh receptors (AChR) and how are they different from each other?

Answer 2

Nicotinic ACh receptor and Muscarinic ACh receptor.
NAChR are found in all postganglionic cells of the parasympathetic and sympathetic nervous system but muscarinic ACh receptors are only found in target tissues of the PNS

Question 3

How is ACh action terminated normally after it has been released into the synaptic cleft?

Answer 3

It is degraded by Acetylcholine esterase enzyme.

Question 4

In what way to M1, M2, and M3 actions differ?

Answer 4

M1 and M3 are excitatory receptors located in smooth muscle and glands causing parasympathetic actions of smooth muscle constriction and glandular secretions. M2 is an inhibitory receptor located in the heart. Activation of M2 receptors causes inhibitory actions of the PNS, primarily inducing bradycardia.

Question 5

What has muscarinic receptors, but no PNS innervation, and that muscarinic agonists will affect, mimicking the PNS?

Answer 5

Blood vessels

Question 6

Where are muscarinic AChR located?

Answer 6

Smooth muscle (viscera), glands, cardiac muscle, sweat glands

Question 7

Explain why nicotinic and muscarinic agonists have different effects, but they both act like ACh?

Answer 7

Because they activate the nACh and mACh receptors respectively. They muscarinic agonists are going to only activate parasympathetic nervous system whereas activation of nicotinic receptors is going to activate both parasympathetic and sympathetic response as well as cholinergic responses at the NMJ.

Question 8

How will muscarinic agonists affect blood vessels?

Answer 8

At high enough doses, muscarinic agonists can bind to mACHR on blood vessels to induce a PNS effect of vasodilation to viscera and skin.

Question 9

Why will nicotinic receptor agonists and antagonists have complex effects?

Answer 9

Because they will stimulate both parasympathetic and sympathetic effects since all postganglionic cells (PNS and SNS and NMJ) have nAChR

Question 10

What are muscarinic receptor antagonist effects dependent on?

Answer 10

The parasympathetic tone of the tissue to begin with (no tone, no antagonistic effects).

Question 11

Why is it important to know what there are drugs selective for muscle versus neuronal nicotinic AChR?

Answer 11

So you can use the correct drug without inducing unnecessary side effects.

Question 12

What are- in broad terms- 4 effects of ACh esterase inhibitors?

Answer 12

1. Enhance muscarinic (parasympathetic) effects
2. Enhance ACh concentrations at the NMJ
3. CNS effects
4. Combo of nicotinic and muscarinic effects

Question 13

Define Cholinergic:

Answer 13

Induces acetycholine-like effects across the board

Question 14

Define Parasympathomimetic:

Answer 14

ACh-like effect on parasympathetic targets

Question 15

Define muscarinic:

Answer 15

Induces muscarinic ACh effects by targeting muscarinic receptors. (Parasympathetic at glands, smooth muscle, heart)

Question 16

Define Nicotinic:

Answer 16

Causes PNS and SNS effects by targeting nACh receptors.

Question 17

Where does the name “Muscarine” come from?

Answer 17

A mushroom (Toadstool)- amanita muscaria

Question 18

What are the 4 major actions of muscarinic AChR agonists (on nonvascular smooth muscle)?

Answer 18

Bronchoconstriction
Urinary muscle constriction
Urinary sphincter relaxation
Increased GI motility (constriction)

Question 19

Give 4 examples of muscarinic agonists effects on exocrine glands.

Answer 19

1. Lacrimation
2. Salivation
3. Sweating
4. Bronchial secretion

Question 20

Explain DUMBSLED!

Answer 20

These are the results of parasympathetic stimulation: 
D-iarrhia 
U-rination
M-iosis
B-radychardia
S-wetting
L-acrimation
E-mesis
D-yspnea

Question 21

What are 3 cardiac muscarinic agonist effects and explain them (why these effects?)

Answer 21

1. Bradycardia leading to reduced cardiac output (M2 inhibitory receptor on cardiac tissue)
2. Reduced blood pressure (vasodilation and reduced cardiac output cause reduction in blood pressure)
3. Vasodilation (mAChR activation on blood vessels induced NO release. NO is a potent vasodilator)

Question 22

Provide 3 clinical uses of muscarinic agonist drugs (with example of drug).

Answer 22

1. Bethanechol- treat bladder atony by increasing constriction of smooth mm in bladder.
2. Pilocarpine- reduce intraocular pressure for glaucoma patients by increasing ocular drainage.
3. Carbachol- treat GI atony by increasing intestinal motility.

Question 23

What are 5 common adverse effects of muscarinic agonist drugs?

Answer 23

1. Constriction of the pupil, lack of accomodation for vision
2. Excess inhibition of the heart (excessive bradycardia)
3. Excess vasodilation causing hypotension
4. Diarrhea
5. Bronchoconstriction and excess bronchial secretions leading to breathing difficulties

Question 24

Which are 6 contraindication for the administration of muscarinic agonists?

Answer 24

Pneumonia 
Asthmatics/bronchoconstriction
Urinary blockage
Intestinal blockage
Arrhythmia
Pregnancy

Question 25

How do you explain these adverse effects and contraindications?

Answer 25

Muscarinic agonists stimulate the parasympathetic NS.
Pneumonia already has a ton of crap in the lungs, and muscarinic agonists will increase pulmonary secretions causing it to worse.
Asthamatics or anyone with bronchoconstriction will have their brionchioles constricted further by muscarinic agonists, preventing them from breathing.
Muscarinic agonsits in both a urinary blockage and intestinal blockage will be painful for the animal and cause a lot of pressure to buildup cranial to the blockage, potentially leading to rupture.
Arrhythmic patients should not have muscarinic agonsits as it will reduce their cardiac output and heart rate, putting them at higher risk for thrombosis.
Pregnancies can be aborted by uterine contractions induced by muscarinic agonsits.

Question 26

Why are most (synthetic) muscarinic agonsits relatively highly charged and what does that mean for their ability to cross the blood brain barrier?

Answer 26

They are highly charged so they will not cross the membranes and get into systemic circulation. They will not cross the blood brain barrier.