Cholinergic effect

Question 1

Comment on pre-ganglionic nerve of cholinergic nerve

Answer 1

• Have a long pre-ganglionic nerve

Question 2

What are parasympathomimetics?

Answer 2

Compound that mimics the stimulation of parasympathetic nerves

Question 3

List of cholinoreceptors and what do they do?

Answer 3

○ List of cholinesterase inhibitors and they will all boost the level of Ach in the vincity of the receptor
	§ Neostigmine
	§ Physostigmine
	§ Edrophonium
	§ Parathion

Question 4

What are cholinoreceptors separated into?

Answer 4

○ Cholinoreceptors are serperated into two branches
§ Nicotonic Ach receptors are LGICR
□ N1 or NM- Skeletal muscle
□ N2 or NN- Autonomic Ganglia(CNS)
§ Muscarinic receptors which are GPCR
□ M1- CNS, peripheral neurones, gastric pariteal cells
□ M2- Atria, SAN, AVN
□ M3- Visceral smooth muscle, secretory glands, endothelial cells
□ M4- CNS
□ M5- CNS

Question 5

Nicotinic selective agonists

Answer 5

○ Nicotine

○ Lobeline

Question 6

Nicotinic selective antagonists

Answer 6

○ Tubocararine
○ Hexamethonium
○ Pancuronium

Question 7

Muscaranic selective agonists

Answer 7

○ Muscarine
○ Bethanecol-relatively resistant to cholinesterase’s
Pilocarpine

Question 8

Muscaranic selective antagonists

Answer 8

○ Atropine
○ Hyoscine
○ Pirenzepine
○ Ipratopium

Question 9

Muscaranic selective antagonists

Answer 9

○ Atropine
○ Hyoscine
○ Pirenzepine
○ Ipratopium

Question 10

Stimulation of nAChr and its termination

Answer 10

• Ach binding produces a conformational change that opens channel pores
• Allows influx of cations
• Produces an excitatory junction potential in the target cell
• Effect terminated by unbinding of Ach

Question 11

Main parasympathetic effects

Answer 11

• Reduce heart rate
• Vasodilation
• Increased saliva and gastric acid production
• Increased tear formation
• Visceral smooth muscle contraction
• Pupil constriction

Question 12

What is limited in cardiac cells?

Answer 12

• Limited parasympathetic innervation to the heart

Question 13

Where does parasympathetic innervation only go to in the heart?

Answer 13

• Only goes to atria and pacemaker cells

Question 14

What parts of the heart does the vagus nerve effect

Answer 14

SAN and atria

Question 15

When vagus nerve stimulated…

Answer 15

○ Membrane potential hyperpolarises
○ Frequency slows
○ Aps decrease

Question 16

How is the heart rate reduced?

Answer 16

• M2 receptor in heart is negatively coupled to cAMP
○ Less cAMP so pacemaker channels will be less active
○ Less PKA so less calcium channel activity
○ The beta-gamma subunits dissociate and interact with a potassium channel(GIRK)
○ Potassium channel is open all the time and will drive the membrane potential more negative
○ Also suppresses action potentials so more depolarisation needed to get the action potential hence heart rate slows down

Question 17

What are the vascular effects?

Answer 17

Arterial relaxation

Question 18

How are smooth muscles relaxed?

Answer 18

• Arteries do express M3 receptors
○ Receptors located on endothelial cells of blood vessels
○ Endothelium releases NO which is made from arginine by NO synthase
○ No synthase is calcium activated
○ NO binds to guanylyl cyclase
○ GTP goes to cGMP
○ Leads to rapid relaxation of smooth muscle cells

Question 19

Equation for blood pressure

Answer 19

Blood pressure=cardiac output x peripheral resistance

Question 20

Contraction of non-vascular smooth muscles(Activation of M3 receptors)

Answer 20

○ Increased activation of phospholipase C

○ Calcium release

Question 21

Examples of non-vascular smooth muscles

Answer 21

GI tract
Bladder
Airways

Question 22

Effects on secretory cells and the receptor stimulated

Answer 22

• Acetylcholine from vagus augments acid production(M1)
• Salivary glands(M3)
• Sweat glands(M3)
○ Are under sympathetic control

Question 23

Effects on eye

Where are parasympathetic nerves found?

Answer 23

• Parasympathetic receptors found on circular muscle

Question 24

Effects on eye

What do sympathetic nerves innervate?

Answer 24

• Sympathetic nerves innervate the radial muscle

Question 25

What does the stimulation of cholinergic receptors in eyes do?

Answer 25

• Contraction of ciliary muscle • Relaxes suspensory ligaments Allows lens to bulge

Question 26

How is glaucoma arisen and what is it often due to

Answer 26

* Glaucoma stems from poor drainage of fluid through trabecular network * Often due to a dilated iris

Question 27

Directly acting parasympathomimetics

Answer 27

``` ○ Piolocarpine(mAchR agonist) § Used to treat glaucoma and dry mouth § Used in sweat tests ○ Bethanecol(mAchR agonist) § Occasionally used to aid bladder/gastric emptying ○ Succinylcholine § High affinity nAChR agonist which is used in surgery § Depolarising paralysis ```

Question 28

Clinical uses of muscaranic blockers

Answer 28

* Premedication before anaesthesia to reduce secretions, sedations(hyoscine), prevent vagal effects * In the heart, they block to increase AV conduction * Ophthalmology-used to produce mydriases for examination * Bronchodilation in COPD * Anti-spasmodic in GI colic * Treatment of antiChE poisoning * Motion sickness

Question 29

Clinical uses of nicotinic blockers

Answer 29

``` • Muscle relaxants • Direct nAChR blocker: ○ Tubocurarine ○ Pancuronium ○ Vecuronium ○ Atacurium • Depolarising blockers • Direct nAchR agonists Suxamethonium ```