Lecture 15

Question 1

How is ACh produced in a cholinergic synapse?

Answer 1

Glucose is used as a precursor, this is then transformed to pyruvate and acetyl coA
Acetyl Coa and Choline react via choline acetyltransferase to form ACh and HSCoA
The ACh is then stored in vesicles for use as a neurotransmitter

Question 2

What is the role of ACh in a Cholinergic synapse when acting as a transmitter?

Answer 2

Can signal M receptors on both pre and post ganglionic neuron
Can be degraded by Acetylcholinesterase to form Choline and acetate
Choline and acetate may be uptaken into the presynaptic neuron (this is the rate limiting step in ACh synthesis)

Question 3

What are the sites for drug action at a cholinergic synapse?

Answer 3

Hemicholinim which prevents choline uptake
Vesamicol which prevents vesicular storage of ACh
4-aminopyridine which enahcnes ACh release
Botulin toxin (Botox) which prevents ACh release
Neostigmine which inhibits AChE to prevent ACh breakdown
Agonists or antagonists that mimic or block the actions of ACh (e.g. pilocarpine or atropine)

Question 4

What are the receptors for ACh?

Answer 4

Muscarinic receptors which are found at target organs

Nicotinic receptors which are found at ganglia, motor endplate and adrenal medulla

Question 5

What are the characteristics of muscarinic receptors?

Answer 5

G-protein coupled receptors
M1,M3,M5 are coupled with Gq to activate the inositol pathway
M2, M4 are coupled to Gi to inhibit adenylate cyclase, reducing cAMP levels

Question 6

What are the characteristics of Nicotinic receptors?

Answer 6

Ligand gated ion channels from 5 subunits
Nm-found at neuromuscular junction
Nn-found in the brain
ganglionic- found in autonomic ganglia
Leads to ion channel activation passage of Na+ and K+ causing depolarisation and a fast excitatory postsynaptic potential

Question 7

Why are Muscarinic receptors a much better drug target than nicotinic receptors?

Answer 7

Nicotinic receptors are widespread throughout the autonomic nervous system
Most agonists affect both ganglion and neuromuscular receptors
Nicotine can be clinically used

Question 8

What are the actions of drugs that act as agonists at cholinergic receptors?

Answer 8

Mimic the effects of ACh

Have affinity for muscarinic and/or nicotinic receptors but are fairly non-selective

Question 9

What are the actions of antagonists that act on muscarinic receptors?

Answer 9

Wide spread clinical applications

can inihibit bronchial and gastric secretion, relax smooth muscle (bronchii, pupil) increase heart rate

Question 10

What are the actions of antagonists that act on nicotinic receptors?

Answer 10

Ganglion specific blockers which have no clinical application
Neuromuscular blockers which can act as muscle relaxants

Question 11

What are the effects ofcholinergic drugs on the heart?

Answer 11

Agonists act to slow heart rate and cause vasodilation mediated by NO
Antagonists such as atropine can be used to increase the heart rate in the case of bradycardia

Question 12

What are the effects of cholinergic drugs on smooth muscle?

Answer 12

Agonists can stimulate the contraction of smooth muscle in bronchi, gall bladder, bile duct, bladder
Antagonists can produce relaxation of smooth muscles such as Ipratoprium which is a bronchodilator for asthma

Question 13

What are the effects of cholinergic drugs on exocrine glands?

Answer 13

Agonists can stimulate secretion from sweat, salivary, mucous and lacrimal glands as well as gastric, intestinal and pancreatic secretions
Antagonists can inhibit secretions such as atropine which, when used as an adjunct for anaesthesia can reduce secretions and act as a bronchodilator or Pirenzepine which inhibits gastric acid production to prevent peptic ulcers

Question 14

What are the effects of cholinergic drugs on the GI tract?

Answer 14

Agonists relax sphincters in GI, Biliary and urinary tracts such as Bethanechol which can assist with bladder emptying
Antagonists can inhibit GI tract motility such as atropine inhibiting gastric hypermotility

Question 15

What are the effects of cholinergic drugs on the eye?

Answer 15

Agonists stimulate contraction of the circular muscles of the iris and muscles of accommodation changing lens curvature, e.g. Pilocarpine used to treat glaucoma
Antagonists dilate pupils which will become unresponsive to light- leading to a rise in intraocular pressure
e.g. Tropicamide- opthalmic use, short-acting dilation of pupils to allow examination of retina and lens

Question 16

What is the role of the agonist neuromuscular blockers?

Answer 16

Agonists are depolarising blockers which cause sustained depolarisation of the muscle preventing new action potentials from being generated, this effect can not be reduced by ACh conc and is used by Suxamethonium as a muscle relaxant for anaesthesia

Question 17

What is the role of the antagonist neuromuscular blockers?

Answer 17

Non-depolarising blockers, compete with ACh for binding to nicotinic receptors preventing end plate depolisation, this can have its effect reversed through ACh addition an example is Pancuronium used in the lethal injection

Question 18

What is the function of hemicholinim?

Answer 18

Prevents reuptake of choline by the neuron at cholinergic syapse

Question 19

What is the function of Vesamicol?

Answer 19

Prevents storage of ACh into a vesicle

Question 20

What is the function of botox?

Answer 20

Prevents release of ACh at a cholinergic synapse

Question 21

What is the function of 4aminopyridine?

Answer 21

Promotes release of ACh at a cholinergic synapse

Question 22

What is the function of neostigme?

Answer 22

Prevents breakdown of ACh by AChesterase

Question 23

What are the effects of agonists to muscarnic receptors in the heart?

Answer 23

Slows the heart down to cause a decrease in force of contraction and has mediated

Question 24

What are the effects of antagonists to muscarnic receptors in the heart?

Answer 24

Atropine is used to increase heart rate in cases of bradycardia

Question 25

What are the effects of agonists to muscarninc receptors in non-vascular smooth muscle?

Answer 25

Stimulate contraction of smooth muscle in bronchi, gall bladder, bile duct, bladder and stimulate peristaltic activity in GI tract

Question 26

What are the effects of antagonists on nonvascular smooth muscles?

Answer 26

Ipratoprium can relax smooth muscles and act as a bronchodilator

Question 27

What are the effects of agonists on muscarinic receptors to exocrine glands?

Answer 27

Stimulate secretion from glands

Question 28

What are the effects of antagonists on muscarnic receptors on exocrine glands?

Answer 28

Atropine reduces secretions and acts as a bronchodilator

Pirenzepine is used to inhibit gastric acid production preventing peptic ulcers formation

Question 29

What are the effects of agonists on muscarinic in the GI tract?

Answer 29

Relaxation of sphincters

Bethanechol used to assist bladder emptying

Question 30

What are the effects of antagonists on muscarinic receptors in the GI tract?

Answer 30

GI tract mobility is inhibited, atropine can be used to treat gastric hyper mobility

Question 31

What is the function of Pilocarpine?

Answer 31

Acts as agonist to the cholinergic receptors in the eye to treat glaucoma as it leads to muscle contraction to restore eye curvature

Question 32

What is the function of tropicamide?

Answer 32

Acts as antagonist to the muscarinic receptors on the eye to relax the muscles allowing eye examination