Pharmacology Of Cholinergic Transmission

Question 1

What neurotransmitter is released at most autonomic synapses?

What is the exception?

Answer 1

Acetylcholine

Sympathetic (eg.blood vessels)

Question 2

What is ACh formed from?

Answer 2

Choline

Acetyl coenzyme A

Question 3

What enzyme catalyses the formation of ACh?

Answer 3

Choline acetyl transferase (CAT)

Question 4

What is ACh stored in?

Answer 4

Pre-synaptic vesicles

Question 5

By what process are the contents of pre-synaptic vesicles released?

Answer 5

Exocytosis

Question 6

What causes the release of ACh?

Answer 6

Increased intracellular calcium ion concentration within nerve terminal

Question 7

What are the two types of cholinergic receptor?

Answer 7

Muscarinic

Nicotinic

Question 8

What enzyme catalyses the breakdown of ACh?

Answer 8

Acetylcholine-esterase (AChE)

Question 9

Where is acetylcholine-esterase found?

Answer 9

In synaptic cleft tethered to post-synaptic membrane

Question 10

What type of receptor is present at neuromuscular junctions?

Answer 10

Cholinergic nicotinic

Question 11

What is the small brief depolarisation that occurs in the muscle fibre to trigger an action potential?

Answer 11

End plate potential

Question 12

What causes sustained muscle fibre contraction?

Answer 12

Frequent action potentials

Causing twitch summation

Question 13

What three pre-synaptic processes could be targeted to modify synaptic transmission?

Answer 13

Synthesis

Storage

Release

Question 14

What drugs inhibit ACh synthesis?

Answer 14

Hemicholiniums

Question 15

What enzyme do hemicholiniums inhibit?

Answer 15

Choline acetyl transferase (CAT)

Question 16

What drug inhibits storage of ACh?

Answer 16

Vesamicol

Question 17

What does vesamicol inhibit?

Answer 17

ACh storage

Question 18

What inhibits the release of ACh?

Answer 18

Botulinum toxin

Question 19

What is the (only) clinical use of nicotinic agonists?

Answer 19

Nicotine patches

Question 20

What type of drug are muscle relaxants?

Answer 20

Reversible competitive antagonists of cholinergic nicotinic receptors

Question 21

What are the properties of antagonists?

Answer 21

Have affinity but no efficacy

Question 22

What do muscle relaxants do?

Answer 22

Bind to cholinergic nicotinic receptors on muscle fibres

Prevents ACh binding/activating receptor

Question 23

What is an example of a skeletal muscle relaxant?

Answer 23

Vecuronium

Atracurium

Pancuronium

TUBOCURARINE

Question 24

Why are ganglion blockers not used clinically (often)?

Answer 24

Many side effects

Question 25

What is the major effect caused by ganglion blockers?

Answer 25

Reduction in blood pressure

Question 26

What is an example of a ganglion blocker?

Answer 26

Hexamethonium Trimetaphan

Question 27

What is trimetaphan used for clinically?

Answer 27

Reduces bleeding during brain surgery | Reduces blood pressure

Question 28

What is botulism?

Answer 28

Paralysis (of respiratory muscles)

Question 29

What does botulinum toxin do?

Answer 29

Destroys key proteins involved in exocytosis (inhibiting release of ACh)

Question 30

What are some key proteins involved in exocytosis?

Answer 30

SNAP-25 Synaptobrevin Syntaxin

Question 31

How many serotypes of botulinum toxin are there? Which is most commonly used clinically?

Answer 31

7 Serotype A

Question 32

What is botulinum toxin used to treat?

Answer 32

Bletharospasm (involuntary tight closure of eyelids) Bladder hyperreactivity

Question 33

Why is botulinum toxin injected locally?

Answer 33

Toxic in blood —> botulism

Question 34

What type of receptor alters ANS (especially parasympathetic) activity?

Answer 34

Muscarinic

Question 35

What are parasympathomimetics?

Answer 35

Muscarinic agonists that mimic effects of parasympathetic NS

Question 36

What are parasympatholytics?

Answer 36

Muscarinic antagonists that block effects of parasympathetic NS

Question 37

Why do drugs acting on muscarinic receptors tend to have side effects when given systemically?

Answer 37

Difficult to distinguish between subtypes

Question 38

Which glands are typically innervated by the sympathetic and parasympathetic NS?

Answer 38

S = sweat P = salivary and others

Question 39

What are some effects of activating M3 receptors?

Answer 39

Pupil constriction/miosis Ciliary muscle contraction Lacrimal gland secretion Airway smooth muscle constriction Increased peristalsis Detrusor contraction Increased bronchial secretions

Question 40

Where is the M2 receptor found?

Answer 40

Heart/SAN

Question 41

What does activation of M2 cause?

Answer 41

Decreased heart rate

Question 42

What does M1 activation cause?

Answer 42

Gastric acid secretion

Question 43

What is bethanacol used for?

Answer 43

Stimulant laxative Prevent constipation after surgery

Question 44

What are pilocarpine eye drops used to treat? How?

Answer 44

Glaucoma (Miosis and) contraction of ciliary muscle so suspensory ligaments lose tension Lens becomes more spherical Improves aqueous humour flow to reduce intraocular pressure (canal of Schlemm)

Question 45

What was the ‘pilocarpine sweat test’ used to diagnose in the past?

Answer 45

Cystic fibrosis

Question 46

What can atropine be used for? (2)

Answer 46

Sinus bradycardia (M2) Preparing patients for surgery by reducing bronchial secretions (M3)

Question 47

What type of drug is atropine?

Answer 47

Muscarinic antagonist

Question 48

What drugs may be used to dilate the pupil?

Answer 48

Tropicamide Cyclopentolate

Question 49

What drugs (parasympathetic) may be used to treat asthma (and other chronic obstructive pulmonary diseases)?

Answer 49

Ipratropium Tiotropium

Question 50

What drug is used to treat motion sickness?

Answer 50

Hyoscine

Question 51

What drugs may be used to treat Parkinson’s disease?

Answer 51

Benzhexol Benztropine

Question 52

What drug may be used to treat urinary incontinence?*

Answer 52

Tolterodine Oxybutynin

Question 53

What is an example of an AChE inhibitor?

Answer 53

Neostigmine Edrophonium Dyflos

Question 54

How do AChE inhibitors affect transmission?

Answer 54

Prevent breakdown of ACh so increased ACh concentration in synaptic cleft Enhances transmission in all autonomic ganglia and at parasympathetic neuroeffector junctions

Question 55

What are some physical effects of AChE inhibitors? (5)

Answer 55

Increased secretions (saliva, sweat, gastric acid, mucus, lacrimal) Increased smooth muscle tone (bronchoconstriction, increased peristalsis) Miosis (decreased intraocular pressure) Bradycardia Hypotension

Question 56

What drug is used to reverse the effects of muscle relaxants?

Answer 56

Neostigmine

Question 57

What is neostigmine used to treat?

Answer 57

Myasthenia gravis (autoimmune disease where autoAbs destroy nicotinic receptors)/neuromuscular weakness