Pharm 6 - Cholinomimetics

Question 1

Describe the synthesis of acetylcholine.

Answer 1

Acetylcholine is synthesised from Acetyl CoA and choline via choline acetyltransferase

Question 2

Why are the receptors described as nicotinic and muscarinic?

Answer 2

muscarinic effects can be replicated by muscarine

nicotinic effects can be replicated by nicotine

Question 3

What can be given to abolish muscarinic effects?

Answer 3

Atropine - competitive muscarinic antagonist

Question 4

State where you would find the different types of muscarinic receptors.

Answer 4

M1 - salivary, CNS
M2 - heart
M3 - salivary, bronchial/smooth muscle, eyes, sweat glands

Question 5

What type of receptor are all muscarinic receptors?

Answer 5

G protein coupled receptors

Question 6

What is the difference in the G-protein receptors of M1/3/5/ and M2/4?

Answer 6

m1/3/5/= stimulate PLC which increases IP3 and DAG

M2/4 = inhibitory

Question 7

Describe the structure of nicotinic receptors.

Answer 7

Ligand gated ion channel

5 subunits

Question 8

What are the two main types of nicotinic receptors?

Answer 8

Muscle and Ganglion

Muscle = 2 alpha, beta, delta, epsilon

Ganglion = 2 alpha + 3 beta

Question 9

Compare the effects of acetylcholine on nicotinic receptors compared to muscarinic receptors.

Answer 9

weak effect on nicotinic

Question 10

What are the 3 effects of muscarinic stimulation on the eye?

Answer 10

Contraction of the ciliary muscle (near vision)

Constriction of sphincter pupillae (circular muscle of the eye) constricts pupil

Lacrimation

Question 11

What are the two effects of constriction of sphincter pupillae?

Answer 11

constricts the pupil

increases drainage of intraocular fluid

Question 12

What is glaucoma?

Answer 12

Sustained raised intraocular pressure

can damage optic nerve and retina and cause blindness

Question 13

Where is aqueous humour produced?

Answer 13

ciliary body

Question 14

Describe the passage of aqueous humour through the eye.

Answer 14

passes anteriorly from the ciliary body into the anterior chamber

Question 15

What drains aqueous humour?

Answer 15

Canals of Schlemm

Question 16

What is the role of aqueous humour?

Answer 16

provides oxygen and nutrients to the cornea and iris as they don’t have blood supply as would not be transparent

Question 17

What happens in angle-closure glaucoma?

Answer 17

angle between cornea and iris is narrowed decreasing drainage of humour through canal of Schlemm

Question 18

What are the effects of giving a muscarinic agonist to people with angle closure glaucoma?

Answer 18

causes constriction of sphincter pupillae and opens up the angle to increase drainage of intraocular fluid

Question 19

Describe the muscarinic effects on the heart.

Answer 19

Binding of M2 receptors causes a decrease in cAMP production

triggers a decrease in Ca2+ influx leading to decrease in cardiac output

Question 20

Describe the muscarinic effects on vasculature.

Answer 20

triggers production of NO causing vasodilation and drop in TPR

Question 21

Summarise the muscarinic effects on the cardiovascular system.

Answer 21

• decrease in heart rate
• decrease in cardiac output
• decrease in TPR
• decrease in blood pressure

Question 22

Describe the muscarinic effects on non-vascular smooth muscle.

Answer 22

causes CONTRACTION
lungs - bronchoconstriction
GI - increased motility
bladder - increased bladder emptying

Question 23

Describe the muscarinic effects on exocrine glands.

Answer 23

salivation
increased bronchial secretions
increased GI secretions

Question 24

What are two types of cholinomimetic drugs?

Answer 24

Directly acting - muscarinic agonists

Indirectly acting - acetylcholinesterase inhibitors

Question 25

What are the two types of muscarinic receptor agonists and give an example of each?

Answer 25

Choline Esters - bethanechol alkaloids - pilocarpine

Question 26

Describe the selectivity of pilocarpine.

Answer 26

Non selective muscarinic receptor agonist stimulates all muscarinic agonists

Question 27

What is pilocarpine used for?

Answer 27

Glaucoma (as used locally so cannot stimulate all muscarinic agonists)

Question 28

State some of the side effects of pilocarpine.

Answer 28

``` Blurred vision Hypotension Sweating Respiratory difficulty GI disturbance ```

Question 29

Describe the selectivity of bethanechol.

Answer 29

M3 selective agonist

Question 30

What are the effects of bethanechol?

Answer 30

assisted bladder emptying | enhanced gastric motility

Question 31

State some side effects of bethanechol.

Answer 31

``` Blurred vision Hypotension Sweating Respiratory difficulty GI disturbance Bradycardia ```

Question 32

What are the two types of acetylcholinesterases?

Answer 32

Reversible | Irreversible

Question 33

Give examples of reversible and irreversible acetylcholinesterases.

Answer 33

reversible - physostigmine, neostigmine irreversible - ecothiopate

Question 34

Where is acetylcholinesterase found?

Answer 34

In all cholinergic synapses | Highly selective and rapic

Question 35

Where is butyrylcholinesterase found?

Answer 35

found in plasma and most tissues broad specificity

Question 36

State the effects of low, moderate and high doses of cholinesterase inhibitors.

Answer 36

low - enhances muscarinic effects moderate - further enhances muscarinic effects + stimulates nicotinic receptors High - depolarising block

Question 37

Describe the mechanism of action of reversible anticholinesterases.

Answer 37

Donate carbamyl group which blocks the active site of acetylcholinesterase carbamyl groups are removed by slow hydrolysis

Question 38

Which synapses does pilocarpine primarily act on?

Answer 38

Postganglionic parasympathetic synapses

Question 39

What is physostigmine used to treat?

Answer 39

Glaucoma

Question 40

What type of poisoning is physostigmine used to treat?

Answer 40

Atropine poisoning

Question 41

How does physostigmine treat atropine poisoning?

Answer 41

increases synaptic concentration of acetylcholine so it can outcompete atropine

Question 42

What type of compounds are irreversible anticholinesterases?

Answer 42

Organophosphates

Question 43

Describe the mechanism of action irreversible anticholinesterases.

Answer 43

react with enzyme active site leaving a large blocking group blocking group is resistance to hydrolysis

Question 44

What is ecothiopate used to treat?

Answer 44

Glaucoma

Question 45

State some side effects of ecothipate.

Answer 45

``` Blurred vision Hypotension Sweating Respiratory difficulty GI disturbance Bradycardia ```

Question 46

What type of anticholinesterase can cross the BBB?

Answer 46

non-polar

Question 47

Describe the effects of low and high doses of anticholinesterase drugs on CNS activity.

Answer 47

LOW - CNS excitation High - unconciousness, resp depression and death

Question 48

State 2 anticholinesterases that are used to treat Alzheimer's.

Answer 48

Donepezil | Tacrine

Question 49

Describe the treatment of organophosphate poisoning.

Answer 49

IV atropine

Question 50

What is the acute treatment of organophosphate poisoning?

Answer 50

Pralidoxime