Overview of the Pharmacology of the Autonomic Nervous System

Question 1

What are the breakdown products of acetylcholine by acetylcholinesterase?

Answer 1

Choline and acetate.

Question 2

Give an example of an anticholinesterase. What could this be used to treat?

Answer 2

Neostigmine.

Myasthenia Gravis.

Question 3

What is hexamethonium?

Answer 3

An antagonist for nicotinic receptors.

Question 4

How many transmembrane segments comprise muscarinic receptors?

Answer 4

7

Question 5

How many subtypes of muscarinic receptors are there?

Answer 5

5 (M1, M2, M3, M4, M5)

Question 6

What are parasympathomimetic drugs?

Answer 6

Drugs that mimic the effects of parasympathetic stimulation.

Question 7

What is glaucoma and how can it be treated?

Answer 7

An eye condition where the optic nerve is damaged by high pressure of fluid in the eye.

Treat using pilocarpine or timolol.

Question 8

What is the mechanism of action of pilocarpine for treating glaucoma?

Answer 8

Pilocarpine is an agonist for M3 muscarinic receptors on the ciliary muscle of the eye.

This improves drainage of aqueous humour (similar to plasma but lower protein concentrations).

Question 9

Where can M1 muscarinic receptors be found?

Answer 9

In the stomach.

In salivary glands.

Question 10

Where can M2 muscarinic receptors be found?

Answer 10

In cardiac tissue.

Question 11

Where can M3 muscarinic receptors be found?

Answer 11

In smooth muscle tissue.

Question 12

List 5 muscarinic antagonists.

Answer 12

IATTH: Ibrahim Ali tortures the homeless.

Ipratropium
Atropine
Tropicamide
Tolterodine
Hyoscine

Question 13

What is ipratropium used for?

Answer 13

Treating asthma.

Question 14

List 2 uses of atropine.

Answer 14

Treating bradycardia.

Decreasing secretions during operations.

Question 15

What is tropicamide used for?

Answer 15

Dilating the pupils.

Question 16

What is tolterodine used for?

Answer 16

Treating urinary incontinence.

Question 17

What is hyoscine used for?

Answer 17

Treating motion sickness.

Question 18

How many subtypes of adrenoceptors are there?

Answer 18

5:

a1, a2, b1, b2, b3

Question 19

What are the effect(s) of stimulating a1 adrenoceptors?

Answer 19

Smooth muscle contraction (e.g. vasoconstriction and GIT smooth muscle constriction).

Question 20

What are the effect(s) of stimulating a2 adrenoceptors?

Answer 20

Presynaptic inhibition of sympathetic outflow by inhibiting the release of noradrenaline (a negative feedback mechanism).

Question 21

What are the effect(s) of stimulating b1 adrenoceptors?

Answer 21

Increase heart rate and contractility.

Question 22

What are the effect(s) of stimulating b2 adrenoceptors?

Answer 22

Smooth muscle relaxation (i.e. vasodilation and bronchodilation).

Question 23

What are the effect(s) of stimulating b3 adrenoceptors?

Answer 23

Smooth muscle relaxation in the bladder wall.

Stimulates lipolysis.

Question 24

List 4 clinical uses of a-adrenoceptor agonists.

Give an example of a drug for each use.

Give the name of the alpha adrenoceptor subtype targeted by each drug.

Answer 24

To treat anaphylactic shock. (α/β)
-Adrenaline and noradrenaline.

To treat hypertension (α2)
-Clonidine

Nasal decongestants. (α1)
-Phenylephrine.

To treat erythema (redness of skin due to hyperemia / increased blood flow) in rosacea. (α2)
-Brimonidine

Question 25

What type of receptors are adrenoceptors?

Answer 25

G-protein coupled receptors.

Question 26

What type of alpha subunit are a1-adrenoceptors associated with?

Answer 26

Gq: Activates phospholipase C -> DAG -> IP3 + PKC.

Question 27

What type of alpha subunit are a2-adrenoceptors associated with?

Answer 27

Gs: Activates adenylyl cyclase, ATP -> cAMP -> PKA.

Question 28

What type of alpha subunit are all b-adrenoceptors associated with?

Answer 28

Gs: Activates adenylyl cyclase, ATP -> cAMP -> PKA.

Question 29

What type of alpha subunit are M1, M2 and M3 muscarinic receptors associated with?

Answer 29

M1 and M3 are Gq: Activates phospholipase C -> IP3 + DAG etc. M2 are Gs: Activates adenylyl cyclase, ATP -> cAMP -> PKA.

Question 30

List 2 clinical uses of a-adrenoceptor antagonists. Give an example of a drug for each use. Name the subtype of alpha adrenoceptor targeted by each drug.

Answer 30

To treat hypertension. (a1) -Doxazosin To treat benign prostatic hyperplasia. (a1) -Tamsulosin

Question 31

List 5 clinical uses of b-adrenoceptor agonists. Give an example of a drug for each use. Name the subtype of beta adrenoceptor for each drug.

Answer 31

1 - To treat cardiogenic shock. (β1) – adrenaline, dobutamine 2 - To treat anaphylactic shock. (α/β) – adrenaline 3 - To treat asthma. (β2) and 4 - To delay premature labour. (β2) - salbutamol 5 - To treat bradycardia. (β1) - dobutamine

Question 32

List 6 clinical uses of b-adrenoceptor antagonists.

Answer 32

Metropolol: * To treat angina. (β1) * To treat cardiac arrhythmias. (β1) * To treat hypertension. (β1) * To treat anxiety. (β1) * To treat chronic heart failure. (β1) Timolol: •To treat glaucoma. (β1 and β2)

Question 33

Starting from tyrosine, what are the intermediates in NAd synthesis?

Answer 33

Tyrosine -> DOPA -> Dopamine -> NAd

Question 34

What is the name of the transporter that is responsible for NAd exocytosis?

Answer 34

VMAT (vesicular monoamine transporter)

Question 35

What is the name of the transporter that is responsible for NAd uptake to the adrenal medulla?

Answer 35

NAT (Noradrenaline transporter)

Question 36

What are the 3 main catecholamines?

Answer 36

Dopamine Adrenaline Noradrenaline - Catecholamines are basically all of the monoamines except serotonin.

Question 37

List 4 monoamine neurotransmitters.

Answer 37

Dopamine Serotonin Adrenaline Noradrenaline

Question 38

What is the main mechanism for terminating the actions of NAd at the synapse?

Answer 38

Uptake of NAd by NAT transporter.

Question 39

What type of transporter is NAT?

Answer 39

A secondary active transporter (cotransporter).

Question 40

What is cotransported with catecholamines at NAT cotransporters?

Answer 40

Na+ and Cl-

Question 41

List 2 agents that inhibit catecholamine reuptake.

Answer 41

Cocaine Tricyclic antidepressants

Question 42

What is desipramine? What are its adverse effects?

Answer 42

A tricyclic antidepressant. Adverse effects: - Tachycardia - Dysrhythmia

Question 43

List 4 effects of cocaine.

Answer 43

- Euphoria. - Tachycardia. - Increased peripheral BP. - Local anaesthesia.

Question 44

What are MAOIs used to treat? How do they work? List 5 adverse effects.

Answer 44

Used as antidepressants. Work by blocking MAO, usually irreversibly. This increases levels of monoamines (adrenaline, noradrenaline, dopamine and serotonin). Adverse effects: - Postural hypotension (low BP after standing up, due to some MAOIs preventing the release of noradrenaline from sympathetic nerve endings) - Weight gain - Restlessness - Insomnia - Cheese reaction!!!

Question 45

List 4 examples of mono-amine oxidase inhibitors.

Answer 45

Phenelzine Tranylcypromine Iproniazid Moclobemide (reversible)

Question 46

List 3 examples of indirectly acting sympathetic amines.

Answer 46

Amphetamine Ephedrine Tyramine

Question 47

How do indirectly acting sympathetic amines work?

Answer 47

- Transported into nerve terminals and into vesicles. - Displace noradrenaline, which leaks out via NAT (reverse transport). - Similar effect on dopamine and serotonin in CNS (this underlies their use as substances of abuse). - Long lasting effects.

Question 48

What do monoamine oxidases do?

Answer 48

Metabolise cytoplasmic monoamines, reducing their concentration.