11 - Noradrenaline

Question 1

Noradrenaline biochemistry

Describe the process of NA synthesis…

Answer 1

1. Tyrosine transported into the presynaptic cell
2. Tyrosine converted to DOPA by tyrosine hydroxylase
3. DOPA converted to dopamine by DOPA carboxylase
4. Dopamine converted to noradrenaline by dopamine β-hydroxylase

Question 2

Name the two types of noradrenergic receptor and their subclasses…

Answer 2

α_(1,2) and β_(1,2,3)

Question 3

Noradrenaline is metabolised in the ( pre-synaptic cell / synapse / post-synaptic cell ) by the enzyme…

Answer 3

Noradrenaline is metabolised in the pre-synaptic cell by the enzyme monoamine oxidase

Question 4

Noradrenergic receptors are present at the effector tissues of the ( sympathetic / parasympathetic ) system.

Answer 4

Noradrenergic receptors are present at the effector tissues of the sympathetic system.

Question 5

Noradrenergic receptors are:

a) G-Protein coupled
b) Ionotropic
c) Enzyme-linked
d) All of the above

Answer 5

Noradrenergic receptors are:

a) G-Protein coupled

b) Ionotropic
c) Enzyme-linked
d) All of the above

Question 6

List the alpha 1 noradrenoreceptor mediated effects via the sympathetic system…

Answer 6

• Pupil dilation
• Blood vessel constriction (to visceral organs and skin)
• General alertness

Question 7

State the effect of alpha 2 noradrenoreceptor activation…

Answer 7

Inhibition of neurotransmitter release from presynaptic cell

(Alpha 2 NA receptors are presynaptic)

Question 8

List beta 1 noradrenoreceptor mediated effects…

Answer 8

• Increased heart rate
• Increased heart force of contraction

Question 9

List beta 2 noradrenoreceptor mediated effects…

Answer 9

• Ciliary relaxation (increased focal distance)
• Bronchodilation
• Dilation of blood vessels to limbs

Question 10

State the effect of beta 3 noradrenoreceptors…

Answer 10

An increase in lipolysis and metabolic rate

Question 11

List 5 drugs which are noradrenergic agonists…

Answer 11

1. Adrenaline _(all)
2. Clonidine _(α2)
3. Dobutamine _(β1)
4. Salbutamol _(β2)
5. Clenbuterol _{(β2, β3)}

Question 12

List 3 drugs which can act as noradrenergic antagonists…

Answer 12

1. Prazosin _(α1)
2. Propanolol _{(β1, β2)}
3. Atenelol _(β1)

Question 13

Which drug targets NA synthesis?

Answer 13

Methyldopa

A false substrate mimicking DOPA. This reduces the amount of NA, as methylnoradrenaline is produced instead (which is also an α₂ agonist– decreasing NA release)

Question 14

Which drug targets NA storage?

Answer 14

Reserpine

Disrupts NA storage in the vesicles. This reduces the amount of NA available. Used to treat hypertension.

Remember: Reserp -> reserve -> storage

Question 15

Which drug targets NA release?

Answer 15

Clonidine

Inihibts NA release via α₂ agonism (decreased release of NA). Used to treat hypertension.

Remember: Clon. -> Clog = blocked -> release blocked

Question 16

Drugs targeting NA reuptake…

Answer 16

Desipramine (TCA) and Reboxetine (SNRI) are noradrenaline reuptake inhibitiors

Remember: Re-box -> Re-uptake

Question 17

Which drug targets NA metabolism?

Answer 17

Tranylcypramine (MAOI)

Blocks MAO which along with COMT metabolises NA. This increases recycling of NA, increasing NA availability.

Remember: MAOI -> Metabolism

Question 18

Describe the MAOI ‘cheese reaction’ 🧀

Answer 18

MAOIs also block the metabolism of dietary amines (such as those found in cheese, marmite and cold remedies). This leads to accumulation. Accumulated amines have a sympathomimetic* effect, leading to hypertension.

(* sympathomimetic, e.g. mimics the effects of noradrenaline)

Question 19

Noradrenergic antagonists are used to treat…

Answer 19

Hypertension

Question 20

Adrenaline is administered by injection, as it is destroyed by the gut.

Give two uses of adrenaline…

Answer 20

• Subcutaneous dose to prolong and isolate anaesthesia
• Intramuscular delivery to treat anaphylactic shock

Question 21

A common side effect of clonidine is xerostomia (a dry mouth).

Why?

Answer 21

1. Clonidine is an α₂ agonist
2. This inhibits NA release
3. Post-ganglionic synapse for salivary glands use NA (despite being part of parasymp.)
4. Salivary gland secretions are reduced