PHARM - Pharmacology of the Autonomic Nervous System: Adrenergics - Week 4

Question 1

What are three requirements for chemical signalling by a signalling nerve cell?

Answer 1

Neutrotransmitter must be present
It must be released
It must be inavticated

Question 2

Where from the spinal cord do the sympathetic fibres originate from, and what length of pre/post ganglionic fibres do they have?

Answer 2

Originates from the thoraco-lumbar region.

Has short pre-ganglionic fibres, and long post-ganglionic fibres.

Question 3

Where from the spinal cord do the parasympathetic fibres originate from, and what length of pre/post ganglionic fibres do they have?

Answer 3

Originates from the cranio-sacral region.

Has long pre-ganglionic fibres, and short post-ganglionic fibres.

Question 4

What receptor and neurotransmitter is found at the pre-ganglionic fibre synapses for the sympathetic and parasympathetic systems?

Answer 4

Nicotinic receptors and acetylcholine

Question 5

What are the post-ganglionic fibre receptor and neurotransmitter for the sympathetic pathway? Are there exceptions? Explain.

Answer 5

Uses a and B adrenergic receptors and noradrenaline.

The exception is Ach and muscarinic receptors for sweat glands.

Question 6

What are the post-ganglionic fibre receptor and neurotransmitter for the parasympathetic pathway?

Answer 6

Muscarinic receptors and acetylcholine

Question 7

How do systemic vs peripheral blood vessels react to sympathetic innervation? How does strong sympathetic innervation affect peripheral vessels, and by what agent?

Answer 7

Systemic vessels have a strong reaction to sympathetic innervation. Peripheral vessels do not. Under strong sympathetic innervation involving adrenaline, peripheral vessels will dilate.

Question 8

What is the difference between adrenaline and noradrenaline?

Answer 8

A methyl group.

Question 9

What is the essential amino acid required for noradrenaline synthesis and what enzyme does it involve for the rate-limiting step?

Answer 9

Tyrosine is converted first to dopamine, and then noradrenaline.
The rate-limiting step is the conversion of tyrosine to L-DOPA by tyrosine hydroxylase.

Question 10

What is parkinsons disease thought be be a deficiency of?

Answer 10

Dopamine

Question 11

How is noradrenaline converted to adrenaline, and where?

Answer 11

In chromaffin cells within the adrenal gland by an enzyme called PNMT.

Question 12

Which is more stable, adrenaline or noradrenaline?

Answer 12

Adrenaline

Question 13

What happens to noradrenaline after is activates adrenergic receptors (2)?

Answer 13

It is reuptaken into the nerve terminal where it was released - 90-95%
The remaining 5-10% is uptaken by extraneuronal tissue.

Question 14

Where is monoamine oxidase found and what does it do?

Answer 14

In the mitochondira, and modulates noradrenaline levels in the nerve cells.

Question 15

How does cocaine act?

Answer 15

Prevents noradrenaline reuptake by nerve terminals.

Question 16

Rank the following in terms of their potency on a-adrenoceptors:
Adrenaline
Noradrenaline
Isoprenaline
Phenylephrine

Answer 16

Phenylephrine > Noradrenaline > Adrenaline > > Isoprenaline

Question 17

Rank the following in terms of their potency on B-adrenoceptors:
Adrenaline
Noradrenaline
Isoprenaline
Phenylephrine

Answer 17

Isoprenaline > Adrenaline > Noradrenaline > Phenylephrine

Question 18

Name what agent the following are on a- and B-adrenoreceptors:
Phentolamine
Propranolol

Answer 18

Phentolamine - a-adrenoceptor antagonist

Propranolol - B-adrenoceptor antagonist

Question 19

What effect does a- and B-adrenoceptors have on smooth muscles?

Answer 19

a-adrenoceptor - smooth muscle contraction

B-adrenoceptor - smooth muscle relaxation

Question 20

What effect does a-adrenoceptors have on blood vessels, nerve transmitters, pupils, and the GIT tract? What subtype of a-adrenoceptors do they fall under?

Answer 20

a1
Blood vessel constriction
GIT sphincter constriction
Pupil radial muscle constriction
a2
Nerve transmitter release inhibition

Question 21

What effect does B-adrenoceptors have on the heart, kidneys, skeletal BVs, and bronchi? What subtype of B-adrenoceptors do they fall under?

Answer 21

B1
Heart - increased force and rate
Kidneys - renin secretion
B2
Skeletal BVs - dilation
Bronchi - dilation

Question 22

Compare the effects of adrenaline and noradrenaline at the same dose on blood pressure and heart rate, and why this occurs.

Answer 22

Adrenaline - increase in heart rate, and an initial increase to blood pressure from a-effect, then a subsequent decrease due to B-effect.
Noradrenaline - at the same dose, will cause a sharp rise in blood pressure, but no change to heart rate.
This is because the increase to blood pressure is great enough that parasymapthetic innervation is increased, and sympathetic is decreased by reflex due to baroreceptors detecting the pressure change.
There is no fall to heart rate as the effect of increasing heart rate by noradrenaline is counteracted, and it flatlines as a result.

Question 23

Consider a case of selective inhibiton of the a-effect using phentolamine. Compare the effects of adrenaline and noradrenaline at the same dose on blood pressure and heart rate, and why this occurs.

Answer 23

Adrenaline - an increase in heart rate, but only a decrease in blood pressure due to the B-effect.
Noradrenaline - increase in heart rate, but no change to blood pressure.

Question 24

By what action do the a1, a2, B1, and B2 receptors signal, via what 2nd messenger?

Answer 24

a1 - DAG
a2 - decreased cAMP
B1 - increased cAMP
B2 - increased cAMP

Question 25

Describe in 3 steps the synthesis of noradrenaline.

Answer 25

• Tyrosine is converted to L-DOPA by tyrosine hydroxylase
• L-DOPA is converted to dopamine by DOPA decaboxylase
• Dopamine is converted to noradrenaline by dopamine B-hydroxylase within a synaptic vesicle

Question 26

What happens if there is excess noradrenaline in a nerve cell after reuptake?

Answer 26

An enzyme called monoamine oxidase converts excess noradrenaline into metabolites.

Question 27

Describe the non-exocytotic release pathway for noradrenaline in nerve cells, and the class of drugs that can induce it.

Answer 27

Uptake 1 channels can be competitively saturated by a class of drugs called indirectly acting sympathomimetics.
Some noradrenaline will be converted to metabolites by MAO, but the channel can act in reverse, and some noradrenaline can be released into the cleft.