SNS agonists.

Question 1

Understand the locations of key nervous system receptors -

a1, a2, b1, b2, nicotinic, muscarinic.

Answer 1

Question 2

How do different adrenoceptors have their effects?

Answer 2

a1 - PLC, IP3, DAG.

a2 - reduced cAMP

b1 - increased cAMP

b2 - increased cAMP

Question 3

Diagram outlining which SNS target organs have which receptors.

Answer 3

Question 4

Why are adrenoceptors always only relatively selective.

Answer 4

All adrenoceptors can be activated by NA and A, but to varying degrees.

A > selectivity for NA than B.

B> selectivity for Adrenaline than A

Question 5

Diagram outlining NA metabolism. Why are NA effects never particularly profound?

Answer 5

A2 is a feedback receptor - slowing down NA secretion. Autoinhibition.

Question 6

Name an agonist for each adrenoceptor.

Answer 6

• Phenylephrine (a1)
• Clonidine (a2)
• Dobutamine (b1)
• Salbutamol (b2)

Question 7

Why is adrenaline used in the reatment of anaphylaxis?

Answer 7

B2 receptors in airways bronchodilate

B1 receptors in heart increase heart rate (counteract hypotension with anaphylaxis).

a1 receptors vasoconstrict blood vessels to increase BP.

Increased SNS innervation has relaxing effect on gut, reducing stomach cramps.

Question 8

Name some other clinical uses of adrenaline.

Answer 8

Acute bronchospasm associated with chronic bronchitis or emphysema - B2 –> increased airway mediator release.

Cardiogenic shock - sudden inability of heart to pump sufficient blood - B1 –> ionotropic effects.

During spinal anaesthesia to maintain BP

To prolong action of local anaethesia with local vasoconstriction so anaesthetic cannot leave area - A1

Question 9

List some unwanted actions of adrenaline.

Answer 9

Secretions - reduced and thickened mucus.

CVS - tachycardia, palpitations, arrhythmia, cold extrmeties, hypertension. Overdose –> cerebral haemorrhage, pulmonary oedema.

Skeletal muscle - tremor.

Question 10

What is phenylephrine selective for? what is it’s use and why?

Answer 10

Alpha selective. Used as nasal decongestant - vasoconstriction gives white cells less access to nose to generate mucus.

Pupil dilation.

Other uses related to vasoconstriction.

Question 11

Why does phenylephrine last longer in peripheral tissues?

Answer 11

Resistant to COMT but not MAO. Chemically related to adrenaline.

Question 12

Why does Clonidine appear to be an SNS antagonist?

Answer 12

Agonist for A2 receptor which promotes negative feedback, inhibiting SNS effects.

Question 13

What is glaucoma characterised by? What causes it?

What are the potential complications if untreated?

Answer 13

Increase in intraocular pressure.

Poor drainage of aqueous humour.

Permanent damafe to optic nerve, blindess.

Question 14

How can glaucoma be treated?

Answer 14

B1 receptor stimulation contributes to aqueous humour formation.

A2 agonist (-ve feedback, reducing B1 function) OR

A1 agonist (vasoconstriction - less blood available to create aqueous humour).

Question 15

Give uses of clonidine.

Answer 15

Treatment of hypertension and migraine.

A2 receptor - inhibited NA, vasodilation.

Question 16

What is isoprenaline selective for? What are its uses?

Answer 16

Beta selective.

Used for - cardiogenic shock, acute heart failure, myocardial infarction.

Question 17

How is isoprenaline functionally different to adrenaline - more resistant to MAO and uptake 1.

Question 18

Why might B2 receptor stimulation be a problem?

Answer 18

B2 receptors on VSMC stimulate NO release and significant vasodilation. Fall in TPR triggers a reflex tachycardia through baroreceptor stimulation.

Question 19

Why might dobutamine be more useful than isoprenaline?

Answer 19

Lacks stimulation of reflex tachycardia.

However, plasma half life of only 2 minutes, rapidly metabolised by COMT.

Treat cardiogenic shock.

Question 20

What is salbutamol derived from?

Answer 20

Catecholamine derivative with resistance to MAO and COMT.

Question 21

Diagram outlining mechanism of action of salbutamol.

Answer 21

Question 22

Give the clinical uses of salbutamol.

Answer 22

Asthma treatment - B2 relaxation of bronchial smooth muscle.

-inhibition of release of bronchoconstrictor substances from mast cells.

Treatment of threatened premature labour - B2 relaxation of uterine smooth muscle.

Side effects - reflex tachycardia, temor, blood sugar dysregulation.