SNS Agonists

Question 1

SNS agonists work like sympathetic nervous system so which receptors do they affect?

Answer 1

Adrenergic receptors

Question 2

What are the classes of adrenergic receptors?

Answer 2

alpha 1/2

beta 1/2

Question 3

Which reaction cascade do the adrenergic receptors use e.g. cAMP?

Answer 3

alpha 1 - PLC, IP3 and DAG

alpha 2 - decrease cAMP

beta 1 - increase cAMP

beta 2 - increase cAMP

Question 4

What are some of the effects of the SNS on different organs and what receptors mediate these effects?

Answer 4

eye - dilation of pupil (a1) and aqueous humour production (b)

trachea and bronchioles - dilation (b2)

liver - glycogenolysis and gluconeogenesis (b2 and a1)

adipose - lipolysis (b1 qnd a1)

ureters and bladder - detrussor relaxation (b2) and constriction of trigone and sphincter (a1)

kidney - more renin (b1)

salivary glands - thick viscous secretion (a/b)

skin - piloerection (a1)

heart - increased heart rate and contractility (b1)

GI - reduced motility and tone, sphincter contraction (a/b)

blood vessels (skeletal) - dilation (b2)

blood vessels (other) - constriction (a1)

Question 5

Where do NA and A predominantly come from?

Answer 5

NA - nerves

A - adrenal glands

Question 6

What are NA and A more selective for individually?

Answer 6

NA - alpha

A - beta

Question 7

NA synthesis and metabolism

Answer 7

LEARN

Tyr -> DOPA -> DA -> NA

Question 8

What do the different adrenergic receptors do?

Answer 8

A1 - Vasoconstriction, relaxation of GIT
A2 – Inhibition of NT release, contraction of VSMC, CNS
B1 – Cardiac stimulation, relaxation of GIT, renin release
B2 – Bronchodilation, vasodilation, relaxation of VSMC, hepatic glycogenolysis
B3 – Lipolysis

Question 9

Why is adrenaline used to treat anaphylaxis?

ADRENALINE IS NON SELECTIVE EXAMPLE

Answer 9

Treats many sysmptoms caused by histamine e.g. acts on
B2 -bronchodilation
B1 - tachycardia
A1 - vasoconstriction

Can also bind to mast cells and stop histamine release

Question 10

Which other conditions is adrenaline used for and what receptors will be involved?

Answer 10

B2

• asthma (emergencies)
• acute bronchospasm associated with chronic bronchitis or emphysema

B1
- cardiogenic shock

A1 - to vasoconstrict and maintain BP as anesthetics tend to drop BP and local anesthetic also needs localised effects so constriction reduces blood flow so less chance of spreading

• spinal anesthesia
• local anesthesia

Question 11

What are the side effects of adrenaline?

Answer 11

• reduced and thickened mucous
• minimal CNS effects
• tachycardia, palpitations, arrhythmias, cold extremities, hypertension, overdose (cerebral hemorrhage of pulmonary oedema)
• minimal GIT effects
• skeletal muscle tremor

Question 12

Which receptor is phenylephrine selective for?

Answer 12

A1 mainly

Question 13

What are some of the features of phenylephrine (metabolic)?

Answer 13

chemically related to adrenaline but more resistant to COMT, not to MAO

Question 14

Why is phenylephrine used as a decongestant?

Answer 14

Inflammation of nasal sinus so plasma leakage

- vasoconstriction needed, less blood flow means less leakage

Question 15

What else can phenylephrine be used for?

Answer 15

Mydriatic - binds to the alpha 1 receptor on iris and cause pupil dilation (mild)

Question 16

What does clonidine act on?

Answer 16

A2 - this will be like an antagonist as it reduces NA function

Question 17

What is glaucoma?

Answer 17

Increased intraocular pressure caused by poor drainage of aqueous humour so production is greater than drainage. Can permanently damage optic nerve and cause blindness if untreated

Question 18

Which receptors are targetted for glaucoma treatment?

Answer 18

Activate a1 - vasoconstriction of blood vessel so less resources to ciliary epithelium and less aqueous humour made

Activate 2 - decreases aqueous humour production

Question 19

How do alpha 2 receptors affect NA release?

Answer 19

Have a negative feedback on NE release. NE binding to presynaptic a2 adrenoreceptors causes negative feedback on NA exocytosis

Question 20

What are the clinical uses of clonidine?

Answer 20

• hypertension and migraine
• anti glaucoma
• can decrease sympathetic tone in the brain by affecting NA release so has systemic affect of reducing sympathetic outflow

Question 21

What does isprenaline work on?

Answer 21

B1 and B2

Question 22

Describe how isoprenaline is metabolised

Answer 22

chemically related to adrenaline but more resistant to MAO and uptake 1

Question 23

What are the clinical uses of isoprenaline?

Answer 23

• cardiogenic shock
• acute heart failure
• MI

Question 24

What might be an effect of isoprenaline due to its effect on both B1 and B2 receptors?

Answer 24

B2 stimulation in vascular smooth muscle in skeletal muscle results in a fall in venous blood pressure (due to muscle relaxation) which triggers a reflex tachycardia due to stimulation of baroreceptors

Question 25

Why is dobutamine preferred to isoprenaline?

Answer 25

• has same used as isoprenaline
• lacks the isoprenaline reflex tachycardia as acts on b1
• half life is 2 minutes so short acting, good for emergencies

Question 26

What does salbutamol act on?

Answer 26

b2 receptors mainly in airway (more cAMP so more relaxation of muscles etc)

Question 27

What is salbutamol used for?

Answer 27

• treating asthma (b2 relaxation of bronchial smooth muscle and inhibits release of bronchoconstrictors from mast cells
• treatment of premature labour (b2 relaxation of uterine smooth muscle)

Question 28

What are the side effects of salbutamol?

Answer 28

tremor, blood sugar dysregulation and reflex tachycardia (as does act on some b1 receptors too)

Question 29

Give examples of some SNS agonists and which receptors they are most selective for

Answer 29

Adrenaline – non-selective.

Phenylephrine - a1-selective

Clonidine - a2-selective

Isoprenaline - b1=b2-selective

Dobutamine - b1-selective

Salbutamol - b2-selective