SNS Agonists

Question 1

From which region of the spinal cord do sympathetic fibres originate?

Answer 1

Thoracolumbar

Question 2

Most sympathetic post-ganglionic neurones release noradrenaline. State 2 exceptions.

Answer 2

Adrenal medulla: A (80%) + NA (20%)

Sweat glands: ACh

Question 3

How do directly acting sympathomimetics work? Where are they principally used?

Answer 3

Mimic the actions of A + NA by binding to + stimulating adrenoceptors (GPCRs)
Principally used for their actions in the CVS, eyes + lungs

Question 4

Describe the mechanism of action of the 4 different types of adrenoceptor.

Answer 4

Alpha 1 = PLC -> IP3 + DAG
Alpha 2 = decrease cAMP
Beta 1 + Beta 2 = increase cAMP

Question 5

State the 2 main actions of beta-1 receptors.

Answer 5

HEART: increase HR + contractility
KIDNEYS: increase renin release -> increase BP

Question 6

State the 5 main actions of beta-2 receptors.

Answer 6

Bronchodilation  
HGO: glycogenolysis + gluconeogenesis  
Vasodilation of vessels to skeletal muscle  
Relaxation of detrusor
Lipolysis

Question 7

State 2 effects that are mediated by both alpha and beta-receptors.

Answer 7

Exocrine secretions (e.g. salivary gland secretions become thick) 
GIT motility: decreased muscle motility + tone + contraction of sphincters

Question 8

What receptors are responsible for the production of aqueous humour by the ciliary body?

Answer 8

Beta receptors

Question 9

State 7 effects of alpha-1 receptors.

Answer 9

Mydriasis (contraction of radial muscles of the iris- dilation)
Vasoconstriction (skin, mucous, membranes + splanchnic area)
Constriction of trigone + sphincter in bladder
Piloerection
Increased sweating
HGO (glycogenolysis + gluconeogenesis)
Lipolysis

Question 10

What is the principle action of beta-blockers?

Answer 10

KIDNEYS – it inhibits the beta-1 mediated increase in renin secretion
It also decreases heart rate and contractility but its main action in reducing blood pressure is through the kidneys

Question 11

Describe the relative selectivity of adrenaline and noradrenaline.

Answer 11

Noradrenaline is more selective for ALPHA-receptors

Adrenaline is more selective for BETA-receptors

Question 12

Describe the action of pre-synaptic alpha-2 receptors.

Answer 12

Pre-synaptic alpha-2 receptors have a negative influence on NA synthesis + release

Question 13

State 5 directly acting SNS agonists.

Answer 13

Adrenaline (non-selective)
Phenylephrine (alpha-1)
Clonidine (alpha-2)
Dobutamine (beta-1)
Salbutamol (beta-2)

Question 14

Why is adrenaline used in the treatment of anaphylactic shock?

Answer 14

Causes beta-2 mediated bronchodilation
Stimulates the heart via beta-1 to support BP
Acts on alpha-1 receptors to cause vasoconstriction + an increase in TPR + BP
Slows the release of histamine from mast cells via beta-2.

Question 15

State 2 pulmonary obstructive conditions in which adrenaline is used therapeutically and explain why.

Answer 15

Asthma
Acute bronchospasm associated with chronic bronchitis or emphysema
It causes beta-2 mediated bronchodilation + suppresses mediator release.
(Selective beta-2 agonists are preferable, though adrenaline is useful in a hypotensive crisis)

Question 16

Which receptors are involved in the generation of aqueous humour in the eye?

Answer 16

Alpha-1 involved in vasoconstriction of the vessels in the ciliary body
Beta-receptors control the enzyme that makes the aqueous humour

Question 17

Why is adrenaline used as a treatment for glaucoma?

Answer 17

Adrenaline can stimulate the alpha-1 receptors to cause vasoconstriction of the vessels in the ciliary body thus reducing the blood flow within the ciliary body -> reduced production of aqueous humour

Question 18

State and explain 3 other clinical uses of adrenaline.

Answer 18

Cardiogenic Shock (sudden inability of heart to pump sufficient oxygenated blood)
Beta-1 stimulation has a positive inotropic effect
Spinal Anaesthesia
Anaesthetising through the spine can take away sympathetic output to peripheral resistance vessels
This leads to relaxation of peripheral vasculature, thus patient can’t maintain their BP
Adrenaline with the anaesthetic can constrict blood vessels to maintain BP
Local Anaesthesia
Adrenaline can cause local vasoconstriction, which prevents clearance of anaesthetic from that area due to alpha-1 mediated vasoconstriction

Question 19

State 3 unwanted actions of adrenaline, what an overdose may cause and what is minimally effected

Answer 19

Secretions are reduced + thickened
CVS: tachycardia, palpitations, arrhythmias, cold extremities, hypertension
Overdose of adrenaline can lead to: cerebral haemorrhage, pulmonary embolism
Skeletal muscle: Tremor
Minimal CNS + GIT effects

Question 20

Describe the resistance to degradation of phenylephrine.

Answer 20

Phenylephrine is MORE resistant to COMT degradation than adrenaline but it is NOT resistant to MAO degradation

Question 21

State 3 clinical uses of phenylephrine.

Answer 21

Mydriatic
Nasal decongestant (reduces white cell infiltration, less fluid exudation + mucous)
Vasoconstriction

Question 22

Describe and explain the effects of clonidine.

Answer 22

Stimulates alpha-2 receptors so has a negative effect on NA synthesis + release.
Decrease in NA release -> less vasoconstriction via alpha-1 action -> fall in TPR + BP
Central action on brainstem: acts on baroreceptors + reduces sympathetic drive from brain.
Reduction in sympathetic activity reduces TPR + reduces amount of NA released at the nerve terminals thus reducing TPR further.
So there are 2 routes of clonidine action in reducing NA release + TPR.
Alpha-2 mediated reduction in NA release in the kidneys will also reduce renin release + hence reduce AII

Question 23

State 2 clinical uses of clonidine.

Answer 23

Hypertension

Migraine

Question 24

Describe the susceptibility to breakdown of isoprenaline compared to adrenaline.

Answer 24

Isoprenaline is less susceptible to uptake 1 + MAO breakdown

Question 25

State 3 clinical uses of isoprenaline.

Answer 25

Cardiogenic Shock
Myocardial Infarction
Acute Heart Failure

Question 26

What is a big problem with isoprenaline with regards to its action on beta 2 receptors?

Answer 26

Isoprenaline brings about positive effects via Beta-1 stimulation
However, stimulation of Beta-2 leads to vasodilation of blood vessels in the muscles -> pooling of blood within muscles -> reduced venous return, reduced BP
Via the baroreceptors, this triggers a reflex tachycardia
So beta-1 effects are good for patients with heart failure but beta-2 effects are not

Question 27

State a clinical use of dobutamine.

Answer 27

Cardiogenic shock
It lacks isoprenaline’s reflex tachycardia effect.
Has a short half life, used for its acute effects

Question 28

Describe the relative resistance of salbutamol to degradation.

Answer 28

Relative resistance to MAO + COMT

Question 29

State and explain 2 clinical uses of salbutamol.

Answer 29

Asthma
Beta-2 mediated bronchodilation
Inhibition of release of bronchoconstrictor molecules from mast cells
Threatened premature labour
Beta-2 mediated relaxation of uterine smooth muscle
Prevents abortion

Question 30

State 3 side effects of salbutamol.

Answer 30

Reflex tachycardia
Tremor
Blood glucose dysregulation

Question 31

How can sympathomimetics be used to treat Glaucoma?

Answer 31

A1 agonist causes vasoconstriction, reduces blood flow to the eye, reduces ability to produce aqueous humour
A2 agonist interferes with B1 function (stops production of aqueous humour)