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 two exceptions.

Answer 2

Adrenal medulla – adrenaline (80%) and noradrenaline (20%)

Sweat glands – acetylcholine

Question 3

State the difference between directly and indirectly acting sympathomimetics.

Answer 3

Directly acting – binds to the adrenoceptor and mimic the action of adrenaline and noradrenaline by stimulating the receptors
Indirectly acting – inhibits the uptake and breakdown systems leading to the accumulation of neurotransmitter in the synaptic cleft

Question 4

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

Answer 4

ALL adrenoceptors are G-protein coupled
Alpha 1 = PLC -> IP3 + DAG
Alpha 2 = decrease cAMP
Beta 1 + Beta 2 = increase cAMP

Question 5

State the main actions of beta-1 receptors.

Answer 5

HEART – increase heart rate + increase contractility
KIDNEYS – increase renin release -> increase blood pressure
Lipolysis

Question 6

State the main actions of beta-2 receptors.

Answer 6

Bronchodilation
Hepatic glucose output – glycogenolysis + gluconeogenesis
Vasodilation of vessels to skeletal muscle
Relaxation of the uterus (in women)

Question 7

State some 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 and tone + contraction of sphincters

Question 8

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

Answer 8

Beta receptors

Question 9

State some effects of alpha-1 receptors.

Answer 9

Mydriasis (contraction of radial muscles of the iris)
Vasoconstriction
Constriction of trigone and sphincter in the bladder
Increased motility and tone of the ureters
Stimulates ejaculation (in males)
Lacrimation
Contraction of pilomotor muscle + increased localised secretion of sweat glands e.g. palm of hands
Hepatic glucose output (glycogenolysis and 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 noradrenaline synthesis and release

Question 13

State five directly acting SNS agonists.

Answer 13

Phenylephrine – alpha-1 
Clonidine – alpha-2 
Dobutamine – beta-1 
Salbutamol – beta-2 
Isoprenaline – beta 1+ beta 2

Question 14

Describe the development of hypersensitivity following first exposure.

Answer 14

After the first exposure you generate antibodies to the antigen andthese circulate around the body and bind to mast cells.
In the subsequent exposure, the mast cells are primed with the antibody on its surface.
Cross-linking of these antibodies on the surface of mast cells causes massive release of the stored mediators leading to the symptoms of hypersensitivity.

Question 15

State some symptoms of hypersensitivity.

Answer 15

Increase in capillary permeability leads to increased movement of fluid into the tissues. This depletes the circulating fluid volume leading to adrop in blood pressure -> ANAPHYLACTIC SHOCK (and collapse the circulatory system leading to unconsciousness)
This can also lead to contraction of bronchial smooth muscle and constriction of muscles around the throat causing respiratory distress. It can also constrict GI smooth muscle causing vomiting and diarrhoea.

Question 16

Why is adrenaline more effective than noradrenaline in dealingwith hypersensitivity?

Answer 16

During the hypersensitivity reaction, the most important problem to deal with is BREATHING.
Adrenaline is more selective for beta receptors than noradrenaline so is better at causing beta-2 mediated bronchodilation, thus opening up the airways.
Adrenaline also stimulates the heart via beta-1 to support blood pressure.
Adrenaline also acts on the alpha-1 receptors to cause vasoconstriction and an increase in TPR and blood pressure. Adrenaline can also slow down the release of histamine from mast cells via beta-2.

Question 17

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

Answer 17

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

Question 18

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

Answer 18

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

Question 19

Why is adrenaline used as a treatment for glaucoma?

Answer 19

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 20

State and explain three other clinical uses of adrenaline.

Answer 20

Cardiogenic Shock (the sudden inability of the heart to pump sufficientoxygenated blood)
 Beta-1 stimulation has a positive inotropic effect
 Cardiogenic shock can happen in MI or cardiac arrest
Spinal Anaesthesia
 Anaesthetising through the spine can take away the sympathetic output to the peripheral resistance vessels
 This leads to relaxation of the peripheral vasculature so the patient can’t maintain their blood pressure
 Giving a little adrenaline with the anaesthetic can constrict the blood vessels to maintain blood pressure
Local Anaesthesia
 Giving adrenaline with the LA can cause local vasoconstriction, which prevents clearance of the anaesthetic from that area
 This is due to alpha-1 mediated vasoconstriction

Question 21

State some unwanted actions of adrenaline.

Answer 21

Secretions are reduced and thick
CVS – tachycardia, palpitations, arrhythmias, cold extremities, hypertension
Overdose of adrenaline can lead to: cerebral haemorrhage, pulmonary embolism

Question 22

Describe the resistance to degradation of phenylephrine.

Answer 22

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

Question 23

State some clinical uses of phenylephrine.

Answer 23

Mydriatic
Nasal decongestant
It causes vasoconstriction

Question 24

Describe and explain the effects of clonidine.

Answer 24

Clonidine stimulates alpha-2 receptors so has a negative effect on NA synthesis and release.
Decrease in NA release -> less vasoconstriction via alpha-1 action -> fall in TPR and blood pressure
Clonidine also has a central action on the brainstem – acts on baroreceptors and reduces the sympathetic drive coming out of the brain.
Reduction in sympathetic activity reduces TPR and reduces the amount of NA released at the nerve terminals thus reducing TPR further.
So there are two routes of clonidine action in reducing NA release and TPR.
Alpha-2 mediated reduction in NA release in the kidneys will also reduce renin release and hence reduce angiotensin II.

Question 25

State some clinical uses of clonidine.

Answer 25

It is used to treat hypertension and migraine.

Question 26

Describe the susceptibility to breakdown of isoprenaline compared to adrenaline.

Answer 26

Isoprenaline is less susceptible to uptake 1 and MAO breakdown

Question 27

State clinical uses of isoprenaline.

Answer 27

Cardiogenic Shock
Myocardial Infarction
Acute Heart Failure

Question 28

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

Answer 28

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 the muscles -> reduced venous return
Via the baroreceptors, you get a reflex tachycardia
So the beta-1 effects are good for patients with heart failure but the beta-2 effects are not

Question 29

State a clinical use of dobutamine.

Answer 29

Cardiogenic shock
It lacks isoprenaline’s reflex tachycardia effect
Administration via IV infusion (half-life = 2 mins)

Question 30

Describe the relative resistance of salbutamol to degradation.

Answer 30

Relative resistance to MAO and COMT

Question 31

State and explain two clinical uses of salbutamol.

Answer 31

Asthma
 Beta-2 mediated relaxation of bronchial smooth muscle (bronchodilation)
 Inhibition of release of bronchoconstrictor molecules from mast cells
Threatened premature labour
 Beta-2 mediated relaxation of uterine smooth muscle
 This will prevent abortion

Question 32

State some side effects of salbutamol.

Answer 32

Reflex tachycardia
Tremor
Blood glucose dysregulation

Question 33

State two indirectly acting SNS agonists.

Answer 33

Cocaine

Tyramine

Question 34

Describe the mechanism of action of cocaine.

Answer 34

Cocaine inhibits uptake 1 for both noradrenaline and dopamine leading to an accumulation of dopamine or noradrenaline within the synapse

Question 35

Which nucleus within the hypothalamus uses dopamine as its neurotransmitter?

Answer 35

Nucleus accumbens

Question 36

Describe the effects of cocaine on the CNS and CVS.

Answer 36

CNS
 Low dose = euphoria
 High dose = activation of chemotactic trigger zones (causing vomiting), CNS depression, respiratory failure, convulsions, death
CVS
 Low dose = tachycardia, vasoconstriction, raised blood pressure
 High dose = ventricular fibrillation and cardiac arrest

Question 37

What is tyramine and what foodstuffs is it found in?

Answer 37

It is a dietary amino acid

Found in cheese, soy sauce and red wine

Question 38

Describe the mechanism of action of tyramine.

Answer 38

Tyramine acts as a false transmitter
It acts as a weak agonist at the effector organ at which NA will be stimulating receptors
It piggy backs on the uptake systems and competes with NA for the uptake 1 site
Tyramine starts being taken up into vesicles and it displaces NA from the vesicles
Normally MAO breaks down the displaced NA

Question 39

In which subset of patients is tyramine a problem?

Answer 39

Patients taking MAO inhibitors

This means that the break down of NA is inhibited so it accumulates in the synapse leading to a hypertensive crisis