8: SNS Agonists

Question 1

Most S post-ganglionic neurones release NA but there are 2 exceptions

Answer 1

• Adrenal medulla: preganglionic S neurone drives the release of Adrenaline (80%) and Noradrenaline (20%)
• Sweat glands: S post-ganglionic neurone that innervates sweat glands releases ACETYLCHOLINE

Question 2

B3 adrenoceptors are mainly involved in

Answer 2

glycolysis.

Question 3

Which type of receptor are adrenoreceptors

Answer 3

G-protein coupled

Question 4

Mechanism of actionof adrenoreceptors

Answer 4

Alpha 2, B1+2 all work through adenylate cyclase to up/downregulate cAMP
- Alpha 2 decreases cAMP
- B1+2 increase cAMP
Alpha 1 works through PLC to make IP3 and DAG

Question 5

NORADRENALINE is more selective for

Answer 5

ALPHA receptors

Question 6

ADRENALINE is more selective for

Answer 6

BETA receptors

Question 7

Noradrenaline Metabolism

Answer 7

1. Tyrosine from the diet is converted to DOPA by tyrosine hydroxylase (rate limiting enzyme) in the nerve endings.
2. DOPA = dopamine and the dopamine = NA in the vesicles by the action of dopamine = hydroxylase.
3. Upon an AP, influx of Ca2+ and the vesicles migrate to the nerve ending, emerge out and release the NT into the synapse.
4. Once its been released, it will act on the post-synaptic receptors.
5. Deactivation is via reuptake into the nerve terminal itself or into extraneuronal tissue

Question 8

How do alpha 2 receptors work

Answer 8

They have a negative effect on the synthesis and release of NA. If there is a high [NA] in the synapse, it will stimulate the presynaptic alpha 2 receptors and this will reduce NA synthesis and release

Question 9

Which receptor does adrenalien stimulate

Answer 9

Non-selective

Question 10

Example of alpha1 selective drug

Answer 10

phenylephrine

Question 11

What does clonidine stimulate

Answer 11

alpha 2 receptors

Question 12

Example of beta 1 selective drug

Answer 12

dobutamine

Question 13

What does salbutamol stimulate

Answer 13

beta 2 receptors

Question 14

What happens in allergic reaction

Answer 14

• Blood vessels: increased capillary permeability. Endothelial cells within the membranes of the blood vessels move apart so you get a lot of fluid moving into the tissues. This leads to swelling of tissues (inc tongue) + fall in circulating fluid volume. Histamine is also profound vasodilator, reduced TPR = a fall in BP
o = ANAPHYLACTIC SHOCK and collapse of the circulatory system that leads to unconsciousness.

• Lungs: contraction of bronchial SM and constriction of the muscles around the throat, causing respiratory distress, difficulty breathing + swallowing
• GI tract: constrict SM in the GI tract causing vomiting and diarrhoea, stomach cramps.

Question 15

Adrenaline’s effects in hypersensitivity reactions

Answer 15

• Heart: β1 effects in heart, increases CO and stimulates tachycardia, support BP. Alsp via α1 receptors cause vasoconstriction.
• Lungs: β2 effects causing bronchodilation and relaxation of throat muscles
• Mast cells: β2 effects suppress histamine release from mast cells

Question 16

Why adrenaline used for pulmonary obstructive conditions

Answer 16

B2 mediated bronchodilation+ suppresses mediator release. Selective B2 agonists preferable but adrenaline useful in hypotensive crisis

Question 17

What is cardiogenic shock and what is used to treat it

Answer 17

The sudden inability of the heart to pump sufficient oxygen-rich blood. This can happen when you have a heart attack/MI or cardiac arrest. This action mainly happens via the beta 1 receptor - positive inotropic action - Adrenaline stimulates this to restore CO.

Question 18

Why adrenaline used for spinal anaethesia

Answer 18

Anaesthetising through the spine, removehe S output to the peripheral resistance vessels = relaxation of peripheral resistance vessels so the patient wont be able to maintain their BP.

Administer a little bit of adrenaline at the same time you can constrict the blood vessels so you can maintain the BP. This is due to alpha-1 mediated vasoconstriction

Question 19

Why adrenaline used for local anaesthetic

Answer 19

causes constriction of the blood vessels in the local area thus preventing the clearance of the anaesthetic from the area. If the anaesthetic was given without adrenaline, then it will wear off faster. This is due to alpha-1 mediated vasoconstriction

Question 20

Unwanted Actions of Adrenaline

Answer 20

These are due to adrenaline being non-selective
• Secretions - reduced and thick

• CNS - minimal

• CVS Effects:
o Tachycardia, palpitations, arrhythmias
o Cold extremities, hypertension
o OVERDOSE - cerebral haemorrhage, pulmonary embolism

• GIT - minimal
• Skeletal muscle - tremor

Question 21

Phenylephrine selectivity and structural properties

Answer 21

Alpha 1 selective
Chemically related to adrenaline. Slight change in structure means that phenylephrine is more resistant to COMT degradation but it is not resistant to MAO degradation – lasts longer in system.

Question 22

Phenylephrine clinical uses

Answer 22

• Vasoconstriction (people on phenylephrine have a slightly elevated blood pressure)
• Mydriatic: dilates pupils by binding alpha 1 receptors on iris
• Nasal Decongestant- as it vasoconstricts and dries secretions/fluid leakages up. Less fluid flow there also reduces likelihood of gluid leakage

Question 23

Clonidine selectivity and effects

Answer 23

Alpha 2 selective

• Fall in BP
o Less NA = less vasoconstriction hence a fall in TPR
o Brainstem: has a central effect through the brainstem where it works on the baroreceptors in this pathway and reduces the sympathetic drive coming out of the brain = reduces the TPR and amount of NA released at the nerve terminal = reducing TPR further.

• Kidneys: alpha-2 mediated reduction in NA release = reduced NA binding to beta-1 receptors in kidney = reduced renin secretion and hence reduced Ang2 production (this is a potent vasoconstrictor)

Question 24

Clinical use of clonidine

Answer 24

hypertension + migraine

Question 25

What can beused to treat glaucoma

Answer 25

• Phenylephrine: Alpha 1 receptors in the vessels within the ciliary body causing vasoconstriction of these vessels. This means that less blood will be delivered to the ciliary body and the production of aqueous humour is reduced.
• Clonidine: Alpha 2 receptors can also be stimulated, to decrease humour formation
• Beta-blockers would have negative effect in aqueous humour formation by blocking beta-1 receptors

Question 26

Isoprenanline selectivity and structural properties

Answer 26

Beta selective -both b1 +b2

Chemically similar to adrenaline but less susceptible to uptake 1 and MAO breakdown.

Question 27

clinical uses of isoprenaline

Answer 27

• Cardiogenic Shock
• Acute Heart Failure
• Myocardial Infarction

Question 28

Negative effect of isoprenaline

Answer 28

Drives b1 receptors in heart to support heart. Also stimualte b2 receptors VSMC = dilation of vessels = pooling of blood = decreased venous return

Fall in pressure detected by baroreceptors, send message to heart, reflex tachycardia, may give irregular HR and neg impact increased CO

B2 receptor stimualtion not good for pt w heart failure

Question 29

clinical use of dobutamine

Answer 29

cardiogenic shock.

Lack isoprenaline’s reflex tachycardia bc b1 selective.

Question 30

Salbutamol selectivity and structural properties

Answer 30

B2 receptor selective.

Synthetic catecholamine derivative with relative resistance to MAO and COMT.

Question 31

Clinical uses of salbutamol

Answer 31

Asthma: b2 relaxation of bronchial SM. Inhibit release of bronchoconstrictor substances from mast cells.

Threatened premature labour: b2 mediated relaxation of uterine SM. Prevent fetus abortion

Question 32

Side effects of salbutamol

Answer 32

relflex tachycardia bc some b1 stimulation

tremor

blood sugar dysregulation