1. SNS Drugs
Anita Bolina
23rd March 2019

2. SNS Agonists

3. Learning Objectives
List the clinical uses, principal pharmacological features, mechanism of action and unwanted effects of selective and non- selective α and β adrenoceptor agonists.

4. Physiological SNS transmitters
Noradrenaline and adrenaline are the endogenous transmitters of the SNS
Fight or flight response – what do you need to get away from predators?
NA favours α>>>β
Adrenaline favours β>>>α
Metabolism of NA:
- Thoraco-lumbar – ACh secreted acts on adrenal gland
Made in ADRENAL MEDULLA (after synapse 1)
One extra step to produce it from dopamine
Acts on alpha and beta adrenoceptors (differing affinities)
Fight or flight- these actions are what occurs when the SNS is stimulated. Either stimulated normally using NA or A , or via drugs
Pupil dilation – to see your predator
Skeletal muscles contraction – to run away
Bronchodilation – increased airflow
Increased HR and contraction – supply oxygen and increased circulation in order to run away (or fight I guess)

5. MOST IMPORTANT: Bronchioles – airway dilation – β2
When you stimulate:
Bronchioles – airway dilation – β2
Liver- gluconeogenesis (increased blood sugar) – β2
Kidney – renin production – increased blood pressure – β1
Blood vessels:
Β2 causes dilation – decrease BP
Α1 causes constriction – increase BP
Heart – β1 – increases HR, contractility and increased heart workload (NOT good in HF/ blood pressure)

6. Pharmacology of the SNS drugsGq
Target – the receptors of the post ganglionic synapse on the effector organ
Alpha and beta adrenoceptors – these are all G-protein coupled!!!
Agonists- bind to receptor and cause the physiological response
Antagonists – bind to receptor and block the normal response Gi Gs Gs
Constriction – a1- due to IP3 acting on ryanodine – Ca influx causes contraction
Dilation – B2 – CAMP is a vasodilator

7. Non selective agonist- adrenaline
Anaphylactic shock
A severe allergic reaction in response to IGE and mast cell degranulation.
Difficulty breathing, major vasodilation leading to plasma leakage >> decreased blood volume >> decreased BP
b2 – broncho dilation
b1 – tachycardia
a1 – vasoconstriction
Suppression of mediator release (histamine etc from mast cell)

8. Adrenaline continued
UNWANTED EFFECTS Every SNS receptor is being stimulated – what extra SNS effects would be a problem?
Thick and viscous secretions
B2 overstimulate – skeletal muscle tremor due to contractions
CVS:
Tachycardia
Arrythmia
Hypertension – increased renin production and increased a1 vasoconstriction
Cold extremities – a1 vasoconstriction
No GIT effects – controlled by parasympathetic mainly

9. Alpha selective agonists
Phenylephrine – a1
Similar to adrenaline (aka epinephrine)
More resistant to COMT but not MAO
Vasoconstriction
Mydriasis (pupil dilation)
Nasal decongestant
Clonidine – a2
Hypertension (although not used anymore for this)
Migraine – Gi receptor ↓ CAMP therefore ↓ vasodilation (stops blood pulsating round head)
Acts on presynaptic a2, -VE feedback to decrease NA/A release

10. Beta selective agonists
Dobutamine β1
Cardiogenic shock
No reflex tachycardia
Metabolised by COMT
Salbutamol – β2
Resistant to COMT and MOA breakdown
Clinical Uses
Asthma
- b2 relaxation of bronchial smooth muscle
inhibition of release of brochoconstrictor substances from mast cells.
Threatened premature labour
- b2-relaxation of uterine smooth muscle
Side effects- Reflex tachycardia, Tremor, blood sugar dysregulation
Isoprenaline – β1 and β2
Uses:
- cardiogenic shock
-MI
- Acute HF
B2 stimulation – vasodilation – reduced BP – reflex tachycardia

11. SNS Antagonists

12. Learning Objectives
Adrenoceptor antagonists: List the clinical uses, principal pharmacological features, mechanism of action and unwanted effects of selective and non-selective α and β adrenoceptor antagonists and compare the pharmacology of selective and non- selective adrenoceptor antagonists.
Methyldopa: Identify the actions of the false transmitter methyldopa and identify its clinical uses and side effects.

15. UNWANTED EFFECTS: Bronchoconstriction – Asthma/COPD
Cardiac Failure – Need some sympathetic drive to the heart
Hypoglycemia - inhibit glycogen breakdown
Fatigue - ↓ cardiac output and ↓ muscle perfusion.
Cold Extremities - Loss of b-receptor mediated vasodilatation in cutaneous vessels.
Bad Dreams
1- propranolol will act on b2 receptors and therefore is CI in asthmatics
2- alpha 1 properties of carvedilol means that it can reduce vasoconstriction
Questions:
1- What is the advantage of atenolol over propranolol?
2- What is the advantage of carvedilol?

16. Alpha antagonists 1-receptors Gq-linked
Postsynaptic on vascular smooth muscle
2-receptors
Gi-linked
Presynaptic autoreceptors inhibiting NE release
NOTE – BLOCKING THIS WILL RESULT IN AN INCREASE IN NA RELEASE (DUE TO DECREASED NEGATIVE FEEDBACK)
phentolamine - used to treat phaechromocytoma-induced hypertension
Reflex tachycardia
GI and diarrhoea S/Es
1 specific blocker: prazosin inhibit the vasoconstrictor activity of NE
Reduced tachycardia
Dramatic decrease in BP

17. False transmitter- methyldopa
NOTE – this has nothing to do with Parkinson’s disease
Used in hypertension
Taken up by nerve terminal and converted to methyl-NA
A2 receptor on presynaptic terminal remains unblocked – causes –VE feedback
USES:
Hypertension
Renal disease
Cerebrovascular disease
Adverse effects – dry mouth, sedation, Orthostatic hypotension, Male sexual dysfunction – rarely used!
QUESTION – Side effects of methyldopa?

18. Other uses of beta blockers- arrhythmia
Main cause: myocardial ischaemia
SNS antagonists - class II
antiarrhythmics
- Propranolol - Non -
selective b- antagonist
Class II drug, effects mainly attributed
to b1 -antagonism

19. Angina

21. SNS treatments of glaucoma
Agonist
Vasoconstriction – reduced blood flow A1
Decreased vitreous humour formation
Clonidine A2
Antagonist
Timolol
S/Es – bradycardia, bronchoconstriction (uncommon) B1

22. Exemplar question Name a Beta-Adrenorecptor antagonist (1)
Describe 2 ways in which Beta antagonists help treat hypertension (2)
Give 2 reasons why Beta Blockers should not be given to diabetics (2)
Name an alternate anti-hypertensive that could be used safely in diabetics and explain its method of action? (2)

23. Of course, I had to end on a meme
DISCLAIMER – Please do not listen to Ryan Gosling or you may fail LCRS

24. Feedback link
bit.ly/muslimmedics