9: SNS Antagonists Flashcards
Explain the role of alopha 2 adrenoreceptors in Noradrenaline release
As soon as Noradrenaline is released into the synapse it binds to alpha 1+2 receptors
- Alpha 1: effect of Noradrenaline (vasoconstriction)
- Alpha 2: negative feedback on Noradrenaline release in presynaptic neuron to ensure short acting action of Noradrenaline
Explain the effects and mechanisms of action in the clinical use of ß-Blockers
ß Blockers
- Reduce blood volume (ß1 on kidney Via less Renin–> Aldosterone production)
- Reduce TPR (less Renin –> less Vasocontriction as AGTII response)
- Reduce CO (ß1 on heart: reduced cAMP leading to redcued HR+ Force of Contraction)
- Minor effect: blockage of presynaptic ß receptors leading to a reduced NA release
Which drug class of SNS antagonists is commonly used in the chronical treatment of hypertension?
ß-Blockers
What is Propanolol?
It is a non-selective ß antagonist (equal afinity for ß1+2 receptors)
What is Atenolol?
It is a ß1 “selective” antagonist
What is Carvedilol?
Mixed b and a blockers
•a1 blockade gives additional vasodilator properties
Which different ß Blocker classes are there?
Name examples for each class
- Non selective (ß1+2)
- Propanolol
- Cardio-selective
- Atenolol
- Mixed ß-a- blockers
- Cervedilol
- Other
- Nebivolol: also potentiates NO
- Sotalol: also inhibits K+ channels
What are the side effects of Beta-blockers
1+2 are the major concerns
- Bronchoconstriction (no pure slectivity for ß1)–> might not be tolerated by astmathics (ß2 activity)
- Hypoglycaemia –> might not be toleareated by Diabetics
- masking of hypoglycaemic symptoms
- Inhibits glycogen break down in liver (ß2)
- Cardiac failure (some SNS activity required for heart)
- Cold extremitis (no cutaneous ß2 mediated vasodilation)
- Fatigue (reduced CO+ reduced muscle blood flow (ß2 antagonism))
- Bad dreams
Which group of patients might not tolerate ß-blockers?
- Astmatics (inhibitionof ß2-mediated bronchiodilation)
- Diabetics (risk of hypoglycaemia –> inhibition ß-2 mediated glycogen break down and release)
- Cardiac failure –> loss of SNS innervation to the heart which keeps the heart running
What is the clinical use for alpha blockers?
Limited use in treament of hypertension
Name 2 alpha-blockers and explain their mechanism of action, effect and use
- Phenotolamine
- used in reduceing phaeochomocytoma-induced hypertension
- alpha-non selective antagonist
- Prazosin
- limited BP lowering effect
- only used in combination with other hypertensive drugs
What is Phenotolamine?
When is it used?
It is a non-selective adrenergic alpha antagonist
Used in management of phaechromycytoma-induced hypertension
What is prazosin?
What is its clinical use?
It is a alpha1 selective adrenergic antagonist
- used in hypertension treatment (in combination with other hpyertensive drugs due to limited effects)
What are the side-effects of alpha-blocker?
Side effect mainly GI tracts
- reduces SNS innervation to gut –> leading to increased gut activity
- diarreah etc.
Explain the mechnism of action of Methyldopa
It is a false substrate for DOPA-methyltransferase that gets converted into alpha-methylnoradrenaline
Alpha-methylnoradrenaline is a false transmitter resulting in
- Increased selectivity for alpha2 receptors
- Decreased sensitivity for alpha1+ß receptors
- Decreased break down by MAO
–> Higher concentration of alpha-methylnoradrenaline in synapse with high A2 affinity
–> Decreased SNS activtity–> hypotension
Explain the use of SNS antagonists in the treatment of Glaucoma
Target: ß1 receptors on cliary body –> reduction in production of aqueous humor (ß-blockers)
