SNS Agonists Flashcards
What do SNS agonists do?
Mimic the actions of NA/A by binding to and stimulating adrenoceptors (GPCRs)
What are SNS agonists used principally for?
Their actions in the CVS, eyes and lungs
What type of adrenoceptor is noradrenaline more selective for?
a1=a2 > b1=b2.
What type of adrenoceptor is adrenaline more selective for?
b1=b2 > a1=a2
Where is noradrenaline made?
In nerve terminals
Where is adrenaline made?
In adrenal medulla
What is the noradrenaline metabolism?
Tyr -> DOPA -> DA -> NE
What effect does norepinephrine have on a2 adrenoceptors?
NE binding to prejunctional a2 adrenoceptors negatively feedbacks on NE exocytosis
What adrenoceptor is adrenaline selective for?
Adrenaline is non selective
What adrenoceptor is phenylephrine selective for?
a1»a2»>b1/b2
What adrenoceptor is clonidine selective for?
a2»a1»>b1/b2
What adrenoceptor is isoprenaline selective for?
b1=b2»»a1/a2
What adrenoceptor is dobutamine selective for?
b1»b2»>a1/a2
What adrenoceptor is salbutamol selective for?
b2»b1»>a1/a2
How is adrenaline used to treat anaphylaxis?
It is non selective - and therefore is used in the management of airways - b2, tachycardia - b1, peripheral vasodilation - a1, suppression of mediator release
How is adrenaline used to treat COPD?
Used in asthma - emergencies via I.M or S.C in the management of airway - b2 and suppression of mediator release but a selective b2 agonist is preferable
How is adrenaline used to treat glaucoma?
Vasoconstriction of ocular blood vessels restricts blood flow and therefore decrease production of aqueous humour - production being derived from blood flow therefore management of IOP - a1
What are other uses of adrenaline as a treatment (not glaucoma, copd or anaphylaxis)
Cardiogenic shock
Spinal anaesthesia
Local anaesthesia - prolong duration of action using a1 action to reduce blood flow thus removal of anaethesia drug
What are unwanted actions of adrenaline as an SNS agonist
Because so non- selective there are lots of unwanted actions eg.
Secretions - reduced and thickened
CVS - tachycardia, palpitations, arrhythmia, hypertension/cold extremities, overdose, cerebral haemorrhage and pulmonary oedema
Skeletal muscle - tremor
CVS issues usually occur if already have underlying heart issue
What are the similarities and differences between adrenaline and phenylephrine
Molecularly similar to adrenaline but resistant to COMT (but not MAO)
What are the clinical uses of phenylephrine?
Vasoconstriction Mydriasis (dilation) Nasal decongestant via vasoconstriction
What receptor does clonidine mainly act on and what is the result?
Mainly acts on prejunctional neuronal a2 receptor to inhibit NA release
What are the clinical uses of clonidine?
Treat hypertension and migrane
Reduce sympathetic tone - a2 mediated presynaptic inhibition of NA release
Central brainstem action within baroreceptor pathway to reduce sympathetic outflow
What are the similarities and differences between adrenaline and isoprenaline
Molecularly similar but isoprenaline less susceptible to uptake 1 and MAO breakdown
What are clinical uses of isoprenaline?
Cardiogenic shock
Acute heart failure
MI
Why may b2 receptor stimulation be a problem?
b2 stimulation in VSM in skeletal muscle triggers a fall in venous BP triggering a reflex tachycardia via stimulation of BR
How is dobutamine administered and what is the half life? What metabolises it?
Administered by IV infusion with very short half life of 2 minutes - rapidly metabolised by COMT
What are the clinical uses of dobutamine?
Treat cardiogenic shock as lacks isoprenaline’s reflex tachycardia
What is salbutamol (with reference to catecholamines)
Synthetic catecholamine derivative with resistance to COMT and MAO
What are the clinical uses of salbutamol?
Treat asthma - by b2 relaxation of sm and inhibition of release of bronchoconstriction substances
Treatment of threatened premature labour by b2 relaxation of SM
What are the side effects of salbutamol?
reflex tachycardia, tremor, blood sugar dystregulation
How does cocaine work as an indirectly acting SNS agonist?
It is an uptake 1 blocker
What are the SNS effects of cocaine on CNS in low doses?
Euphoria, excitement, increased motor activity
What are the SNS effects of cocaine on CNS in high doses?
Activation of CTZ, CNS depression, resp failure, convulsions and death
What are the effects of cocaine on the CVS in low doses?
Tachycardia, vasoconstriction, raised BP
What is tyramine also known as?
cheese reaction
How does tyramine act?
As a false neurotransmitter -
- Weak action at the receptors for NA.
- Weak inhibitory effect on the uptake 1.
- Displaces NA from the vesicles.
- Competes for MAO breakdown so less breakdown of NA.
- Leakage of NA out of the vesicles.
What happens if you use tyramine and a MAO inhibitor?
Tyramine can compete with any MAO left and can lead to a massive hypertensive crisis when NA build up is more than usual
When are MAO inhibitors prescribed?
As antidepressants
