SNS Agonists Flashcards
Neurotransmitter of SNS preganglionic fibres
ACh
Neurotransmitter of SNS postganglionic fibres Exception?
NA. Exception sweat glands - ACh, and adrenal medulla - NA and A
Type of adrenoceptor involved in glycolysis
B3
MOA of A1 adrenoceptor
PLC –> IP3 and DAG
MOA of A2 adrenoceptor
decreases cAMP
MOA of B1 adrenoceptor
Increases cAMP
Which adrenoceptor increases cAMP
B1 and B2
MOA of B2 adrenoceptor
Increases cAMP
Which adrenoceptor decreases cAMP
A2
Which adrenoceptor converts PLC to IP3 and DAG
A1
What is a directly acting sympathomimetic
mimic the actions of adrenaline and noradrenaline by stimulating adrenoceptors
What type of adrenoceptor controls aqueous humour production of ciliary body
B
What type of adrenoceptor dilates trachea and bronchioles
B2
What type of adrenoceptor controls glycogenolysis and gluconeogenesis
A1 and B2
What type of adrenoceptor lipolysis
A1 and B1
What type of adrenoceptor increases renin secretion
B1
What type of adrenoceptor found in salivary glands
A and B
What type of adrenoceptor in the skin
A1
What type of adrenoceptor in the heart
B1
What type of adrenoceptor in the GIT
A and B
Why must you be careful prescribing a beta blocker for diabetes
As beta receptors cause break down glycogen
What type of adrenoceptor is found in skeletal blood vessels
B2
B2 effect on skeletal blood vessels
Dilation
What type of adrenoceptor visceral blood vessels
A1
NA vs A more selective for A receptors?
NA
NA vs A more selective for B receptors?
A
Which endogenous catecholamine is more selective for A receptors
NA
Which endogenous catecholamine is more selective for B receptors
A
NA synthesis, excretion and metabolism?
- Tyrosine is converted to DOPA by tyrosine hydroxylase in the nerve endings.
- DOPA is then converted to dopamine and the dopamine is converted to noradrenaline in the vesicles by the action of dopamine B-hydroxylase.
- Upon an AP, there is an influx of Ca2+ and the vesicles migrate to the nerve ending, emerge out and release the NT into the synapse.
- Deactivation is via reuptake into the nerve terminal itself to be reused or into extraneuronal tissue
What amino acid is used to make DOPA and ultimately NA
Tyrosine
What enzyme is the rate-limiting step for the synthesis of NA
Tyrosine hydroxylase
What enzyme converts tyrosine to DOPA
Tyrosine hydroxylase
What converts DOPA to dopamine
DOPA decarboxylase
What converts dopamine to NA
Dopamine B-hydroxylase
What does DOPA decarboxylase do
Covert DOPA to dopamine
What can mediate NA synthesis and release
Presynaptic A2 receptors
5 SNS agonists?
adrenaline, phenylephrine, clonidine, dobutamine and salbutamol
A1 selective drug?
Phenylephrine
A2 selective drug?
Clonidine
B1 selective drug?
Dobutamine
B2 selective drug?
Salbutamol
What does Phenylephrine act on?
A1
What does Clonidine act on?
A2
What does Dobutamine act on?
B1
What does Salbutamol act on?
B2
What does the selectivity of a directly acting SNS agonist depend on?
concentration, high concentrations lose selectivity
Symptoms of hypersensitivity? (6…)
blood vessels move apart so you get a lot of fluid moving into the tissues
This leads to a fall in circulating fluid volume and hence a fall in blood pressure
Also contraction of bronchial smooth muscle and constriction of the muscles around the throat, causing respiratory distress
It can also constrict the smooth muscle in the GI tract causing vomiting and diarrhoea
why is A better than NA for anaphylaxis (4)
o Adrenaline acts more on the beta receptors than noradrenaline and this stimulates bronchodilation and relaxation of the throat muscles B2
o Adrenaline will also stimulate the heart so you get tachycardia, this will support the blood pressure B1
o Adrenaline also acts on alpha receptors and causes vasoconstriction A1
o Adrenaline also, via the beta 2 receptors, slows down the release of histamine from the mast cell
What to remember when thinking about NA vs A for anaphylaxis
BLS - ABC
What pulmonary conditions can A be used for and why can it be used for this (4 and 2)
Asthma, acute bronchospasm, chronic bronchitis, emphysema
It is used for these purposes because it causes B2 mediated bronchodilation and it also suppresses mediator release
How does adrenaline work for glaucoma
Adrenaline is good for glaucoma because it stimulates the alpha receptors in the vessels within the ciliary body causing vasoconstriction of these vessels. This means that less blood containing substrates will be delivered to the ciliary body and the production of aqueous humour is reduced. A2 also inhibit the production of aqueous humour
How is A used with local anaesthetic
causes A1 constriction of the blood vessels in the local area thus preventing the clearance of the anaesthetic from the area.
How is A used with spinal anaesthetics
If you give a little bit of adrenaline at the same time you can constrict the blood vessels so you can maintain the blood pressure
How is A used for cariogenic shock
Stimulates B1 receptor so heart starts pumping again
Unwanted effects of A (5+3)
Why does this happen
Because A is 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
which adrenoceptor is found in the presynaptic membrane?
A2
What effect does clonidine have on NA release and how
Clonidine will stimulate the pre-synaptic alpha 2 receptors - this has a negative effect on the synthesis and release of noradrenaline
How does clonidine lower blood pressure and TPR (2)
- Clonidine will stimulate the pre-synaptic alpha 2 receptors - this has a negative effect on the synthesis and release of noradrenaline
- If you release less NA then you are going to get less stimulation at the effector organ - this means you get less vasoconstriction hence a fall in TPR and blood pressure
o Within the brainstem it works on the baroreceptors reduces the sympathetic drive coming out of the brain
This reduces the TPR and it also reduces the amount of noradrenaline released at the nerve terminal thus reducing TPR further
Also less NA means less renin secretion and so less ATII so less vasoconstriction
What is clonidine used for
Hypertension, glaucoma and migraines
what is isoprenaline selective for
Beta receptors
what drug is beta selective
Isoprenaline
Metabolism of phenylephrine?
More resistant to COMT degradation but not MAO
Metabolism of isoprenaline? Half life?
Less susceptible to uptake 1 and MAO breakdown. This makes half-life much longer (2 hours)
Clinical uses of isoprenaline
Cariogenic shock, acute heart failure, myocardial infarction
What must you be cautious of when using isoprenaline?
it stimulates beta 2 receptors in the vasculature causing dilation which can mean blood pools so you get less venous return. This causes baroreceptors to fire and increase heart rate, but isoprenaline has already increased heart rate via b1 agonism, and this can lead to arrhythmias
Use of dobutamine
Cardiogenic shock
Plus side to dobutamines short half life?
You can stop administering it as soon as normal cardiac output is restored
Why is dobutamine preferred to isoprenaline for cariogenic shock
B1 selectivity
Metabolism of salbutamol?
Relatively resistant to COMT and MAO
Clinical uses of salbutamol? Why? Which adrenoceptor
B2 selective agonist. Used to treat asthma, b2 mediated bronchial smooth muscle dilation. inhibits bronchoconstricting substance degranulation from mast cells via b2.
Can also be used to relax uterine smooth muscle via B2 to prevent abortion.
Side effects of salbutamol?
Reflex tachycardia, tremor, blood sugar dysregulation
