Adrenoceptors Flashcards
How is NA released to target organs?
Sympathetic ganglia are organised close to the spinal cord in sympathetic chain….
Sympathetic fibres from ganglia end in variscosities - where NA is stored, synthesised adn released from.
What are the exceptions to sympathetic innervation of target organs with NA?
Sweat glands use ACh….
But are controlled by sympathetic NS.
Renal vessels use dopamine, not NA.
What is the process of NA synthesis?
How is Adrenaline formed?
L-Tyrosine converted to L-DOPA by Tyrosine hydroxylase.
L-DOPA converted to dopamine by DOPA decarboxylase.
On vessicle membrane, Dopamine B hydroxylase converts dopamine to NA!!!
Dopamine Beta hydroxylase is also expressed in Chromaffin cells of adrenal medulla, where PNMT converts NA to Adrenaline!!!
How does Metirosine/a-methyl-p-tyrosine work?
Metirosine inhibits Tyrosine Hydroxylase which converts L-Tyrosine to L-DOPA.
Used to treat Pheochromocytoma - tumour in adrenal medulla produces excessive catecholamines.
= Need to decrease NA and adrenaline in order to stabilise patient for surgery.
What are the symptoms of Pheochromocytoma?
Headaches.
Heavy sweating.
Tachycardia.
high BP.
Tremours.
= Excessive catecholamines.
How does carbidopa work?
Carbidopa inhibits peripheral DOPA decarboxylase which converts L-DOPA into dopamine.
Given alongside L-DOPA treatment for Parkinson’s Disease to prevent peripheral decarboxylation of L-DOPA.
DOESN’t cross the BBB.
= STOPS L-DOPA being metabolised into NA/Dopamine in the periphery to reduce the sympathetic activation it would cuase…
= so more L-DOPA available for Dopamine in CNS but less in periphery.
How does Methyldopa work?
Methyldopa is metabolised to methyl-NA.
= False precursor molecule so reduces NA synthesis.
= A2 agonist = reduced NA release at sympathetic ganglia.
= Inhibits DOPA decarboxylase = reduces peripheral NA/Dopamine.
= PREFERRED TREATMENT FOR Pre-ECLAMPSIA….
How is NA removed from synapses?
NET = Neuronal Epinephrine Transporter.
- NET takes NA back into pre-synaptic nerve.
MAO degrades NA in cytosol….
MOST!
VMAT then reuptakes NA into vessicles
EMT uptakes NA into post-synaptic cell, whereby:
COMT degrade NA post-synaptically.
How is NA stored in vessicles?
Beta dopamine hydroxylase converts dopamine to NA on vesicle and taken up by VMAT.
Stored alonside ATP to prevent leakage and for fast + long lasting post-synaptic response
What is Guanethedine?
Taken up into pre-synaptic cell by NET.
Taken up into NA vessicles by VMAT.
Slowly displaces NA from vessicles, which are degraded by MAO in cytosol.
So reduces NA in synapse.
Experimentally.
What is reserpine?
VMAT inhibitor.
Stops transport of NA into vesicles.
Cytosolic NA is metabolised by MAO.
= Depleting NA in vesicles.
= induces depression and Parkinsonism..
What are the side effects of Guanethedine, reserpine, Metirosine/a-methyl-p-dopa, Carbidopa?
Bradycardia, Hypotension, ED, Sedation, mood disturbance but this is less so with Carbidopa as does not cross BBB.
What are the effects of the Alpha and Beta adrenoceptors?
B3 = thermogenesis in skeletal muscles.
B2 = dilates SM in vascular + airways, increases NA release in sympathetic nerves.
B1 = Raises heart rate and contractility = CARDIAC ONLY.
A2 = autoreceptor - presynaptic inhibition of NA release.
A1 = SM constriction, except in GI tract where causes relaxation.
A1 and B2 have mostly opposite effects.
Where is NA and A more potent?
Adrenaline is more potent at Beta receptors tahn NA.
What is Phenylephrine and (Ephedrine)
Selective a1 agonist.
Nasal decongestant, pupil dilation (myrdriasis), BP raiser, relieve Haemorrhoids.
Nasal congestant but B-agonist leading to NA release.
What is clonidine?
Selective a2 agonist!
= reduces NA release
= reduces BP but has central effects for ADHD, anxiety..
When is adrenaline used?
In cardiac arrest and anaphylactic shock!
Adrenaline more potent at Beta receptors.
= ACtivates B1 in the heart to raise HR and contraciliity.
Aswell as induce B2 activation for bronchodilation!!
When is Dobutamine used?
B1 agonist = increase contracility and raise HR in severe HF.
When is salbutamol used?
B2 selective agonist for COPD and asthma to induce bronchodilation.
(as increases protein mass and lipolysis with Clenbuterol)
What is Mirabegron??
B3 selective agonist.
B3 in thermogenesis and lipolysis in adipose tissue.
= Mirabegron used for overactive bladder syndrome
How does cocaine work?
Cocaine inhibits NET = causing increased NA in synapse.
How does Tyramine work?
In cheese, boosts NA release in synapse.
= Sympathomimetic.
= Tachycardia, hypertension,
What are Labetalol and Carvedilol?
Are non-selective Alpha and Beta blockers.
Labetalol does not cross placenta = used in pre-eclampsia.
Carvedilolol is used in HF to reduce TPR = a1 antagonism induces vasodilation and beta blocking reduces HR.
What are Prazosin and Doxazosin?
Selective a1 antagonists used in anti-hypertensives.
= Reduces vasoconstriction and induces peripheral vasodilation.
and has less tachycardiac effects due to A1 selectivity.
