L12 The PNS : Adrenergic Agonists And Antagonists Flashcards
Describe the biochemistry of noradrenaline
Precursor = tyrosine
Tyrosine converted into DOPA via tyrosine hydroxylase
DOPA converted into dopamine via DOPA decarboxylase
Dopamine into noradrenaline via DA-beta-hydroxylase
What are the fundamentals of noradrenaline neurotransmission?
Synthesis - tyrosine, hydroxylase/DOPA, decarboxylase, DA beta hydroxylase
Storage - vesicles
Release - exocytosis
Receptor interaction - alpha and beta receptors
Termination - uptake and recycled by monoamine oxidase
Which 2 main classes of NA receptor mediate the actions of noradrenaline?
1) alpha receptors
2) beta receptors
Outline alpha-noradrenergic receptors
- alpha 1 and 2
- located on the effector tissues/targets of sympathetic system
- G-protein coupled receptors
- slow responses
Outline beta-noradrenergic receptors
- beta 1,2 and 3
- located in effector tissues/targets of sympathetic system
- G-protein coupes receptors
Slow responses
Which sympathetic effects are mediated by alpha-1 receptors
1) pupils dilate
2) blood vessels to visceral organs and skin constricts
3) brain activity and general alertness
Outline alpha-2 receptors
They are presynaptic receptors
- inhibit neurotransmitter release (negative feedback)
- located on the terminal
Which sympathetic effects are mediated by beta-1 receptors?
Heart rate increases and the force of contraction increases
Which sympathetic effects are mediated by beta-2 receptors?
- Airways in lungs dilate
- Lens of eye adjust for far vision (ciliary muscle relaxation)
- Blood vessels to limb muscles dilate
Which sympathetic effects are mediated by beta-3 receptors?
Increases lipolysis - breakdown of triglycerides to fatty acids
What effects do noradrenergic agonists (adrenaline) have on NA receptors?
ADRENALINE
- agonist at all NA receptors (a1, a2, b1, b2)
- given locally and can prolong and isolate local anaesthesia
- used to treat anaphylactic shock
What effects do noradrenergic agonists (alpha2 agonist) have on NA receptors?
Used for hypertension : decrease NA release and dampen down overall sympathetic system
Decrease of sympathetic outflow because it involves the central effect
Used to treat withdrawal symptoms in morphine withdrawal
- inhibits central NA release which drives withdrawal symptoms
What are alpha-2 receptors?
They are presynaptic autoreceptors which regulate release and the agonist inhibits NA release
What effects do noradrenergic agonists (beta-1) have on NA receptors?
Beta-1 receptors - increased cardiac rate and force
Used to treat heart failure
- beta1 mediated cardiac stimulation (increased firing rate)
What effects do noradrenergic agonists (beta-2) have on NA receptors?
Beta-2 receptors : bronchodilation
Used to treat asthma
- beta2 mediated bronchiol smooth muscle relaxation
What effects do noradrenergic agonists (beta-3) have on NA receptors?
Beta-3 receptors : lipolysis/increased metabolism
Increases muscle bulk in athletes/body builders/livestock
What effects do noradrenergic antagonists (alpha1) have on NA receptors?
Blocks alpha1 - mediated smooth muscle and vasoconstriction
PRAZOSIN
Used to treat hypertension
- a1 antagonism : vasodilation and decreased vascular resistance
Side effects : orthostatic or postural hypotension due to some loss in sympathetic reflex
TAMSULSON
Used to treat urination problems in prostate hyperplasia
-a1 antagonism : relaxation of smooth muscle in bladder neck, ease of urinary flow
Side effects : orthostatic or postural hypotension due to some loss in sympathetic reflex
What effects do noradrenergic antagonists (b1 and b2) have on NA receptors?
Block b1 and b2 receptors
Used to treat hypertension and angina
- blocking b1 receptors decreased cardiac output
- decreases oxygen demand
- blocking b2 causes bronchoconstriction therefore contra-indicative in asthmatics
What effects do noradrenergic antagonists (b1) have on NA receptors?
Blocks b1 receptors
Used to treat hypertension and angina
- blocking b1 decreases cardiac output and also decreases oxygen demand
Side effect : rebound hypertension/angina on abrupt withdrawal due to b1 receptor supersensitivity
What effects do noradrenergic antagonists (b2) have on NA receptors?
Block b2 receptors - mediate ciliary muscles/lens of eye relaxation
Used to treat glaucoma
-antagonism of b2 : receptors cause ciliary contraction and decreased intraocular pressure
How can drugs affect NA synthesis?
Inhibit enzymatic activity and synthesis with a false substrate (meDOPA)
- converted to meDA and then meNA
- meNA produced over NA which isn’t as effective on the noradrenergic receptors
Why does meNA affect NA release?
It has alpha 2 agonists which decrease the NA release
- used in the treatment for hypertension
How do drugs affect NA storage?
NA is stored in synaptic vesicles
- reserpine disrupts storage
- overall decrease in neurotransmission
- used to treat hypertension
How do drugs affect NA release?
NA release is subject to autoinhibitory control via presynaptic a2-autoreceptor
- clonidine (a2 agonist) causes inhibition of NA release
- used to treat hypertension
