Autonomic Nervous System 3 Flashcards
State the Adrenergic neurotransmitters
Catecholamines :
- Dopamine
- Adrenaline
- Noradrenaline
Describe the production of adrenaline
Tyrosine
DOPA
Dopamine
Noradrenaline
Adrenaline
Describe the enzymes produced between each step to produce adrenaline
Tyrosine
(Tyrosine hydroxylate)
DOPA
(DOPA decarboxylase)
Dopamine
(Dopamine Beta-hydroxylase - DBH)
Noradrenaline
(PNMT)
Adrenaline
Tyrosine hydroxylate
- rate limiting step (most sensitive to disruption)
- inhibited by catecholamines
DOPA decarboxylase
METHYLDOPA - inhibits DOPA decarboxylase
Methyldopa is useful in some cases treating hypertension in pregnancy
Dopamine Beta-hydroxylase
DBH
Membrane bound
PNMT
Location
Induced by
Mainly located in adrenal medulla
Induced by adrenal cortex hormones
Function of tyrosine hydroxylate
Converts tyrosine into DOPA
Function of DOPA decarboxylase
Converts DOPA into Dopamine
Function of Dopamine Beta-hydroxylase
Converts Dopamine into Noradrenaline
Function of PNMT
Converts Noradrenaline into Adrenaline
What is the release of noradrenaline facilitated by ?
Calcium
How can we limit the duration of action of noradrenaline ?
By re-uptake
State the mechanisms in place to take noradrenaline back up into cells
NET
VMAT
transporters
NET transporter
Norepinephrine transporter
75% recaptured by neurons
Function of NET transporter
Transport nor-adrenaline back into the presynaptic neurones. (75%)
Alpha 2 Adrenoreceptor location
Presynaptic terminal
VMAT transporter
“Repackaged” by vesicular monoamine transporter
Function of VMAT transporter
Packages the nor-adrenaline into vesicles by vesicular monoamine transporter.
Alpha 2 Adrenoreceptor Function
Reduces Calcium influx
Reduces NA release
Almost exclusively expressed on neurones.
Inhibits further release of noradrenaline if there is an XS already being released out.
Activation of Alpha 2 Adrenoreceptor
Reduces the amount of noradrenaline released
Storage of noradrenaline
Stored with ATP in a vesicles in the presynaptic neurone.
How do amphetamines work ?
Work by slowly, insidiously releasing noradrenaline from cells and bypassing a lot of the feedback mechanisms.
Results of amphetamines
Large amount of continuous release of noradrenaline in the CNS.
Describe the action of amphetamines
Making NET and VMAT work in reverse.
Rather than taking noradrenaline up and repackaging it, what happens is you displace noradrenaline out and pump it out into the synaptic region.
Amphetamines
Indirectly acting sympathomimetic drugs
What is noradrenaline uptake and degradation affected by ?
Amphetamines
Monoamine oxidase inhibitors (MAO)
Uptake inhibitors
MAO - Monoamine oxidase
Normally if you get an XS of noradrenaline in the neurone, that isn’t packaged within vesicles.
It gets degraded by the action of enzymes called monoamine oxidases.
Drugs that affect catecholamine synthesis
Methyldopa
Drugs that affect catecholamine release
Indirectly acting sympathomimetics - amphetamines
By acting on alpha-2 adreno-receptors : clonidine
Inhibitors of catecholamine uptake
NET inhibitors
Cocaine, Tricyclic antidepressants
Inhibitors of catecholamine metabolic degradation
Monoamine oxidase inhibitors used in depression
Adrenergic receptor type
Metabotropic (G-protein coupled receptors)
State the 2 main groups of adrenoreceptors
Alpha 1 and 2
Beta 1,2 and 3
Alpha 1 - ANS location
Cardiovascular
GI tract
Genitourinary
Alpha 2 - ANS location
Neuronal
Beta 1 - ANS location
Heart
Kidneys
Beta 2 - ANS location
Lungs
Smooth muscle
Skeletal muscle
Alpha 1 - cellular response
Increases IP3 and DAG
Alpha 2 - cellular response
Decreases cAMP
Beta 1 cellular response
Increases cAMP
Beta 2 cellular response
Increases cAMP
Alpha 1 - Functional ANS response
Vasoconstriction
Smooth muscle contraction
Alpha 2 - Functional ANS response
Decreases Transmitter release
Beta 1 - Functional ANS response
Increases cardiac rate
Increases cardiac force
Renin release
Beta 2 - Functional ANS response
Broncho-dilation
Relaxation of visceral smooth muscle
Vasodilation (sk. muscle)
Tremor
What adrenoreceptor is used for : Upper respiratory tract infection (nasal congestion) ?
Alpha 1 agonist
Constriction of airway blood vessels
PHENYLEPHRINE
What adrenoreceptor is used for : Asthma ?
Beta 2 agonists
All cause bronchodilation
SALBUTAMOL or SALMETEROL
Duration of action of salbutamol
SABA
Short acting
Duration of action of salmeterol
LABA
Long acting
What adrenoreceptor is used for : Premature labour (to delay delivery) ?
Salbutamol
Relaxation of uterine smooth muscle
Beta 2 agonists
Why use salbutamol instead of salmeterol for premature delivery ?
As soon as the patient is in the right location, you want the effects of the drug to wear off rather than waiting hours for the birth to continue.
How to calculate mean arterial blood pressure ?
Cardiac output X total peripheral resistance
Heart X Blood Vessels
Function of sympathetic stimulation on the heart
Increases cardiac output :
- By increasing heart rate
- By increasing volume pumped on each stroke
- Both mediated by beta 1 receptors
Function of sympathetic stimulation on blood vessels
Increases total peripheral resistance :
- By constricting blood vessels
- Mediated by alpha 1 receptors
What adrenoreceptor is used for : Cardiogenic shock ?
DOBUTAMINE
Beta 1 agonists
Alpha 1 antagonists
Increases heart rate and force
What adrenoreceptor is used for : Hypertension ?
Antagonists for alpha 1
Antagonist for beta 1
Agonist for alpha 2
Function of agonising alpha 2
Prevent the release of noradrenaline
Reduce the effect on the heart
Prazosin
Vasodilation by blocking alpa 1 receptors
Propranolol
Decreases heart rate and force by blocking beta 1 receptors
Decreases renin release by kidneys (Beta 1)
Atenolol
Decreases heart rate and force by blocking beta 1 receptors
Decreases release by kidneys (beta 1)
Clonidine
Stimulation of pre-synaptic alpha 2 receptors to decrease NA release.
Also has central effect.
Beta blockers
Often referred to as cardioselective or non-cardioselective.
IN asthmatic - non-cardioselective is not permitted
What adrenoreceptor is used for : cardiac arrest ?
ADRENALINE
Vasoconstriction
Alpha 1 agonist
Increases heart rate and force
Beta 1 agonist
What adrenoreceptor is used for : Anaphlyaxis ?
ADRENALINE
Vasoconstriction
Alpha 1 agonist
Increases heart rate and force
Beta 1 agonist
Bronchodilation
Beta 2 agonist
Decreased histamine release by mast cells
Beta 2 agonist
What adrenoreceptor is used for : Benign prostatic hyperplasia ?
Prazosin
Alpha 1 antagonists
Tamsulosin
(prostate specific)
