10- Adrenergic Pharmacology Flashcards
What are the 3 main NT’s of the adrenergic system?
Dopamine, Norepinephrine and Epinephrine
What AA is Dopamine, Norepinephrine and Epinephrine synthesized from?
Tyrosine
Give the general pathway from Tyr –> E
Tyr –> L-DOPA –> dopamine –> NE –> E
What are the systemic effects of SANS activation?
increase of rate/force of cardiac function, resistance (constriction of blood vessels and dilation of bronchioles), inhibition of the release of insulin, and breakdown of fat
What is the transporter that puts Dopamine into presynaptic vesicles?
VMAT
What causes the vesicle to exocytose?
Ca++ influx
When is dopamine turned into NE?
Once inside the synaptic vesicle
What is the name of the transporter on presynaptic cells that transports NE and Na back into the cell?
NET
What drug inhibits NET, thus increasing [NE] in the synapse?
COCAINE AWWWWWWWWWWWWW YUSSSSSSSS
What drug inhibits VMAT, thus preventing dopamine from entering vesicles?
Reserpine
What 2 enzymes degrade catecholamines?
MAO and COMT
Where are the 2 sources of catecholamines?
The two sources are either from synthesis de novo, or are molecules that are recycled via neuronal reuptake.
Which catecholamines does MAO A degrade?
degrades serotonin, norepinephrine, and dopamine
Which catecholamines does MAO B degrade?
degrades dopamine more quickly than A.
What type of G protein is alpha1 receptors?
Gq/Gi/Go
What are the systemic effects of alpha1 activation?
heavily involved in increasing blood pressure, and antagonists target the receptors for hypertension
What are the tissue effects of alpha1 activation?
vascular smooth muscle contracton, GI contraction
Which G protein is alpha2 receptors associated with?
Gi
What is the MOA of the Gi protein on alpha2 receptors?
decreases cAMP
What is the effect of alpha2 stimulation on the pancreas?
decreased insulin release
What is the effect of alpha2 stimulation on vascular smooth muscle?
vascular contraction
What type of G protein are Beta1 receptors coupled with?
Gs
Where are Beta1 receptors (typically)?
The heart
What is the effect of beta1 stimulation?
Increased heart rate (chronotropy) and contractility (inotropy)?
What type of G protein are Beta2 receptors?
Gs
What are the effects of Gs activation? (think smooth muscle)
Smooth muscle relaxation, which included relaxation of the GI and vasodilation
What molecule binds to G-protein receptors when theyre overstimulated and down-regulates them?
BARK (Beta-Arrestin receptor Kinase)
Though Epi will bind to both alpha and beta proteins, which type does it bind a little stronger?
Beta
What are the systemic effects of Epi administration?
cardiac output and force, increases in blood pressure, relaxation of bronchial smooth muscle, and increase in concentration of glucose and fatty acids in blood
What type of adrenergic receptors does NE bind well to?
Beta 1 and alpha 1
What type of adrenergic receptors does NE not bind well to?
Beta 2
What are the systemic effects of NE administration?
Increases systemic blood pressure and stroke volume, but not heart rate. Used to treat distributive shock.
True or False: Dopamine does not cross the BBB.
True
What are the systemic effects of low [dopamine] infusion?
D1 receptors activate adenylyl cyclase, increase cAMP levels and vasodilation
What are the systemic effects of middle [dopamine] infusion?
positive inotrope due to B1 receptor activation
What are the systemic effects of high [dopamine] infusion and what is it used to treat?
alpha-1 receptor binding causes vasoconstriction, and is used in treatment of shock due to low cardiac output and compromised renal function from oliguria
α-methyltyrosine- MOA
inhibits catecholamine synthesis by inhibiting tyrosine hydroxylase
