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
α-methyltyrosine- use
Hypertension with pheocytochroma
Reserpine- MOA
inhibits VMAT, so no D into vesicles
Reserpine- use
HTN
Tyramine- MOA
competes with NE in vesicles, especially if taken with MAOi’s
Tyramine- use
found in the diet, normal
Guanethidine- MOA
dispaces NE in vesicles
Guanethidine- use
HTN
Amphetamine- MOA
displaces endogenous catecholamines, weak MAOi, blocks reuptake by NET
Amphetamine- use
depression/narcolepsy
Ephedrine/Pseudoephredine- MOA
Stimulation of Beta receptors
Ephedrine/Pseudoephredine- use
nasal/sinus congestion
Cocaine- MOA
blocks NET, no NE into presynaptic cell
Cocaine- use
can be used as an anasthetic
Tricyclics- MOA
inhibit NET and block serotonin reuptake
Tricyclics- use
depression
Phenelzine- MOA
nonselective irreversible MAOi
Phenelzine- use
depression
Selegiline- MOA
MAO-B inhibitor
Selegiline- use
Parkinsons
Methoxamine- MOA
alpha1 agonist
Methoxamine- use
shock
Phenylephrine- MOA
alpha1 agonist
Phenylephrine- use
Shock
Oxymetazoline- MOA
alpha1 agonist
Oxymetazoline- use
nasal congestion
Clonidine- MOA
alpha2 agonist, can cross BBB
Clonidine- use
HTN, especially in pregnancy
Guaficine- MOA
alpha2 agonist
Guaficine- use
HTN
Dexmedomidine- MOA
alpha 2 agonist
Dexmedomidine- use
sedative
Alpha-methyldopa- MOA
Alpha 2 agonist
Alpha-methyldopa- use
pregnancy related HTN
Isoproterenol- MOA
nonselective Beta agonist
Isoproterenol- use
bronchoconstriction
Dobutamine- MOA
beta1 agonist, increases cardiac output
Dobutamine- use
heart failure
Albuterol- MOA
beta2 agonist, short acting
Albuterol- use
asthma
Terbutaline/Salmetrol- MOA
beta2 agonist, long acting
Terbutaline/Salmetrol- use
asthma
Phenoxybenzamine/Phentolamine- MOA
nonselective irreversible alpha antagonist
Phenoxybenzamine/Phentolamine- use
Pheochromocytoma
Prazosin/Terazosin/Doxazosin- MOA
alpha1 antagonist
Prazosin/Terazosin/Doxazosin- use
HTN and BPH
Tamsulosin- MOA
alpha1 antagonist
Tamsulosin- use
BPH
Propanolol- MOA
nonselective beta blocker
Propanolol- use
HTN
Carvedilol- MOA
nonselective beta blocker
Carvedilol- use
HTN
Pindolol- MOA
partial agonist for beta1 and beta2
Pindolol- use
HTN pt’s that have bradycardia or decreased cardiac reserve
Acebutolol- MOA
partial beta1 agonist
Acebutolol- use
HTN
Esmolol- MOA
beta1 antagonist
Esmolol- use
thyroid storm, very short acting so IV only.
