Adrenergic Pharmacology I

Question 1

What is the rate-limiting step in dopamine, epi, and NE synthesis?

Answer 1

Conversion of Tyrosine into DOPA via Tyrosine Hydroxylase

Question 2

What is tyrosine hydroxlyase inhibited by?

Answer 2

Metyrosine

Question 3

Accessory pathways utilizes what substrate?

Answer 3

Tyramine

Question 4

Vesicular monoamine transporter (VMAT) is blocked by what drug and for what purpose?

Answer 4

Blocked by Reserpine for treatment of HTN

Question 5

Vesicle associated membrane proteins (VAMP) does what? Inhibited by what drug?

Answer 5

VAMPs help fuse vesicles to the membrane and release NE and ATP.
Inhibited by Bretylium

Question 6

NE is metabolized in liver by which enzyme?

Answer 6

Catechol-O-methyltransferase

Question 7

How is NE taken up by the nerve terminal? What drugs inhibit this process?

Answer 7

Re-uptake through NET1 transporter.

Blocked by cocaine and tricyclic antidepressants

Question 8

NE is metabolized by which mitochondrial enzyme after re-uptake? What drugs inhibit this process?

Answer 8

Mitochondrial monoamine oxidase

MAO-Is inhibit this process

Question 9

Alpha-1 receptor is what kind of receptor?

What are the effects of activation?

Answer 9

Alpha-1 receptor is a Gq coupled receptor
Activated phospholipase C which leads to increased Ca2+ and PKC activation
Primary effect is increased BP

Question 10

Beta 1 and 2 are what kind of receptor?

What are the effects of activation?

Answer 10

B1 and B2 are Gs (stimulatory) receptors

Increase cAMP concentrations

Question 11

Alpha-2 is what kind of receptor?

What are the effects of activation?

Answer 11

Alpha-2 is Gi (inhibitory) coupled receptor
Decreased cAMP concentrations
Does have homotropic capabilities

Question 12

What are the effects of Alpha-1 stimulation in the:
Eyes
Arterioles
Veins
Bladder
Penis
Liver
Kidney

Answer 12

Eyes: radial muscle contraction leads to mydriasis
Arterioles: contraction leading to increased afterload
Veins: contraction leading to increased preload
Bladder: contraction of trigone and internal sphincter causing urinary retention
Penis: stimulates ejaculation
Liver: increase in glycogenolysis
Kidney: decreased renin release

Question 13

What are the effects of Alpha-2 stimulation on:
Prejunctional nerve terminal
Platelets
Pancreas

Answer 13

Prejunctional nerve terminal: decreased NE synthesis and release
Platelets: aggregation
Pancreas: decreased insulin secretion

Question 14

What are the effects of Beta-1 stimulation on:
SA node
AV node
Atrial and ventricular muscle
His/Purkinje fibers
Kidney

Answer 14

SA- positive chronotropy
AV- positive dromotropy
AV muscle- increased inotropy, conduction velocity, cardiac output, and oxygen consumption
His/Purkinje- Automaticity and conduction velocity
Kidney- increased renin release

Question 15

What are the effects of Beta-2 stimulation on:
Vasculature
Uterus
Bronchioles
Skeletal muscle
Liver
Pancreas

Answer 15

Vasculature: vasodilation which decreases afterload
Uterus: relaxation
Bronchioles: dilation
Skeletal muscle: glycogenolysis
Liver: glycogenolysis
Pancreas: insulin secretion

Question 16

What are the effects of D1 stimulation?

Renal, mesenteric, and coronary vasculature

Answer 16

Vasodilation to those vessels.

Increase GFR, RBF and Na+ excretion in kidney

Question 17

How is epinephrine dose-dependent?

Answer 17

First comes B2 receptor response. Higher doses affect A1 activation. This is due to differing receptor affinities