Adrenergic Agonists

Question 1

In general terms, what are the steps to synthesis of NE and epi?

Answer 1

from tyrosine to DOPA, then dopamine, norepinephrine, epinephrine

Question 2

What is the rate limiting step for adrenergic amine synthesis

Answer 2

tyrosine hydroxylase (the first step)

Question 3

How are adrenergic amines stored?

Answer 3

in granules with ATP-protein complexes

Question 4

IN order for NE to be released, a preganglionic sympathetic nerves releases ___ onto ___ receptors on the postganglionic nerve.

Answer 4

ACh onto nicotinic nerves

Question 5

How do the indirectly-acting sympathomimetics work?

Answer 5

they reverse the direction of the axoplasmic catecholamine transporter, so you don’t get NE taken back up into the cell and it stays in the synapse

Question 6

What are three indirectly-acting sympathomimetics?

Answer 6

tyramine, amphetamine, ephedrine

Question 7

What are two drugs that inhibit the axoplasmic pump to potentiate sympathetic responses?

Answer 7

cocaine and imipramine

Question 8

What drug inhibits the granular pump and what does this lead to?

Answer 8

Reserpine inhibits the granular pump so NE can’t get put in vesicles. This means it’s out in the cytosol with the degradation enzymes so you get a depetion of catecholamines

Question 9

What drugs induce catecholamine release from the vesicles via displacement? WHat does this do to NE stores?

Answer 9

Guanethidine and Guanadrel

this depletes NE stores because the NE is out in the cytosol and gets degraded by MAO

Question 10

How does the ody terminate adrenergic amine signals?

Answer 10

either reuptake or degradation with COMT and MAO

Question 11

What is the example of MAOI we should know from this lecture?

Answer 11

pargyline

Question 12

What are the adrenergic receptors and where are they located?

Answer 12

alpha 1 smooth muscle
alpha 2 prejunctional nerve terminal, platelets, gut, medulla oblongata
beta 1 heart, JG aparatus
beta 2 lungs and smooth muscle

Question 13

Order epi, NE and isoproterenol for alpha1 receptors

Answer 13

epinephrine > norepinephrine&raquo_space; isoproterenol

Question 14

Order epi, NE and isoproterenol for alpha 2

Answer 14

epinephrine > norepinephrine&raquo_space; isoproterenol

Question 15

Order epi, NE and isoproterenol for beta 1

Answer 15

isoproterenol > epinephrine = norepinephrine

Question 16

Order epi, NE and isoproterenol for beta 2

Answer 16

isoproterenol > epinephrine&raquo_space; norepinephrine

Question 17

What does activation of alpha 1 receptors do? How?

Answer 17

smooth muscle contraction = vasoconstriction

activates phospholipase C with a Gq dependent process to increase intracellular calcium

Question 18

What does activation of alpha 2 receptors do? How?

Answer 18

inhibits neural NE release to dull the general sympathetic response

decreases cAMP or activates an Na/H antiporter in a Gi dependent process

Question 19

WHat does activation of beta 1 receptors do?How?

Answer 19

increases HR and contractility, stimulates renin release

increases cAMP via Gs

Question 20

What does activation of beta 2 receptors do? How?

Answer 20

relaxation of smooth muscle and metabolic glycogenolytic effects (bronchodilation too)

increases cAMP via Gs

Question 21

What is the one beta 1 agonist?

Answer 21

dobutamine

Question 22

What is dobutamine used for? Contraindicated in?

Answer 22

used for congestive heart failure or acute MI with heart failure

contraindicated in a fib

Question 23

What does dobutamine do to blood pressure?

Answer 23

Directly causes an increase in blood pressure

Question 24

What is the alpha 1 agonist we learned?

Answer 24

phenylephrine

Question 25

What does phenylephrine do to BP?

Answer 25

increases BP by causeing vasoconstrction and increase in TPR

Question 26

What are some examples of beta 2 selective agonists? What are they used for?

Answer 26

used for either asthma or to delay labor: metaproterenol, terbutaline, albuterol, ritodrine, salmeterol

Question 27

What do the beta 2 agonists do for BP?

Answer 27

They decrease BP by their vasodilatory effects

Question 28

What are the effects of isoproterenol?

Answer 28

vasodilation with activation of beta 2 | tachycardia with activation of beta 1 (conflicting response!)

Question 29

What is the overall effect on blood pressure by isoproterenol?

Answer 29

Although it causes tachycardia with increased SV, the effect on radius is more important, so overall it causes a decrease in blood pressure

Question 30

What can you use to block the effects of isorpoterenol>

Answer 30

beta blockers (nonspecific) like propranolol

Question 31

WHat are the effects of norepinephrine?

Answer 31

vasocosntriction via alpha 1 increased HR and contractility via beta 1 reflex reduction in HR mediated by vagus nerve

Question 32

What does NE do to blood pressure then?

Answer 32

increases blood pressure - used to treat hypotension as a pressor

Question 33

If you block the alpha 1 receptors with terazosin, what does NE do to blood pressure?

Answer 33

you still get a slight increase in BP because of the increased HR and contractility thorugh beta 1

Question 34

What are the effects of epinephrine?

Answer 34

vasoconstriction via alpha` at high doses vasodilation at lower doses via beta 2 increase HR and contractility via beta 1, but reflexes can suppress heart rate

Question 35

What does epinephrine do to blood pressure?

Answer 35

at the doses we generally use (high), it increases BP

Question 36

If you give terazosin before epinrphine, what does it do to blood pressure?

Answer 36

decreases it now! If the alpha 1 receptors are blocked, beta 2 activity will occur and you get vasodilation with decrease in BP. This is "epinephrine reversal"

Question 37

If drug X causes an increase in BP, but no response after terazosin, what is the drug?

Answer 37

an alpha1 agonist like phenylephrine

Question 38

If drug x causes a decrease in BP, but no response after propranolol, what was drug x?

Answer 38

a beta 2 agonist like isoproterenol | note, also has beta 1 effect, but radius wins out to cause decreased BP

Question 39

If drug X causes an increase in BP, but only a slighter increase in BP after terazosin, what is drug X?

Answer 39

Norepinephrine | still causes icnreased HR and contractility after terazosin, but doesn't stimulate beta 2=

Question 40

If drug X causes an increase in BP, but then a decrease in BP after terazosin, what was drug X?

Answer 40

epinephrine - this is epinephrine reversal - after terazosin, epinephrine activates beta 2, leading to vasodilation and decreased BP

Question 41

What do amphetamines do in this system?

Answer 41

they cause release of catecholamines from nerves by reversing the catecholamine axoplasmic uptake pump are thus noncatecholamine sympathomimetics

Question 42

How does ephedrine work?

Answer 42

same as amphetamine - reverses axopaslmic transporter to mimic sympathetic stimulation