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CRRAB Week 6 > Adrenergic Agonists > Flashcards

Adrenergic Agonists Flashcards

1
Q

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

A

from tyrosine to DOPA, then dopamine, norepinephrine, epinephrine

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2
Q

What is the rate limiting step for adrenergic amine synthesis

A

tyrosine hydroxylase (the first step)

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3
Q

How are adrenergic amines stored?

A

in granules with ATP-protein complexes

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4
Q

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

A

ACh onto nicotinic nerves

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5
Q

How do the indirectly-acting sympathomimetics work?

A

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

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6
Q

What are three indirectly-acting sympathomimetics?

A

tyramine, amphetamine, ephedrine

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7
Q

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

A

cocaine and imipramine

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8
Q

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

A

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

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9
Q

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

A

Guanethidine and Guanadrel

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

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10
Q

How does the ody terminate adrenergic amine signals?

A

either reuptake or degradation with COMT and MAO

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11
Q

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

A

pargyline

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12
Q

What are the adrenergic receptors and where are they located?

A

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

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13
Q

Order epi, NE and isoproterenol for alpha1 receptors

A

epinephrine > norepinephrine&raquo_space; isoproterenol

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14
Q

Order epi, NE and isoproterenol for alpha 2

A

epinephrine > norepinephrine&raquo_space; isoproterenol

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15
Q

Order epi, NE and isoproterenol for beta 1

A

isoproterenol > epinephrine = norepinephrine

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16
Q

Order epi, NE and isoproterenol for beta 2

A

isoproterenol > epinephrine&raquo_space; norepinephrine

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17
Q

What does activation of alpha 1 receptors do? How?

A

smooth muscle contraction = vasoconstriction

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

18
Q

What does activation of alpha 2 receptors do? How?

A

inhibits neural NE release to dull the general sympathetic response

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

19
Q

WHat does activation of beta 1 receptors do?How?

A

increases HR and contractility, stimulates renin release

increases cAMP via Gs

20
Q

What does activation of beta 2 receptors do? How?

A

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

increases cAMP via Gs

21
Q

What is the one beta 1 agonist?

A

dobutamine

22
Q

What is dobutamine used for? Contraindicated in?

A

used for congestive heart failure or acute MI with heart failure

contraindicated in a fib

23
Q

What does dobutamine do to blood pressure?

A

Directly causes an increase in blood pressure

24
Q

What is the alpha 1 agonist we learned?

A

phenylephrine

25
Q

What does phenylephrine do to BP?

A

increases BP by causeing vasoconstrction and increase in TPR

26
Q

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

A

used for either asthma or to delay labor:

metaproterenol, terbutaline, albuterol, ritodrine, salmeterol

27
Q

What do the beta 2 agonists do for BP?

A

They decrease BP by their vasodilatory effects

28
Q

What are the effects of isoproterenol?

A

vasodilation with activation of beta 2

tachycardia with activation of beta 1 (conflicting response!)

29
Q

What is the overall effect on blood pressure by isoproterenol?

A

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

30
Q

What can you use to block the effects of isorpoterenol>

A

beta blockers (nonspecific) like propranolol

31
Q

WHat are the effects of norepinephrine?

A

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

32
Q

What does NE do to blood pressure then?

A

increases blood pressure - used to treat hypotension as a pressor

33
Q

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

A

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

34
Q

What are the effects of epinephrine?

A

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

35
Q

What does epinephrine do to blood pressure?

A

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

36
Q

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

A

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”

37
Q

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

A

an alpha1 agonist like phenylephrine

38
Q

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

A

a beta 2 agonist like isoproterenol

note, also has beta 1 effect, but radius wins out to cause decreased BP

39
Q

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

A

Norepinephrine

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

40
Q

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

A

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

41
Q

What do amphetamines do in this system?

A

they cause release of catecholamines from nerves by reversing the catecholamine axoplasmic uptake pump

are thus noncatecholamine sympathomimetics

42
Q

How does ephedrine work?

A

same as amphetamine - reverses axopaslmic transporter to mimic sympathetic stimulation

CRRAB Week 6 (8 decks)

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