Is epinephrine a vasodilator or a vasoconstrictor?

[eNVyKillaBeez]

I'm hoping someone can help me with this question. So epinephrine is one of the drugs we learned that is used in treating anaphylactic shock. From looking at one of the charts in the pharm book we use, the overall effect of epi seems to be lowering total peripheral resistance because of its effect on beta-2 receptors causing vasodilation of skeletal muscle. In anaphylactic shock, there would already be vasodilation caused by the release of histamine. Since epi seems to also be a vasodilator, why is it safe to give epi to a patient in anaphylactic shock?

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[link2swim06]

I'm hoping someone can help me with this question. So epinephrine is one of the drugs we learned that is used in treating anaphylactic shock. From looking at one of the charts in the pharm book we use, the overall effect of epi seems to be lowering total peripheral resistance because of its effect on beta-2 receptors causing vasodilation of skeletal muscle. In anaphylactic shock, there would already be vasodilation caused by the release of histamine. Since epi seems to also be a vasodilator, why is it safe to give epi to a patient in anaphylactic shock?

The goal during anaphylactic shock is to stop/reverse shock aka increase BP.

Dont think of skeletal muscle, its simpler to think of it generally just as a fight or flight chemical. When u are in fight or flight mode does your BP go up or down? Obviously it goes up....to do this it is a vasoconstictor (and positive effects on heart output).

Edit:
Forget to add, obviously in shock you are giving a high dosage of EPI, here is the explanation why that is needed

"Epinephrine acts on alpha receptors causing vasoconstriction and on beta receptors causing vasodilation. The affinity of epinephrine for beta receptors is somewhat greater than its affinity for alpha receptors. When given in low doses, or by slow IV infusion in humans, the beta effects of epinephrine may predominate. When given in a large IV bolus dose, as here, the alpha effects (vasoconstriction) predominate when the concentration of epinephrine is high, and the beta effects (vasodilation) may sometimes be seen as the concentration is falling. From these facts you may be able to infer the relative affinity of epinephrine for alpha receptors on the one hand, and beta receptors on the other hand.The fact that vasoconstriction predominates when both alpha and beta receptors are activated shows that the capacity for vasoconstriction mediated by alpha receptors is very great, whereas the capacity for vasodilation mediated by beta receptors is somewhat limited."

 

[eNVyKillaBeez]

That helps clear it up, thank you! What source did you use to find that effect of epi?

 

[qmcat]

It's been a while since I've looked at the details, but from what I remember, I think epi works on alpha-1, alpha-2, beta-1, and beta-2, with low doses favoring beta-1.

I know in clinic we use lidocaine + epinephrine for local anesthesia so we can get vasoconstriction of the vessels and less bleeding when we are excising a mole or doing some small procedures/cutting the skin.

I also know that we use Epi-pens on people who have anaphylactic shocks after a flu shot, for example.

So, I'm a little rusty on the high/low dose stuff, but I think that a low dose of epi (as in local anesthesia) would favor beta-1 over beta-2, so you get vasoconstriction. That's because out of alpha1/2 and beta1/2, only the beta-2 receptors do vasodilation. So, the vasoconstriction you get from low dose epi subcutaneous injection would be mostly coming from the alpha-1 action.

In an anaphylactic situation, you are jabbing the epi-pen into the patient and giving a pretty large bolus of epi, so I'm guessing that would be a large dose, which would give you more beta-2 selectivity, and thus vasodilation and bronchodilation, which I think is the main point for anaphylaxis treatment cuz usually the patient will be SOB.

I think that sounds right, but feel free to correct me if I'm wrong... yea it's been a while...

 

[link2swim06]

That helps clear it up, thank you! What source did you use to find that effect of epi?

http://courses.washington.edu/chat543/cvans/vlab/control.html

 

[El Dooderino]

It's been a while since I've looked at the details, but from what I remember, I think epi works on alpha-1, alpha-2, beta-1, and beta-2, with low doses favoring beta-1.

I know in clinic we use lidocaine + epinephrine for local anesthesia so we can get vasoconstriction of the vessels and less bleeding when we are excising a mole or doing some small procedures/cutting the skin.

I also know that we use Epi-pens on people who have anaphylactic shocks after a flu shot, for example.

So, I'm a little rusty on the high/low dose stuff, but I think that a low dose of epi (as in local anesthesia) would favor beta-1 over beta-2, so you get vasoconstriction. That's because out of alpha1/2 and beta1/2, only the beta-2 receptors do vasodilation. So, the vasoconstriction you get from low dose epi subcutaneous injection would be mostly coming from the alpha-1 action.

In an anaphylactic situation, you are jabbing the epi-pen into the patient and giving a pretty large bolus of epi, so I'm guessing that would be a large dose, which would give you more beta-2 selectivity, and thus vasodilation and bronchodilation, which I think is the main point for anaphylaxis treatment cuz usually the patient will be SOB.

I think that sounds right, but feel free to correct me if I'm wrong... yea it's been a while...

You're going to need to review this, it's important

 

[TexasMDtobe]

It's been a while since I've looked at the details, but from what I remember, I think epi works on alpha-1, alpha-2, beta-1, and beta-2, with low doses favoring beta-1.

I know in clinic we use lidocaine + epinephrine for local anesthesia so we can get vasoconstriction of the vessels and less bleeding when we are excising a mole or doing some small procedures/cutting the skin.

I also know that we use Epi-pens on people who have anaphylactic shocks after a flu shot, for example.

So, I'm a little rusty on the high/low dose stuff, but I think that a low dose of epi (as in local anesthesia) would favor beta-1 over beta-2, so you get vasoconstriction. That's because out of alpha1/2 and beta1/2, only the beta-2 receptors do vasodilation. So, the vasoconstriction you get from low dose epi subcutaneous injection would be mostly coming from the alpha-1 action.

In an anaphylactic situation, you are jabbing the epi-pen into the patient and giving a pretty large bolus of epi, so I'm guessing that would be a large dose, which would give you more beta-2 selectivity, and thus vasodilation and bronchodilation, which I think is the main point for anaphylaxis treatment cuz usually the patient will be SOB.

I think that sounds right, but feel free to correct me if I'm wrong... yea it's been a while...

Epi selectivity is dose-dependent with β2 > β1 > α1

Low dose - direct β2 stimulation causes vasodilation / bronchodilation
Larger dose - β2 + β1 stimulation, adds in increases in HR, contractility, etc for heart
Huge dose - β2 + β1 + α1 stimulation, adds in vasoconstriction among other things.

The s.c. administration of epi is a huge dose, so the hypotension of anaphylactic shock reverses with vasoconstriction and increases in cardiac output.

 

[qmcat]

ah crap lol. i'm taking a year off right now and i guess i forgot a lot of things already. thanks.

 

[CodeBlu]

I remember AC/BD as a general rule for what receptors activate what.

Realized, I should say A=Constrict/B=Dilate

Sometimes I thinK AC/DC... and hells bells start ringing.

 

[qmcat]

I have a question... if alpha receptors are only stimulated with high dose epi, how do you explain the vasoconstriction effect from lidocaine + epinephrine? I believe epinephrine is diluted 1:100,000 in the injection solution, and that seems like a really small dose to me. Wouldn't that favor beta stimulation then, and thus vasodilation of the skin blood vessels?

 

[dyeguy21]

Epi does have a higher affinity for the B-2 receptors, but vascular smooth muscle also has a higher number of alpha receptors. Technically when you reach the critical level to shift the affinity, you get vasoconstriction.

NorEpi is better in terms of alpha affinity, but injecting it can cause an increase in MAP since it preferentially goes to B-1 (heart). Thus, NorEpi increases the risk of hypertensive crisis.

Epi is instead used at a "high enough" concentration to achieve alpha-1 constriction in order to keep the anesthesia at the site to avoid systemic uptake.

 

[Sammons]

Taking this question a little further, would low dose epi, such as that found in local anesthetics, prolong anaphylactic shock? If epi is added to local anesthetics to cause vasoconstriction and slow the distribution of the anesthetic (thus increasing its effective time), wouldn't this also result in a prolonged allergic reaction time to an anesthetic allergen by having is slowly absorb in the system?

Anesthetics without epi have a shorter active period, faster metabolism rate, and a lower total body dose due to the increased distribution rate. Therefore, an anesthetic without epi would be metabolized by the system faster and naturally shorten the allergic reaction time. I understand that a larger dose of epi would counteract the anaphylxis, but just curious about the longer time period of anaphylaxis for local anesthetics with epi.

 

[SurfingDoctor]

Taking this question a little further, would low dose epi, such as that found in local anesthetics, prolong anaphylactic shock? If epi is added to local anesthetics to cause vasoconstriction and slow the distribution of the anesthetic (thus increasing its effective time), wouldn't this also result in a prolonged allergic reaction time to an anesthetic allergen by having is slowly absorb in the system?

Anesthetics without epi have a shorter active period, faster metabolism rate, and a lower total body dose due to the increased distribution rate. Therefore, an anesthetic without epi would be metabolized by the system faster and naturally shorten the allergic reaction time. I understand that a larger dose of epi would counteract the anaphylxis, but just curious about the longer time period of anaphylaxis for local anesthetics with epi.

No, because it is local. Systemic low dose epinephrine has the ability to cause vasodilation by beta-2 agonist effect > alpha-1 agonist effect. Local epinephrine in low doses does just that, stays local. But even then, in the local environment, there is probably more alpha-1 effect then beta-2. Additionally, studies have demostrated that even local epinephrine can cause increases in HR and BP. In anaphylaxis, it would likely be ineffective, maybe slightly help, but not make anaphylaxis worse.

 

[Psai]

Taking this question a little further, would low dose epi, such as that found in local anesthetics, prolong anaphylactic shock? If epi is added to local anesthetics to cause vasoconstriction and slow the distribution of the anesthetic (thus increasing its effective time), wouldn't this also result in a prolonged allergic reaction time to an anesthetic allergen by having is slowly absorb in the system?

Anesthetics without epi have a shorter active period, faster metabolism rate, and a lower total body dose due to the increased distribution rate. Therefore, an anesthetic without epi would be metabolized by the system faster and naturally shorten the allergic reaction time. I understand that a larger dose of epi would counteract the anaphylxis, but just curious about the longer time period of anaphylaxis for local anesthetics with epi.

Think about where you're starting from in regards to vascular resistance. The beginning isn't the same and the receptors don't act the same.

Blowing up a balloon is a lot easier when there's already a little air in it already. You don't get the same change in volume with the same force at different diameters.

 

[soop]

Epi at high doses causes vasoconstriction of splanchnic vessels and vasodilation in skeletal muscles while simultaneously saturating b1 receptors in the heart & lungs leading to increased cardiac output and bronchodilation. The overall effect is shunting of blood from splanchnic organs to muscles/brain while simultaneously increasing cardiac output. Bronchodilation helps the body cope with the increased oxygen demand.