epinephrine with alpha blockade in FA2012-where is the B1 effect at?

[lemonade90]

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A figure from the 2012 FA (pg 267) shows decreased systolic BP with epinpehrine after alpha blockade is instituted. I understand the B2 effect but why doesn't the B1 effect (pg 266) contribute and raise the systolic BP (by virtue of increased contractility-->increased SV-->inc systolic BP)?

 

[shan564]

That figure is for norepinephrine, not epinephrine. Norepinephrine is relatively selective for alpha over beta.

 

[lookmanohands]

A figure from the 2012 FA (pg 267) shows decreased systolic BP with epinpehrine after alpha blockade is instituted. I understand the B2 effect but why doesn't the B1 effect (pg 266) contribute and raise the systolic BP (by virtue of increased contractility-->increased SV-->inc systolic BP)?

Your page numbers are off

You're right that the b1 effects should raise SBP if you only focus only on what epi does at b1, but the massive drop in BP, both SBP and DBP, by epi's effect on B2 outweighs the B1 effects and will drop SBP as well (after alpha blockade)

 

[Phloston]

Agonism of beta-2 and beta-1, both by epinephrine, following alpha-blockade, induce a reduction in BP.

Agonism of beta-2 induces an overwhelming decrease in TPR.

 

[lemonade90]

I meant page 268, sorry for the confusion. The explanation on how B2 effects will dominate over B1 makes sense but what is confusing is on pae 266 how Epi has ++++ for B1 but only ++ for B2 meanining that Epi has a stronger effect at B1 receptors (strong enough to at least increase the pulse pressure by raising SBP).

What am I missing? Am I misinterpreting what the + means (efficacy vs potency)?

 

[Phloston]

I meant page 268, sorry for the confusion. The explanation on how B2 effects will dominate over B1 makes sense but what is confusing is on pae 266 how Epi has ++++ for B1 but only ++ for B2 meanining that Epi has a stronger effect at B1 receptors (strong enough to at least increase the pulse pressure by raising SBP).

What am I missing? Am I misinterpreting what the + means (efficacy vs potency)?

I was going to mention that before, but decided to just be short with my answer.

The only point they're trying to make is that beta-2 agonism results in a significant decrease in TPR such that MAP drops despite substantial beta-1 agonism.

The other important side-point of that chart is that epinephrine has some beta-2 agonism whereas NE has none.

Therefore, NE is the drug of choice for septic shock, not E.

 

[lemonade90]

I was going to mention that before, but decided to just be short with my answer.

The only point they're trying to make is that beta-2 agonism results in a significant decrease in TPR such that MAP drops despite substantial beta-1 agonism.

The other important side-point of that chart is that epinephrine has some beta-2 agonism whereas NE has none.

Therefore, NE is the drug of choice for septic shock, not E.

I understand your explanation but then why doesn' the table show B1 as being ++ and B2 as being ++++?

 

[Phloston]

I understand your explanation but then why doesn' the table show B1 as being ++ and B2 as being ++++?

Epinephrine acts more strongly at beta-1 (++++) than it does at beta-2 (++). Regardless of that being the case, the agonism of beta-2 is still sufficient enough to drop the MAP during alpha-blockade.

I'm not a pharmacologist, but that's how I'm interpreting things.

 

[lemonade90]

I thought about this some more and I think the diagram is correct not for the reasons mentioned but rather the fact that no alpha agonists are able to work (i.e. from what I remember sympathetic innervation is dominant on blood vessels, so they are usually contracted). The fact that alpha receptors (which is itself a vasodilatory effect) are blocked and B2 are stimulated overpowers the effect of the B1 agonist acting alone to try to increase SV and HR.

This theory would also be more consistent with the chart in FA.