Does infusing EPI vasoconstrict or vasodilate?

[Aclamity]

---

Members don't see this ad.

I got a kaplan question where one of the answer choices said "infusing EPI will preferentially stimulate b2 receptors and cause an overall decrease in DBP"

I get that, but I thought this really only applied to physiological doses of EPI (e.g. when you're exercising). Pharmacologic doses of EPI should cause an overall vasoconstrictive effect because of the overwhelming majority of a1 receptors on blood vessels, right? This is pretty much the basis behind using EPI in anaphylaxis, as well as the basis behind the experiment in the FA pharm section where they give EPI alone (vasoconstriction), and then EPI + phentolamine (vasodilation)

So I guess my question is: for the purposes of exam, should we just assume that giving an infusion of EPI will lead to overall vasoconstriction (with reflex bradycardia)?

 

[loveoforganic]

Your memory is the same as mine from phys. Low level vasodilate, high level vasoconstrict

 

[rocketbooster]

Your memory is the same as mine from phys. Low level vasodilate, high level vasoconstrict

Yep, that's what I was taught in our pharm module, too. It's because the beta2s are more sensitive than alpha1s to Epi stimulation. On the BP graph, Epi always started with a large increased BP from baseline and then ended with a slightly lower BP than baseline before its effects fully wear off. NE always had the large increased BP from baseline curve and then only returned to baseline. NE never dipped below baseline BP at the end of it wearing off. The Epi effects are like that because initially both alpha1+beta2 are being stimulated and alpha1 stimulation has a stronger effect. Towards the end as Epi is wearing off, the alpha1s are no longer being stimulated and only the beta2s are sensitive enough to have any effect from Epi. Unopposed beta2 = vasodilation; alpha1+beta2 = vasoconstriction. Like the OP said, I think it's because there are way more alpha1s than beta2s. But, remember, beta2s are still more sensitive than alphas 1 to Epi. Hence, low Epi dose = beta2, high Epi dose = alpha1+beta 2 (alpha1 effect>beta2 since more alpha1s).

I don't know if you really see a low vs high dose difference, though, when you actually give Epi. I never saw a test question say a low dose was given. In all our test questions, the Epi given was already considered to be enough to stimulate alpha1s. Like I mentioned, the beta2 effect was only seen on the BP graphs and you always had to use it to differentiate Epi and NE.

Hope that makes sense. Makes more sense to draw it but can't really draw on here.

 

[Aclamity]

Yep, that's what I was taught in our pharm module, too. It's because the beta2s are more sensitive than alpha1s to Epi stimulation. On the BP graph, Epi always started with a large increased BP from baseline and then ended with a slightly lower BP than baseline before its effects fully wear off. NE always had the large increased BP from baseline curve and then only returned to baseline. NE never dipped below baseline BP at the end of it wearing off. The Epi effects are like that because initially both alpha1+beta2 are being stimulated and alpha1 stimulation has a stronger effect. Towards the end as Epi is wearing off, the alpha1s are no longer being stimulated and only the beta2s are sensitive enough to have any effect from Epi. Unopposed beta2 = vasodilation; alpha1+beta2 = vasoconstriction. Like the OP said, I think it's because there are way more alpha1s than beta2s. But, remember, beta2s are still more sensitive than alphas 1 to Epi. Hence, low Epi dose = beta2, high Epi dose = alpha1+beta 2 (alpha1 effect>beta2 since more alpha1s).

I don't know if you really see a low vs high dose difference, though, when you actually give Epi. I never saw a test question say a low dose was given. In all our test questions, the Epi given was already considered to be enough to stimulate alpha1s. Like I mentioned, the beta2 effect was only seen on the BP graphs and you always had to use it to differentiate Epi and NE.

Hope that makes sense. Makes more sense to draw it but can't really draw on here.

Yeah, definitely makes sense. What you wrote in bold has been pretty much my experience with most of these questions (i.e. whenever they give EPI it's always a pharmacologic dose), up until this kaplan one. I'm just going to ignore this one then

 

[Phloston]

I encountered a question in Kaplan QBook that asked about low-dose epinephrine. 🙂 I actually learned from it so I'll share...

You know how in FA, they love to show you those graphs of BP/HR after giving epinephrine, then they give an alpha-blocker (e.g. phentolamine / phenoxybenzamine), then give epinephrine again, and the BP drops bc the alpha-receptors are blocked? In other words, they're trying to demonstrate epinephrine's beta-2 effects?

Well this Kaplan QBook question showed BP and HR increasing and decreasing, respectively, after drug X was given (opposite-facing bell-shaped curves for each that were temporary and then went back to baseline), then drug Y was given, and BP decreased and HR increased as SUBTLE, linear changes (then they resumed zero-slope again, but BP and HR now had baselines slightly lower and higher, respectively, than they had prior to drug Y), then drug X was given again. This time, BP and HR BOTH increased, and they wanted to know what drugs X and Y were, naturally.

The answers were drug X = norepinephrine and drug Y = hexamethonium.

Low-dose epinephrine was also an answer choice.

The basis of the question was to show that norepinephrine induces a basoreceptor reflex, causing a decrease in HR when BP increases. Hexamethonium, since that's a nicotinic receptor blocker, is a drug that inhibits the baroreceptor reflex from subsequently occurring (however, giving the drug itself will initially cause a slight one). Then when norepinephrine is given again, BP and HR both increase because the baroreceptor reflex is inhibited.

Anyway, their reasoning as to why low-dose epinephrine was wrong but high-dose epinephrine would have been right (if it had been given as an answer choice), was that only high-dose epinephrine induces a baroreceptor reflex, whereas low-dose does not. Therefore, low-dose epinephrine could be eliminated as the answer because it wouldn't have been expected to induce the baroreceptor reflex that had initially occurred, as had been the case with norepinephrine. Therefore, the bell-shaped curves both before and after hexamethonium would have looked the same for low-dose epinephrine.

Hope that helps,