Low dose vs high dose Epinephrine

[iA-MD2013]

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I tried searching but didn't work...

Low dose epi - decreases BP and increases HR
High dose epi - increases BP and _____ HR

Does HR increase or decrease with high dose epi?

 

[tco]

It should still increase HR. The low dose shows a preference for beta receptors over alpha, leading to the reflexive decrease in BP, but even at a high dose, it would still act on them.

Think about your fight or flight response for high dose epi.

 

[iA-MD2013]

Thanks!

I was also trying to figure out how pulse pressure changes with NE, epi, and ISO and came to the conclusion that if they work on B1, they would increase pulse pressure by increasing inotropy. Is that true or did I just make that up?

 

[tco]

You have to look at how each substance acts independently.

Page 240 in first aid is a good summary of the receptors that each act on and at the bottom it shows NE and Iso's actions.

If you think of the vessels as controlling diastolic pressure and the heart controlling systolic pressure, it might help you out a little. The systolic pressure will be increased by anything that increases diastolic, but it won't necessarily lead to an increase in pulse pressure.

An example:
So, NE acts on alpha receptors more than beta. If you administer it, it's going to cause vasoconstriction. Anything that causes vasoconstriction will also cause a reflexive decrease in HR through a parasympathetic response, so the pulse pressure won't change, but both the systolic and diastolic BP have increased.

This is actually a tough subject for me...I'm still figuring it out...If I said something wrong, please correct me.

 

[tco]

I thought about Epi a lot last night. Here are my conclusions...

No source that I checked (FA, Lange's Pharm, Lippincott) actually states what happens with beta receptors when you administer a high dose of epi. I'm assuming that the reason that beta receptors are selectively activated with low dose is because they have a much higher affinity. So you get a drop in BP (beta2) and increase in HR (beta1). Plus, there's the reflexive decrease in BP due to the increase in HR.

When you administer Epi at high dose, it's the equivalent of dumping it in and saturating your body. While the beta receptors will be still be activated, it depends on the alpha receptors as to what the response will be. Alpha1 receptors will be activated, which will lead to phosphorylation of MLCK and activation of smooth muscle. Beta2 receptors are...Whatever...Who cares, the smooth muscle will contract if enough MLCK are activated. Alpha2 receptors will be activated but, again, who cares? They just inhibit endogenous release of transmitters.

Beta1 will still activate the heart's smooth muscle. You'll still have an increase in HR...

I don't know if this actually clarified anything or not. Let me know!

 

[mastamark]

I thought about Epi a lot last night. Here are my conclusions...

No source that I checked (FA, Lange's Pharm, Lippincott) actually states what happens with beta receptors when you administer a high dose of epi. I'm assuming that the reason that beta receptors are selectively activated with low dose is because they have a much higher affinity. So you get a drop in BP (beta2) and increase in HR (beta1). Plus, there's the reflexive decrease in BP due to the increase in HR.

When you administer Epi at high dose, it's the equivalent of dumping it in and saturating your body. While the beta receptors will be still be activated, it depends on the alpha receptors as to what the response will be. Alpha1 receptors will be activated, which will lead to phosphorylation of MLCK and activation of smooth muscle. Beta2 receptors are...Whatever...Who cares, the smooth muscle will contract if enough MLCK are activated. Alpha2 receptors will be activated but, again, who cares? They just inhibit endogenous release of transmitters.

Beta1 will still activate the heart's smooth muscle. You'll still have an increase in HR...

I don't know if this actually clarified anything or not. Let me know!

Very nice!

But one thing worth mentioning is that Epi and other B-1 agonist cause increased HR and contactility by working on the cardiac muscle mostly by increasing cAMP not sm. muscle. edit: (forgot to mention via Gs but ya'll knew that)

cAMP phosphorylates the calcium channels on the myocytes, and then you know the rest, more Ca2+= more Ca2+ you get your stronger/prolonged plateu and whoosh.

cAMP also does the same thing on SA node membranes, more calcium in i think, but only for your phase 0 not for the SR release of Ca2+.<----Man I can be totally wrong on this last thing, but I remembered it from somewhere.