ANS Pharm Q

[Focused1]

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What is the effect of Epinephrine + Propranolol on Pulse Pressure ?

EDIT: High dose Epinephrine

 

[dfib slim]

Unopposed alpha induced vasoconstriction will lead to an increased blood pressure but I think the pulse pressure would not change much?

 

[Nabin]

I think you need to clarify whether its low dose or high dose epinephrine?

 

[tropocollagen]

Epinephrine has both beta and alpha effects with stronger beta effects except at very high dose. Propranolol is a nonselective beta antagonist. So Epinephrine + Propranolol will results in dominant alpha effect, which increases pulse pressure.

 

[Nabin]

Epinephrine has both beta and alpha effects with stronger beta effects except at very high dose. Propranolol is a nonselective beta antagonist. So Epinephrine + Propranolol will results in dominant alpha effect, which increases pulse pressure.

Wouldn't dominant alpha effect increase the diastolic blood pressure and then decrease the pulse pressure?

 

[Focused1]

Wouldn't dominant alpha effect increase the diastolic blood pressure and then decrease the pulse pressure?

Clarification: High Dose...edited it...(Low dose Beta would actually I guess not have any effect at all coz we have given propranolol a non specific beta antagonist)

 

[Focused1]

Unopposed alpha induced vasoconstriction will lead to an increased blood pressure but I think the pulse pressure would not change much?

I think the following would happen:
DBP: Increase (Alpha 1 action)
PP: Constant (No Beta 1 action)
SBP= DBP + PP = Increased ?

What do you guys think about that ?

 

[Nabin]

I think the following would happen:
DBP: Increase (Alpha 1 action)
PP: Constant (No Beta 1 action)
SBP= DBP + PP = Increased ?

What do you guys think about that ?

With high dose of epinephrine, we should expect greater alpha-1 vasoconstrictive effect which would directly increase the TPR and then the DBP. Since, beta-1 and beta-2 are blocked by propanolol, there is no beta-2 mediate vasodilation in the skeletal muscle vasculature and no beta-1 mediated increased contractility of the heart. I am not sure what would happen to the SBP, it might be normal or decreased even. All in all, PP = SBP - DBP so PP should decrease due to increased DBP.

 

[tropocollagen]

I think the following would happen:
DBP: Increase (Alpha 1 action)
PP: Constant (No Beta 1 action)
SBP= DBP + PP = Increased ?

What do you guys think about that ?

Agree. Since all the beta effects are blocked, heart contractility will not change, which means PP will not change, and both SBP and DBP will increase due to alpha effect.

 

[tropocollagen]

Wouldn't dominant alpha effect increase the diastolic blood pressure and then decrease the pulse pressure?

Yes, the diastolic blood pressure will increase. But the systolic pressure will increase, too.

 

[dfib slim]

I think the following would happen:
DBP: Increase (Alpha 1 action)
PP: Constant (No Beta 1 action)
SBP= DBP + PP = Increased ?

What do you guys think about that ?

Yeah, that's what I meant. Blood pressure, both systolic and diastolic, increased so PP wouldn't change by much. Wouldn't giving high dose epi + propanolol look just like phenylephrine? Page 255 of FA 2015 shows the PP pretty constant.

 

[Nabin]

Yeah, that's what I meant. Blood pressure, both systolic and diastolic, increased so PP wouldn't change by much. Wouldn't giving high dose epi + propanolol look just like phenylephrine? Page 255 of FA 2015 shows the PP pretty constant.

you mean the graph of use of alpha-blocker?

 

[dfib slim]

you mean the graph of use of alpha-blocker?

No, the bottom left with just the alpha agonist alone. The PP before and after phenylephrine are pretty much the same. The alpha 1 agonist is increasing the SBP and DBP together. With epi + propanolol SBP and DBP should both increase due to the unopposed alpha 1 effects. I'm just guessing they may increase together at a pretty close rate.

 

[Nabin]

No, the bottom left with just the alpha agonist alone. The PP before and after phenylephrine are pretty much the same. The alpha 1 agonist is increasing the SBP and DBP together. With epi + propanolol SBP and DBP should both increase due to the unopposed alpha 1 effects. I'm just guessing they may increase together at a pretty close rate.

Okay that one. Yeah you are right. I was too concentrated on the reflex baroreceptor mechanism playing its effect (due to increased TPR) and slowing the heart down. Katzung says that reflex bradycardia doesn't diminish the cardiac output much in case of a pure alpha-1 agonist stimulation, due to increased SV coming from venoconstriction. So, yeah then a modest increase in SBP can be expected too then. That would balance out the pulse pressure. Cheers!

 

[delta14]

First, propronalol (prop) should also be used at high doses as well because its action is competitive. If prop is used at sufficient doses so that all b1 and b2 receptors are blocked then, high epi will create a massive vasoconstriction and elevation of DBP. The lack of b2 activation will further increase DBP. High epi will also activate a2 and thereby, inhibit NE release in the brainstem (like high doses of clonidine) and central sympathetic outflow. But that won't change much because b1-2 already inhibited by high doses of prop. The HR will drop because of the vagal reflex bradycardia. What will happen to SBP is not very clear. There is no reason for SBP to increase (the heart is not additionally stimulated because of b1 block and a2 activation), but SBP cannot be lower than DBP and so, it will probably increase, just to follow DBP and probably, not as much as DBP. As a result, PP should drop, but the drop could be small and/or patient-dependent.