Question about Drugs

[LubDub0824]

Good afternoon,

I am currently very confused about adrenergic drugs and their toxic effects particularly reflex bradycardia or tachycardia.

Will someone please clarify the mechanism of this?

Here's what I understand thus far:

1) Decrease in blood pressure can stimulate baroreceptor firing, which will cause a vagal response via parasymphathetics and can lead to reflex tachycardia. (vice versa for an increase in blood pressure)
Eg. This can be seen with use of isoproterenol, which is essentially a beta-receptor agonist. Isoproterenol will increase HR (beta-1 agonism) and decrease MAP (beta-2 agonism) and there is a potential for reflex tachycardia. (vice versa for Norepinephrine)

2) Nonselective alpha blockers can cause reflex tachycardia as NE will essentially only bind to beta-1 and lead to increase MAP and HR directly in the heart.
Eg. This can be seen with phentolamine or phenoxybenzamine, which causes alpha-1 and -2 blockade and lead to unopposed beta-1 stimulation and tachycardia in the heart. (this is why a beta-blocker is also administered in the setting of a pheochromocytoma after alpha blockade).

Sorry for the long post...but, am I understanding this correctly? Are there any other mechanisms of reflex bradycardia or tachycardia that I missed?

Thanks in advance.

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[mik30102]

1 sounds good to me.

For 2 MAP would not be increasing, it would be decreasing. Alpha blockers prevent vasoconstriction, leading to the baroreceptor response you mentioned in one. Non selective alpha blockers like phentolamine can cause worse tachycardia then say prazosin since alpha 2 will also be blocked. Alpha2 is the negative feedback for central sympathetic tone, and more norepi could be released. Like you mentioned norepi/epi will be stuck with only activating beta receptors which will further increase hr then an alpha1 selective. For the pheochromocytoma you are correct, but you could also just use a dual alpha/beta blocker like labetalol and skip the alpha.

 

[LubDub0824]

1 sounds good to me.

For 2 MAP would not be increasing, it would be decreasing. Alpha blockers prevent vasoconstriction, leading to the baroreceptor response you mentioned in one. Non selective alpha blockers like phentolamine can cause worse tachycardia then say prazosin since alpha 2 will also be blocked. Alpha2 is the negative feedback for central sympathetic tone, and more norepi could be released. Like you mentioned norepi/epi will be stuck with only activating beta receptors which will further increase hr then an alpha1 selective. For the pheochromocytoma you are correct, but you could also just use a dual alpha/beta blocker like labetalol and skip the alpha.

Oops, yes you are correct. MAP would be decreasing in #2. I was too fixated on the effects of beta-1 agonism to realize that alpha-1 and -2 blockade would lead to vasodilation and decrease in MAP. (hence, we use them for hypertension). Thanks for the explanation!