Unopposed alpha stimulation

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cbrons

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Anyone have a good monograph that explains this?

Reason I am inquiring: stimulant + beta blocker therapy for anxious patients with ADD/ADHD, narcolepsy. Purely for self-interest.

- Yes I have looked for good resources online
- Yes I have talked with physicians but did not receive a very good/in-depth answer.

Seems in normotensive patients that the combo of amphetamine stimulants and low-dose beta blockers do not cause this problem and I've encountered several patients on the combo of Vyvanse/Adderall XR and beta blockers. I am just not well educated on the issue, and I know from my own education that beta blockers are never used in amphetamine overdose (although I have heard of labetolol being used owing to its alpha activity).

Yes I am a medical student posting on the pharmacy boards, please help point me to a good resource or lets have a discussion. Thank you for your valuable time.

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A contraindicated combo that may result in hypertensive crisis. Here is the reason:

B2 receptors cause peripheral vasodilation
A1 receptors cause peripheral vasoconstriction

This combo will result in A1 receptor activity and a resultant vasoconstriction that can not otherwise be compensated by the blocked B2 receptors.
 
A contraindicated combo that may result in hypertensive crisis. Here is the reason:

B2 receptors cause peripheral vasodilation
A1 receptors cause peripheral vasoconstriction

This combo will result in A1 receptor activity and a resultant vasoconstriction that can not otherwise be compensated by the blocked B2 receptors.

I get that, but what is the relative risk? I am not talking about treating amphetamine overdose, but low doses of cardioselective beta blockers (i.e. Lopressor, Tenormin) with therapeutic doses of stimulants (i.e. 50mg Vyvanse, 20mg Adderall XR, etc.) in normotensive patients.
 
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I thought the mechanism was that beta-blockage w/o alpha stimulation will cause problems via decreased cardiac output. So you get vasoconstriction and perfusion pressure can't be maintained
 
if you're using a non-selective beta blocker with an alpha1 selective agent (PE) it could be a potential issue whereas a low dose cardio-selective beta blocker with amphetamine/methylphenidate should not be a problem, assuming the patient is normotensive.
 
I get that, but what is the relative risk? I am not talking about treating amphetamine overdose, but low doses of cardioselective beta blockers (i.e. Lopressor, Tenormin) with therapeutic doses of stimulants (i.e. 50mg Vyvanse, 20mg Adderall XR, etc.) in normotensive patients.

I could be wrong, but I don't believe that would be an issue at therapeutic doses. The classic example of unapposed alpha stimulation is when someone comes into the ER with some sort of acute hypertensive crisis and the ER physician has to ask the patient prior to administration of a Beta Blocker whether or not they have used Cocaine, because if they have it can kill them. I would wager it is more of an issue in these cases of induced catecholamine "surge".
 
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I get that, but what is the relative risk? I am not talking about treating amphetamine overdose, but low doses of cardioselective beta blockers (i.e. Lopressor, Tenormin) with therapeutic doses of stimulants (i.e. 50mg Vyvanse, 20mg Adderall XR, etc.) in normotensive patients.
This article suggests that "the heart risk is remote", so why treat normotensive patients? You'll need to do look further if you want a journal article. I'm too tired at the moment to look any further. :sleep:

A contraindicated combo that may result in hypertensive crisis. Here is the reason:

B2 receptors cause peripheral vasodilation
A1 receptors cause peripheral vasoconstriction

This combo will result in A1 receptor activity and a resultant vasoconstriction that can not otherwise be compensated by the blocked B2 receptors.
This is what I understand as well.

Blocking vasodilation with a beta blocker leads to an "unopposed" alpha, which could be bad news.

Edit: As far as treating anxiety associated with stimulants goes, clonidine and guanfacine come to mind. They use them at bedtime to help with sleep, ie "take the edge off".
 
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if you're using a non-selective beta blocker with an alpha1 selective agent (PE) it could be a potential issue whereas a low dose cardio-selective beta blocker with amphetamine/methylphenidate should not be a problem, assuming the patient is normotensive.

I could be wrong, but I don't believe that would be an issue at therapeutic doses. The classic example of unapposed alpha stimulation is when someone comes into the ER with some sort of acute hypertensive crisis and the ER physician has to ask the patient prior to administration of a Beta Blocker whether or not they have used Cocaine, because if they have it can kill them. I would wager it is more of an issue in these cases of induced catecholamine "surge".

This article suggests that "the heart risk is remote", so why treat normotensive patients? You'll need to do look further if you want a journal article. I'm too tired at the moment to look any further. :sleep:

This is what I understand as well.

Blocking vasodilation with a beta blocker leads to an "unopposed" alpha, which could be bad news.

Thank you. Anyone know definitively if this is the case?:

I could be wrong, but I don't believe that would be an issue at therapeutic doses. The classic example of unapposed alpha stimulation is when someone comes into the ER with some sort of acute hypertensive crisis and the ER physician has to ask the patient prior to administration of a Beta Blocker whether or not they have used Cocaine, because if they have it can kill them. I would wager it is more of an issue in these cases of induced catecholamine "surge".
 
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on one of my rotations i learned something about unopposed alpha stimulation in hepatic encephalopathy, and thats why they use propranolol or esmolol, can someone explain this too me again? or direct me to where i can find more info about it?
 
http://www.nytimes.com/2006/02/21/health/21psyc.html?pagewanted=all

Edit: As far as treating anxiety associated with stimulants goes, clonidine and guanfacine come to mind. They use them at bedtime to help with sleep, ie "take the edge off".

Yes but so far as I understand (please correct me if I am wrong) guanfacine and clonidine do not directly reduce HR. For a very select group of patients (w/ high baseline HRs), it is the sensation of the racing heart itself that is the problem.
 
Drugs like clonidine block alpha 2 receptors on presynaptic neurons, causing a negative feedback that decreases subsequent release of norepi from that neuron. So then it is that decrease in norepi release that decreases heart rate. If I am wrong please correct me but I think that is how it works if I remember correctly from my therapeutic modules.
 
Drugs like clonidine block alpha 2 receptors on presynaptic neurons, causing a negative feedback that decreases subsequent release of norepi from that neuron. So then it is that decrease in norepi release that decreases heart rate. If I am wrong please correct me but I think that is how it works if I remember correctly from my therapeutic modules.
Doesn't block alpha 2.
 
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Sorry, you are correct. It would appear that I should have said stimulates alpha 2 receptors, but the effect is still the inhibition of NE.
 
Drugs like clonidine block alpha 2 receptors on presynaptic neurons, causing a negative feedback that decreases subsequent release of norepi from that neuron. So then it is that decrease in norepi release that decreases heart rate. If I am wrong please correct me but I think that is how it works if I remember correctly from my therapeutic modules.
As much as drug rep videos make me want to barf :barf:, this little video says that "guanfacine is believed to work independently of norepinephrine", so perhaps this mechanism works by forcing the reuptake of norepi? Sleepy time anyone? :sleep: Guanfacine is an Alpha-2A receptor agonist...[YOUTUBE]http://www.youtube.com/watch?v=ipWdbM9MRyg[/YOUTUBE]
 
So back to the topic at hand, there is no real need to have a patient do extensive monitoring (aka ambulatory BP) when starting a therapeutic dose of amphetamines and a beta blocker?
 
So back to the topic at hand, there is no real need to have a patient do extensive monitoring (aka ambulatory BP) when starting a therapeutic dose of amphetamines and a beta blocker?

I'm just curious at to when you would start a patient on an amphetamine and a beta blocker at the same time. I'm just wondering as in the community setting you always see amphetamines used for ADHD and no one seems to worry about the cardiovascular risks.
 
I'm just curious at to when you would start a patient on an amphetamine and a beta blocker at the same time. I'm just wondering as in the community setting you always see amphetamines used for ADHD and no one seems to worry about the cardiovascular risks.

Not worried about CV risks, worried about comorbid panic/anxiety. Some patients intolerant to guanfacine/clonidine. Know doctors will mix the two and don;t worry about unopposed alpha at low doses, just double checking what you all think.
 
Looking for updated response to the original post.
Not sure how much this will help, but have dispensed this combo many times without batting an eye. My supervising pharmacist at the time said that the only people who call DR to verify on this are overachiever with no real world sense.

Some other personal anecdotes, I have had a professor tell me once that the unopposed alpha situation is only relevant in setting of hypertensive or catecholamine crisis/ surge and that it was only ever observed a few times, in patients on cocaine overdose.

The use is for reducing physical anxiety symptoms in amphetamine patients where clonidine/guanfacine are too heavy of sedation (which you clearly know -- not many people seem to understand that) .. a2 agonists are blocking stimulants at the most basic level, limiting their effectiveness. BB doesn't have much in the way of mental effects (besides epic dose propranolol) so will not block stimulants helpful properties.

In someone using amphetamine for adhd, there is not a high enough level of adrenergic activity to cause this kind of crisis (unopposed vasoconstriction). At least that is what I was taught and how I practice.

Unopposed alpha is a classic example of irrelevant minutiae being taught as important in order to satisfy some academic ego.
 
Not sure how much this will help, but have dispensed this combo many times without batting an eye. My supervising pharmacist at the time said that the only people who call DR to verify on this are overachiever with no real world sense.

Some other personal anecdotes, I have had a professor tell me once that the unopposed alpha situation is only relevant in setting of hypertensive or catecholamine crisis/ surge and that it was only ever observed a few times, in patients on cocaine overdose.

The use is for reducing physical anxiety symptoms in amphetamine patients where clonidine/guanfacine are too heavy of sedation (which you clearly know -- not many people seem to understand that) .. a2 agonists are blocking stimulants at the most basic level, limiting their effectiveness. BB doesn't have much in the way of mental effects (besides epic dose propranolol) so will not block stimulants helpful properties.

In someone using amphetamine for adhd, there is not a high enough level of adrenergic activity to cause this kind of crisis (unopposed vasoconstriction). At least that is what I was taught and how I practice.

Unopposed alpha is a classic example of irrelevant minutiae being taught as important in order to satisfy some academic ego.

Lol, thank you, great response. This will sound like a very dumb question even coming from a med student, but what about the situation where you have massive endogenous release of catecholamines (i.e. patient has a panic attack) while on this combo? I would guess this wouldn't change anything, since I doubt the average healthy individual produces enough (for long enough time) of an epi surge to kill themselves, but I was unsure.
 
Lol, thank you, great response. This will sound like a very dumb question even coming from a med student, but what about the situation where you have massive endogenous release of catecholamines (i.e. patient has a panic attack) while on this combo? I would guess this wouldn't change anything, since I doubt the average healthy individual produces enough (for long enough time) of an epi surge to kill themselves, but I was unsure.
Yeah not sure that can be answered easily.. But would think really unlikely. Would I hesitate to dispense bb to a pt on stimulants with panic disorder because of unopposed alpha? No way. If Id question anything in that situation it would be whether stimulants and anxiety are a good mix to begin with , but as they say about psych, predicting those drugs' effects subjective value is not an exact science.

Imho.
 
I would be more worried if the person had an underlying vasoconstrictive issue, like raynauds or some other CVD, but you have to have some professional expectation that their MD is checking their cv risks if they are starting stims and b blockers
 
I remember reading newer research are actually saying BB in cocaine overdose is not harmful but actually helpful which completely contradict prior belief on unopposed alpha. No one really knows but I'd find this unlikely to happen unless they're on high dose amp/coke or something
 
I know I'm bumping this is a bit, but why wouldn't you merely provide benzodiazepines as treatment for anxiety/panic attacks from stimulant use? I know it won't stop the tachycardia which is a major part of the anxiety, but it has 0 interactions with stimulants. Or give a half dose of a beta blocker + a therapeutic dose of a short acting benzodiazipine? Then the fears of unopposed alpha adrenergic stimulation could be mitigated, at least in half.
 
Anyone that wants a real life example of how this can go horribly wrong, it happened to me.

Basically if you're vasodilated and pulse is high enough to inhibit ventricular filling because of the limited time in diastole your BP will plummet and you'll have a syncopal event. It's the perfect storm of events, but it's definitely possible.

I was getting a little cardio in that night with my gf + had taken adderall that day + guanfacine before bed + extremely stressed from the exam results from that day + borderline hemoglobin level = Scary Trip to the ER.
 
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