epinephrine and alpha blocker

[deleted500612]

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I am getting conflicting information between uworld and first aid as to how these drugs would interact if administered consecutively. Uworld says that administration of an irreversible alpha blocker such as phenoxybenzamine, followed subsequently by administration of epinephrine will result in a less efficacious pressor effect than epinephrine alone, but will still cause a partial pressor effect nonetheless. First Aid says (pg 255, 2015 edition) that irreversible alpha blocker administration followed by high-dose epinephrine (when alpha adrenergic pressor effect of epi should be highest) will actually result in *decreased* vascular resistance --> decreased blood pressure due to irreversible alpha blockade and unupposed beta2 mediated vasodilation from the epi... to me first aid explanation makes more sense, how can you still get a partial pressor effect if a1 receptors are irreversibly blocked and now you are giving a drug with beta 2 adrenergic activity? Maybe I am missing something...

 

[tasar1898]

Maybe this particular patient had other factors in play?? normally FA is correct

 

[Polycherry]

after alpha blockade, if there is rapid infusion, partial pressor effect is seen, with time there is this vasomotor reversal (vasodilation). Because obviously you cant block ALL the alpha receptors. best image i could get 😛 Correct me if wrong!

 

[tasar1898]

makes sense.. hope they don't ask such pedantic details...

 

[Transposony]

makes sense.. hope they don't ask such pedantic details...

It's an important clinically relevant concept.
It is possible that they might ask this concept in a clinical setting.
For example:
You are managing a patient with Pheochromocytoma who is due for an laproscopic adrenalectomy. However, you notice that his BP is not controlled despite increasing doses of Phenoxybenzamine.
What is your next step in management:
1. Add prazosin
2. Add Labetalol
3. Add Propanolol
4. MIBG scan
5. Metyrosine

 

[tasar1898]

add labetalol / propranolol or a direct vasodilator [ CCB/K blocker/Hydralazine etc etc.. ] wouldn't be equal?? Whats the difference between propranolol and labetalol besides some extra a block with labetalol??

Edit : Or is the answer metyrosine to to completely block catecholamine synthesis?? ARGHH everything sounds good to me…

please explain ...

 

[tasar1898]

OHH i see now… don't give b blocker --> unopposed a effect like in cocaine… Can you explain prazosin vs metyrosine??

 

[Transposony]

add labetalol / propranolol or a direct vasodilator [ CCB/K blocker/Hydralazine etc etc.. ] wouldn't be equal?? Whats the difference between propranolol and labetalol besides some extra a block with labetalol??

Edit : Or is the answer metyrosine to to completely block catecholamine synthesis?? ARGHH everything sounds good to me…

please explain ...

I just made this question up to stress the point I was making.
You can rule out (1) since if it is not responding to one alpha blocker it is unlikely to respond to another alpha blocker.
You can also rule out (2) and (3) since you never give beta blockers in Pheochromocytoma until the BP is well controlled.
The answer is MIBG scan.
If the Pheochromocytoma is not responding to Phenoxybenzamine then you have to rule out metastasis.
OK , so, the MIBG scan shows multiple foci.

Now, what is your next step in management:
1. MRI Brain/Liver/Lungs
2. Rule out MEN 2 syndrome
3. FDOPA-PET scan
4. HED-PET scan
5. Metyrosine

 

[tasar1898]

Isn't that more like Step 2?? I guess give the damn metyrosine and rule out MEN 2 / VHL / NF syndromes via MRI ?? I have no clue what MIBG/FDOPA-PET / HED-PET scan is…

Edit : @Transposony Also why metastatic pheo won't respond to phenoxybenzamine?? Its not like you locally inject the drug ? Unless its just through huge dosage of catecholamines via widespread disease that overwhelms the phenoxy.. Would appreciate if you could answer when you have time

 

[Transposony]

Also why metastatic pheo won't respond to phenoxybenzamine?? Its not like you locally infuse the drug ? Unless its just through huge dosage of catecholamines via widespread disease that overwhelms the phenoxy.. Would appreciate if you could answer when you have time

Metyrosine is indicated in patients refractory to phenoxybenzamine.
Moreover, the catecholamine load is much higher in metastatic pheochromocytoma and you can't keep on giving higher and higher doses of phenoxybenzamine due to it's side effects.

 

[tasar1898]

Thanks , I hope they don't ask about these weird scans you mentioned..

 

[Transposony]

Thanks , I hope they don't ask about these weird scans you mentioned..

Unlikely for step 1.

 

[Brorthopedic]

Also, remember that, in general context, a low concentration of epinephrine causes vasodilation. However, at higher concentrations, it will act as a vasoconstriction.