Pharmacy Consult: Beta Blockers and Epinephrine

I had an interesting discussions in the ED the otherday when I was talking about the importance of administering epi via IM for anaphylaxis.  Is there a diminished response to epi if a patients is on a beta-blocker?

Let’s clarify: patients on chronic non-selective beta-blocker therapy may have a blunted effect of epinephrine in anaphylaxis but epinephrine administration may also result in profound hypertension and bradycardia or heart block.

Non-selective beta-blockers will blunt the bronchodilatory effects of epinephrine causing a sort of “resistance” to epinephrine in anaphylaxis. The same will hold true if epi is administered via nebulization or albuterol is given. If a patient is on chronic cardioselective beta-blocker therapy, this is generally not a concern, unless they’re on a high dose since these agents loose selectivity (for metoprololgreater than 100mg/day will do the trick). Alternatively, glucagon (1-5mg IV) can be given since it has sympathomimetic activity through cAMP, not alpha or beta receptor activation.

The mechanisms at play causing a significant blood pressure elevations and bradycardia share similarities. In this case, an unopposed alpha-adrenergic receptor activation causes profound vasoconstriction. Normally, epinephrine activates both alpha 1,2 and beta 1,2. Though the alpha activation leads to vasoconstriction, there is a balance of beta 2 mediated vasodilation. But by blocking this beta 2 activation you’ll have unchecked alpha 1 mediated vasoconstriction. The resulting effects are significant increases in blood pressure and subsequent reflex (vagally mediated) bradycardia. Again, in cases where the patients are on chronic cardioselective beta-blocker therapy, this effect is generally not observed if they’re on normal beta-blocker doses. Here is an interesting case report highlighting the concern.

Non-Selective (beta 1 and beta 2)	Cardioselective (beta 1)
Carteolol Carvedilol (has additional α-blocking activity) Labetalol (has additional α-blocking activity) Nadolol Penbutolol Pindolol Propranolol Sotalol (but really a class III antiarrhythmic) Timolol	Acebutolol Atenolol Betaxolol Bisoprolol Esmolol Metoprolol Nebivolol

Epinephrine IM for Anaphylaxis

Epinephrine dosing and administration for anaphylaxis can be a tricky situation. In a strange, non-conformist type of stubbornness, the concentration parenteral epinephrine products are listed as a ratio (1:1000 vs 1:10,000 vs 1:100,000), rather than a percentage. There have been numerous reports, and personal experiences, where patients end up getting a significant overdose, or underdose of epi from miscommunication, dosing error or picking the wrong ampule/vial/syringe.

An often-overlooked administration (won’t call it an error) issue is administering epinephrine for anaphylaxis SubQ. When epi is administered SubQ, its alpha agonist properties (vasoconstriction) predominate, limiting blood flow to the area and therefore absorption into systemic circulation.

When administered IM, on the other hand, the beta-2 agonist properties (vasodilation) predominate in skeletal muscle, allowing for rapid absorption.  Importantly, the site of IM administration plays a large role: the preferred site for IM administration being the vastus lateralis.