Propranolol with Epinephrine Interaction Details

Brand Names Associated with Propranolol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

Hypertension, bradycardia, resistance to epinephrine in anaphylaxis

Interaction Summary

The concomitant use of epinephrine, a sympathomimetic agent, and propranolol, a nonselective beta-adrenergic antagonist, may result in severe and prolonged hypertension due to unopposed alpha-receptor stimulation. Concomitant use of epinephrine and propranolol should be avoided, however, if concurrent therapy is necessary, the patient should be closely monitored . Propranolol may also cause resistance to epinephrine in cases of anaphylaxis . Glucagon, which has some sympathomimetic effects mediated through cAMP activity that is not beta-receptor linked, has been effective in cases of resistant anaphylactic shock .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Concomitant use of epinephrine and propranolol should be avoided; however, if concomitant therapy is necessary, carefully monitor patient for severe and prolonged hypertension. If a nonselective beta blocker causes resistance to epinephrine in anaphylactic shock, glucagon may be effective. The adult glucagon dose is 1 to 5 mg IV over 5 minutes followed by an infusion of 5 to 15 mcg/min titrated to response; the pediatric dose is 20 to 30 mcg/kg (maximum 1 mg) IV over 5 minutes followed by an infusion of 5 to 15 mcg/min titrated to response .

Mechanism Of Interaction

Unopposed alpha-receptor stimulation

Literature Reports

A) Following inhalation therapy with epinephrine, concurrent propranolol administration may inhibit epinephrine-induced bronchodilatation (mediated through beta-2 receptors) and increase the patient's blood pressure (due to unopposed alpha stimulation), especially if the epinephrine dose is repeated. Epinephrine failed to reverse an anaphylactic reaction to a maintenance allergy injection in a patient on chronic oral propranolol. Intubation, neuromuscular blockade, antihistamine, and steroids were used during supportive care . Cardioselective beta blockers (atenolol, metoprolol, acebutolol), however, appear to have little effect on the pressor response to epinephrine and low doses are not likely to interfere with epinephrine-induced bronchodilatation. The effect of larger doses on bronchodilatation produced by epinephrine is not well studied at this time .

B) Acute hypertension followed by a reflex bradycardia can occur during combined propranolol (or other nonselective beta-blockers) and epinephrine therapy . The hypertensive effect is related to blocking of beta-receptors resulting in alpha-receptor dominance and a paradoxical hypertension. Bradycardia represents a secondary reflex cardiac response mediated by vagally-innervated aortic arch and carotid baroreceptors. Propranolol results in this latter effect by inhibiting the ability of the cardiovascular system to respond appropriately to this added stress. Elevated peripheral resistance increases the work load of the myocardium, and it is unable to be stimulated to increase its output, thus resulting in reflex bradycardia. This sequence of events may result in cardiac arrest or hypertensive stroke .

C) Propranolol pretreatment followed by epinephrine infusion was reported to lower the pulse rate to 30 beats per minute with first- and second-degree AV block in a healthy 22-year-old male . In 4 hypertensive patients and 5 normal subjects, epinephrine alone (0.4 mg subcutaneously) produced an increase in heart rate and minimal effects on blood pressure; but with propranolol pretreatment (40 mg orally), epinephrine produced a 20 to 40 mmHg rise in blood pressure and a 23 to 26 beats per minute decrease in heart rate .

D) An interaction was demonstrated in a hemodynamic study evaluating the effect of low-dose epinephrine (in an attempt to simulate situations of daily life stress) on patients receiving either propranolol or metoprolol. Epinephrine was infused at graded rates of 0.5, 1, 2, and 4 mcg/min, with each dose sustained for 8 minutes. While the hypertensive patients were maintained on propranolol 80 mg/day, low-dose epinephrine infusion caused a marked rise in systolic as well as diastolic blood pressure and decreases in heart rate. However, when patients were maintained on metoprolol 100 mg daily, epinephrine infusion induced only a slight rise in blood pressure and an increase in heart rate. The effect of epinephrine may have relevance in the choice of which beta-blocker should be used for the treatment of hypertension. Metoprolol, because it is selective for beta-1 receptor blockade, appears to be a better choice than propranolol in the treatment of hypertension .

Propranolol Overview

• Propranolol is used to treat high blood pressure, irregular heart rhythms, pheochromocytoma (tumor on a small gland near the kidneys), certain types of tremor, and hypertrophic subaortic stenosis (a heart muscle disease). It is also used to prevent angina (chest pain), migraine headaches, and to improve survival after a heart attack. Propranolol is in a class of medications called beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.