Situation: A 52-year-old man weighing 62 kg receives his first intravenous (IV) dose of an antibiotic in the emergency department. Within 5 minutes he develops generalized hives, lip swelling, wheezing, and a blood pressure of 78/50 mmHg. The nurse stops the infusion and calls for help. His home medications are metoprolol, amlodipine, metformin, and atorvastatin. Fifteen minutes later, after two intramuscular doses of adrenaline and 2 L of IV crystalloid, his blood pressure is 76/48 mmHg and he is still wheezing. Considering his home medications, which drug should the nurse anticipate next?

Beta blockers such as metoprolol can make anaphylaxis resistant to adrenaline. Glucagon raises cyclic AMP without using beta receptors and is the recommended addition for clients on beta blockers who do not respond. Corticosteroids are adjuncts that act too slowly to treat refractory shock.

Pathophysiology of Beta-Blocker–Induced Epinephrine Resistance

Anaphylaxis produces vasodilation, increased vascular permeability, bronchoconstriction, and hypotension through massive release of histamine, tryptase, leukotrienes, and other mediators from mast cells and basophils. Epinephrine reverses these effects primarily by stimulating beta-1 receptors (increasing cardiac contractility and heart rate), beta-2 receptors (bronchodilation, reducing mediator release), and alpha-1 receptors (vasoconstriction). When a patient takes a nonselective or cardioselective beta blocker such as metoprolol, those beta receptors are occupied and cannot respond to endogenous catecholamines or to administered adrenaline. The alpha-mediated vasoconstriction may still occur, but the cardiac and bronchial responses are blunted. The result is a clinical picture of persistent hypotension and wheezing that does not improve after repeated doses of adrenaline, exactly as described in this scenario ^[1][2].

Watch out! The patient’s blood pressure remains 76/48 mmHg after two intramuscular doses of adrenaline and 2 L of crystalloid. This is refractory anaphylactic shock, not a simple delayed response. Beta blockade is the most likely explanation because metoprolol is on his home medication list.

Why Glucagon Is the Next Anticipated Drug

Glucagon is a polypeptide hormone that activates glucagon receptors on cardiac myocytes and vascular smooth muscle. These receptors are coupled to Gs proteins, which stimulate adenylyl cyclase and increase intracellular cyclic AMP (cAMP). The critical point is that glucagon raises cAMP through a receptor pathway that does not require beta-adrenergic receptors. In a patient whose beta receptors are blocked by metoprolol, glucagon can still produce positive inotropic and chronotropic effects on the heart and can help relax bronchial smooth muscle. This bypass mechanism is why glucagon is recommended as an adjunct when anaphylaxis is refractory to adrenaline in the setting of beta-blocker use ^[1].

The dosing in this context is typically an intravenous bolus of 1 to 5 mg in adults, followed by an infusion if needed. The question asks which drug to anticipate next, and glucagon by IV bolus is the correct choice because it directly addresses the pharmacologic blockade that is preventing adrenaline from working.

Why the Other Options Are Incorrect

Drug	Mechanism	Why It Is Not the Next Step
Atropine	Muscarinic acetylcholine receptor antagonist; increases heart rate by blocking vagal tone	Atropine does not increase cAMP, does not improve myocardial contractility, and does not reverse beta-receptor blockade. It may raise heart rate slightly but will not correct the profound vasodilation or bronchospasm of anaphylaxis.
Calcium gluconate	Provides calcium ions for myocardial and vascular smooth muscle contraction	Calcium is used for hyperkalemia, hypocalcemia, or calcium channel blocker toxicity. It has no role in reversing beta-blocker-induced epinephrine resistance and does not address the cAMP-mediated pathway needed here.
Methylprednisolone	Corticosteroid; suppresses gene transcription and reduces late-phase inflammatory mediator production	Corticosteroids act over hours, not minutes. They are useful for preventing biphasic or protracted reactions but cannot rescue a patient who is currently in refractory shock. Giving methylprednisolone now would not raise blood pressure or relieve wheezing in time .

Clinical Reasoning and Priority

The sequence of care in anaphylaxis begins with stopping the trigger, calling for help, administering intramuscular adrenaline, and providing rapid IV crystalloid. When the patient remains hypotensive and wheezing despite these measures, the nurse must reassess for factors that make the reaction refractory. Key point! A home medication list that includes a beta blocker is a red flag for adrenaline resistance. The next pharmacologic intervention should target the mechanism of resistance, which is beta-receptor blockade. Glucagon is the only option listed that does this.

The evidence supports this approach. Case reports and reviews describe anaphylactic shock in patients on beta blockers as characterized by severe hypotension and bradycardia resistant to adrenaline, and they identify glucagon as a therapeutic option because it stimulates cAMP independently of beta receptors ^[2]. More recent analyses also note that beta-blocker use is associated with refractory anaphylaxis and that alternative vasopressors or glucagon may be required ^[1]. Although the evidence is not from large randomized trials, the pharmacologic rationale is consistent across sources and aligns with the expected answer.

Watch out! Do not confuse the treatment of beta-blocker overdose with the treatment of anaphylaxis in a beta-blocked patient. In beta-blocker overdose, glucagon is also used for its inotropic effects, but the dose is often higher and given as a continuous infusion. In anaphylaxis, the goal is a rapid IV bolus to restore cAMP signaling and support blood pressure while other resuscitative measures continue .