A 47-year-old female was brought to the emergency room by EMS after her husband found her unresponsive. He reports finding empty medication bottles but cannot remember which ones. She has a PMH of hypertension and atrial fibrillation. Her current medications include Cozaar 100 mg daily, Lopressor 50 mg BID, Eliquis 5 mg BID, and Tylenol 325 mg Q6h PRN.

Vitals/Labs

HR: 45 bpm

BP: 75/45 mmHg

RR: 17 

Temp: 38.2 C

Glucose: 60 mg/dL

The ED physician wants to order glucagon as one of the medications to manage the patient’s symptoms. Which of the following would glucagon be indicated for?

A. Tylenol

B. Lopressor

C. Eliquis

D. Cozaar

Answer with rationale

When confronted with an overdose, always treat the patient first by ensuring they have an airway–perform CPR if needed, and stop the exposure to the offending agent. Analgesics make up the majority of medication-related toxic exposures in adults and pediatrics, and Tylenol is the most common cause of drug-induced liver injury. When the conjugation pathways in the liver are saturated, the excess Tylenol is metabolized by CYP2E1 which converts it to NAPQI (a toxic metabolite). Glutathione is responsible for binding to NAPQI and converting it to a nontoxic conjugate that is excreted in the urine. When the glutathione stores are depleted, such as in patients with chronic alcohol use/abuse, NAPQI accumulates and causes cell injury and death.

Despite cardiovascular medications (i.e., beta blockers and calcium channel blockers) constituting a smaller percentage of overdoses, their toxic exposure can be life-threatening. Beta blockers (BBs) bind to beta receptors and prevent catecholamines, such as epinephrine, from binding and activating adenylyl cyclase. Adenylyl cyclase leads to the production of cyclic adenosine monophosphate (cAMP) which is responsible for increasing intracellular calcium and increasing heart rate and contractility. This is why BBs cause a decrease in heart rate and blood pressure. 

Activated charcoal can often be a good intervention if an overdose is caught early enough, and it should be given with sorbitol in order to clear the charcoal and the drug from the body. It is only indicated within a few hours of ingestion, and it is most effective within one hour to decrease the absorption of a drug. Furthermore, it is contraindicated if the patient has a bowel obstruction or is unconscious, as the patient’s airway must be protected in order to prevent aspiration.

Answer A is incorrect. N-acetylcysteine (NAc) is the preferred antidote in Tylenol overdose because it restores glutathione in order to prevent hepatotoxicity. There is no evidence of glucagon being used for Tylenol overdose.

Answer B is correct. Glucagon binds to glucagon receptors in order to activate adenylyl cyclase. Unlike catecholamines, glucagon does not have to compete with Lopressor for beta receptors in order to activate the pathway that increases heart rate and contractility. Therefore, glucagon would be a good option in this patient considering the likelihood that she is experiencing a BB overdose. While inhaled glucagon exists, it is used for low blood sugar. For cases of beta blocker overdose, intravenous glucagon would be used. 

Answer C is incorrect. Direct-oral-anticoagulants (DOACs) that inhibit factor Xa, such as Eliquis and Xarelto, can be reversed by Andexxa in the event of an overdose. This patient is not exhibiting signs of bleeding, so this agent would not be indicated.  

Answer D is incorrect. There is no specific antidote for this class of agents. The most appropriate supportive care in an angiotensin receptor blocker overdose will depend on the patient’s symptoms and may include fluid resuscitation, vasopressors, IV angiotensin II, and hyperkalemia management. 

Brand/Generic: Andexxa (andexanet alfa), Baqsimi (intranasal glucagon for hypoglycemia), Cozaar (losartan potassium), Eliquis (apixaban), Kcentra (prothrombin complex concentrate), Lopressor (metoprolol tartrate), Tylenol (acetaminophen), Xarelto (rivaroxaban)

NAPLEX Content Domains Covered:

1.A.1 Pharmacology

2.A.1 Drug names and therapeutic classes

2.A.2 Indications, usage, and dosing regimens

3.C.2 Appropriateness of therapy

3.C.6 Toxicologic exposures and overdoses