Take Home Points
- Methylxanthines are a drug class that includes caffeine, theophylline, and theobromine.
- The three main mechanisms that account for the clinical presentation of methylxanthine toxicity are: catecholamine release, adenosine antagonism, and phosphodiesterase inhibition.
- Beta agonism will lead to hyperlactatemia, hypokalemia, hyperglycemia, and tachycardia. Adenosine antagonism may lead to seizures and/or supraventricular tachycardia that is unresponsive to pushes of adenosine. Phosphodiesterase inhibition may lead to peripheral vasodilation and a wide pulse pressure (ie. blood pressures of 120/30 mmHg) and possible hypotension.
- Treatment includes activated charcoal if the patient can tolerate PO. Short acting beta or calcium blockers such as esmolol or diltiazem may be useful in order to reduce the heart rate and increase filling time and thus peripheral perfusion. Hemodialysis should also be considered in cases of refractory shock, dysrhythmias, or seizures.
REBEL Core Cast 105.0 – Methylxanthine Toxicity
Definition and Physiology
- Historically, methylxanthines (caffeine, theophylline, and theobromine) were frequently used to treat lung disease such as asthma/COPD due to their beta-agonism. However, given their multitude of side effects, they have generally been replaced by more targeted treatment such as beta-2 agonists (ie. albuterol) and anti-cholinergics (ie. ipratropium). Caffeine is still used today in neonatal ICUs for apnea in preterm infants.
- In today’s world, methylxanthine toxicity often manifests in the context of significant coffee or “energy drink” intoxication – which specifically is caffeine mediated.
- The three major mechanisms of methylxanthines include: beta-agonism, adenosine antagonism, and phosphodiesterase inhibition.
Clinical Manifestations
- Beta agonism will lead to hyperlactatemia, hypokalemia, hyperglycemia, and tachycardia. Many patients will also exhibits tremulousness, nausea, vomiting, and diarrhea.
- Adenosine antagonism may lead to supraventricular tachycardia that is unresponsive to pushes of adenosine. It is critical to note that adenosine is also the body’s endogenous anti-convulsant. (Eldridge 1989) Thus adenosine antagonism may lead seizures and/or status epilepticus.
- Phosphodiesterase inhibition may lead to peripheral vasodilation and a wide pulse pressure (ie. blood pressures of 120/30 mmHg) and possible hypotension.
Management
- Activated charcoal is a mainstay of treatment in order to reduce systemic absorption if the patient can tolerate PO. Methylxanthines undergo enterohepatic circulation – they are metabolized by the liver, secreted into the bile, stored in the gallbladder, and then re-released back into the gut. Which means even if they are not in the gut in real time, charcoal will enhance elimination by drawing it out of circulation – a concept known as “gut dialysis.” (Berlinger 1983)
- Hemodynamics should be supported by a judicious amount of crystalloid, alpha agonism (ie. phenylephrine), and short acting beta/calcium channel blockers in the setting of supraventricular tachycardia.
- Don’t forget to correct electrolyte abnormalities in the context of beta-agonism.
- Lastly, for patients in refractory shock or seizures or with life-threatening dysrhythmias, hemodialysis should be considered.3
References
- Eldridge FL, Paydarfar D, Scott SC, Dowell RT. Role of endogenous adenosine in recurrent generalized seizures. Exp Neurol. 1989 Feb;103(2):179-85. doi: 10.1016/0014-4886(89)90080-0. PMID: 2912762.
- Berlinger WG, Spector R, Goldberg MJ, Johnson GF, Quee CK, Berg MJ. Enhancement of theophylline clearance by oral activated charcoal. Clin Pharmacol Ther. 1983 Mar;33(3):351-4. doi: 10.1038/clpt.1983.44. PMID: 6337763.
- https://www.extrip-workgroup.org/theophylline
Resources
- Post Created By: Sanjay Mohan, MD
- Post Peer Reviewed By: Anand Swaminathan MD, MPH (Twitter @EMSwami)
Cite this article as: Anand Swaminathan, "REBEL Core Cast 105.0 – Methylxanthine Toxicity", REBEL EM blog, July 26, 2023. Available at: https://rebelem.com/rebel-core-cast-105-0-methylxanthine-toxicity/.