Metoprolol and epinephrine interaction in dental local anesthesia

4.1. Clinical Management Strategies

The DDIs identified by the DrugBank DDI checker analysis in our dental patient dataset revealed several major interactions between medications commonly used in dental procedures and those prescribed for underlying systemic conditions. Epinephrine, frequently used in dental local anesthetics, appears in multiple high-risk pairs with beta-blockers (e.g., nebivolol, metoprolol, atenolol, bisoprolol, carvedilol); these DDIs present substantial risks for patients with cardiovascular comorbidities, potentially exacerbating hypertension—the local anesthetics containing epinephrine require cautious administration in patients on cardiovascular medications [5,22,23,40,50]. Epinephrine in dental anesthesia should be used at the lowest effective concentration, tailored to each patient’s clinical profile, as even low doses can influence cardiovascular function. Guimaraes et al. confirm that locally administered epinephrine can cause transient but clinically significant systemic effects, especially in sensitive individuals or those taking beta-blockers, even with proper technique, due to its vasoconstrictive properties [50].

Unveiling Drug-Drug Interactions in Dental Patients: A Retrospective Real-World Study. © 2025 by the authors. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

4.1. Clinical Management Strategies

Notably, around 20% of intraoral injections may transiently elevate systemic adrenaline levels, potentially contributing to complications such as ischemic events, arrhythmias, tremors, glycemic shifts, and exacerbation of drug interactions; these effects arise both from direct stimulation of adrenergic receptors and indirect disturbances in potassium balance [51]. Psychological stress from anticipating dental injections can also activate the sympathetic nervous system, mimicking epinephrine’s cardiovascular effects [51]. Therefore, some observed cardiovascular responses may reflect anxiety rather than solely drug interactions, further emphasizing the complexity of assessing epinephrine-DDIs in dental settings. In this context of potential epinephrine-associated DDIs, a practical and safe management strategy in dental settings is using mepivacaine, a well-tolerated and alternative local anesthetic [52]; although mepivacaine does possess mild vasoconstrictive properties, it may present a safer alternative in patients treated with beta-blockers, as it avoids the potent sympathomimetic effects of epinephrine [53].

Unveiling Drug-Drug Interactions in Dental Patients: A Retrospective Real-World Study. © 2025 by the authors. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

7. Use of Local Anaesthetics with Vasoconstrictor

(a) Unstable angina (b) Recent myocardial infarction (c) Recent coronary artery bypass surgery (d) Refractory arrhythmias (e) Untreated or uncontrolled severe hypertension (f) Untreated or uncontrolled congestive heart failure Also, it is contraindicated to use epinephrine impregnated retraction cords, intraligamentary, and intrabony injections in these patients due to adverse hydrodynamic effects similar to I.V. epinephrine injection [168]. Though local anesthetics can lead to a decrease in the rate of amide metabolism in hypertensive patients taking beta-blockers [15], generally non-epinephrine-containing local anesthetics do not have significant drug interactions [169]. Drug interactions mostly stem from the incorporated vasoconstrictor [169]. For example, epinephrine can interact with commonly used antihypertensives like non-selective beta-blockers causing significant hypertensive episodes [170] and reflex bradycardia [15]. Though the response is dose-dependent and rarely seen in dental clinics, the dentist must be careful in using vasoconstrictors in patients with significant cardiac disease due to the serious sequelae of this drug combination. Agents like clonidine [171] and dexmedetomidine [172] can be used as safer alternatives to epinephrine with the local anesthetic solution in hypertensive patients. In such patients, it can also be prudent to use lidocaine, prilocaine, and mepivacaine solutions without vasoconstrictor [173].

Dental Management Considerations for Patients with Cardiovascular Disease—A Narrative Review. Copyright: © 2022 The Author(s). Published by IMR Press. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).