Objective: Adrenaline (epinephrine) is routinely combined with local anaesthetic agents in dentistry to prolong pulpal and soft-tissue anaesthesia, reduce systemic toxicity of the anaesthetic base, and improve haemostasis at the surgical site. Despite this, many clinicians restrict or avoid its use in patients with hypertension, ischaemic heart disease, arrhythmia, diabetes mellitus, thyroid disease and other systemic conditions, out of a belief that the drug poses a meaningful systemic cardiovascular or metabolic risk. This review examines the pharmacological and clinical evidence for the systemic safety of adrenaline-containing dental local anaesthetics in patients with common comorbidities. Methods: A narrative review of the pharmacokinetic and pharmacodynamic literature on adrenaline, together with clinical trials, systematic reviews and evidence reports addressing the cardiovascular, endocrine and pharmacological safety of epinephrine-containing dental local anaesthetics, was undertaken using PubMed/MEDLINE, ScienceDirect, and the Agency for Healthcare Research and Quality evidence library. English-language systematic reviews, randomised and prospective clinical studies, and authoritative pharmacology references published up to 2024 were included. Results: The mass of adrenaline delivered in one to two standard dental cartridges (0.009-0.036 mg at 1:100,000 or 1:80,000 concentration) is far below the therapeutic doses used for anaphylaxis or cardiac arrest (0.3-1.0 mg) and is rapidly inactivated by monoamine oxidase and catechol-O-methyltransferase, with a plasma half-life of only a few minutes. Systematic reviews in hypertensive and coronary disease patients report only small, clinically insignificant changes in blood pressure and heart rate, with no serious adverse cardiovascular events attributable to correctly administered epinephrine-containing anaesthesia. Controlled trials in heart failure, diabetes mellitus and coronary artery disease similarly demonstrate haemodynamic and metabolic stability. The principal, well-documented systemic hazard is a pharmacodynamic interaction with non-selective beta-adrenergic blocking agents, and true contraindication is limited to decompensated or uncontrolled endocrine disease such as unstable hyperthyroidism or pheochromocytoma. Conclusion: When administered within recommended dose limits, using an aspirating technique and appropriate patient selection, adrenaline in dental local anaesthesia does not produce clinically meaningful systemic harm even in patients with common cardiovascular, endocrine or other systemic comorbidities. Withholding adrenaline in these patients is frequently more hazardous than its judicious use, because it results in inadequate anaesthesia and a larger, uncontrolled release of endogenous catecholamines in response to pain and stress.

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