PHARMACOKINETIC AND PHARMACODYNAMIC ALTERATIONS OF LOCAL ANESTHETICS IN PATIENTS WITH SYSTEMIC DISORDERS: A NARRATIVE REVIEW

INTRODUCTION: The pharmacokinetics, metabolism, and bioavailability of local anesthetics are well established to date. However, in individuals with concomitant systemic diseases, these parameters may undergo significant alterations. AIM: To analyze the influence of hepatic, renal, cardiovascular, and endocrine comorbidities on the bioavailability, metabolism, and pharmacokinetics of local anesthetics used in dental practice. MATERIALS AND METHODS: A narrative review was conducted using relevant data from electronic databases including PubMed, Google Scholar, and the Cochrane Library, from 2019 to 2025. DISCUSSION: Hepatic dysfunction and Gilbert's syndrome reduce the activity of hepatic microsomal enzymes, leading to elevated plasma concentrations of active metabolites and increased systemic toxicity. In renal disease, elevated levels of alpha-1-acid glycoprotein decrease the concentration of unbound local anesthetics, thereby reducing anesthetic efficacy while promoting drug accumulation and systemic toxicity. Cardiovascular disorders impair hepatic perfusion and cardiac output, prolonging the elimination half-life and increasing the risk of cardiotoxicity. Hyperthyroidism accelerates metabolism and shortens the duration of anesthetic action, whereas hypothyroidism and diabetes mellitus slow drug clearance, alter plasma protein binding, and enhance systemic toxicity. CONCLUSION: Since systemic diseases can significantly modify the bioavailability, metabolism, and pharmacokinetics of local anesthetics, anesthetic protocols should be individualized for each patient based on their specific comorbid condition and metabolic status.