Abstract

Approximate serum concentrations and systemic influences of lidocaine.

Cardiovascular influences of epinephrine. The graph is adapted from Hersh et al. ¹⁸ Average of cardiovascular changes were recorded following injection of 7 cartridges (11.9 mL) of articaine containing either 1 : 100,000 or 1 : 200,000 concentrations of epinephrine (∼120 and 60 μg respectively). Although actual changes were mild, consider that all volunteers were healthy young adults taking no medications. Even so, 2 volunteers experienced palpitations. Also note confirmation of the dose-dependent responses for 60 versus 120 μg.

Acetaminophen toxicity. The major portion of acetaminophen is metabolized to nontoxic metabolites excreted in urine. Only 5–15% is oxidized by cytochrome P450 (CYP 450) enzymes to a potentially toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). The normally small amounts of this metabolite are readily converted to harmless mercapturic acid conjugates by glutathione. When high doses of acetaminophen are consumed, glutathione can be depleted, allowing NAPQI to accumulate and produce hepatic necrosis. Also, normal biotransformation is diminished with compromised liver function, including that associated with malnutrition and alcohol abuse. Toxicity can be further accentuated by ethanol consumption, which induces CYP 450 activity, leading to greater portions of acetaminophen converted to NAPQI. Emergency management of acetaminophen overdose consists of administering high doses of acetylcysteine, which replenishes glutathione.