Articaine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Articaine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Articaine HCl is an amide local anesthetic. Local anesthetics block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of the affected nerve fibers. Epinephrine is a vasoconstrictor added to articaine HCl to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Articaine HCl is an amide local anesthetic.
Local anesthetics block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential.
In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of the affected nerve fibers.
Epinephrine is a vasoconstrictor added to articaine HCl to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
12.2 Pharmacodynamics Clinically, the order of loss of nerve function is as follows: pain; temperature; touch; proprioception; and skeletal muscle tone.
The onset of anesthesia has been shown to be within 1 to 9 minutes of injection of Articaine HCl and Epinephrine.
Complete anesthesia lasts approximately 1 hour for infiltrations and up to approximately 2 hours for nerve block.
Administration of Articaine HCl and Epinephrine results in a 3- to 5-fold increase in plasma epinephrine concentrations compared to baseline; however, in healthy adults it does not appear to be associated with marked increases in blood pressure or heart rate, except in the case of accidental intravascular injection [see Warnings and Precautions ].
12.3 Pharmacokinetics Absorption: Following dental injection by the submucosal route of an articaine solution containing epinephrine 1:200,000, articaine reaches peak blood concentration about 25 minutes after a single dose injection and 48 minutes after three doses.
Peak plasma levels of articaine achieved after 68 and 204 mg doses are 385 and 900 ng/mL, respectively.
Following intraoral administration of a near maximum dose of 476 mg, articaine reaches peak blood concentrations of 2037 and 2145 ng/mL for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively, approximately 22 minutes post-dose.
Distribution: Approximately 60 to 80% of articaine HCl is bound to human serum albumin and γ-globulins at 37°C in vitro .
Elimination Metabolism: Articaine HCl is metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive.
In vitro studies show that the human liver microsome P450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid.
Excretion: At the dose of 476 mg of articaine, the elimination half-life was 43.8 minutes and 44.4 minutes for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively.
Articaine is excreted primarily through urine with 53-57% of the administered dose eliminated in the first 24 hours following submucosal administration.
Articainic acid is the primary metabolite in urine.
A minor metabolite, articainic acid glucuronide, is also excreted in urine.
Articaine constitutes only 2% of the total dose excreted in urine.
Pharmacokinetics
12.3 Pharmacokinetics Absorption: Following dental injection by the submucosal route of an articaine solution containing epinephrine 1:200,000, articaine reaches peak blood concentration about 25 minutes after a single dose injection and 48 minutes after three doses. Peak plasma levels of articaine achieved after 68 and 204 mg doses are 385 and 900 ng/mL, respectively. Following intraoral administration of a near maximum dose of 476 mg, articaine reaches peak blood concentrations of 2037 and 2145 ng/mL for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively, approximately 22 minutes post-dose. Distribution: Approximately 60 to 80% of articaine HCl is bound to human serum albumin and γ-globulins at 37°C in vitro . Elimination Metabolism: Articaine HCl is metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive. In vitro studies show that the human liver microsome P450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid. Excretion: At the dose of 476 mg of articaine, the elimination half-life was 43.8 minutes and 44.4 minutes for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively. Articaine is excreted primarily through urine with 53-57% of the administered dose eliminated in the first 24 hours following submucosal administration. Articainic acid is the primary metabolite in urine. A minor metabolite,