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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.
Clinically, the order of loss of nerve function is as follows: (1) pain; (2) temperature; (3) touch; (4) proprioception; and (5) skeletal muscle tone.
The onset of anesthesia has been shown to be within 1 to 9 minutes of injection of Septocaine® (articane hcl and epinephrine injection) . Complete anesthesia lasts approximately 1 hour for infiltrations and up to approximately 2 hours for nerve block.
Administration of Septocaine® (articane hcl and epinephrine injection) 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].
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.
Approximately 60 to 80% of articaine HCl is bound to human serum albumin and γ-globulins at 37°C in vitro.
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.
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.
No studies have been performed to evaluate the pharmacokinetics of Septocaine® (articane hcl and epinephrine injection) injection in pediatric subjects. There is insufficient information to determine whether the pharmacokinetics of Septocaine® (articane hcl and epinephrine injection) injection differs by race.
Three randomized, double-blind, active-controlled studies were designed to evaluate effectiveness of Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:100,000 as a dental anesthetic. Patients ranging in age from 4 years to over 65 years old underwent simple dental procedures such as single uncomplicated extractions, routine operative procedures, single apical resections, and single crown procedures, or complex dental procedures such as multiple extractions, multiple crowns and/or bridge procedures, multiple apical resections, alveolectomies, muco-gingival operations, and other surgical procedures on the bone. Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:100,000 was administered as submucosal infiltration and/or nerve block. Efficacy was measured immediately following the procedure by having the patient and investigator rate the patient's procedural pain using a 10 cm visual analog scale (VAS), in which a score of zero represented no pain and a score of 10 represented the worst pain imaginable. Mean patient and investigator VAS pain scores were 0.3-0.4 cm for simple procedures and 0.5-0.6 cm for complex procedures.
Four randomized, double-blind, active-controlled studies were performed comparing Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:100,000 versus Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:200,000. The first two studies used electric pulp testers (EPT) to evaluate the success rate (maximum EPT value within 10 minutes), onset, and duration of Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:100,000 versus Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:200,000 and articaine solution without epinephrine in healthy adults between 18 and 65 years old. Results indicated that the anesthetic characteristics of the 1:100,000 and 1:200,000 formulations are not significantly different.
A third study compared the difference in visualization of the surgical field after administration of Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:100,000 versus Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:200,000 during bilateral maxillary periodontal surgeries in patients ranging from 21 to 65 years old. Septocaine® (articane hcl and epinephrine injection) containing epinephrine 1:100,000 provided better visualization of the surgical field and less blood loss during the procedures. In a fourth study, designed to assess and compare cardiovascular safety, when the maximum dose of each formulation was administered, no clinically relevant differences in blood pressure or heart rate between formulations were observed.
Kaplan, EL, editor. Cardiovascular disease in dental practice. Dallas; American Heart Association; 1986.
Last reviewed on RxList: 3/12/2010
This monograph has been modified to include the generic and brand name in many instances.
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