Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1) Pharmacodynamic properties:
Pharmacotherapeutic group: Nervous System / Anaesthetics / Local anaesthetics / Amides / Mepivacaine.
ATC code: N01 BB 03
Mepivacaine stabilizes the neuronal membrane and prevents the initiation and transmission of nerve impulses, thereby effecting local anesthesia.
Mepivacaine is rapidly metabolized, with only a small percentage of the anesthetic (5 to 10 percent) being excreted unchanged in the urine. Mepivacaine because of its amide structure, is not detoxified by the circulating plasma esterases. The liver is the principal site of metabolism, with over 50 percent of the administered dose being excreted into the bile as metabolites. Most of the metabolized Mepivacaine is probably resorbed in the intestine and then excreted into the urine since only a small percentage is found in the feces. The principal route of excretion is via the kidney. Most of the anesthetic and its metabolites are eliminated within 30 hours. It has been shown that hydroxylation and N-demethylation, which are detoxification reactions, play important roles in the metabolism of the anesthetic. Three metabolites of Mepivacaine have been identified from adult humans: two phenols, which are excreted almost exclusively as their glucuronide conjugates, and the N-demethylated compound (2’, 6’ - pipecoloxylidide).
The onset of action is rapid (30 to 120 seconds in the upper jaw; 1 to 4 minutes in the lower jaw) and Mepivacaine HCl 3% (30 mg/mL) will ordinarily provide operating anesthesia of 20 minutes in the upper jaw and 40 minutes in the lower jaw.
Mepivacaine does not ordinarily produce irritation or tissue damage.
Mechanism of action: Mepivacaine is an amide local anaesthetic. Mepivacaine reversibly inhibits the conduction of nerve impulses by decreasing or blocking sodium (Na+) flow during propagation of the nerve action potential. As the anaesthetic action progressively develops in the nerve, the threshold for electrical excitability gradually increases, the rate of rise of the action potential declines and impulse conduction slows. Mepivacaine has a rapid onset, a high potency of anaesthesia and a low toxicity.
The mepivacaine displays slight vasoconstrictive properties leading to a longer duration of action than with most other local anesthetics when administered without a vasoconstrictor. Studies revealed, that mepivacaine has vasoconstrictive properties. This property could be beneficial when the use of vasoconstrictor is contraindicated. Several factors such as pH of tissue, pKa, lipid solubility, local anaesthetic concentration, diffusion in the nerve of local anaesthetic, etc., may influence the onset and the duration of the local anaesthetic.
Onset of action: When a dental peripheral nerve block is performed, mepivacaine effect occurs rapidly (generally within 3 to 5 minutes).
Analgesia duration: Pulp anaesthesia generally lasts approximately 25 minutes after maxillary infiltration and around 40 minutes after inferior alveolar block, whereas anaesthesia of soft tissue was maintained around up to 90 minutes after maxillary infiltration and approximatively 165 minutes after inferior alveolar nerve block.
Bioavailability: The bioavailability is 100% at the action site.

Pharmacokinetic Properties