Classification:
Anesthetics
Local Anesthetics
Amide local anesthetics

Oropharyngeal Agents
Local Anesthetics

Oropharyngeal Agents
Local Anesthetics
Amide local anesthetics

NOTE: Bupivacaine in combination with epinephrine is discussed in a separate monograph.

Description: Bupivacaine is a long-acting local anesthetic of the amide type recommended for local or regional anesthesia. Bupivacaine's onset of action is rapid (1—10 minutes), and its duration is significantly longer (3—9 hours) than other commonly used local anesthetics. Also, analgesia persists longer than anesthesia, which postpones the need for postoperative narcotics. Bupivacaine is available in multiple forms including sterile isotonic solutions with or without the preservative methyl paraben, and hyperbaric solutions consisting of bupivacaine hydrochloride in dextran. All forms are available with epinephrine. Bupivacaine received FDA approval in 1972.

Mechanism of Action: Like all local anesthetics, bupivacaine causes a reversible nerve-conduction blockade by decreasing nerve membrane permeability to sodium. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade effects all nerve fibers in the following sequence: autonomic, sensory, and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by injecting the local anesthetic solution subcutaneously, intradermally, or submucosally around the nerve trunks or ganglia supplying the area to be anesthetized. Bupivacaine's effect on motor function varies with concentration. Specifically, when used for epidural, caudal, or peripheral nerve block, the 0.25% solution results in incomplete motor block, the 0.5% solution results in moderate muscle relaxation only, and the 0.75% solution provides complete muscle relaxation.

Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported. Toxic blood concentrations depress cardiac conduction and excitability, which may lead to AV block, ventricular arrhythmia, and cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Local anesthetics can produce central nervous system stimulation, depression, or both following systemic absorption. CNS stimulation is usually manifested as restlessness, tremors, and shivering progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest. However, local anesthetics have a primary depressant effect on the medulla and higher centers. The depressed stage may occur without the prior excitatory stage.

Pharmacokinetics: Bupivicaine is administered parenterally. Absorption depends on the dose, concentration, route of administration, tissue vascularity, and degree of vasodilation surrounding the area of injection. The use of preparations containing a vasoconstrictor will counteract the vasodilation produced by bupivacaine. This will slow the rate of absorption, prolong the duration of action, and maintain hemostasis.

After injection for caudal, epidural, or peripheral nerve block, peak blood levels are achieved in 30—45 minutes. Bupivacaine's onset of action is rapid (1—10 minutes), and it is significantly longer lasting than other commonly used local anesthetics (3—9 hours). Bupivacaine is distributed to all tissues, with a high concentration in well-perfused organs such as the liver, lung, heart, and brain. Bupivacaine is metabolized primarily in the liver via conjugation and excreted renally, with approximately 5% being excreted unchanged. Its half-life is 3.5 ± 2 hours in adults and 8.1 hours in neonates.


Drug Information Provided by
Gold Standard Inc. � 2007