Brands, Medical Use, Clinical Data
Drug Category
Dosage Forms
- Liquid (for injection)
- Solution
Brands / Synonyms
(+-)-Bupivacaine; Anekain; Bloqueina; Bupivacaina [INN-Spanish]; Bupivacaine; Bupivacaine and Epinephrine; Bupivacaine HCL; Bupivacaine HCL KIT; Bupivacainum [INN-Latin]; Bupivacine HCL Preservative Free; Bupivan; Carbostesin; cBupivacaine
; Chirocaine; DL-Bupivacaine; LAC-43; Marcaina; Marcaine; Marcaine HCL; Marcaine Spinal; Sensorcaine; Sensorcaine Forte; Sensorcaine MPF; Sensorcaine-MPF; Sensorcaine-MPF Spinal
Indications
For the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
Pharmacology
Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to 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. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.
Mechanism of Action
Local anesthetics such as bupivacaine block the generation and the 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 affected nerve fibers. 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 analgesic effects of Bupivicaine are thought to be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.
Absorption
The rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution.
Toxicity
The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 to 8 mg/kg and 38 to 54 mg/kg respectively. Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.
Biotrnasformation / Drug Metabolism
Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid. The major metabolite of bupivacaine is 2,6-pipecoloxylidine, which is mainly catalyzed via cytochrome P450 3A4.
Contraindications
Sensorcaine (bupivacaine HCl) is contraindicated in obstetrical paracervical block anesthesia. Its use by this
technique has resulted in fetal bradycardia and death.
Sensorcaine is contraindicated in patients with a known hypersensitivity to it or to any local anesthetic agent of
the amide type or to other components of bupivacaine solutions.
Drug Interactions
The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving
monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use
of these agents should generally be avoided. In situations in which concurrent therapy is necessary, careful patient
monitoring is essential.
Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe, persistent
hypertension or cerebrovascular accidents.
Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.
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