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Pharmacotherapeutic group: Local anesthetics, amides.
Pharmacology: Pharmacodynamics: Sergivell Plain: Bupivacaine is a long acting local anaesthetic agent of the amide type.
Moderate muscular relaxation of lower extremities.
Motor blockade of the abdominal muscles.
Bupivacaine Hydrochloride is hyperbaric and its initial spread in the intrathecal space is affected by gravity.
Sergivell Iso: Bupivacaine hydrochloride is a long-acting local anesthetic of the amide type with both anesthetic and analgesic effects. At high doses, it produces surgical anesthesia, at lower doses it produces sensory blockade (analgesia) with a less pronounced motor blockade.
Onset and duration of the local anesthetic effect of bupivacaine depend on the dose and the site of administration.
Bupivacaine, like other local anesthetics, causes a reversible blockade of impulse propagation along nerve fibers by preventing the inward movement of sodium ions through the cell membrane of the nerve fibers. The sodium channels of the nerve membrane are considered a receptor for local anesthetic molecules.
Local anesthetics may have similar effects on the other excitable membranes, e.g. in the brain and myocardium. If excessive amounts of the drug reach the systemic circulation, symptoms and signs of acute toxicity may occur, especially central and cardiovascular.
Central nervous system toxicity usually precedes the cardiovascular effects as central nervous system toxicity occurs at lower plasma concentrations of anesthetic. Direct effects of local anesthetics on the heart include negative dromotropic and negative inotropic effects and eventually cardiac arrest.
Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural administration depending on the extent of the concomitant sympathetic blockade.
Pharmacokinetics: Pediatric population: Pharmacokinetics of bupivacaine in children is similar to that in adults.
Sergivell Plain: Rapid onset of action and long duration i.e. T10-T12 segments-duration 2-3 hours.
Muscular relaxation of lower extremities lasts 2-2.5 hours.
Blockade of the abdominal muscles lasts 45-60 minutes. The duration of motor blockade does not exceed duration of analgesia.
Sergivell Iso: Bupivacaine has a value of dissociation constant (pKa)=8.2 and a value of partition coefficient (D)=348 (25°C n-octanol/phosphate buffer pH 7.4). The metabolites have less pharmacological activity than bupivacaine.
Absorption: The plasma concentration of bupivacaine depends on the administered dose, the route of administration, and vascularity in the injection site.
Bupivacaine shows complete biphasic absorption from the epidural space with half-lives in the order of 7 min and 6 h respectively. The slow absorption is rate-limiting in the elimination of bupivacaine, which explains why the apparent half-life after epidural administration is longer than that after intravenous administration.
Distribution: Bupivacaine has a total plasma clearance of 0.58 L/min, a volume of distribution at a steady state of 73 L, a terminal half-life (t1/2) of 2.7 hours, and an intermediate hepatic extraction ratio of 0.38 after intravenous administration. It is mainly bound to alpha-acid glycoprotein with plasma binding of 96%. Clearance of bupivacaine is almost entirely due to liver metabolism and it is more sensitive to changes in intrinsic hepatic enzyme function than to liver perfusion.
An increase in total plasma concentration has been observed during continuous epidural infusion. It is a consequence of a postoperative increase in alpha 1-acid glycoprotein in plasma. The unbound, i.e. pharmacologically active, concentration is similar before and after surgery.
Bupivacaine readily crosses the placenta barrier and equilibrium with regard to the concentration of the unbound fraction is rapidly reached. The degree of plasma protein binding in the fetus is less than in the mother, which results in lower total plasma concentrations in the fetus.
Biotransformation: Bupivacaine is extensively metabolized in the liver, predominately by aromatic hydroxylation to 4 hydroxy bupivacaine and N-dealkylation to pipecoloxylidide (PPX), both mediated by cytochrome P450 3A4.
Elimination: About 1% of bupivacaine is excreted in the urine as an unchanged drug in 24 h and approximately 5% as PPX. The plasma concentrations of PPX and 4-hydroxy-bupivacaine during and after continuous administration are low compared to the parent medicine.
