Bupicasan Mechanism of Action

Pharmacology: Bupivacaine Hydrochloride is a long acting local anaesthetic agent of the amide type. Bupivacaine Hydrochloride has rapid onset of action and long duration. The duration of analgesia in the T10-T12 segments is 2-3 hours.
Bupivacaine Hydrochloride is a hyperbaric solution and its initial spread in the subarachnoid space is considerable affected by gravity. Moreover, its spread cephalad more extensively than the isobaric solutions, even in the horizontal position when the effect gravity is minimal. Due to the larger intrathecal distribution and the consequently lower mean concentration the duration of anaesthesia tends to be shorter. In the isobaric solution without added dextrose produces a lower level of block, but of longer duration than the hyperbaric solution.
Bupivacaine Hydrochloride, like the other local anaesthetics, causes a reversible blockade of impulse propagation along nerve fibers by preventing the inward movement of sodium ions through the nerve membrane. Local anaesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.
Bupivacaine Hydrochloride has a pKa of 8.1 at 25°C and an oil/water partition coefficient of 27.5.
Absorption from the subarachnoid space is relative slow and this, together with the small dose required for spinal anaesthesia, limits the maximum plasma concentration, which is approximately 0.4 mg/mL for every 100 mg injected. This means that the maximum recommended dose (20 mg) would result in plasma levels of less than 0.1 mg/mL.
After IV Injection Bupivacaine Hydrochloride has a total plasma clearance of 0.58 L/min, a volume of distribution at steady state of 73 L, an elimination half-life of 2.7 h and a hepatic extraction ratio 0.40. Clearance of Bupivacaine Hydrocloride is almost entirely due to liver metabolism, and depends upon both liver blood flow and the activity of the metabolizing enzymes.
Bupivacaine Hydrochloride readily crosses the placenta and equilibrium in regards of free drug will be reached. Because the degree protein binding in the foetus is less than in the mother, the total plasma will be greater in the mother, although the free concentration will be the same. Bupivacaine is excreted in breast milk, but in such small quantities that there is no risk to the child.
Only 8% of Bupivacaine excreted in unchanged form, primary metabolite which becomes 2,6 pipecolyxylidine (PPX), and its derivates.