Marcain 0.5% Spinal Heavy Mechanism of Action

Pharmacotherapeutic group (ATC code): N01B B01.
Pharmacology: Pharmacodynamics: Marcain Spinal Heavy contains bupivacaine, which is a long-acting local anaesthetic of the amide type. Bupivacaine reversibly blocks impulse conduction in the nerves by inhibiting the transport of sodium ions through the nerve membrane. Similar effects can also be seen on excitatory membranes in the brain and myocardium.
Marcain Spinal Heavy is intended for hyperbaric spinal anaesthesia. The relative density of the solution for injection is 1.026 at 20°C (equivalent to 1.021 at 37°C) and the initial distribution into the subarachnoid space is markedly influenced by gravity.
For administration into the spine, a small dose is given, which gives a relatively low concentration and short duration of effect.
Pharmacokinetics: Bupivacaine is very liposoluble with an oil/water distribution coefficient of 27.5.
Bupivacaine displays complete and bi-phasic absorption from the subarachnoid space, with half-lives for the two phases of approx. 50 and approx. 400 minutes, with large variations. The slow absorption phase is the rate-determining factor in the elimination of bupivacaine, which explains why the apparent half-life is longer than after intravenous administration.
Absorption from the subarachnoid space is relatively slow, which, in combination with the low dose required for spinal anaesthesia, gives a relatively low plasma concentration (approx. 0.4 mg/ml per 100 mg injected).
After intravenous administration, total plasma clearance is approx. 0.58 l/min, the volume of distribution in steady state is approx. 73 l, the elimination half-life is 2.7 hours, and the hepatic extraction ratio is approx. 0.40. Bupivacaine is metabolised almost completely in the liver, predominantly through aromatic hydroxylation to 4-hydroxybupivacaine and N-dealkylation to PPX, both of which are mediated by cytochrome P450 3A4. Clearance is thus dependent on hepatic perfusion and the activity of the metabolising enzyme.
Bupivacaine crosses the placenta and the concentration of free bupivacaine is the same in the mother and the foetus. However, the total plasma concentration is lower in the foetus, which has a lower degree of protein binding.
Toxicology: Pre-Clinical Safety Data: There are no preclinical data of relevance for an evaluation of safety other than what has already been mentioned in this monograph.