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Pharmacological particulars
Pharmacotherapeutic group: Anaesthetics for topical use; lidocaine, combinations
ATCvet code: QD04AB51
Pharmacodynamic properties
Lidocaine is an amide local anaesthetic agent which works by blocking the sodium channels in the neuronal cell membrane and other excitable cells. Lidocaine is characterized as having a fast onset of action, within 30 seconds of application to mucosal tissues.
Bupivacaine is also an amide agent that, like lidocaine, works by blocking ion channels to prevent nerve conduction. Bupivacaine has a slower onset of action when compared to lidocaine, but a longer duration of action (1 hour). Lidocaine in combination with bupivacaine results in an additive effect of both, with the rapid onset of action of lidocaine and the prolonged effect of bupivacaine.
Adrenaline (also known as epinephrine) is an endogenous catecholamine produced naturally by the medulla of the adrenal glands. It is a neurotransmitter with a sympathomimetic effect and is an agonist of alpha and beta-adrenergic receptors. The alpha-adrenergic stimulation leads to vasoconstriction. Topical adrenaline produces vasoconstriction at the treated site, counteracting the vasodilatory properties of the local anaesthetics. By reducing the rate of systemic absorption of the active substances, this results in prolonging the anaesthetic effect, minimising the risk of systemic toxicity, and helping produce haemostasis.
Cetrimide is an antiseptic (quaternary ammonium) and has the typical actions and uses of a cationic surfactant, binding strongly to skin and mucous membranes, but with weak percutaneous absorption. Cetrimide delivers its antiseptic effect by its surfactant effect on bacterial cytoplasmic membranes causing cellular lysis and leakage of cytoplasmatic contents.
Pharmacokinetic properties
Lidocaine and bupivacaine distribution is extensive with the ability to cross the blood-brain and placental barriers, and can be found in milk. There is initial widespread distribution, particularly to highly perfused tissues including kidney, liver, lung and heart, followed by slower redistribution to muscle and fat. These local anaesthetics are eliminated more slowly from fat. Metabolism, through hydroxylation and alkylation via the P450 pathway, and (for lidocaine), amide hydrolysis via hepatic carboxylesterase enzymes, occurs rapidly in the liver with elimination via urine.
Adrenaline is poorly absorbed following topical administration. It is very rapidly metabolised by the liver with a plasma half-life of 2.5 minutes. It is metabolised by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) to inactive metabolites which are then excreted in the urine after conjugation with glucuronic acid or sulfates.
Cetrimide is poorly absorbed due to its cationic nature and binds strongly to the skin surface, mucosae and tissues. It is rapidly excreted in bile and faeces, mostly unmetabolised.
After application to piglet castration wounds, the following concentration (Cmax) and time (Tmax ) of maximum levels in plasma of the active substances have been measured:
Parameter
Lidocaine
Bupivacaine
Cetrimide
Cmax (μg/ml)
5.1
2.8
0.03
Tmax (hours)
1.5
12
0.083