Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Sintetica Limited, 30<sup>th</sup> Floor, 40 Bank Street, Canary Wharf, London, E14 5NR, United Kingdom
Pharmacotherapeutic group: anaesthetics, local; amides
ATC code: N01BB04
Prilocaine is an amide-type local anaesthetic. Prilocaine inhibits the function of the excitable structures (e.g. all types of nerve fibres [sensory, motor, autonomous nerve fibres]).
Prilocaine inhibits the excitability of sensory pain receptors and the conductivity of the sensory nerve fibres, at local level and in a reversible way, reducing the perception of pain and, subsequently, that of cold, heat, touch and pressure.
Prilocaine reduces membrane permeability to sodium. This reduces the excitability of the nerve fibres in accordance with its concentration, through reducing the sudden peak sodium permeability, needed to form the potential for action. The effect depends on the pH of the substance and the pH of the environment. The local aesthetic effect is due to the protonated form. In inflamed tissues, the effect of the local anaesthetics is lower because of the lower pH of the environment.
The plasma concentration should be negligible for intrathecal use.
The plasma protein binding is approximately 55%.
The bioavailability of prilocaine at the application site is 100%.
The principal metabolites of prilocaine are o-toluidine and N-n-propylalanine, both produced in the liver and kidneys by amidases. o-Toluidine undergoes extensive hydrolytic metabolism in vivo, with the bulk of the dose being excreted in the urine within 24 h. Like other aromatic amines, it is thought to undergo metabolic activation initially via N-hydroxylation, leading to covalent binding to tissue macromolecules. o-Toluidine is potent oxidant of the ferric iron of hemoglobin.
The terminal elimination half-life of prilocaine is 1.6 hours.
The therapeutic dose used locally in humans is close to the dose which is toxic in animals after intravenous administration. In animals, signs of acute toxicity are reduced activity, convulsions, dyspnea, cyanosis and death on account of cardiac insufficiency.
The subcutaneous injection of 3 ml/kg of body weight of prilocaine hydrochloride induced reversible local necrosis in the rat. At the same posology no damaging effects were observed in the monkey.
The administration of 60 mg/kg body weight of prilocaine for 5 days a week for 7 weeks induced slight weight loss in the rat.
In mutagenesis tests, prilocaine did not demonstrate any mutagenic effects. The indices for a potential mutagen are based on knowledge relating to the metabolite o-toluidine, which caused genetic damage and cell proliferation (chromosome mutations, aneuploidy, DNA repair, cell conversion) in various tests in vitro.
In carcinogenicity studies performed in the rat and the mouse with high doses of the metabolite o-toluidine, an increase in the frequency of tumours of the spleen and the bladder were observed.
Neither of the results seem significant for humans in the case of the therapeutic short-term use of prilocaine; nevertheless, for safety reasons avoiding the administration of high doses over prolonged periods is recommended.
Prilocaine has no effect on the fertility of male and female rats. However, the postnatal survival of the offspring of treated females was reduced. In one study on embryotoxicity in the rat lethal effects on the foetus were observed, and dose-dependent hydronephrosis occurred in the foetuses.
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