Local anaesthetics metabolites

Unconscious patients are usually catheterised and, in this case, the sample may be contaminated with the catheter lubricant which frequently contains lignocaine as a local anaesthetic. Urine is ideal for qualitative screening as it is available in large volumes, and usually contains higher concentrations of drugs or poisons than blood. The presence of drug metabolites can be used to assist identification if chromatographic techniques which can separate them are used. A 50-ml sample is sufficient for a comprehensive series of tests, and no preservative should be added. 

Hydrolysis. Hydrolysis of esters and amides is a common pathway of drug metabolism. The liver microsomes contain non-specific esterases, as do other tissues and plasma. Hydrolysis of an ester results in the formation of an alcohol and an acid hydrolysis of an amide results in the formation of an amine and an acid. The ester procaine, a local anaesthetic, is rapidly hydrolysed by plasma cholinesterases and, to a lesser extent, by hepatic microsomal esterase. An example of an amide which is hydrolysed, is the antiarrhythmic drug procainamide. Enalapril, a prodrug, is hydrolysed by esterases to the active metabolite enalapri-late, which inhibits the angiotensin-converting enzyme. 

Rop, P.P. Grimaldi, F. Bresson, M. Fornaris, M. Viala, A. Liquid chromatographic analysis of cocaine, benzoylecgonine, local anaesthetic agents and some of their metabolites in biological fluids, J.Liq.Chro-matogr., 1993, 16, 2797—2811. 

Cocaine has a half-life of 0.5-1.5 h but its metabolites such as benzoylecgonine and cocaethylene have much longer half-lives. The authors report that the clinical use of ILE in the treatment of local-anaesthetic-associated cardiac toxicity was first reported in 2006. This helped to move treatment from supportive management to more specific intervention. Now, ILE is incorporated into current guidelines for management of local anaesthetic toxicity. This treatment is hypothesised to work by absorbing the circulating toxins. There are other hypotheses too about how this may work. The authors report that other case reports have also documented the benefits of ILE in treatment of cocaine toxicity and have the potential to prevent mortality. 

Ethylglycinexylidide, the mono-desethyl metabolite of the local anaesthetic lido-caine, is hydrolysed by hepatic microsomal enzymes. This amidase activity is somewhat atypical in that it can be solubilized with retention of activity. It is of interest that although the monoethyl metabolite ethylglycinexylidide serves as a substrate for the microsomal amidase, neither the parent compound lidocaine nor the completely desethylated metabolite undergoes deamidation. 

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