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Le métabolisme comme source de variabilité de l'efficacité et de la toxicité des analgésiques

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Douleur et Analgésie

Résumé

La plupart des analgésiques sont éliminés de l'organisme par biotransformation au niveau hépatique, le plus souvent consécutivement à une oxydation par les cytochromes P450. Compte tenu de la diversité de ce groupe d'enzymes et de l'importante variabilité inter- et intraindividuelle de leur activité, il est indispensable de connaître avec précision les interactions existant entre les médicaments et les différentes isoenzymes.

Les caractéristiques d'élimination des principaux groupes de médicaments utilisés pour combattre les syndromes douloureux (AINS, paracétamol, opioïdes, antidépresseurs) sont passés en revue, tout comme les différents facteurs de variabilité (intrinsèque, génétique et environnementale). Il s'avère qu'il est nécessaire d'être particulièrement vigilant aux substances pouvant moduler la pharmacocinétique des analgésiques majeurs et, en cas d'utilisation des antidépresseurs, de faire preuve d'une certaine prudence, compte tenu de l'important potentiel inhibiteur de certains dérivés. Les facteurs génétiques sont également évoqués, notamment l'incidence de certaines déficiences sur le métabolisme des médicaments.

Grâce à une meilleure connaissance des facteurs de variabilité, il devrait être possible pour les cliniciens d'anticiper un certain nombre de problèmes pouvant aboutir à une toxicité ou au contraire à un échec thérapeutique et ainsi d'améliorer la prise en charge de leurs patients douloureux.

Summary

Most analgesics are eliminated by cytochrome P450-dependent hepatic biotransformation. Owing to the diversity of this enzyme family and to large inter- and intraindividual variabilities in their activity, it is very important to precisely know interactions existing between drugs and specific isozymes.

Elimination characteristics of drugs used to treat painful syndromes (NSAIDs, paracetamol, opioids, antidepressants) are reviewed, as well as variability factors (intrinsic, genetic and environmental). It is necessary to be particularly vigilant to drugs modulating the activity of major analgesics and, for anti-depressants, to care about the inhibition potential of some substances. Genetic deficiencies are mentioned, with a special focus on their incidence on drug metabolism.

Thanks to a better knowledge of variability factors, it should be possible for clinicians to anticipate the occurrence of problems leading to toxicity or to therapeutic failure, and then to improve the treatment of their algic patients.

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Authors and Affiliations

  1. Centre multidisciplinaire d'évaluation et de traitement de la douleur, Hôpitaux Universitaires Genève, Genève

    P. Bonnabry, J. Desmeules & P. Dayer

  2. Hôpitaux Universitaires Genève, 24, rue Micheli-du-Crest, CH-1211, Genève 14

    P. Bonnabry, J. Desmeules & P. Dayer

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  1. P. Bonnabry
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  2. J. Desmeules
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  3. P. Dayer
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Bonnabry, P., Desmeules, J. & Dayer, P. Le métabolisme comme source de variabilité de l'efficacité et de la toxicité des analgésiques. Doul. et Analg. 11, 77–82 (1998). https://doi.org/10.1007/BF03013287

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  • DOI: https://doi.org/10.1007/BF03013287

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