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Stress-induced lidocaine modification in serum and tissues

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Summary

The aim of this study is to examine the influence of acute (trauma) and chronic (cold swimming and adjuvant rheumatoid arthritis) stress on lidocaine concentrations in plasma. Forty male Wistar rats were used. The animals were divided into four groups. Group A served as control. Group B underwent mandible osteotomy. Group C was submitted to swimming stress in cold water 4°C for ten minutes daily for 15 minutes, while group D underwent experimental arthritis with Freud’s adjuvant. All groups received lidocaine i.m (2.5 mg/kg). Blood samples were collected and FFA (free fatty acid), unbound-lidocaine, albumin and a1-acid glycoprotein concentrations were estimated. Furthermore, the adrenals, heart and liver were isolated. The adrenals’ relative weight (adrenal weight/body weight) was assessed, while lidocaine concentrations in the heart and the liver incubation medium were measured by intertechnic a-counter.

Lidocaine and FFA levels in serum as well as the adrenal weights demonstrated a significant elevation in stress-groups as compared to the control group. Furthermore, in the stress-groups, lidocaine concentrations in heart tissue were significantly increased, whereas in the liver they were significantly reduced as compared to the control group. Our results indicate that stress can alter lidocaine levels in plasma and tissues, suggesting that stress should be considered an important factor when determining the dosage of lidocaine in clinical application.

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References

  1. Trujillo TC, Nolan PE (2000): Antiarrythmic agents: drug interactions of clinical significance. Drug Saf., 23(6), 509–532.

    Article  CAS  PubMed  Google Scholar 

  2. Nakamoto T, Oda Y, Imaoka S, Funae Y, Fujimori M (1997): Effect of phenobarbitalon the pharmacokinetics of lidocaine, monoethylglycinexylidide and 3-hydroxylidocaine in the rat: correlation with P450 isoforms levels. Drug Metab Dipos., 25(3), 296–300.

    CAS  Google Scholar 

  3. Mac Mahon S, Collins R, Peto R, Koster RN, Yusuf S. (1988): Effect of prophylactic lidocaine in suspected acute myocardial infraction: an overview from the randomised controlled trials. JAMA. 260, 1910–1916.

    Article  Google Scholar 

  4. Elad S, Cohen G, Zylber-Katz E, Findler M, Galili D, Garfunkel AA et al. (1999): Systemic absorption of lidocaine after topical application for the treatment of oral mucositis in bone marrow transplatation patients. J Oral Pathol Med., 28(4), 170–172.

    Article  CAS  PubMed  Google Scholar 

  5. Patterson SM, Gottdience JS, Hecht G, Vargot S, Krantz DS (1993): Effect of acute mental stress on serum lipids: mediating effect of plasma volume. Psychosom Med., 55, 525–532.

    CAS  PubMed  Google Scholar 

  6. Steinbrech DS, Mehrara BJ, Rowe NM, Dudziak ME, Luchs JS, Saadeh PB et al. (2000): Gene expression of TGF-beta, TGF-beta receptor, and extracellular matrix proteins during membranous bone healing in rats, Plast Reconstr Surg., 105(6), 2028–2038.

    Article  CAS  PubMed  Google Scholar 

  7. Tesseromatis C, Trichilis A, Saranteas T. (1994): Effect of stress on lidocaine levels in serum and tissues in rats. N.S Arch of Pharm., Supp 2, Vol. {vn349}.

  8. Van den Berg WB. (1998): Animals models in arthritis, In: Maddison PJ, Isenberg DA, Woo P, Glass D eds. Oxford textbook of Rheumatology, Oxford University Press: 561–563.

  9. Trichilis A, Tesseromatis C, Varonos P. Changes in serum levels of quinolones in rats under influence of experimental trauma. Eur J Drug Metab Pharmacokinet 25(2): 73–78.

  10. Katsunori N, Akihisa I. (1997): Stress, acute hyperglycemia and hyperlipidemia. Role of the cytokines. Trends Endocrin and Metab., 8(5): 192–197.

    Article  Google Scholar 

  11. Nies AS, Evans GH, Shaud DG. (1973): Regional hemodynamic effect of beta adrenergic blockade with propranolol in the unanesthetized primate. Am Heart J., 85, 97–102.

    Article  CAS  PubMed  Google Scholar 

  12. Hein L, Kobilka BK (1995): Adrenergic receptor signal transduction and regulation. Neuropharmacol., 34, 357–366.

    Article  CAS  Google Scholar 

  13. Imaoka S, Enomoto K, Oda Y, Asada A, Fujimori M, Shimada T et al. (1990): Lidocaine metabolism by human Cyt-P450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P450s. J Pharm Exp Ther., 25, 1385–1391.

    Google Scholar 

  14. Masubuchi Y, Umeda S, Igarashi S, Fujita S, Narimatsu S, Suzuki T. (1993): Participation of the cyt-2D subfamily in lidocaine 3-hydroxylation and formation of a reactive metabolite covalently bound to liver microsomal protein in rats. Bioch Pharmac., 17:46(10), 1867–1869.

    Google Scholar 

  15. Holford N.V (1995): Pharmacokinetics and Pharmacodynamics. In: Katzung B, ed. Basic and clinical pharmacology. Norwalk: Lange Int, 35–36.

    Google Scholar 

  16. Morgan DJ, Koay BB, Paull JD. (1982): Plasma protein binding of etidocaine during pregnancy and labour. Eur J Clin Pharmacol., 22(5), 451–457.

    Article  CAS  PubMed  Google Scholar 

  17. Tsopanakis C, Tesseromatis C. (1991): Cold swimming stress. Effect on serum lipids, lipoproteins and LCAT activity in male and female rats. Pharmacol Bioch Behav., 38, 813–816.

    Article  CAS  Google Scholar 

  18. Tinnikov AA. (1999): Responses of serum corticosterone and corticosteroid-binding globulin to acute and prolonged stress in rat. Endocrine, 11(2), 145–150.

    Article  CAS  PubMed  Google Scholar 

  19. Sfikakis A, Galanopoulou P, Konstadi M, Tsakayannis D. (1996): Stress through handing for vaginal screening, serotonin and ACTH response to ether. Pharm Bioch Behav., 53(4), 965–970.

    Article  CAS  Google Scholar 

  20. Tsopanakis C, Kostarellis D, Karayanakos P, Skalkeas G. (1988): Effect of cold stress on serum lipid lipoproteins and the activity of LCAT in rabbits. Bioch Med Metabol Biol., 39, 148–157.

    Article  CAS  Google Scholar 

  21. Bendele AM. (2001): Animals models of rheumatoid arthritis. J Muscoskel Neuron Interact., 1(4), 377–385.

    CAS  Google Scholar 

  22. Hanyu T, Choranaphuti T, Arai K, Tanaka T, Takahashi HE. (1999): Histomorphometric assessment of bone changes in rats with type II collagen-induced arthritis. Bone, 24, 485–490.

    Article  CAS  PubMed  Google Scholar 

  23. Sjoqvist O, Borga M, Dahl L, Orme ML. (1997): Fundementals of clinical pharmacology. In: Speight T, Holford N, eds. Avery’s drug treatment. Aucland: Adis Inter., 21–22.

    Google Scholar 

  24. Coyle DE, Denson DD, Essell SK, Santos DJ. (1986): The effect of unesterified fatty acids and progesterone on bupivacaine protein binding. Clin Pharm Ther., 399(5), 559–563.

    Google Scholar 

  25. Rauckman EJ, Rosen GM, Post SE, Gillogly SD. (1980): Effect of model traumatic injury on hepatic drug metabolizing enzymes. J Trauma, 20, 884–886.

    Article  CAS  PubMed  Google Scholar 

  26. Borga O, Piafsky KM, Nielsen OG. (1977): Plasma protein binding of basic drugs selective displacement from al-acid glycoprotein by tris phosphate. Clin Pharm Ther., 22, 539–542.

    CAS  Google Scholar 

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Saranteas, T., Tesseromatis, C., Potamianou, A. et al. Stress-induced lidocaine modification in serum and tissues. Eur. J. Drug Metab. Pharmacokinet. 27, 229–232 (2002). https://doi.org/10.1007/BF03192332

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