Immunological Effect of Tramadol, Codeine, Flunitrazepam on Plasma Cortisol (Anti-inflammatory Agent), Cortisol Binding Globulin (Acute Phase Protein) and Total Bile Acid in Rabbits

Abstract

Study Background: Flunitrazepam, Tramadol and Codeine are irrationally used as energy booster, psychoactives and as recreational drugs apart from their normal applications to relieve pains (Tramadol and Codeine), cough (Codeine) or as sedative (Flunitrazepam). High doses could induce inflammatory and acute phase responses. Aim and Objectives: This work was designed to determine the Immunological Effect of low and High Doses of Tramadol, Codeine and Flunitrazepam on fasting Plasma Total Bile Acid, Cortisol(Anti-inflammatory Agent) and Cortisol Binding Globulin (Acute Phase Protein) in rabbits given normal and high doses. Materials and Methods: The subjects include thirty five (35) male rabbits weighed 0.8 kg-1.3 kg. grouped into control (Group A; 5 rabbits on normal meal and water without drugs), 5 rabbits given 15 mg/kgBW of Tramadol per 24 hrs (Group B1), 100 mg/kgBW of Tramadol per 24 hrs (Group B2), 10 mg/kgBW of Codeine per 24 hrs (Group C1), 100 mg/kgBW of Codeine per 24 hrs (Group C2), 0.5 mg/kgBW of Flunitrazepam (D1) and 5 mg/kgBW of Flunitrazepam (D2). Early morning fasting Plasma Cortisol. Total Bile Acid (TBA) and Cortisol Binding Globulin were determined immunochemically by ELISA and spectrophotometry. Results: The result obtained from this work showed a significantly lower plasma value of cortisol in rabbits given 100 mg/kgBW of tramadol per 24 hrs for 14 days and also in the rabbits given 100 mg/kgBW of Codeine per 24 hrs for 14 days compared with the control rabbits on normal meal and water without drug administration with p<0.05. There was a significantly lower plasma value of cortisol binding globulin in rabbits given 100 mg/kgBW of tramadol per 24 hrs for 14 days compared with the control rabbits and those given 15 mg/kgBW of tramadol per 24 hrs for 14 days with p<0.05.There was a significantlyhigher plasma value of Total bile acid  in rabbits given 100 mg/kgBW of tramadol per 24 hrs for 14 days than the rabbits administered with 15 mg/kgBW of tramadol per 24 hrs for 14 days and when compared with normal control rabbits with p<0.05. There was significantlyhigher plasma value of Total bile acid  in rabbits given 100 mg/kgBW of codeine per 24 hrs for 14 days than the rabbits administered with 10 mg/kgBW of codeine per 24 hrs for 14 daysand when compared with normal control rabbits with p<0.05. Conclusion: High Doses of Tramadol (100 mg/kgBW) and Codeine (100 mg/kgBW) could trigger inflammatory responses which could alter the plasma levels of Total Bile Acid (TBA), cortisol (glucocorticoid anti-stress and anti-inflammatory hormone) and cortisol binding globulin (Cortisol storage protein and a negative acute phase protein). Measurement of cortisol and globulin binding globulin in those addicted to the drug will tremendously improve on the management of possible Tramadol and Codeine induced toxicity and inflammation.