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The effect of amitriptyline, gabapentin, and carbamazepine on morphine-induced hypercarbia in rabbits

Authors :
Eran Kozer
Gideon Koren
Zina Levichek
Bhushan Kapur
Facundo Garcia-Bournissen
Shinya Ito
John Paul Leombruno
Nobuko Taguchi
Noriko Hoshino
Source :
Anesthesia and analgesia. 107(4)
Publication Year :
2008

Abstract

BACKGROUND: Severe exacerbation of chronic neuropathic pain often requires morphine in patients already treated with drugs such as tricyclic antidepressants, carbamazepine and gabapentin. However, it is unclear if a combination of these drugs intensifies the effects of morphine on the respiratory system and, if so, whether these effects are due to pharmacokinetic or pharmacodynamic interaction. METHODS: We gave rabbits (n = 6 per group) the following drugs daily for 4 days: subcutaneous normal saline 1 mL (control); amitriptyline subcutaneously 7 mg/kg; carbamazepine orally 100 mg/kg; gabapentin subcutaneously 25 mg/kg; and all three drugs concurrently (combination). On the fifth day, morphine 5 mg/kg was given IV, and Paco 2 , Pao 2 and pH were measured. Morphine, morphine 3-glucoronide and morphine 6-glucoronide concentrations were measured in the plasma over the 4 h period after morphine injection. RESULTS: Compared with controls, premorphine baseline Paco 2 was significantly higher (P < 0.05) in the amitriptyline group. Postmorphine Paco 2 was significantly higher in the amitriptyline and combination groups at all time points over the 240 min, and in the gabapentin group at 10 and 30 min after morphine injection (P < 0.05). Peak Paco 2 was significantly higher in the amitriptyline group (58.4 ± 1.6 mm Hg; mean SD, P < 0.005) and in the combination group (57.4 ±1.0 mm Hg, P < 0.02) than in the control group (50.2 ± 5.2 mm Hg). Similarly, the area under the curve of Paco 2 from zero to 240 min was significantly higher in the amitriptyline and combination groups than in the control (P < 0.001). There were no significant differences among the groups in plasma concentrations of morphine and its metabolites. CONCLUSIONS: We conclude that pretreatment with amitriptyline increases morphine-induced hypercarbia through pharmacodynamic processes. The effects of carbamazepine or gabapentin were not obvious in this model.

Details

ISSN :
15267598
Volume :
107
Issue :
4
Database :
OpenAIRE
Journal :
Anesthesia and analgesia
Accession number :
edsair.doi.dedup.....36814495cae8e66c1089ff09da887ea4