The influence of hemorrhagic shock on the pharmacokinetics and the analgesic effect of morphine in the rat

Abstract

The influence of hemorrhagic shock (removal of 30% of the blood volume) on the pharmacokinetics and the analgesic effect of morphine was investigated in conscious rats. Plasma concentrations of morphine after a bolus injection (5 mg/kg) are higher in the shock animals, which is attributed to a small decrease in clearance (-22%; P > 0.05) and a significant decrease in distribution volume (-33%; P < 0.05) of the drug. The areas under the plasma concentration-time curve of the metabolite morphine-3-glucuronide (M3G) are significantly higher (+237%; P < 0.01) in the shock rats, which is probably explained by a decreased distribution and renal excretion. The analgesic effect of morphine was evaluated using the tail-flick test during a continuous infusion (10 mg/kg/h) with measurement of the plasma concentrations of morphine and M3G. Data from these experiments show higher plasma concentrations of morphine (+33%; P < 0.05) and M3G (+66%; P > 0.05) during shock, and a significantly increased analgesic effect (+43%; P < 0.05). Our data suggest that the increased analgesic effect of morphine during hemorrhagic shock can most likely be explained by pharmacokinetic changes resulting in higher morphine concentrations.

Lack of Effect of Experimental Hypovolemia on Imipenem Muscle Distribution in Rats Assessed by Microdialysis

“…The experimental model of hypovolemia used throughout this study with removal of 40% of the blood volume, which corresponded to about 5 ml of blood, was adapted from the (8,9,10). With the initial model, 30% of the blood volume was removed.…”

Influence of blood loss on the pharmacokinetics of citalopram

“…In line with this presumption, earlier studies have reported about alterations in both pharmacokinetics and pharmacodynamics following drug administration to hypovolemic animals [2][3][4][5].…”

The Influence of Hemorrhagic Shock on the Minimum Alveolar Anesthetic Concentration of Isoflurane in a Swine Model

“…Such an activation would not be expected to materially alter the EEG, an expectation consistent with our previous finding that hemorrhagic shock minimally alters the EEG. Hemorrhagi c shock increases the effect of several classes of IV anesthetics because of pharmacokinetic and pharmacodynamic changes (1)(2)(3)(4)(5), and such changes sometimes complicate the management of patients who have significant blood loss before or during surgery (6). We previously examined the influence of hemorrhagic shock on the electrolencephalogram (EEG) effect of isoflurane using a stepwise hemorrhagic model in swine, and concluded that hemorrhage, even at a level at which hemorrhagic shock progresses to a decompensated state, minimally alters the EEG effect of isoflurane (7,8).…”