Problems With Morphine Use in Patients With a Severe Brain Injury

Summary

Hypothesis: During severe brain trauma (injury, surgery) the ensuing inflammatory response in the central nervous system (CNS) results in a decrease in the expression of the transporter protein p-glycoprotein (PGP) in the blood brain barrier. This loss results in the penetration into the brain of certain drugs that are normally excluded by the transporter protein. In this study the working hypothesis is that the agitation observed in patients with CNS trauma treated with morphine is related to the inflammation evoked loss of PGP in the blood brain barrier and the accumulation of the morphine metabolite 3-morphine glucuronide.

Timeline

Start

2005-01

Primary completion

—

Completion

2008-04

Publications

• Background Goralski KB, Hartmann G, Piquette-Miller M, Renton KW. Downregulation of mdr1a expression in the brain and liver during CNS inflammation alters the in vivo disposition of digoxin. Br J Pharmacol. 2003 May;139(1):35-48. doi: 10.1038/sj.bjp.0705227.

Drugs

Indications