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The following message was posted to: PharmPK
Hello everybody,
I would like to get the list's wisdom on anesthesia-induced changes in
drug pharmacokinetics in rats. Are you aware of changes in cerebral
blood flow or circulation induced by agents like Halothane or
Isoflurane in rats(especially under treatment with vasoconstricting
agents)?
I appreciate your input.
Alessandra
Alessandra Milesi-Halle, M.D.
Department of Pharmacology and Toxicology
UAMS College of Medicine
4301 West Markham, slot 611
Little Rock, Arkansas 72205
Phone: (501)686-6551
Fax: (501)686-5521
MilesihalleAlessandr.at.uams.edu
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The following message was posted to: PharmPK
Dear Alessandra,
In most species halothane and isoflurane produce dose- and
time-dependent changes in the circulation, halothane more so than
isoflurane. Cardiac output and blood pressure are decreased. Both
agents suppress cerebral metabolism, but also cause cerebral
vasodilation so that cerebral blood flow will often increase.
Vasocontricting agents will probably counter this effect on cerebral
blood flow, but drive cardiac output even lower. Both agents can also
suppress the activity of drug metabolising enzymes. All together, the
kinetic profile of a drug under anaesthesia with volatile anaesthetics
can be quite different to that under awake conditions.
This reference is old and not specific to rats, but may get your
literature search started:
Runciman WB, Myburgh J, Upton RN , Mather LE. Effects of anaesthesia on
drug disposition. In: Feldman S, Scurr CF et al., eds. Drugs in
Anaesthesia: Mechanisms of Action. 2nd ed. London: Edward Arnold, 1993
p. 93-128.
Regards, Richard
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