TY - JOUR
T1 - Effects of imposed acid-base derangement on the cardiovascular effects and pharmacokinetics of bupivacaine and thiopental
AU - Mather, L.
AU - Ladd, Leigh A.
AU - Copeland, Susan E.
AU - Chang, Dennis Hsu-Tung
PY - 2004
Y1 - 2004
N2 - By changing physicochemical properties such as effective lipophilicity, changes in blood pH could alter the distribution, elimination, and effects of weakly ionizing drugs. The authors examined the outcome of imposed acidââ"šÂ¬Ã¢â‚¬Å“base derangement on cardiovascular effects and myocardial and whole body pharmacokinetics of bupivacaine, a weak base, and thiopental,a weak acid. Intravenous infusions of rac-bupivacaine HCl (37.5 mg) or rac-thiopental sodium (250 mg, subanesthetic dose) were administered over 3 min to previously instrumented conscious ewes with normal blood pH, acidemia imposed by lactic acid infusion, or alkalemia imposed by bicarbonate infusion. Hemodynamic and electrocardiographic effects were recorded; arterial and coronary sinus drug blood concentrations were analyzed by chiral high-performance liquid chromatography. Bupivacaine decreased myocardial contractility, coronary perfusion, heart rate, and cardiac output; however, cardiac output and stroke volume were not as affected by bupivacaine with acidemia. Thiopental decreased myocardial contractility and stroke volume and increased heart rate; acidemia enhanced the tachycardia and produced a greater decrease in stroke volume than with alkalemia. Taken as a whole, the cardiovascular changes were not systematically modified by acidââ"šÂ¬Ã¢â‚¬Å“base derangement. Overall, the tissue distribution of bupivacaine was favored by alkalemia, but thiopental pharmacokinetics were essentially unaffected by acidââ"šÂ¬Ã¢â‚¬Å“base derangement. Acidââ"šÂ¬Ã¢â‚¬Å“base derangement did not influence the kinetics of either drug enantioselectively. At the doses used, the hemodynamic and electrocardiographic effects of bupivacaine and thiopental were not systematically modified by acidââ"šÂ¬Ã¢â‚¬Å“base derangement, nor were there changes in regional or whole body pharmacokinetics of either drug that were clearly related to acidââ"šÂ¬Ã¢â‚¬Å“base status.
AB - By changing physicochemical properties such as effective lipophilicity, changes in blood pH could alter the distribution, elimination, and effects of weakly ionizing drugs. The authors examined the outcome of imposed acidââ"šÂ¬Ã¢â‚¬Å“base derangement on cardiovascular effects and myocardial and whole body pharmacokinetics of bupivacaine, a weak base, and thiopental,a weak acid. Intravenous infusions of rac-bupivacaine HCl (37.5 mg) or rac-thiopental sodium (250 mg, subanesthetic dose) were administered over 3 min to previously instrumented conscious ewes with normal blood pH, acidemia imposed by lactic acid infusion, or alkalemia imposed by bicarbonate infusion. Hemodynamic and electrocardiographic effects were recorded; arterial and coronary sinus drug blood concentrations were analyzed by chiral high-performance liquid chromatography. Bupivacaine decreased myocardial contractility, coronary perfusion, heart rate, and cardiac output; however, cardiac output and stroke volume were not as affected by bupivacaine with acidemia. Thiopental decreased myocardial contractility and stroke volume and increased heart rate; acidemia enhanced the tachycardia and produced a greater decrease in stroke volume than with alkalemia. Taken as a whole, the cardiovascular changes were not systematically modified by acidââ"šÂ¬Ã¢â‚¬Å“base derangement. Overall, the tissue distribution of bupivacaine was favored by alkalemia, but thiopental pharmacokinetics were essentially unaffected by acidââ"šÂ¬Ã¢â‚¬Å“base derangement. Acidââ"šÂ¬Ã¢â‚¬Å“base derangement did not influence the kinetics of either drug enantioselectively. At the doses used, the hemodynamic and electrocardiographic effects of bupivacaine and thiopental were not systematically modified by acidââ"šÂ¬Ã¢â‚¬Å“base derangement, nor were there changes in regional or whole body pharmacokinetics of either drug that were clearly related to acidââ"šÂ¬Ã¢â‚¬Å“base status.
KW - drug effects
KW - metabolism
KW - pharmacology
UR - http://handle.uws.edu.au:8081/1959.7/10511
M3 - Article
C2 - 15166565
SN - 0003-3022
JO - Anesthesiology
JF - Anesthesiology
ER -
