Effects of alpha-1-acid glycoprotein on the cardiovascular toxicity of nortriptyline in a swine model.
Tricyclic antidepressant toxicity is a frequently encountered and life-threatening problem in emergency medicine. This trial investigated the effect of alpha-1-acid glycoprotein (AAG), an acute phase reactant with a high affinity for basic drugs, on the clinical and pharmacological manifestations of nortriptyline (NT) toxicity. Fourteen pentobarbital-anesthetized swine (10-13 kg) were given a 10-min loading dose followed by a 45-min maintenance infusion of NT to achieve a plasma level of approximately 1000 ng/ml. At the end of the infusion, 7 control (C) animals were given 50 ml of 0.9% saline and 7 AAG animals were given 50 ml of 10% AAG, both over 15 min. Heart rate, QRS duration, QTc interval, blood pressure, temperature, arterial blood gases, albumin, and plasma-free and plasma-bound NT levels were measured at baseline and at every hour for 4 h. One death was noted in the AAG group and none in the C group (p = NS). Mean total NT levels after infusion in the C group was 1240 +/- 1118 ng/ml and in the AAG group 804 +/- 194 ng/ml (p = NS). No significant differences were found in the plasma-free fractions between groups at any time interval. However, significantly shorter QTc intervals were found during treatment with AAG compared to controls (P = 0.02). A trend toward increased systolic blood pressure (p = 0.09) and shorter QRS duration (p = 0.09) was noted during AAG treatment. No significant changes were shown between groups with respect to heart rate, arterial blood gases, or albumin measurements.(ABSTRACT TRUNCATED AT 250 WORDS)
Seaberg
D C
DC
University of Pittsburgh, Pennsylvania.
Weiss
L D
LD
Yealy
D M
DM
Kaplan
R M
RM
Krenzelok
E P
EP
Stiller
R L
RL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004562:Electrocardiography / Q000187:drug effects; D007262:Infusions, Intravenous; D009661:Nortriptyline / Q000097:blood / Q000633:toxicity*; D009961:Orosomucoid / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine
D009961:Orosomucoid; D009661:Nortriptyline