ABSTRACT
To define the relative toxicities of ritodrine sulfate, terbutaline sulfate, hexaprenaline
sulfate, and ritodrine with betamethasone mongrel dogs were treated with these agents
for 19 hours. The maximum dose of ritodrine was 900 μg/min (N = 5), terbutaline 120
μg/min (N = 4) and hexaprenaline 1.5 μg/min (N = 4). Betamethasone was given intramuscularly
(12 mg) at initiation of ritodrine and repeated in 12 hours in four animals. Arrhythmias
were responsible for five deaths; 2/4 terbutaline, 2/4 ritodrine and betamethasone,
1/5 ritodrine, 0/4 hexaprenaline treated animals. Terbutaline-treated animals developed
arrhythmias during more treatment cycles (50%) and at lower drug concentrations, whereas
hexaprenaline-treated animals developed arrhythmias at higher drug concentrations,
with an overall arrhythmia frequency of 14%. Terbutaline animals had the highest heart
rate (P = 0.02) and lowest mean arterial pressure (P = 0.18); the least effect on these parameters being seen with hexaprenaline. Cardiac
index was higher with terbutaline and hexaprenaline compared to ritodrine with or
without betamethasone (P = 0.02). Hypoxemia was most severe with terbutaline (pO2 = 58 mm Hg) and least severe with hexaprenaline (pO2 = 66 mm Hg); however, this does not explain the difference in the frequency of arrhythmias
since the mean pO2 during the initial arrhythmias was 76 mm Hg in terbutaline treated animals compared
to a baseline control of 85 mm Hg. Although all animals developed significant acidosis
during Phases II-IV, hexaprenaline treated animals were the least acidotic (P = 0.036). Hypokalemia was most pronounced with terbutaline (P = 0.08 Phase II, P = 0.07 Phase III). Thus, terbutaline was the most toxic and hexaprenaline the least
toxic of these agents, assuming an equivalent maximum recommended human dose for these
drugs.