A comparison of the relative toxicities of β-sympathomimetic tocolytic agents

Gary Hankins, J. C. Hauth

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 of 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.

Original languageEnglish (US)
Pages (from-to)338-346
Number of pages9
JournalAmerican Journal of Perinatology
Volume2
Issue number4
StatePublished - 1985
Externally publishedYes

Fingerprint

Tocolytic Agents
Terbutaline
Sympathomimetics
Ritodrine
Cardiac Arrhythmias
Betamethasone
Poisons
Sulfates
Pharmaceutical Preparations
Hypokalemia
Acidosis
Arterial Pressure
Heart Rate
Dogs

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Pediatrics, Perinatology, and Child Health

Cite this

A comparison of the relative toxicities of β-sympathomimetic tocolytic agents. / Hankins, Gary; Hauth, J. C.

In: American Journal of Perinatology, Vol. 2, No. 4, 1985, p. 338-346.

Research output: Contribution to journalArticle

@article{f29af2a88a6e4fd7bf2059a628ed5b12,
title = "A comparison of the relative toxicities of β-sympathomimetic tocolytic agents",
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 of 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.",
author = "Gary Hankins and Hauth, {J. C.}",
year = "1985",
language = "English (US)",
volume = "2",
pages = "338--346",
journal = "American Journal of Perinatology",
issn = "0735-1631",
publisher = "Thieme Medical Publishers",
number = "4",

}

TY - JOUR

T1 - A comparison of the relative toxicities of β-sympathomimetic tocolytic agents

AU - Hankins, Gary

AU - Hauth, J. C.

PY - 1985

Y1 - 1985

N2 - 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 of 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.

AB - 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 of 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.

UR - http://www.scopus.com/inward/record.url?scp=0022402862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022402862&partnerID=8YFLogxK

M3 - Article

C2 - 4052188

AN - SCOPUS:0022402862

VL - 2

SP - 338

EP - 346

JO - American Journal of Perinatology

JF - American Journal of Perinatology

SN - 0735-1631

IS - 4

ER -