Abstract
It is not known whether the fetus can develop opiate dependence (OD) as a primary, drug-related effect of maternal to fetal transfer of morphine sulfate (MS) or whether fetal responses are related to altered maternal physiology. Four non-pregnant and 4 pregnant ewes were studied. A continuous intravenous(IV)infusion of MS was given to the ewes(10mg/kg/24 hours). The response was measured to IV administration of naloxone(N), 0.04mg/kg to the ewes and 0.02 mg/kg-estimated weight to the fetuses. As early as 24 hours after beginning the MS infusion,Nincreased arterial blood pressure(ABP) in the non-pregnant ewes (mean ± SE):systolic 120.2±2.2 torr to 137.6±2.4 (p<.001);diastolic 82.3± 1.2 to 95.9 ± 2.7 (p<.001); and in pregnant ewes: systolic 114.2± 2.6 to 140.7±3.0 (p<.001). All animals demonstrated “withdrawal” responses. There was no significant change in heart rate. Maternal N increased fetal ABP: systolic 63.9± 2.1 to 75.0±4.2 (p <.001); diastolic 36.8± 2.0 to 41.8±2.7 (p<.001). In contrast to the mothers,there was a fall in fetal heart rate: 174± 6 to 150±5 (p<.001) and pO2 24.4± 0.81 to 22.2± 1.04 (p<.05) and meconium appeared in the amniotic fluid. N administered to the fetus produced similar significant changes plus arterial pH fell from 7.39±0.01 to 7.35±0.02 (p< .05).In a lamb born after 14 days of MS infusion to the ewe N produced cardiovascular responses similar to those before birth,and the “withdrawal” responses seen in the ewes. MS, therefore, crosses the placenta and has a primary drug effect in the fetus. In addition,the fetus has a unique pharmacologic response to N after exposure to MS. This suggests the potential for development of OD in the fetus as a primary, drug-related effect of maternal to fetal transfer of MS.
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Cohen, M., Rudolph, A. & Melmon, K. 238 RESPONSES TO MORPHINE IN THE PREGNANT EWE. Pediatr Res 12 (Suppl 4), 403 (1978). https://doi.org/10.1203/00006450-197804001-00243
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DOI: https://doi.org/10.1203/00006450-197804001-00243