Action of several β‐adrenoceptor blocking drugs in the pregnant sheep and foetus

Abstract

Summary The effect of several β‐adrenoceptor blocking drugs on the pregnant ewe and foetus were studied. Bunolol, butidrine, oxprenolol, propranolol and USVP65‐24 all crossed the ovine placenta and produced a β‐adrenoceptor blockade in the ovine foetus. AH3474, AY21011 and sotalol did not cross the ovine placenta as assessed by the absence of a β‐blockade in the foetus when these compounds were administered to the pregnant ewe. Of the β‐blocking compounds tested, only propranolol and oxprenolol produced a prolonged blockade in the foetus. The β‐blockade with propranolol was of 3 h duration in the ewe and 10 h duration in the foetus. Oxprenolol produced a β‐blockade of 3 h duration in the ewe and 8 h in the foetus. The β‐blocking drugs which did cross the ovine placenta were more soluble in organic solvents (ether, chloroform, corn oil and olive oil) than those which did not cross the ovine placenta.

Sotalol as a Hypotensive Agent in Pregnancy

“…We have not demonstrated conclusively that beta-adrenoceptor blockade occurred in the fetus and newborn, but the combination of substantial umbilical cord concentrations and bradycardia during the early neonatal period strongly suggest this possibility. These results appear to contrast with failure to demonstrate evidence of fetal betaadrenoceptor blockade with sotalol in the pregnant ewe (Truelove et al, 1973).…”

“…ALTHOUGH only recently shown to be effective (Gallery et al, 1979), beta-adrenoceptor blocking drugs have been quite widely prescribed for some time in the management of hypertension occurring during pregnancy (Lewis et al, 1977), despite concern about possible adverse fetal and neonatal effects (Fiddler, 1974;Gladstone et al, 1975;Cottril et al, 1977;Habib and McCarthy, 1977;Lieberman et al, 1978;Sabom et al, 1978). These reports have described complications attributed to the use of propranolol, the administration of which to the pregnant ewe has been shown to be followed by evidence of betaadrenoceptor blockade in the fetus (Truelove et al, 1973), indicating that this drug crosses the placental barrier. In the same model, sotalol did not appear to enter the fetus (Truelove et al, 1973), a finding which could be consistent with its lower lipid solubility and which, if repeated in humans, would confer considerable advantage for its use in pregnancy.…”

“…These reports have described complications attributed to the use of propranolol, the administration of which to the pregnant ewe has been shown to be followed by evidence of betaadrenoceptor blockade in the fetus (Truelove et al, 1973), indicating that this drug crosses the placental barrier. In the same model, sotalol did not appear to enter the fetus (Truelove et al, 1973), a finding which could be consistent with its lower lipid solubility and which, if repeated in humans, would confer considerable advantage for its use in pregnancy.…”

Effects of racemic, dextro‐laevo‐propranolol and isoxuprine on the metabolic and endocrine response to cold in the newborn rabbit

“…This topic has clinical interest since P-adrenergic drugs are used in pregnancy for their cardiac actions and more commonly to both stimulate and inhibit uterine contractions [21,241 . The sheep placenta is permeable to propranolol and other P blockers [34] and the human placenta may be permeable to both P blockers and agonists such as isoxuprine [3, lo]. Case reports suggest that chronic fetal exposure to propranolol may affect growth as well as having cardiovascular effects [29] and the slower metabolism of such drugs by the newborn means that their effects may alter the normal adaptation to extra-uterine life.…”

The Effect of Racemic, D-, or I-Propranolol and Practolol on the Response to Cold by the Newborn Rabbit

“…The sheep placenta is permeable to propranolol and other ,f? blockers (20) and the human placenta is probably permeable to , B blockers (1, 4). Despite this knowledge that the fetus may be acutely or chronically exposed to such drugs there is little information on the effect of these drugs on the newborn.…”