No abstract

The extensibility of the cervix of rats was measured in vitro on Day 19 of pregnancy and was doubled after 2 s.c. injections of PGF-2 alpha (1 mg/kg) or PGE-2 (5 mg/kg) on Day 18. Progesterone (10 mg/kg) given on Day 18 had no effect alone or on the effect of PGE-2 but abolished the action of PGF-2 alpha. PGE-2, but not PGF-2 alpha, increased extensibility when given on Day 18 to rats which had been bilaterally ovariectomized on Day 16 and given oestradiol benzoate plus progesterone twice daily. High concentrations of PGF-2 alpha or PGE-2 had no effect on the extensibility of Day-18 pregnant rat cervix in vitro. It is suggested that PGF-2 alpha acts via the ovaries to decrease progesterone secretion and perhaps release relaxin, but PGE-2 would appear to have another site of action.

The responses of circularly cut strips of cervix and uterine horn from rats on days 20 and 22 of pregnancy to drugs were compared in vitro. The cervix exhibited similar responses and sensitivities to acetylcholine, bradykinin, prostaglandin (PG) F2a (day 20) and isoprenaline (day 20) as did the uterine horn but was less sensitive or responded less consistently to isoprenaline (day 22), oxytocin and PGEj. PGE2 was more potent on the cervix (day 20). Before term the relatively inextensible connective tissue of the cervix plus contractions of the smooth muscle would help to prevent foetal expulsion. At term the cervical smooth muscle is sufficiently unresponsive to allow cervical dilatation.

Field stimulation of isolated, spirally-cut cervix from day-22 pregnant rats produced contractions which could be inhibited by tetrodotoxin or hyoscine and potentiated by propranolol. The rat cervix would appear to receive both cholinergic and noradrenergic innervations whose transmitters activate muscarinic cholinoceptors and beta-adrenoceptors respectively.

The disposition and elimination of phenoperidine was studied in five normal subjects, and in six patients with hepatic disease. Plasma concentrations of phenoperidine were generally higher in patients with hepatic dysfunction. Secondary peaks were observed between 15 and 105 min (particularly in patients with liver disease). In the patients the terminal half-life of phenoperidine was prolonged by approximately 50%, mainly because of a decrease in the clearance of the drug. There was little or no change in the total apparent volume of distribution. However, the differences between normal subjects and patients with hepatic disease were not statistically significant. The results suggest that slight or moderate impairment of hepatic function does not significantly affect the kinetics of the drug, and that modification of its dosage may not be required.