A mother received ten minutes before the partus an overdose of Nepresol (dihydralazin) (17.5 mg int

Fråga: A mother received ten minutes before the partus an overdose of Nepresol (dihydralazin) (17.5 mg intravenously) after which an apparently healthy child was born. The blood pressure of the mother went down to 100/60 mmHg. The circulation of the child was good. After 1.5 days, the child developed muscle cramps of an unclear type, 2-3 times daily. Could the cramps be caused by the overdose of Nepresol?

Sammanfattning: It is not known if dihydralazine could have caused the cramps of the child in this particular case. Taking into account the short half-life of the drug, the absence of circulatory problems when the child was born and the lag time between delivery and the beginning of the cramps, a cause effect relationship i less likely.

Svar: Dihydralazine is mostly used parenterally in cases of hypertensive emergency, but can also be administered orally. The recommended initial dose is 6.25 mg, given intramuscularly or slowly intravenously, which can be repeated (1). Pharmacokinetic data obtained after oral administration of 20 mg of dihydralazine (2) reveal a mean plasma half-life of 4.9 hours. The formed acid-labile metabolites were included in the analysis. In this study, the acetylator status was not considered to correlate significantly to the plasma concentration. This in contrast to hydralazine, where steady-state plasma concentrations are known to be higher in slow acetylators compared to fast acetylators. Less than 10 per cent of dihydralazine is converted into hydralazine (3). No reports could be found concerning the metabolism of dihydralazine in infants.

The distribution pattern of dihydralazine between maternal and umbilical blood (4) during labor was studied in 12 pregnant patients, who received chronic oral treatment (75-100 mg daily) up to labor, for a period between two days and two months. The umbilical plasma levels of dihydralazine were on average twice as high as the corresponding maternal concentration. However, the patient concerned in the question only received one single dose, given intravenously, 10 minutes before delivery. It´s difficult to predict how much of the drug could have reached the child´s circulation.

According to the clinical data, the child developed the cramps not before 1.5 days after delivery. A very extensive literature search, including a Medline search did not show any report concerning cramps caused by dihydralazine, neither as a toxic, nor as a withdrawal effect. It seems that convulsions have been reported after an overdose of dihydralazine in adults as a consequence of circulatory collaps (personal communication, Ciba-Geigy), but there are no data available. 1 FASS 1990, sid 678 2 Waller AR, Chasseaud LF, Taylor T, Darragh A, O´Kelly DA: Plasma concentrations and pharmacokinetics of dihydralazine after single oral doses to human subjects. Biopharm Drug Dispos 1979; 1: 59-64 3 Rouan MC, Campestrini J: Liquid chromatographic determination of dihydralazine and hydralazine in human plasma and its application to pharmacokinetic studies of dihydralazine. J Pharm Sci 1985; 74: 1270-1273 4 Franke G, Pietsch P, Schneider T, Siegmund W, Grabow D, Schutz H: Studies on the kinetics and distribution of dihydralazine in pregnancy. Biol Res Pregnancy 1986: 7: 30-33