PHENTOLAMINE

Fetal Risk Summary

The short-acting a-adrenergic blocker phentolamine is used for the treatment of severe hypertension secondary to maternal pheochromocytoma. Animal studies with phentolamine have observed neither teratogenicity nor embryotoxicity (1). No reports of adverse fetal outcome in humans have been located, but 1st trimester experience with this agent has not been documented, nor have studies describing the placental transfer of phentolamine in humans been found. However, although apparently not teratogenic, phentolamine must be used with caution because of the marked decrease in maternal blood pressure that can occur with resulting fetal anoxia.

Early in vitro and in vivo investigations of phentolamine indicated the drug inhibited the l-norepinephrine–stimulated contractile activity of human myometrium (2,3 and 4). A 1971 investigation, however, examined the effect of combined a-adrenergic blockade (phentolamine) and b-adrenergic stimulation (isoxsuprine) on oxytocin-stimulated uterine activity in six women just before undergoing therapeutic abortion at 16–20 weeks' gestation (5). The results indicated that phentolamine had no effect on uterine activity, while isoxsuprine inhibited uterine contractions. Moreover, the uterine inhibitory effect of b-stimulation was independent of a-blockade.

In one study, phentolamine was used for approximately 10 weeks for the treatment of toxemia (2). No adverse effects in the fetus were observed and the infant was alive and well at 18 months. However, the authors commented that they had stopped using phentolamine for this purpose because prolonged use in a few cases had resulted in “jitters” in the newborns, especially in premature infants (2).

The most common use of phentolamine in pregnancy is for the diagnosis of pheochromocytoma. Administration of phentolamine to patients with this disease causes a marked drop in blood pressure. Because of the very rapid half-life (19 minutes) of the drug, the return to the pretest blood pressures usually occurs in less than 30 minutes (1). A 1971 review article of pheochromocytoma in pregnancy cited 22 cases of the disease identified between 1955 and 1966 in which the diagnosis was made during pregnancy with phentolamine (6). Three additional cases were published in 1969 (7) and 1973 (8). Reflecting the high maternal and fetal mortality that can occur with this disease, 21% (3 of 14) of the mothers and 43% (6 of 14) of the fetuses died.

Phentolamine has been used for the short-term management of severe hypertension caused by pheochromocytoma, including those cases occurring during surgery to deliver the fetus or to resect the tumor (9,10,11 and 12). No adverse effects on the fetus or newborn attributable to phentolamine from this use have been reported, but fetal hypoxia is a potential complication.

Breast Feeding Summary

No data are available.

References

1. Product information. Regitine. Ciba-Geigy Corporation, 1991.
2. Maughan GB, Shabanah EH, Toth A. Experiments with pharmacologic sympatholysis in the gravid. Am J Obstet Gynecol 1967;97:764–76.
3. Wansbrough H, Nakanishi H, Wood C. The effect of adrenergic receptor blocking drugs on the human uterus. J Obstet Gynaecol Br Commonw 1968;75:189–98.
4. Althabe O Jr, Schwarcz RL Jr, Sala NL, Fisch L. Effect of phentolamine methanesulfonate upon uterine contractility induced by l-norepinephrine in pregnancy. Am J Obstet Gynecol 1968;101:1083–8.
5. Jenssen H. Inhibition of oxytocin-induced uterine activity in midpregnancy by combined adrenergic a-blockade and b-stimulation. Acta Obstet Gynecol Scand 1971;50:135–9.
6. Schenker JG, Chowers I. Pheochromocytoma and pregnancy. Review of 89 cases. Obstet Gynecol Surv 1971;26:739–47.
7. Hendee AE, Martin RD, Waters WC III. Hypertension in pregnancy: toxemia or pheochromocytoma? Am J Obstet Gynecol 1969;105:64–72.
8. Smith AM. Phaeochromocytoma and pregnancy. J Obstet Gynaecol Br Commonw 1973;80:848–51.
9. Anton AH, Brenner WE, Yen SS, Dingfelder JR. Pheochromocytoma: studies during pregnancy, premature delivery and surgery. Abstract Presented at the 5th International Congress on Pharmacology, July 23–28, 1972, San Francisco, California, p. 8, #43.
10. Simanis J, Amerson JR, Hendee AE, Anton AH. Unresectable pheochromocytoma in pregnancy. Pharmacology and biochemistry. Am J Med 1972;53:381–5.
11. Brenner WE, Yen SSC, Dingfelder JR, Anton AH. Pheochromocytoma: serial studies during pregnancy. Am J Obstet Gynecol 1972;113:779–88.
12. Burgess GE III. Alpha blockade and surgical intervention of pheochromocytoma in pregnancy. Obstet Gynecol 1979;53:266–70.