Labetalol-Induced Hepatotoxicity during Pregnancy: A Case Report

Whelan, Anna; Izewski, Joanna; Berkelhammer, Charles; Walloch, Jami; Kay, Helen H.

doi:10.1055/s-0040-1713789

Cited by 15 publications

(15 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the increased Frontiers in Pharmacology frontiersin.org coincidence of ICP with preeclampsia (Raz et al, 2015;Marathe et al, 2017;Mor et al, 2020), there is an increased chance that antihypertensive therapy with labetalol will be used during this form of cholestasis. However, labetalol was previously linked to drug-induced liver damage in pregnant women (Firoz et al, 2015;Whelan et al, 2020). Therefore, we evaluated the impact of labetalol Frontiers in Pharmacology frontiersin.org treatment on BA turnover in estrogen-induced cholestasis, the animal model for ICP.…”

Section: Discussionmentioning

confidence: 99%

Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis

et al. 2023

View full text Add to dashboard Cite

Labetalol is used for the therapy of hypertension in preeclampsia. Preeclampsia is characterized by high soluble endoglin (sEng) concentration in plasma and coincides with intrahepatic cholestasis during pregnancy (ICP), which threatens the fetus with the toxicity of cumulating bile acids (BA). Therefore, we hypothesized that both labetalol and increased sEng levels worsen BA cumulation in estrogen-induced cholestasis. C57BL/6J, transgenic mice overexpressing human sEng, and their wild-type littermates were administrated with ethinylestradiol (EE, 10 mg/kg s.c., the mice model of ICP) and labetalol (10 mg/kg s.c.) for 5 days with sample collection and analysis. Plasma was also taken from healthy pregnant women and patients with ICP. Administration of labetalol to mice with EE cholestasis aggravated the increase in BA plasma concentrations by induction of hepatic Mrp4 efflux transporter. Labetalol potentiated the increment of sEng plasma levels induced by estrogen. Increased plasma levels of sEng were also observed in patients with ICP. Moreover, increased plasma levels of human sEng in transgenic mice aggravated estrogen-induced cholestasis in labetalol-treated mice and increased BA concentration in plasma via enhanced reabsorption of BAs in the ileum due to the upregulation of the Asbt transporter. In conclusion, we demonstrated that labetalol increases plasma concentrations of BAs in estrogen-induced cholestasis, and sEng aggravates this retention. Importantly, increased sEng levels in experimental and clinical forms of ICPs might present a novel mechanism explaining the coincidence of ICP with preeclampsia. Our data encourage BA monitoring in the plasma of pregnant women with preeclampsia and labetalol therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…At present, a single antihypertensive drug combined with lifestyle improvement is used to treat patients with PIH, but the treatment effect is not ideal [ 14 ]. Due to the poor physical quality of pregnant women, this situation is easy to cause adverse effects in the fetus [ 15 , 16 ]. Labetalol hydrochloride is one of the antihypertensive drugs commonly used in the treatment of PIH, which can dilate blood vessels, reduce cardiac load and myocardial oxygen consumption, and increase cardiac output, so as to achieve the purpose of lowering blood pressure [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Evaluation of Pinggan Yiqi Yangshen Recipe Combined with Labetalol Hydrochloride and Magnesium Sulfate in the Treatment of PIH

Zhao²,

Gao³

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. To observe the clinical effect of Pinggan Yiqi Yangshen recipe combined with labetalol hydrochloride and magnesium sulfate in the treatment of pregnancy-induced hypertension (PIH). Methods. A total of 126 patients with PIH diagnosed in our hospital from January 2016 to May 2018 were randomly divided into the control group and the experimental group, with 63 cases in each group. The control group was treated with labetalol combined with magnesium sulfate. On the basis of the control group, the experimental group was treated with Pinggan Yiqi Yangshen recipe. Clinical efficacy, blood pressure, renal function, and biochemical indexes were compared between the two groups. Moreover, pregnancy outcomes and adverse reactions were compared between the two groups. Results. After treatment, the total effective rate in the experimental group was higher than in the control group. Blood pressure and mean arterial pressure in the experimental group were more significantly downregulated than the control group. Renal function indexes and biochemical indexes in the experimental group were more significant than those in the control group. The incidence of cesarean section, preterm birth, and abnormal fetal heart rate in the experimental group was significantly lower than that in the control group. There was no difference in the incidence of fetal distress, postpartum hemorrhage, neonatal asphyxia, and adverse reactions between the two groups. Conclusion. Pinggan Yiqi Yangshen recipe combined with labetalol hydrochloride and magnesium sulfate can effectively reduce the blood pressure of patients with PIH, help patients to return to normal levels of biochemical indexes and renal function indexes, and improve pregnancy outcomes with high safety, which is worthy of further promotion and application in clinical practice.

show abstract

“…Labetalol was ultimately identified as the offending agent due to lack of other supporting evidence for other diagnoses and since labetalol has been shown in other patient populations to cause hepatic injury. The authors conclude that clinicians should be aware of labetalol's adverse effect profile which includes drug-induced liver injury and to not confuse drug-induced liver injury with other conditions which may lead to iatrogenic preterm delivery ( Whelan et al, 2020 ) [A].…”

Section: Labetalolmentioning

confidence: 99%