The Pharmacologic Approach to the Prevention of Preeclampsia: From Antiplatelet, Antithrombosis and Antioxidant Therapy to Anticonvulsants

Abstract

Preeclampsia has been suggested to be a two-stage disorder of an alteration in placental perfusion (stage 1) leading to generalized vascular endothelial damage (stage 2). Because the mechanism linking the two stages remains unclear, effective primary prevention is still impossible. However, advances made in our understanding of the pathophysiology of preeclampsia have paved the way for secondary and tertiary prevention approaches.Platelets are known to be activated in early pregnancy. They also play a pivotal role in the process of inflammation, as demonstrated by the finding that CD40 ligand is shed from activated platelets to directly initiate inflammation of the vessel wall. According to the Cochrane Library Update summarizing data from over 30,000 women, secondary prevention with antiplatelet drugs is associated with a 19% decrease in the risk of preeclampsia.Additional randomized controlled trials are needed to establish the association between preeclampsia and thrombophilia. The effect of the antithrombotic agent heparin on pregnancy outcome in preeclampsia and its potential preventive action in high-risk patients need to be elucidated.One of the several hypotheses of the pathogenesis of preeclampsia focuses on the oxidative stress caused by the imbalance in prooxidant and antioxidant forces. Preliminary findings on vitamin E and vitamin C supplementation in preeclamptic women are encouraging, and suggest a rationale for larger clinical trials.Although there is currently no explanation for the positive effect of magnesium sulfate on eclamptic seizures, studies have provided enough evidence to encourage its worldwide use as the primary anticonvulsant of choice in the tertiary prevention of maternal and perinatal death in severe preeclampsia/eclampsia.In conclusion, secondary and tertiary prevention of preeclampsia is possible when targeted at reducing maternal and neonatal morbidity and mortality.

Magnesium Sulfate Mitigates Lung Injury Induced by Bilateral Lower Limb Ischemia-Reperfusion in Rats

“…Magnesium sulfate (MgSO 4 ) is used clinically for the treatment of severe pre-eclampsia and eclampsia [5]. In addition, cellular data from our group [6] and those from the other group [7] revealed that MgSO 4 possesses potent anti-inflammation capacity, as endotoxin-induced upregulation of inflammatory molecules could be inhibited by MgSO 4 .…”

“…MgSO 4 is a potent vasodilator [5]. One would expect that MgSO 4 administration might cause significant decreases in blood pressure.…”

Renal function in normal and disordered pregnancy

“…Resultant hypoperfusion causes release of angiogenic factors, altering maternal endothelial function and precipitating pre-eclampsia [45,46]. Other contributory factors implicated in the development of pre-eclampsia include RAAS involvement (detailed below), immune mechanisms [47,48] and release of oxidative stress products in the placenta [49–51]. …”

Increased neuronal seizure activity correlates with excessive systemic inflammation in a rat model of severe preeclampsia

“…22 Because PE and eclampsia are often associated with abnormal maternal inflammation, parenteral MgSO 4 has been an important drug for treating severe PE. 23 In the present study, to investigate whether systemic inflammation correlates with seizure activity, we established a new eclampsia-like model using electrical stimulation. We measured systolic blood pressure (SBP), proteinuria, creatinine (Cr), blood urea nitrogen (BUN), alanine transaminase (ALT) and aspartate transaminase (AST) to determine whether the model was successful.…”