Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review.

PURPOSE: Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy. METHODS: A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta. RESULTS: A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied. CONCLUSION: We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects.

Aspirin for the prevention and treatment of pre-eclampsia: A matter of COX-1 and/or COX-2 inhibition?

Since the 1970s, we have known that aspirin can reduce the risk of pre-eclampsia. However, the underlying mechanisms explaining this risk reduction are poorly understood. Both cyclooxygenase (COX)-1- and COX-2-dependent effects might be involved. As a consequence of this knowledge hiatus, the optimal dose and timing of initiation of aspirin therapy are not clear. Here, we review how (COX-1 versus COX-2 inhibition) and when (prevention versus treatment) aspirin therapy may interfere with the mechanisms implicated in the pathogenesis of pre-eclampsia. The available evidence suggests that both COX-1- and COX-2-dependent effects play important roles in the early stage of aberrant placental development and in the next phase leading to the clinical syndrome of pre-eclampsia. Collectively, these data suggest that high-dose (dual COX inhibition) aspirin may be superior to standard low-dose (selective COX-1 inhibition) aspirin for the prevention and also treatment of pre-eclampsia. Therefore, we conclude that more functional and biochemical tests are needed to unravel the contribution of prostanoids in the mechanisms implicated in the pathogenesis of pre-eclampsia and the potential of dual COX and/or selective COX-2 inhibition for the prevention and treatment of pre-eclampsia. This information is vital if we are to deduce the suitability, optimal timing and dose of aspirin and/or a specific COX-2 inhibitor (most likely using modified forms that do not cross the placenta) that can then be tested in a randomized, controlled trial instead of the current practice of empirical dosing regimens.

Effect of postpartum lifestyle interventions on weight loss, smoking cessation, and prevention of smoking relapse: a systematic review.

UNLABELLED: Postpartum lifestyle interventions are recommended for women after pregnancies complicated by preeclampsia, intrauterine growth restriction, and/or gestational diabetes, since they are at increased cardiovascular risk. To identify potential intervention strategies to reduce this risk, a systematic review of the literature is presented on the effectiveness of postpartum lifestyle interventions aimed at weight loss, smoking cessation, and smoking relapse prevention. The main characteristics of these postpartum lifestyle interventions are briefly described. The PubMed, Embase, Web of Science, PsychInfo, and Cinahl databases were searched for studies on the effects of postpartum lifestyle interventions on weight loss, and smoking cessation or prevention of smoking relapse, initiated for up to 1 year postpartum. No studies on the effectiveness of postpartum lifestyle interventions after the aforementioned specific pregnancy complications were found. However, 21 studies are included that describe existing postpartum lifestyle interventions, which were applied to unselected (on the basis of pregnancy complications) postpartum women. Six of 8 weight loss interventions, 4 of 5 smoking cessation interventions, and 4 of 8 smoking relapse prevention interventions were effective. Individually tailored counseling, group counseling sessions, and use of diaries or other correspondence materials were shown to be effective. Currently, postpartum lifestyle interventions tailored specifically for women who experienced the pregnancy complications are lacking. While awaiting their development, it seems reasonable to utilize existing lifestyle interventions shown to be effective in unselected postpartum women. LEARNING OBJECTIVES: After completion of this educational activity, the obstetrician/gynecologist should be better able to: counsel patients on how to apply existing postpartum lifestyle intervention strategies aimed at weight loss, smoking cessation, and smoking relapse prevention to lower future cardiovascular risk; and educate postpartum women who have experienced preeclampsia, intra-uterine growth restriction, and/or gestational diabetes about their increased cardiovascular risk later in life. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.