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Current Hypertension Reports Aug 2017Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth... (Review)
Review
Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes preeclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.
Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Delivery, Obstetric; Endothelium, Vascular; Female; Humans; Hydralazine; Infant, Low Birth Weight; Infant, Newborn; Inflammation; Ischemia; Labetalol; Magnesium Sulfate; Placenta; Pre-Eclampsia; Pregnancy; Premature Birth
PubMed: 28689331
DOI: 10.1007/s11906-017-0757-7 -
High Blood Pressure & Cardiovascular... Jul 2023Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between... (Review)
Review
Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between pre-existing (chronic) hypertension and gestational hypertension, developing after 20 weeks of gestation and usually resolving within 6 weeks postpartum. There is a consensus that systolic blood pressure ≥ 170 or diastolic blood pressure ≥ 110 mmHg is an emergency and hospitalization is indicated. The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. The current European guidelines recommend initiating drug treatment in pregnant women with persistent elevation of blood pressure ≥ 150/95 mmHg and at values > 140/90 mmHg in women with gestational hypertension (with or without proteinuria), with pre-existing hypertension with the superimposition of gestational hypertension, and with hypertension with subclinical organ damage or symptoms at any time during pregnancy. Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice. The results of the CHIPS and CHAP studies are likely to reduce the threshold for initiating treatment. Women with a history of hypertensive disorders in pregnancy, particularly those with pre-eclampsia, are at high risk of developing cardiovascular disease later in life. Obstetric history should become a part of the cardiovascular risk assessment in women.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Hypertension, Pregnancy-Induced; Hypertension; Pre-Eclampsia; Antihypertensive Agents; Blood Pressure; Labetalol
PubMed: 37308715
DOI: 10.1007/s40292-023-00582-5 -
Pediatric Nephrology (Berlin, Germany) May 2019Neonatal hypertension is increasingly recognized as dramatic improvements in neonatal intensive care, advancements in our understanding of neonatal physiology, and... (Review)
Review
Neonatal hypertension is increasingly recognized as dramatic improvements in neonatal intensive care, advancements in our understanding of neonatal physiology, and implementation of new therapies have led to improved survival of premature infants. A variety of factors appear to be important in determining blood pressure in neonates, including gestational age, birth weight, and postmenstrual age. Normative data on neonatal blood pressure values remain limited. The cause of hypertension in an affected neonate is often identified with careful diagnostic evaluation, with the most common causes being umbilical catheter-associated thrombosis, renal parenchymal disease, and chronic lung disease. Clinical expertise may need to be relied upon to decide the best approach to treatment in such patients, as data on the use of antihypertensive medications in this age group are extremely limited. Available data suggest that long-term outcomes are usually good, with resolution of hypertension in most infants. In this review, we will take a case-based approach to illustrate these concepts and to point out important evidence gaps that need to be addressed so that management of neonatal hypertension may be improved.
Topics: Administration, Intravenous; Antihypertensive Agents; Birth Weight; Blood Pressure; Blood Pressure Determination; Clinical Decision-Making; Gestational Age; Humans; Hydralazine; Hypertension; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Intensive Care Units, Neonatal; Kidney; Labetalol; Neuroblastoma; Reference Values; Renal Artery Obstruction; Severity of Illness Index; Treatment Outcome
PubMed: 29808264
DOI: 10.1007/s00467-018-3977-4 -
Lancet (London, England) Sep 2019Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended... (Randomized Controlled Trial)
Randomized Controlled Trial
Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial.
BACKGROUND
Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended to reduce the risk for maternal complications. Regimens for the acute treatment of severe hypertension typically include intravenous medications. Although effective, these drugs require venous access and careful fetal monitoring and might not be feasible in busy or low-resource environments. We therefore aimed to compare the efficacy and safety of three oral drugs, labetalol, nifedipine retard, and methyldopa for the management of severe hypertension in pregnancy.
METHODS
In this multicentre, parallel-group, open-label, randomised controlled trial, we compared these oral antihypertensives in two public hospitals in Nagpur, India. Pregnant women were eligible for the trial if they were aged at least 18 years; they were pregnant with fetuses that had reached a gestational age of at least 28 weeks; they required pharmacological blood pressure control for severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg); and were able to swallow oral medications. Women were randomly assigned to receive 10 mg oral nifedipine, 200 mg oral labetalol (hourly, in both of which the dose could be escalated if hypertension was maintained), or 1000 mg methyldopa (a single dose, without dose escalation). Masking of participants, study investigators, and care providers to group allocation was not possible because of different escalation protocols in the study groups. The primary outcome was blood pressure control (defined as 120-150 mm Hg systolic blood pressure and 70-100 mm Hg diastolic blood pressure) within 6 h with no adverse outcomes. This study is registered with ClinicalTrials.gov, number NCT01912677, and the Clinical Trial Registry, India, number ctri/2013/08/003866.
FINDINGS
Between April 1, 2015, and Aug 21, 2017, we screened 2307 women for their inclusion in the study. We excluded 1413 (61%) women who were ineligible, declined to participate, had impending eclampsia, were in active labour, or had a combination of these factors. 11 (4%) women in the nifedipine group, ten (3%) women in the labetalol group, and 11 (4%) women in the methyldopa group were ineligible for treatment (because they had only one qualifying blood pressure measurement) or had treatment stopped (because of delivery or transfer elsewhere). 894 (39%) women were randomly assigned to a treatment group and were included in the intention-to-treat analysis: 298 (33%) women were assigned to receive nifedipine, 295 (33%) women were assigned to receive labetalol, and 301 (33%) women were assigned to receive methyldopa. The primary outcome was significantly more common in women in the nifedipine group than in those in the methyldopa group (249 [84%] women vs 230 [76%] women; p=0·03). However, the primary outcome did not differ between the nifedipine and labetalol groups (249 [84%] women vs 228 [77%] women; p=0·05) or the labetalol and methyldopa groups (p=0·80). Seven serious adverse events (1% of births) were reported during the study: one (<1%) woman in the labetalol group had an intrapartum seizure and six (1%) neonates (one [<1%] neonate in the nifedipine group, two [1%] neonates in the labetalol group, and three [1%] neonates in the methyldopa group) were stillborn. No birth had more than one adverse event.
INTERPRETATION
All oral antihypertensives reduced blood pressure to the reference range in most women. As single drugs, nifedipine retard use resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa use. All three oral drugs-methyldopa, nifedipine, and labetalol-are viable initial options for treating severe hypertension in low-resource settings.
FUNDING
PREEMPT (University of British Columbia, Vancouver, BC, Canada; grantee of Bill & Melinda Gates Foundation).
Topics: Administration, Oral; Adult; Antihypertensive Agents; Blood Pressure; Female; Humans; Hypertension, Pregnancy-Induced; India; Infant, Newborn; Labetalol; Methyldopa; Nifedipine; Pregnancy; Pregnancy Outcome; Treatment Outcome; Young Adult
PubMed: 31378394
DOI: 10.1016/S0140-6736(19)31282-6 -
European Journal of Clinical... Nov 2022Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and... (Review)
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.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced; Labetalol; Methyldopa; Nifedipine; Pregnancy; Pregnancy Complications, Cardiovascular
PubMed: 36104450
DOI: 10.1007/s00228-022-03382-3 -
F1000Research 2022: Preeclampsia is a highly prevalent disease among pregnant women. In the event of hypertensive emergency, nifedipine, labetalol, and hydralazine are assigned as... (Randomized Controlled Trial)
Randomized Controlled Trial
: Preeclampsia is a highly prevalent disease among pregnant women. In the event of hypertensive emergency, nifedipine, labetalol, and hydralazine are assigned as first-line therapies in preeclampsia. Further studies are needed to compare the effectiveness of these drugs to find the most cost-effective drug with minimal side effects. This study aimed to compare the effectiveness of these drugs in lowering blood pressure during hypertensive emergencies in severe preeclampsia. : 60 pregnant women with severe preeclampsia were recruited in this multiple centre double-blind randomized clinical trial from May 2021 to April 2022 in Indonesia. The patients were divided equally into three groups and treated with three doses of nifedipine, labetalol, and hydralazine, respectively within one hour with 20 minutes interval. The effectiveness was measured based on systolic and diastolic blood pressures, and mean arterial pressure (MAP). The observation was carried out until five hours post-third dose administration. : The blood pressure was reduced significantly after the administration of the first to the third dose of each antihypertensive (p<0.05). A single dose administration, four, one, and three patients had 20% MAP reduction in nifedipine, labetalol, and hydralazine group. Three, seven, and one patient had a failure of reaching 20% MAP reduction even after receiving the third dose. The effectiveness of the drugs to achieve 20% reduction of MAP could be ranked as follows: nifedipine>labetalol>hydralazine (57.49%, 42.13%, and 40.87%, respectively) for single dose and hydralazine>nifedipine>labetalol (111.3%, 85.12%, and 90.04%, respectively) for triple dose. : Nifedipine is the most effective drug to reduce the blood pressure when single dose administration is used, but requires more doses to further reduce the blood pressure. Hydralazine is the most effective when the drug administration is maxed up to three doses within 60 minutes with 20 minutes interval. TCTR20221014007 (14/10/2022).
Topics: Female; Humans; Pregnancy; Labetalol; Nifedipine; Pre-Eclampsia; Antihypertensive Agents; Hydralazine
PubMed: 37273965
DOI: 10.12688/f1000research.125944.2 -
American Journal of Hypertension Oct 2020Elevated blood pressure (BP) is pervasive among patients that visit emergency departments (EDs) for their care. (Review)
Review
BACKGROUND
Elevated blood pressure (BP) is pervasive among patients that visit emergency departments (EDs) for their care.
METHODS
In this review article, we outline the current approach to the management of these individuals and highlight the crucial role emergency medicine clinicians play in reducing the morbidity associated with elevated BP.
RESULTS
We highlight the critical importance of immediate treatment when elevated BP contributes to new or worsening end-organ injury but emphasize that such hypertensive emergencies are rare. For the vast majority of patients with elevated BP in the ED who do not have new or worsening end-organ injury from elevated BP, immediate BP reduction within the ED is not recommended or safe. Nonetheless, within weeks after an ED visit, there is a pressing need to improve the care of patients with elevated or previously undiagnosed hypertension. For many, it may be their only regular point of engagement with the healthcare system. To address this, we present novel perspectives that envision a new role for emergency medicine in chronic hypertension management-one that acknowledges the significant population-level gaps in BP control that contribute to disparities in cardiovascular disease and sets the stage for future changes in systems-based practice.
CONCLUSIONS
Emergency medicine plays a key and evolving role in reducing morbidity associated with elevated BP.
Topics: Acute Disease; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Chronic Disease; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Hypertension; Labetalol; Nicardipine; Nitroprusside; Practice Guidelines as Topic; Pyridines; Referral and Consultation; Sodium Chloride Symporter Inhibitors; Undiagnosed Diseases
PubMed: 32307541
DOI: 10.1093/ajh/hpaa068