Atenolol developmental toxicity: Animal‐to‐human comparisons

Tabacova, Sonia; Kimmel, Carole A.; Wall, Kelly S.; Hansen, Deborah K.

doi:10.1002/bdra.10011

Cited by 44 publications

(21 citation statements)

References 28 publications

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“…Several other studies have been published since then with generally similar results [10][11][12][13]. However, the majority of the evidence for the efficacy of animal studies is based on true positives, with limited analysis of the false positives and false negatives [14,15].…”

Section: Introductionmentioning

confidence: 90%

Prediction of clinical risks by analysis of preclinical and clinical adverse events

Clark

2015

Journal of Biomedical Informatics

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This study examines the ability of nonclinical adverse event observations to predict human clinical adverse events observed in drug development programs. In addition it examines the relationship between nonclinical and clinical adverse event observations to drug withdrawal and proposes a model to predict drug withdrawal based on these observations. These analyses provide risk assessments useful for both planning patient safety programs, as well as a statistical framework for assessing the future success of drug programs based on nonclinical and clinical observations. Bayesian analyses were undertaken to investigate the connection between nonclinical adverse event observations and observations of that same event in clinical trial for a large set of approved drugs. We employed the same statistical methods used to evaluate the efficacy of diagnostic tests to evaluate the ability of nonclinical studies to predict adverse events in clinical studies, and adverse events in both to predict drug withdrawal. We find that some nonclinical observations suggest higher risk for observing the same adverse event in clinical studies, particularly arrhythmias, QT prolongation, and abnormal hepatic function. However the lack of these events in nonclinical studies is found to not be a good predictor of safety in humans. Some nonclinical and clinical observations appear to be associated with high risk of drug withdrawal from market, especially arrhythmia and hepatic necrosis. We use the method to estimate the overall risk of drug withdrawal from market using the product of the risks from each nonclinical and clinical observation to create a risk profile.

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Section: Introductionmentioning

confidence: 90%

Prediction of clinical risks by analysis of preclinical and clinical adverse events

Clark

2015

Journal of Biomedical Informatics

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“…37 β-Blockers are used less commonly in pregnancy because of concerns about fetal growth restriction raised in retrospective studies examining the outcomes of pregnancies in which atenolol was used. 38 Some organizations recommend that atenolol be avoided in pregnancy. 1 Data are sparse for the use of calcium channel blockers in pregnancy to control blood pressure (as opposed to short-term use for the treatment of preterm contractions/preterm labor), and most data are available for long-acting nifedipine.…”

Section: Antihypertensive Medicationsmentioning

confidence: 99%

Chronic Hypertension in Pregnancy

2014

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1254C hronic hypertension in pregnancy is defined by the American College of Obstetrics and Gynecology (ACOG) as blood pressure ≥140 mm Hg systolic and/or 90 mm Hg diastolic before pregnancy or, in recognition that many women seek medical care only once pregnant, before 20 weeks of gestation, use of antihypertensive medications before pregnancy, or persistence of hypertension for >12 weeks after delivery. 1Chronic hypertension needs to be distinguished from new-onset hypertensive complications of pregnancy such as preeclampsia (elevated blood pressure and proteinuria often accompanied by evidence of maternal organ injury and fetal compromise from placental dysfunction) 2 and gestational hypertension (elevated blood pressure alone after 20 weeks of gestation and most commonly in the mid to late third trimester without evidence or history of hypertension before pregnancy; Table 1). EpidemiologyChronic hypertension is estimated to be present in ≈3% to 5% of pregnancies 1,3,4 and is increasingly more commonly encountered. Factors contributing to the increase in prevalence include 2 major risk factors for hypertension, obesity and older age, which are of increasing prevalence in pregnancy. These shifts in risk and childbearing have resulted in an increased number of women who will require counseling on the risks of chronic hypertension in pregnancy and management of their antihypertensive medications both in anticipation of and during pregnancy.5 Because many pregnancies are unplanned, 6 all women with chronic hypertension should receive regular counseling so that they can anticipate any issues that may arise if they become pregnant and optimize their health and care to temper risk. Because blacks have a higher prevalence of chronic hypertension 7 and onset occurs at younger ages, 8 it is more common to encounter chronic hypertension in blacks during pregnancy.Despite its increasing prevalence, the majority of women with chronic hypertension do well in pregnancy, but as we discuss below, some women develop complications such as superimposed preeclampsia, fetal growth restriction, placental abruption, 4,9,10 and preterm birth, and women with chronic hypertension have an increased likelihood of cesarean delivery. Physiological Changes in Blood Pressure During PregnancyWomen who are normotensive entering pregnancy typically experience a decrease in blood pressure toward the end of the first trimester. This decrease is thought to be secondary to the marked vasodilation that occurs despite the increase in plasma volume that comes with pregnancy. Blood pressure usually falls by 5 to 10 mm Hg and remains at this lower level throughout pregnancy until the third trimester, when it rises to return to prepregnancy values. For the majority of women with chronic hypertension, blood pressure changes also follow this same pattern. As a result, some hypertensive women become normotensive during pregnancy, and others who remain hypertensive can have their antihypertensive medications tapered. These physiological changes may confuse t...

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“…Synthesis of this information suggests that while treatment with medication decreases the risk of progression to severe hypertension, it has little effect on pregnancy outcomes including development of preeclampsia, preterm delivery, or fetal/neonatal demise 6 . Antihypertensive exposure may confer some risk to the fetus by increasing rates of intrauterine growth restriction (although whether such associations are causal or confounded by indication or relative hypotension is unknown) 7, 8 and, for some agents, congenital malformations—although data are conflicting and these associations are controversial 9–15 . Further, while methyldopa and labetalol are generally considered in guidelines as the first line/preferred agents for the treatment of hypertension in pregnancy 3, 5, 16 , experts suggest that other antihypertensives can also be safely used 17–19 .…”

Section: Introductionmentioning

confidence: 99%

Patterns of Outpatient Antihypertensive Medication Use During Pregnancy in a Medicaid Population

et al. 2012

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Hypertensive disorders occur in approximately 6–8% of all pregnancies and are a significant source of maternal and fetal morbidity. Little is known about the range of agents routinely used in practice. We used Medicaid claims from 2000–2007 to identify completed pregnancies. We included women who were Medicaid beneficiaries from at least 3 months prior to last menstrual period to 1 month post-delivery, and were successfully linked to infant records. Maternal exposure to antihypertensive medications was derived from Medicaid pharmacy claims files and duration of exposure was assigned based on the days supply dispensed. We identified 1,106,757 Medicaid patients in our cohort of whom 48,453 (4.4%) were exposed to antihypertensive medications during pregnancy. The prevalence of antihypertensive use increased from 3.5% to 4.9% during the study period. Antihypertensive medications users were older than non-users, more likely to be Caucasian or African-American, and more likely to have comorbid diabetes and/or renal disease. Overall, 1.9% of pregnant women were exposed during the 1st trimester, 1.7% during the 2nd trimester, and 3.2% during the 3rd trimester. The range of antihypertensive medications to which patients were exposed was highly heterogeneous and frequently included agents other than methyldopa or labetalol. ACE inhibitor exposure, which is contraindicated in late pregnancy, occurred in 928 (4.9%) antihypertensive medication users in the 2nd trimester and 383 (1.1%) in the 3rd trimester. Antihypertensive use during pregnancy is relatively common and increasing. The wide range of agents used during pregnancy includes medications considered contraindicated during pregnancy.

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Atenolol developmental toxicity: Animal‐to‐human comparisons

Cited by 44 publications

References 28 publications

Prediction of clinical risks by analysis of preclinical and clinical adverse events

Prediction of clinical risks by analysis of preclinical and clinical adverse events

Chronic Hypertension in Pregnancy

Patterns of Outpatient Antihypertensive Medication Use During Pregnancy in a Medicaid Population

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