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Hipertension Y Riesgo Vascular 2021Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as...
Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as non-severe (< 160/110 mmHg) and severe (≥ 160/110 mmHg). Before starting treatment in non-severe HTN, white- coat HTN should be ruled out. If outpatient management is possible, pharmacological initiation is suggested with sustained high values, avoiding < 120/80 mmHg. Safe drugs during pregnancy are methyldopa, labetalol, and nifedipine-retard. The use of nifedipine-XL or amlodipine can be considered with a lower level of evidence of safety. Diuretics, atenolol, and other beta-blockers for antihypertensive purposes is not recommended in this period. Renin-angiotensin-aldosterone system inhibitors are strictly contraindicated. In postpartum and breastfeeding, the same therapeutic regimen used during pregnancy can be maintained, trying early withdrawal of methyldopa. During puerperium, amlodipine and enalapril are safe, with minimal excretion in breast milk.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Breast Feeding; Female; Humans; Hypertension; Methyldopa; Nifedipine; Postpartum Period; Pregnancy
PubMed: 33632659
DOI: 10.1016/j.hipert.2021.01.002 -
The Lancet. Neurology Nov 2023Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial.
BACKGROUND
Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease.
METHODS
We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe. We included participants aged 18 years or older with symptomatic sporadic small vessel disease or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and an indication for antihypertensive treatment. Participants were randomly assigned (1:1:1) to one of three sequences of antihypertensive treatment using a computer-generated multiblock randomisation, stratified by study site and patient group. A 2-week washout period was followed by three 4-week periods of oral monotherapy with amlodipine, losartan, or atenolol at approved doses. The primary endpoint was change in cerebrovascular reactivity (CVR) determined by blood oxygen level-dependent MRI response to hypercapnic challenge in normal-appearing white matter from the end of washout to the end of each treatment period. Efficacy analyses were done by intention-to-treat principles in all randomly assigned participants who had at least one valid assessment for the primary endpoint, and analyses were done separately for participants with sporadic small vessel disease and CADASIL. This trial is registered at ClinicalTrials.gov, NCT03082014, and EudraCT, 2016-002920-10, and is terminated.
FINDINGS
Between Feb 22, 2018, and April 28, 2022, 75 participants with sporadic small vessel disease (mean age 64·9 years [SD 9·9]) and 26 with CADASIL (53·1 years [7·0]) were enrolled and randomly assigned to treatment. 79 participants (62 with sporadic small vessel disease and 17 with CADASIL) entered the primary efficacy analysis. Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10%/mm Hg [19·6; -45·5 to 31·1] for atenolol; p=0·39) but did differ in patients with CADASIL (15·7 × 10%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10%/mm Hg [27·5; -77·7 to 30·0] for atenolol; p=0·019). In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10%/mm Hg [-74·3 to -12·3]; p=0·0061). No deaths occurred. Two serious adverse events were recorded, one while taking amlodipine (diarrhoea with dehydration) and one while taking atenolol (fall with fracture), neither of which was related to study drug intake.
INTERPRETATION
4 weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. Whether antihypertensive drug classes differentially affect clinical outcomes in people with small vessel diseases requires further research.
FUNDING
EU Horizon 2020 programme.
Topics: Humans; Middle Aged; Aged; Antihypertensive Agents; Blood Pressure; Losartan; Atenolol; CADASIL; Cross-Over Studies; Treatment Outcome; Hypertension; Amlodipine; Double-Blind Method
PubMed: 37863608
DOI: 10.1016/S1474-4422(23)00293-4 -
The Medical Letter on Drugs and... May 2024
Review
Topics: Humans; Hypertension; Antihypertensive Agents; Blood Pressure
PubMed: 38771738
DOI: 10.58347/tml.2024.1703a -
American Journal of Kidney Diseases :... May 2021Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including... (Observational Study)
Observational Study
RATIONAL & OBJECTIVE
Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether β-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis.
STUDY DESIGN
Retrospective cohort study.
SETTING & PARTICIPANTS
Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included.
EXPOSURES
Patients were considered treated with β-blockers if they had a quantity of drug dispensed covering the dialysis transition date.
OUTCOMES
All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis.
ANALYTICAL APPROACH
Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between β-blocker use and study outcomes.
RESULTS
3,503 patients were included in the study. There were 2,115 (60.4%) patients using β-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any β-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization.
LIMITATIONS
The observational nature of our study could not fully account for residual confounding.
CONCLUSIONS
Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.
Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Atenolol; Bisoprolol; Carvedilol; Cause of Death; Cohort Studies; Female; Heart Failure; Hospitalization; Humans; Kidney Failure, Chronic; Labetalol; Logistic Models; Male; Metoprolol; Middle Aged; Mortality; Nadolol; Proportional Hazards Models; Propranolol; Protective Factors; Renal Dialysis; Retrospective Studies; Risk; Risk Factors
PubMed: 33010357
DOI: 10.1053/j.ajkd.2020.07.023 -
Expert Review of Clinical Pharmacology Aug 2020Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol... (Review)
Review
INTRODUCTION
Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments.
AREAS COVERED
The demonstration of a hemogenic endothelium origin of IH, with a neural crest phenotype and multi-lineage differentiation capacity, regulated by the renin-angiotensin system, underscores its programmed biologic behavior and accelerated involution induced by propranolol, other β-blockers and ACE inhibitors. We review the indications, dosing regimens, duration of treatment, efficacy and adverse effects of propranolol, and therapeutic alternatives including oral atenolol, acebutolol, nadolol, intralesional propranolol injections, topical propranolol and timolol, and oral captopril.
EXPERT OPINION
Improved understanding of the biology of IH provides insights into the mechanism of action underscoring its accelerated involution induced by propranolol, other β-blockers and ACE inhibitors. More research is required to understand the optimal dosing and duration, efficacy and safety of these alternative therapies. Recent demonstration of propranolol's actions mediated by non-β-adrenergic isomer R-propranolol on stem cells, offers an immense opportunity to harness the efficacy of β-blockers to induce accelerated involution of IH, while mitigating their β-adrenergic receptor-mediated adverse effects.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Hemangioma; Humans; Infant; Propranolol; Renin-Angiotensin System; Skin Neoplasms
PubMed: 32662682
DOI: 10.1080/17512433.2020.1788938 -
Molecules (Basel, Switzerland) May 2021Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete.... (Review)
Review
Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.
Topics: Acyclovir; Atenolol; Atovaquone; Catalysis; Chemistry, Pharmaceutical; Decitabine; Dopamine; Enzymes; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Molecular Conformation; Nucleosides; Phenylephrine; Prodrugs; Protons; Quantum Theory; Software; Technology, Pharmaceutical; Temperature; Tranexamic Acid
PubMed: 34071328
DOI: 10.3390/molecules26113248 -
The New England Journal of Medicine Jan 2021A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease.
METHODS
Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed.
RESULTS
A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups.
CONCLUSIONS
Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).
Topics: Aged; Anticholesteremic Agents; Antihypertensive Agents; Aspirin; Atenolol; Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Incidence; Male; Medication Adherence; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Simvastatin
PubMed: 33186492
DOI: 10.1056/NEJMoa2028220 -
American Journal of Obstetrics and... Oct 2020Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE DATA
Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension.
STUDY
Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension.
STUDY APPRAISAL AND SYNTHESIS METHODS
The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence.
RESULTS
Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery.
CONCLUSION
Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy.
Topics: Abruptio Placentae; Amlodipine; Antihypertensive Agents; Atenolol; Cesarean Section; Chronic Disease; Female; Fetal Growth Retardation; Furosemide; Gestational Age; Humans; Hypertension; Incidence; Infant, Small for Gestational Age; Ketanserin; Methyldopa; Network Meta-Analysis; Nifedipine; Perinatal Death; Pindolol; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Premature Birth; Severity of Illness Index
PubMed: 32199925
DOI: 10.1016/j.ajog.2020.03.016 -
Materials (Basel, Switzerland) Mar 2024Adsorptive, catalytic, and antibacterial properties of clinoptilolite-rich tuffs (ZT) are presented here. ZT transformed into Fe-containing ZT (Fe-ZT) removes various... (Review)
Review
Adsorptive, catalytic, and antibacterial properties of clinoptilolite-rich tuffs (ZT) are presented here. ZT transformed into Fe-containing ZT (Fe-ZT) removes various organic and inorganic anions from water. Fe-ZT, which contains selenium, is beneficial for growing mushrooms. The fungi convert inorganic Se from Fe-ZT into a more useful organically bonded form. ZT and Fe-ZT as supplements retain nitrogen and potassium in sandy, silty loam and silty clay soils. ZT shows an affinity toward toxic metal cations, which are essential for cleaning contaminated water. The adsorption of atenolol, acetylsalicylic, and salicylic acid onto M-ZT (M-Cu, Mn, Ni, or Zn) from water solutions suggests that both the natures of M and pharmaceuticals have a significant impact on the adsorption mechanism and determine the adsorption capability of the ZT. ZT is an excellent carrier for ultrafine (2-5 nm) nano oxide particles, which have been shown to have catalytic activity in different chemical processes and photodegradation reactions of organic pollutants. ZT can also be transformed into SO-SnO-ZT, which is catalytically active as a solid acid. M-ZT is an effective carrier of valuable bacteria. Ag-ZT possesses beneficial bactericidal activity in disinfecting water and soil remediation.
PubMed: 38541460
DOI: 10.3390/ma17061306