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1.
Ter Arkh ; 94(2): 259-264, 2022 Feb 15.
Artigo em Russo | MEDLINE | ID: mdl-36286748

RESUMO

Over the past two years, the entire medical community has taken up the fight against the new coronavirus infection. At the initial encounter with COVID-19, it seemed that this virus mainly affects the respiratory system. Still, with long-term observation, it turned out that the consequences of this disease can be much more severe and associated with lung damage and thromboembolic complications, and be a trigger for autoimmune diseases. According to the literature, after suffering COVID-19, some patients debuted systemic lupus erythematosus, hemolytic anemia, thrombocytopenia, developed GuillainBarr syndrome, vasculitis, and multiple sclerosis, and a case of autoimmune hepatitis (AIH) was described in foreign literature. AIH is a fairly rare disease, the prevalence of which in Europe is 1618 cases per 100 thousand inhabitants, affecting mainly women. It is known that chemicals and drugs (minocycline, diclofenac, methyldopa, infliximab, etanercept), viruses (HAV, HEV, EBV, HCV, CMV), environmental factors can serve as triggers of the autoimmune process in the liver. This article presents two clinical cases of AIH that developed after suffering a new coronavirus infection, which we consider as the initial provoking factor of autoimmune inflammation. Given the rarity of AIH, the description of new triggers is of clinical interest. It may be useful for doctors of different specialties since they faced drug-induced liver damage against the background of antiviral and immunobiological therapy. In the domestic literature, there have not yet been any publications devoted to the debut of AIH in adults after coronavirus infection.


Assuntos
COVID-19 , Hepatite Autoimune , Adulto , Humanos , Feminino , Masculino , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/complicações , COVID-19/complicações , Etanercepte , Infliximab , Metildopa , Diclofenaco , Minociclina , Antivirais
2.
Eur J Clin Pharmacol ; 78(11): 1763-1776, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36104450

RESUMO

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.


Assuntos
Hipertensão Induzida pela Gravidez , Hipertensão , Labetalol , Complicações Cardiovasculares na Gravidez , Anti-Hipertensivos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/prevenção & controle , Labetalol/uso terapêutico , Metildopa/uso terapêutico , Nifedipino , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/prevenção & controle
3.
Hypertens Res ; 45(11): 1823-1831, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36109600

RESUMO

We investigated the trends in the proportion of antihypertensive prescriptions listed in the guidelines for pregnant patients and their pregnancy outcomes before and after regulatory actions in Japan. This retrospective cohort study used the Japan Medical Data Center claims data from January 2005 to April 2020. We identified women who had delivered and had hypertensive disorders before childbirth. To evaluate the influence of regulatory actions (label revision in 2011 and guideline updates in 2014), we divided the study period into three terms based on the year of the last menstrual period. We assessed the time trend of the prescription proportion of antihypertensives and conducted multivariable logistic regression analyses to assess the impact of the investigation terms on pregnancy outcomes (preterm birth, cesarean section, emergency cesarean section, and Hemolysis, Elevated Liver enzymes, and Low Platelets syndrome). Among the 13,797 eligible patients, 1739 (12.6%) were treated with oral antihypertensives during pregnancy. Before the policy revisions, the most frequently prescribed antihypertensive medication was methyldopa, but after the label and guideline revisions, nifedipine was the most frequently prescribed. The trend in the prescription proportion of nifedipine increased (P < 0.001) and that of hydralazine decreased (P < 0.001), while those of methyldopa and labetalol showed no significant trend. The adjusted odds ratios for all four pregnancy outcomes showed no significant differences according to the investigation terms. By investigating the three terms before and after the label and guideline revisions, significant changes were identified in the trend of the prescription proportion for pregnant women-an increase in nifedipine and a decrease in hydralazine-but not in pregnancy outcomes.


Assuntos
Hipertensão , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Anti-Hipertensivos , Metildopa/uso terapêutico , Nifedipino , Gestantes , Período Periparto , Cesárea , Estudos Retrospectivos , Japão , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente , Hidralazina/uso terapêutico , Prescrições de Medicamentos , Resultado da Gravidez
4.
Hypertens Res ; 45(9): 1441-1446, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35715513

RESUMO

Hypertensive disorders of pregnancy cause maternal organ damage. Therefore, appropriate management with antihypertensive medication is required from the first trimester. We aimed to clarify the antihypertensive drug prescription trends in pregnant women with hypertension in Japan. The administrative data of pregnant outpatients aged 16-49 years who visited acute hospitals between 2013 and 2020 were included. The annual antihypertensive drug prescription trends were evaluated based on their prescription proportions. The most prescribed drug in 2020 was nifedipine, followed by methyldopa and amlodipine. The proportion of nifedipine prescriptions significantly increased from 33.5 to 40.8% during the study period, whereas that of methyldopa significantly decreased from 16.6 to 11.6%. There was no change in the prescription trend of amlodipine. Dihydropyridine calcium channel blockers were the most commonly prescribed drug for pregnant women with hypertension.


Assuntos
Anti-Hipertensivos , Hipertensão , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Prescrições de Medicamentos , Feminino , Hospitais , Humanos , Hipertensão/tratamento farmacológico , Japão , Metildopa/uso terapêutico , Nifedipino , Gravidez , Gestantes
5.
Hepatol Commun ; 6(8): 1895-1909, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35596597

RESUMO

Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using search terms "drug-induced liver injury," "autoimmune hepatitis," and "drug-induced autoimmune hepatitis." DI-AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow-up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI-AILH with three possible DI-AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI-AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI-AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well-recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI-AILH, interferons, imatinib, adalimumab, and MPS were the best-documented agents leading to probable DI-AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI-AILH. Long-term immunosuppression appears to be rarely required in patients with DI-AILH due to these drugs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite A , Hepatite Autoimune , Adalimumab , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Diclofenaco , Feminino , Hepatite A/complicações , Hepatite Autoimune/diagnóstico , Humanos , Mesilato de Imatinib , Infliximab , Interferons , Metildopa , Metilprednisolona , Minociclina , Nitrofurantoína
6.
PLoS One ; 17(5): e0268284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35576217

RESUMO

OBJECTIVE: To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente, a large healthcare system in the United States. POPULATION: Women aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension. METHODS: We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. MAIN OUTCOME MEASURES: Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. RESULTS: Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other ß-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. CONCLUSIONS: Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.


Assuntos
Hipertensão Induzida pela Gravidez , Doenças do Recém-Nascido , Labetalol , Nascimento Prematuro , Anti-Hipertensivos/efeitos adversos , Peso ao Nascer , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Labetalol/uso terapêutico , Metildopa/uso terapêutico , Nifedipino/uso terapêutico , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/tratamento farmacológico , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos
7.
Hypertension ; 79(7): 1548-1558, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35502665

RESUMO

BACKGROUND: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes. METHODS: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents. RESULTS: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44-6.07]); PTB (aOR, 2.53 [2.39-2.67]); and FGR (aOR, 2.51 [2.31-2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05-1.30]), PTB (1.25 [1.12-1.39]), and FGR (1.80 [1.51-2.14]). Women prescribed methyldopa (versus ß-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19-1.73]); PTB (1.59 [1.30-1.93]), but lower odds of FGR (aOR, 0.66 [0.48-0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus ß-blockers) except for PTB (aOR, 1.94 [1.15-3.27]). Among women prescribed treatment, lower average blood pressure (<135/85 mm Hg) was associated with better pregnancy outcomes. CONCLUSIONS: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. ß-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy.


Assuntos
Hipertensão , Pré-Eclâmpsia , Nascimento Prematuro , Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Registros Eletrônicos de Saúde , Feminino , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Recém-Nascido , Metildopa , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/epidemiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle
8.
Chemosphere ; 297: 134170, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35247446

RESUMO

Diltiazem (DTZ) is one of the most important drugs in blood pressure that is used to treat cardiovascular diseases. With this overuse of this drug and its use for suicide, swelling and neck cramps and fever has made it important to measure it. So, this paper will give an account of modification of carbon paste electrode with the ternary-nanocomposite including reduced-graphene oxide (rGO), cadmium oxide and 1-ethyl 3- methyl imidazole chloride as ionic liquid for using the determination of DTZ in blood serum samples. Characterization of the synthesized rGO, cadmium oxide, and modified electrodes and their electrochemical performance were studied by, scanning electron microscopy, and X-ray diffraction, electrochemical impedance spectroscopy, and voltammetry technique. The improvement of the DTZ oxidation current by modified electrode originated from the increased electrode surface area. The optimized method was validated and the results showed that LOD = 3 nM and good linearity. Also, a linear concentration range of 0.01-150 µM with a LOD of 0.03 µM in presence methyldopa were achieved based on the electrochemical investigations. The prepared sensor showed good repeatability (RSD = 2.26%) and selectivity for DTZ determination in the real samples (relative recovery of 93-102%).


Assuntos
Grafite , Nanocompostos , Diltiazem , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite/química , Humanos , Metildopa , Nanocompostos/química
9.
Cardiovasc J Afr ; 33(5): 273-276, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35175275

RESUMO

Pre-eclampsia complicated by pulmonary oedema, severe hypertension, tachycardia and desaturation is a devastating condition. A comprehensive understanding of the aetiopathogenesis during such an emergency is challenging in the absence of functional and responsive point-of-care imaging, and laboratory and other critical-care services. An unbooked 26-year-old gravida 3 para 1+1 presented to a primary healthcare clinic with features of pre-eclampsia, severe hypertension and pulmonary oedema. The only available antihypertensive drug, methyldopa, was administered. The patient was transferred to a district hospital and subsequently referred to a tertiary hospital. On arrival, she was booked for caesarean delivery and in the maternity ward a central venous pressure (CVP) line was inserted. The patient developed pneumothorax and died in the intensive care unit undelivered. This case highlights many lessons, which are discussed. If CVP monitoring is indicated before caesarean delivery, consideration must be given to line insertion in the operating room to facilitate rapid delivery should the patient's condition deteriorate.


Assuntos
Hipertensão , Pré-Eclâmpsia , Edema Pulmonar , Feminino , Gravidez , Humanos , Adulto , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/tratamento farmacológico , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Anti-Hipertensivos/uso terapêutico , Metildopa , Hipertensão/tratamento farmacológico
11.
Water Environ Res ; 93(12): 2903-2913, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34363642

RESUMO

In this study, a magnetic nanocatalyst (Fe3 O4 @SiO2 @CeO2 ) was prepared and applied in the catalytic ozonation of methyldopa (MD). The effects of operational parameters on catalytic ozonation performance were investigated, including ozone dosage, catalyst dosage, initial MD concentration, and pH. The removal of MD was 45.2% in ozonation, whereas the efficiency was achieved to 83.0% with the addition of Fe3 O4 @SiO2 @CeO2 . The results showed that Fe3 O4 @SiO2 @CeO2 could significantly improve the catalytic ozonation performance. And the enhanced mechanism study showed that it was attributed to promotion of ozone decomposition to generate hydroxyl radical. The reaction model was explored, and the reaction rates were calculated for the MD degradation in catalytic ozonation. A higher degradation efficiency of MD in catalytic ozonation was attributed to the enhanced surface effect of the catalysts, which was confirmed by using TBA, PO4 3- , and p-BQ as scavengers of hydroxyl radical, surface reaction, and superoxide radical. The hydroxyl radical and superoxide radical played an important role in the degradation of MD. The mechanism of catalytic ozonation by Fe3 O4 @SiO2 @CeO2 was discussed via X-ray photoelectron spectroscopy (XPS) spectra and experimental data.


Assuntos
Ozônio , Poluentes Químicos da Água , Catálise , Metildopa , Dióxido de Silício , Poluentes Químicos da Água/análise
12.
Pregnancy Hypertens ; 25: 179-184, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34175582

RESUMO

OBJECTIVES: To evaluate community-based health workers' ability to identify cases of hypertension in pregnancy, safely deliver methyldopa and magnesium sulphate and make referrals when appropriate. STUDY DESIGN: This was part of Nigeria Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494). Community-based Health Workers (CHW) recruited pregnant women from five Local Government Areas (clusters) and used mobile health aid for clinical assessment of pre-eclampsia. MAIN OUTCOME MEASURES: The primary outcome was the number of adverse events that occurred after the administration of magnesium sulphate and/or methyldopa to pregnant women by CHWs. FINDINGS: Of 8790 women receiving mobile health-guided care, community-based health workers in Nigeria provided 309 women with hypertension (4.2% of delivered women), and safely administered 142 doses of intramuscular magnesium sulphate. Community Heath Extension Workers (CHEWs) and nurses gave fifty-two and sixty-seven doses of intramuscular magnesium sulphate respectively, twenty-three doses were given by other health care workers (midwives, community health officers, health assistants). The high rate of administration by nurses can be explained by turf protection as well as their seniority within the health system. Also, CHEWs and nurses gave 124 doses of oral methyldopa and 126 urgent referrals were completed. There were no complications related to administration of treatment or referral. INTERPRETATION: These findings demonstrate the ability of community-based health workers to safely administer methyldopa and intramuscular magnesium sulphate. The use of task-sharing, therefore, could drastically reduce the three delays (triage, transport and treatment) associated with high maternal mortality and morbidity in rural communities in low- and middle-income countries.


Assuntos
Anti-Hipertensivos/uso terapêutico , Competência Clínica , Serviços de Saúde Comunitária/normas , Pré-Eclâmpsia/prevenção & controle , Adolescente , Adulto , Anti-Hipertensivos/administração & dosagem , Benchmarking , Feminino , Humanos , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/uso terapêutico , Metildopa/efeitos adversos , Metildopa/uso terapêutico , Pessoa de Meia-Idade , Nigéria , Gravidez , Adulto Jovem
14.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652665

RESUMO

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1ß; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor ß-TGF-ß; vascular endothelial growth factor-VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1ß, IL-6, HIF-1α, TGF-ß, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.


Assuntos
Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Metildopa/farmacologia , Doenças Vasculares/tratamento farmacológico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas In Vitro , Inflamação/genética , Inflamação/patologia , Placenta/efeitos dos fármacos , Placenta/patologia , Fator de Crescimento Placentário/genética , Gravidez , Trofoblastos/efeitos dos fármacos , Doenças Vasculares/genética , Doenças Vasculares/patologia
15.
Hipertens Riesgo Vasc ; 38(3): 133-147, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-33632659

RESUMO

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.


Assuntos
Hipertensão , Nifedipino , Anlodipino/farmacologia , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Aleitamento Materno , Feminino , Humanos , Hipertensão/tratamento farmacológico , Metildopa/farmacologia , Metildopa/uso terapêutico , Nifedipino/farmacologia , Período Pós-Parto , Gravidez
16.
Cochrane Database Syst Rev ; 10: CD012039, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628642

RESUMO

BACKGROUND: Hypertension is the leading preventable risk factor for cardiovascular disease and premature death worldwide. One of the clinical effects of hypertension is left ventricular hypertrophy (LVH), a process of cardiac remodelling. It is estimated that over 30% of people with hypertension also suffer from LVH, although the prevalence rates vary according to the LVH diagnostic criteria. Severity of LVH is associated with a higher prevalence of cardiovascular disease and an increased risk of death. The role of antihypertensives in the regression of left ventricular mass has been extensively studied. However, uncertainty exists regarding the role of antihypertensive therapy compared to placebo in the morbidity and mortality of individuals with hypertension-induced LVH. OBJECTIVES: To assess the effect of antihypertensive pharmacotherapy compared to placebo or no treatment on morbidity and mortality of adults with hypertension-induced LVH. SEARCH METHODS: Cochrane Hypertension's Information Specialist searched the following databases for studies: Cochrane Hypertension Specialised Register (to 26 September 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2020, Issue 9), Ovid MEDLINE (1946 to 22 September 2020), and Ovid Embase (1974 to 22 September 2020). We searched the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov for ongoing trials. We also searched Epistemonikos (to 19 February 2021), LILACS BIREME (to 19 February 2021), and Clarivate Web of Science (to 26 February 2021), and contacted authors and funders of the identified trials to obtain additional information and individual participant data. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) with at least 12 months' follow-up comparing antihypertensive pharmacological therapy (monotherapy or in combination) with placebo or no treatment in adults (18 years of age or older) with hypertension-induced LVH were eligible for inclusion. The trials must have analysed at least one primary outcome (all-cause mortality, cardiovascular events, or total serious adverse events) to be considered for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors screened the search results, with any disagreements resolved by consensus amongst all review authors. Two review authors carried out the data extraction and analyses. We assessed risk of bias of the included studies following Cochrane methodology. We used the GRADE approach to assess the certainty of the body of evidence. MAIN RESULTS: We included three multicentre RCTs. We selected 930 participants from the included studies for the analyses, with a mean follow-up of 3.8 years (range 3.5 to 4.3 years). All of the included trials performed an intention-to-treat analysis. We obtained evidence for the review by identifying the population of interest from the trials' total samples. None of the trials provided information on the cause of LVH. The intervention varied amongst the included trials: hydrochlorothiazide plus triamterene with the possibility of adding alpha methyldopa, spironolactone, or olmesartan. Placebo was administered to participants in the control arm in two trials, whereas participants in the control arm of the remaining trial did not receive any add-on treatment. The evidence is very uncertain regarding the effect of additional antihypertensive pharmacological therapy compared to placebo or no treatment on mortality (14.3% intervention versus 13.6% control; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.74 to 1.40; 3 studies; 930 participants; very low-certainty evidence); cardiovascular events (12.6% intervention versus 11.5% control; RR 1.09, 95% CI 0.77 to 1.55; 3 studies; 930 participants; very low-certainty evidence); and hospitalisation for heart failure (10.7% intervention versus 12.5% control; RR 0.82, 95% CI 0.57 to 1.17; 2 studies; 915 participants; very low-certainty evidence). Although both arms yielded similar results for total serious adverse events (48.9% intervention versus 48.1% control; RR 1.02, 95% CI 0.89 to 1.16; 3 studies; 930 participants; very low-certainty evidence) and total adverse events (68.3% intervention versus 67.2% control; RR 1.07, 95% CI 0.86 to 1.34; 2 studies; 915 participants), the incidence of withdrawal due to adverse events may be significantly higher with antihypertensive drug therapy (15.2% intervention versus 4.9% control; RR 3.09, 95% CI 1.69 to 5.66; 1 study; 522 participants; very low-certainty evidence). Sensitivity analyses limited to blinded trials, trials with low risk of bias in core domains, and trials with no funding from the pharmaceutical industry did not change the results of the main analyses. Limited evidence on the change in left ventricular mass index prevented us from drawing any firm conclusions. AUTHORS' CONCLUSIONS: We are uncertain about the effects of adding additional antihypertensive drug therapy on the morbidity and mortality of participants with LVH and hypertension compared to placebo. Although the incidence of serious adverse events was similar between study arms, additional antihypertensive therapy may be associated with more withdrawals due to adverse events. Limited and low-certainty evidence requires that caution be used when interpreting the findings. High-quality clinical trials addressing the effect of antihypertensives on clinically relevant variables and carried out specifically in individuals with hypertension-induced LVH are warranted.


Assuntos
Doenças Cardiovasculares , Hipertensão , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Metildopa
17.
Naunyn Schmiedebergs Arch Pharmacol ; 394(11): 2273-2287, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34468816

RESUMO

Morbidity and mortality risks are enhanced in preeclamptic (PE) mothers and their offspring. Here, we asked if sexual dimorphism exists in (i) cardiovascular and renal damage evolved in offspring of PE mothers, and (ii) offspring responsiveness to antenatal therapies. PE was induced by administering NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, oral gavage) to pregnant rats for 7 days starting from gestational day 14. Three therapies were co-administered orally with L-NAME, atrasentan (endothelin ETA receptor antagonist), terutroban (thromboxane A2 receptor antagonist, TXA2), or α-methyldopa (α-MD, central sympatholytic drug). Cardiovascular and renal profiles were assessed in 3-month-old offspring. Compared with offspring of non-PE rats, PE offspring exhibited elevated systolic blood pressure and proteinuria and reduced heart rate and creatinine clearance (CrCl). Apart from a greater bradycardia in male offspring, similar PE effects were noted in male and female offspring. While terutroban, atrasentan, or α-MD partially and similarly blunted the PE-evoked changes in CrCl and proteinuria, terutroban was the only drug that virtually abolished PE hypertension. Rises in cardiorenal inflammatory (tumor necrosis factor alpha, TNFα) and oxidative (isoprostane) markers were mostly and equally eliminated by all therapies in the two sexes, except for a greater dampening action of atrasentan, compared with α-MD, on tissue TNFα in female offspring only. Histopathologically, antenatal terutroban or atrasentan was more effective than α-MD in rectifying cardiac structural damage, myofiber separation, and cytoplasmic alterations, in PE offspring. The repair by antenatal terutroban or atrasentan of cardiovascular and renal anomalies in PE offspring is mostly sex-independent and surpasses the protection offered by α-MD, the conventional PE therapy.


Assuntos
Atrasentana/farmacologia , Metildopa/farmacologia , Naftalenos/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Propionatos/farmacologia , Animais , Atrasentana/administração & dosagem , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Modelos Animais de Doenças , Antagonistas do Receptor de Endotelina A/administração & dosagem , Antagonistas do Receptor de Endotelina A/farmacologia , Feminino , Nefropatias/etiologia , Nefropatias/prevenção & controle , Masculino , Metildopa/administração & dosagem , NG-Nitroarginina Metil Éster , Naftalenos/administração & dosagem , Pré-Eclâmpsia/fisiopatologia , Gravidez , Cuidado Pré-Natal/métodos , Propionatos/administração & dosagem , Ratos , Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores , Fatores Sexuais , Simpatolíticos/administração & dosagem , Simpatolíticos/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-33217917

RESUMO

Hypertensive disorders of pregnancy account for approximately 22% of all maternal deaths in Latin America and the Caribbean. Pharmacotherapies play an important role in preventing and reducing the occurrence of adverse outcomes. However, the patterns of medications used for treating women with hypertensive disorders of pregnancy (HDP) living in this country is unclear. A population-based birth cohort study including 4262 women was conducted to describe the pattern of use of cardiovascular agents and acetylsalicylic acid between women with and without HDP in the 2015 Pelotas (Brazil) Birth Cohort. The prevalence of maternal and perinatal outcomes in this population was also assessed. HDP were classified according to Ministry of Health recommendations. Medications were defined using the Anatomical Therapeutic Chemical Classification System and the substance name. In this cohort, 1336 (31.3%) of women had HDP. Gestational hypertension was present in 636 (47.6%) women, 409 (30.6%) had chronic hypertension, 191 (14.3%) pre-eclampsia, and 89 (6.7%) pre-eclampsia superimposed on chronic hypertension. Approximately 70% of women with HDP reported not using any cardiovascular medications. Methyldopa in monotherapy was the most frequent treatment (16%), regardless of the type of HDP. Omega-3 was the medication most frequently reported by women without HDP. Preterm delivery, caesarean section, low birth weight, and neonatal intensive care admissions were more prevalent in women with HDP. Patterns of use of methyldopa were in-line with the Brazilian guidelines as the first-line therapy for HDP. However, the large number of women with HDP not using medications to manage HDP requires further investigation.


Assuntos
Anti-Hipertensivos , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Anti-Hipertensivos/uso terapêutico , Brasil/epidemiologia , Cesárea/estatística & dados numéricos , Estudos de Coortes , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Metildopa/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/epidemiologia , Gravidez
19.
Hypertens Pregnancy ; 39(4): 393-398, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32697618

RESUMO

OBJECTIVE: to assess the maternal and fetal outcome in women with mild to moderate chronic hypertension on antihypertensive drug (methyldopa or labetalol) therapy compared to no medication. METHODS: This multicenter randomized clinical study was conducted at Menoufia University hospital, Shibin El-kom Teaching hospital at Menoufia governorate, Egypt.486 pregnant women with mild to moderate chronic hypertension were randomized into three groups; methyldopa group (n = 164), labetalol group (n = 160), and control or no medication group (n = 162) who were followed from the beginning of pregnancy till the end of puerperium to record maternal and fetal outcome. RESULTS: There was a highly significant difference between treatment groups (methyldopa and labetalol) and control group regarding the development of maternal severe hypertension, development of preeclampsia, renal impairment, presence of ECG changes, placental abruption, and repeated admission to hospital for blood pressure control (p < 0.001) with higher occurrence in the control (no treatment) group. Neonates in the labetalol group were more prone for the development of small for gestational age (SGA), neonatal hypotension, neonatal hyperbilirubinemia, and admission to NICU than their counterparts in the methyldopa and control groups (p < 0.001). The rate of prematurity was significantly higher in the control group than the treatment groups (p < 0.05). CONCLUSION: Treatment of mild to moderate chronic hypertension during pregnancy is beneficial in decreasing both maternal and fetal morbidity. The use of labetalol was associated with higher rates of SGA, neonatal hypotension, and neonatal hyperbilirubinemia compared to methyldopa or no medication.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Labetalol/uso terapêutico , Metildopa/uso terapêutico , Adulto , Anti-Hipertensivos/farmacologia , Feminino , Humanos , Hipertensão/fisiopatologia , Labetalol/farmacologia , Metildopa/farmacologia , Gravidez , Resultado do Tratamento , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-32371329

RESUMO

High-performance liquid chromatography (HPLC) and solid phase micro membrane tip extraction (SPMMTE) methods are developed for the simultaneous analysis of eleven cardiovascular drugs in human plasma. Iron nanoparticles were obtained by the green method, characterized by XRD, FT-IR, TEM, and EDS and utilized in SPMMTE for sample preparation. The mobile phase used was ammonium acetate buffer-methanol-acetonitrile (65:18:17) with a 1.0 mL/min flow rate at 260 nm detection. Column used was Sunshell C18 150 × 4.6 mm, 2.6 µm. The values of k, α, and Rs were ranged from 040 to109.22, 1.20 to 2.67 and 1.0 to 26.18. SPMMTE and HPLC methods were fast, reproducible, precise, robust, economic and rugged for analysis of methyldopa, hydrochlorothiazide, prazosin hydrochloride, furosemide, labetalol, propranolol, valsartan, losartan potassium, diltiazem, irbesartan and spironolactone in human plasma. The recoveries (%) of methyldopa, hydrochlorothiazide, prazosin hydrochloride, furosemide, labetalol, propranolol, valsartan, losartan potassium, diltiazem, irbesartan, and spironolactone were 91.0, 85.2, 92.3, 90.4, 90.1, 85.6, 86.6, 86.2, 85.1, 86.6, and 85.7, respectively. These results showed that SPMMTE and HPLC methods can be applied to test the described drugs in several matrices.


Assuntos
Anti-Hipertensivos/sangue , Nanopartículas Metálicas/química , Nanocompostos/química , Adsorção , Cromatografia Líquida de Alta Pressão , Diltiazem/sangue , Furosemida/sangue , Humanos , Hidroclorotiazida/sangue , Irbesartana/sangue , Ferro/química , Labetalol/sangue , Limite de Detecção , Losartan/sangue , Metildopa/sangue , Álcool de Polivinil/química , Prazosina/sangue , Propranolol/sangue , Reprodutibilidade dos Testes , Microextração em Fase Sólida , Espironolactona/sangue , Valsartana/sangue
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