RESUMO
INTRODUCTION: Non-adherence to antihypertensive medication significantly contributes to inadequate blood pressure control. Regarding non-pharmacological interventions to improve medication adherence, the question remains of which interventions yield the highest efficacy.Understanding the complementary perspectives of patients and healthcare professionals can be valuable for designing strategies to enhance medication adherence. Few studies explored the perspectives of patients and healthcare professionals regarding medication adherence. None of them focused specifically on adherence to pharmacological therapy for hypertension in Portugal.Considering the high prevalence of non-adherence and its location-specific aspects, the priority should be identifying its barriers and developing tactics to address them.This study aims to gather the perspectives of patients with hypertension and healthcare professionals such as family doctors, nurses and community pharmacists from Portugal, regarding the most effective strategies to enhance antihypertensive medication adherence and to understand the factors contributing to non-adherence. METHODS AND ANALYSES: We will conduct qualitative research through synchronous online focus groups of 6-10 participants. Some groups will involve patients with hypertension, while others will include family doctors, nurses and community pharmacists. The number of focus groups will depend on the achievement of theoretical saturation. A purposive sample will be used. Healthcare participants will be recruited via email, while patients will be recruited through their family doctors.The moderator will maintain neutrality while ensuring interactive contributions from every participant. Participants will be encouraged to express their opinions on the meeting summary. Meetings will be recorded and transcribed.Two researchers will perform content analyses using MAXQDA V.12 through comparative analyses and subsequent consensus. A third researcher will review the analyses. The results will be presented narratively. ETHICS AND DISSEMINATION: The Ethics Committee of the University of Coimbra has approved this study with the number: CE-026/2021. The results will be disseminated via peer-reviewed publications and national and international conferences.
Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Grupos Focais , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Pesquisa Qualitativa , Pressão Sanguínea/fisiologia , Adesão à MedicaçãoRESUMO
A novel L-rhamnose isomerase was identified and cloned from an extreme-temperature aquatic habitat metagenome. The deduced amino acid sequence homology suggested the possible source of this metagenomic sequence to be Chloroflexus islandicus. The gene expression was performed in a heterologous host, Escherichia coli, and the recombinant protein L-rhamnose isomerase (L-RIM) was extracted and purified. The catalytic function of L-RIM was characterized for D-allulose to D-allose bioconversion. D-Allose is a sweet, rare sugar molecule with anti-tumour, anti-hypertensive, cryoprotective, and antioxidative properties. The characterization experiments showed L-RIM to be a Co++- or Mn++-dependent metalloenzyme. L-RIM was remarkably active (~ 80%) in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges. Optimal L-RIM activity with D-allulose as the substrate occurred at pH 7.0 and 75 °C. The enzyme was found to be excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively. L-RIM catalysis conducted at slightly acidic pH of 6.0 and 70 °C achieved biosynthesis of about 30 g L-1 from 100 g L-1 D-allulose in 3 h. KEY POINTS: ⢠The present study explored an extreme temperature metagenome to identify a novel gene that encodes a thermostable l-rhamnose isomerase (L-RIM) ⢠L-RIM exhibits substantial (80% or more) activity in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges ⢠L-RIM is excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively.
Assuntos
Aldose-Cetose Isomerases , Frutose , Glucose , Anti-Hipertensivos , Escherichia coli/genéticaRESUMO
This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.
Assuntos
Angioedema , Overdose de Drogas , Hipertensão , Pessoa de Meia-Idade , Feminino , Humanos , Olmesartana Medoxomila/uso terapêutico , Telmisartan/efeitos adversos , Vildagliptina/efeitos adversos , Polimedicação , Anlodipino/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Angioedema/tratamento farmacológico , Tetrazóis/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate the efficacy and safety of pharmacogenomics (PGx)-guided treatment in individuals with resistant hypertension (RH). STUDY DESIGN: Randomised controlled open-label study. Place and Duration of the Study: Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China, from June 2019 to November 2021. METHODOLOGY: The study assigned RH patients to two groups. The intervention group (IG) received 12 weeks of PGx-guided treatment, while the control group (CG) followed a consensus-based approach. Examining 10 genes and their alleles with 31 antihypertensive drugs in the IG, the study provided specific medication advice. The primary outcome measured the difference in office systolic blood pressure (SBP) change from baseline at 12 weeks. Secondary outcomes included changes in diastolic blood pressure (DBP), hepatic and renal function, and major adverse cardiovascular events. RESULTS: Fifty-nine patients from the First Hospital of China Medical University participated, with 29 in the IG and 30 in the CG. Significant differences were noted in SBP reduction (IG: 31.26 ± 18.64 mmHg; CG: 14.61 ± 17.74 mmHg; p=0.001) and DBP reduction (IG: 19.61 ± 17.32 mmHg; CG: 7.81 ± 11.23 mmHg; p = 0.003) after 12 weeks. One IG patient had a heart attack, and one CG subject developed heart failure. At week 12, hepatic insufficiency was observed in one IG patient and six CG patients, while renal insufficiency occurred in five patients of both groups. CONCLUSION: Treatment guided by PGx demonstrated significant reductions in both SBP and DBP compared to consensus-based treatment. KEY WORDS: Resistant hypertension, Treatment, Pharmacogenomics, Clinical study.
Assuntos
Hipertensão , Hipotensão , Humanos , Farmacogenética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Anti-Hipertensivos/uso terapêutico , Pressão SanguíneaRESUMO
BACKGROUND AND OBJECTIVES: The time taken to achieve blood pressure (BP) control could be pivotal in the benefits of reducing BP in acute intracerebral hemorrhage (ICH). We aimed to assess the relationship between the rapid achievement and sustained maintenance of an intensive systolic BP (SBP) target with radiologic, clinical, and functional outcomes. METHODS: Rapid, Intensive, and Sustained BP lowering in Acute ICH (RAINS) was a multicenter, prospective, observational cohort study of adult patients with ICH <6 hours and SBP ≥150 mm Hg at 4 Comprehensive Stroke Centers during a 4.5-year period. Patients underwent baseline and 24-hour CT scans and 24-hour noninvasive BP monitoring. BP was managed under a rapid (target achievement ≤60 minutes), intensive (target SBP <140 mm Hg), and sustained (target stability for 24 hours) BP protocol. SBP target achievement ≤60 minutes and 24-hour SBP variability were recorded. Outcomes included hematoma expansion (>6 mL or >33%) at 24 hours (primary outcome), early neurologic deterioration (END, 24-hour increase in NIH Stroke Scale score ≥4), and 90-day ordinal modified Rankin scale (mRS) score. Analyses were adjusted by age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. RESULTS: We included 312 patients (mean age 70.2 ± 13.3 years, 202 [64.7%] male). Hematoma expansion occurred in 70/274 (25.6%) patients, END in 58/291 (19.9%), and the median 90-day mRS score was 4 (interquartile range, 2-5). SBP target achievement ≤60 minutes (178/312 [57.1%]) associated with a lower risk of hematoma expansion (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.23-0.77), lower END rate (aOR 0.43, 95% CI 0.23-0.80), and lower 90-day mRS scores (aOR 0.48, 95% CI 0.32-0.74). The mean 24-hour SBP variability was 21.0 ± 7.6 mm Hg. Higher 24-hour SBP variability was not related to expansion (aOR 0.99, 95% CI 0.95-1.04) but associated with higher END rate (aOR 1.15, 95% CI 1.09-1.21) and 90-day mRS scores (aOR 1.06, 95% CI 1.04-1.10). DISCUSSION: Among patients with acute ICH, achieving an intensive SBP target within 60 minutes was associated with lower hematoma expansion risk. Rapid SBP reduction and stable sustention within 24 hours were related to improved clinical and functional outcomes. These findings warrant the design of randomized clinical trials examining the impact of effectively achieving rapid, intensive, and sustained BP control on hematoma expansion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in adults with spontaneous ICH and initial SBP ≥150 mm Hg, lowering SBP to <140 mm Hg within the first hour and maintaining this for 24 hours is associated with decreased hematoma expansion.
Assuntos
Hipotensão , Acidente Vascular Cerebral , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Estudos Prospectivos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Hematoma/diagnóstico por imagem , Hematoma/tratamento farmacológico , Resultado do TratamentoRESUMO
The benefits of improved clinical outcomes through blood pressure (BP) reduction have been proven in multiple clinical trials and meta-analyses. The new (2023) guideline from the European Society of Hypertension (ESH) includes ß-blockers within five main classes of antihypertensive agents suitable for initiation of antihypertensive pharmacotherapy and for combination with other antihypertensive agents. This is in contrast to the 2018 edition of ESH guidelines that recommended ß-blockers for use primarily in patients with compelling indications such as cardiovascular comorbidities, e.g. coronary heart disease, heart failure. This change was based on the fact that the magnitude of BP reduction is the most important factor for adverse cardiovascular outcomes, over and above the precise manner in which reduced BP is achieved. The ESH guideline also supports the use of ß-blockers for patients with resting heart rate (>80 bpm); high resting heart rate is a sign of sympathetic overactivity, an important driver of adverse cardiac remodelling in the setting of hypertension and heart failure. Hypertension management guidelines support for the use of combination therapies for almost all patients with hypertension, ideally within a single-pill combination to optimise adherence to therapy. Where a ß-blocker is prescribed, the inclusion of a dihydropyridine calcium channel blocker within a combination regimen is rational. These agents together reduce both peripheral and central BP, which epidemiological studies have shown is important for reducing the burden of premature morbidity and mortality associated with uncontrolled hypertension, especially strokes.
Assuntos
Insuficiência Cardíaca , Hipertensão , Hipotensão , Humanos , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipotensão/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológicoRESUMO
Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.
Assuntos
Insuficiência Cardíaca , Humanos , Qualidade de Vida , Volume Sistólico , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Sistema Renina-Angiotensina , Anti-Hipertensivos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
ß-blockers are a heterogeneous class, with individual agents distinguished by selectivity for ß1- vs. ß2- and α-adrenoceptors, presence or absence of partial agonist activity at one of more ß-receptor subtype, presence or absence of additional vasodilatory properties, and lipophilicity, which determines the ease of entry the drug into the central nervous system. Cardioselectivity (ß1-adrenoceptor selectivity) helps to reduce the potential for adverse effects mediated by blockade of ß2-adrenoceptors outside the myocardium, such as cold extremities, erectile dysfunction, or exacerbation of asthma or chronic obstructive pulmonary disease. According to recently updated guidelines from the European Society of Hypertension, ß-blockers are included within the five major drug classes recommended as the basis of antihypertensive treatment strategies. Adding a ß-blocker to another agent with a complementary mechanism may provide a rational antihypertensive combination that minimizes the adverse impact of induced sympathetic overactivity for optimal blood pressure-lowering efficacy and clinical outcomes benefit.
Assuntos
Anti-Hipertensivos , Hipertensão , Masculino , Humanos , Anti-Hipertensivos/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Hipertensão/tratamento farmacológico , Pressão SanguíneaRESUMO
BACKGROUND: Systemic arterial hypertension is a risk factor for cardiac, renal, and metabolic dysfunction. The search for new strategies to prevent and treat cardiovascular diseases led to the synthesis of new N-acylhydrazones to produce antihypertensive effect. Adenosine receptors are an alternative target to reduce blood pressure because of their vasodilatory action and antioxidant properties, which may reduce oxidative stress characteristic of systemic arterial hypertension. OBJECTIVE: To evaluate the antihypertensive profile of novel selenium-containing compounds designed to improve their interaction with adenosine receptors. METHODS: Vascular reactivity was evaluated by recording the isometric tension of pre-contracted thoracic aorta of male Wistar rats after exposure to increasing concentrations of each derivative (0.1 to 100 µM). To investigate the antihypertensive effect in spontaneously hypertensive rats, systolic, diastolic, and mean arterial pressure and heart rate were determined after intravenous administration of 10 and 30 µmol/kg of the selected compound LASSBio-2062. RESULTS: Compounds named LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092, and LASSBio-2093 promoted vasodilation with mean effective concentrations of 15.5 ± 6.5; 14.6 ± 2.9; 18.7 ± 9.6; 6.7 ± 4.1; > 100; 6.0 ± 3.6; 37.8 ± 11.8; and 15.9 ± 5.7 µM, respectively. LASSBio-2062 (30 µmol/kg) reduced mean arterial pressure in spontaneously hypertensive rats from 124.6 ± 8.6 to 72.0 ± 12.3 mmHg (p < 0.05). Activation of adenosine receptor subtype A3 and potassium channels seem to be involved in the antihypertensive effect of LASSBio-2062. CONCLUSIONS: The new agonist of adenosine receptor and activator of potassium channels is a potential therapeutic agent to treat systemic arterial hypertension.
FUNDAMENTO: A hipertensão arterial sistêmica é um fator de risco para disfunções cardíacas, renais e metabólicas. A busca por novas estratégias para prevenir e tratar doenças cardiovasculares levou à síntese de novas N-acilidrazonas para produzir efeito anti-hipertensivo. Os receptores de adenosina são um alvo alternativo para reduzir a pressão arterial devido à sua ação vasodilatadora e propriedades antioxidantes, que podem reduzir o estresse oxidativo característico da hipertensão arterial sistêmica. OBJETIVO: Avaliar o perfil anti-hipertensivo de novos compostos contendo selênio desenvolvidos para melhorar sua interação com os receptores de adenosina. MÉTODOS: Foi avaliada a reatividade vascular, registrando-se a tensão isométrica da aorta torácica pré-contraída de ratos Wistar machos após exposição a concentrações crescentes de cada derivado (0,1 a 100 µM). Para investigar o efeito anti-hipertensivo em ratos espontaneamente hipertensos, foram determinadas a pressão arterial sistólica, pressão arterial diastólica, pressão arterial média e a frequência cardíaca após administração intravenosa de 10 e 30 µmol/kg do composto selecionado LASSBio-2062. RESULTADOS: Os compostos denominados LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092 e LASSBio-2093 promoveram vasodilatação com concentrações efetivas médias de 15,5 ± 6,5; 14,6 ± 2,9; 18,7 ± 9,6; 6,7 ± 4,1; > 100; 6,0 ± 3,6; 37,8 ± 11,8; e 15,9 ± 5,7 µM, respectivamente. O LASSBio-2062 (30 µmol/kg) reduziu a pressão arterial média em ratos espontaneamente hipertensos de 124,6 ± 8,6 para 72,0 ± 12,3 mmHg (p < 0,05). A ativação do receptor de adenosina subtipo A3 e dos canais de potássio parece estar envolvida no efeito anti-hipertensivo do LASSBio-2062. CONCLUSÕES: O novo agonista do receptor de adenosina e ativador dos canais de potássio é um potencial agente terapêutico para o tratamento da hipertensão arterial sistêmica.
Assuntos
Anti-Hipertensivos , Hipertensão , Ratos , Animais , Masculino , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Ratos Endogâmicos SHR , Ratos Wistar , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Canais de PotássioRESUMO
Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, and chronic hypertension with superimposed preeclampsia. For patients with chronic hypertension, oral antihypertensive therapy should be initiated or titrated at a blood pressure threshold of 140/90 mm Hg or greater. Gestational hypertension and preeclampsia without severe features can be managed with blood pressure monitoring, laboratory testing for disease progression, antenatal testing for fetal well-being, and delivery at 37 weeks' gestation. The use of antihypertensive drugs to control nonsevere hypertension in the setting of gestational hypertension and preeclampsia does not improve outcomes and is not recommended. Antihypertensive therapy should be initiated expeditiously for acute-onset severe hypertension to prevent hemorrhagic stroke. Preeclampsia with severe features requires immediate stabilization and inpatient treatment with magnesium sulfate for seizure prophylaxis and antenatal corticosteroids (if preterm). Patients in the preterm period should receive antenatal corticosteroids without delaying delivery to complete courses. Hypertensive disorders of pregnancy can worsen or initially present after delivery and account for up to 44% of pregnancy-related deaths in the first six days postpartum. Patients should be monitored closely in the early postpartum period. Hypertensive disorders of pregnancy are linked to poor long-term maternal and fetal outcomes, including increased maternal lifetime risk of cardiovascular disease. Daily low-dose aspirin therapy starting at 12 to 16 weeks' gestation is safe and effective for reducing the risk of preeclampsia for patients with risk factors.
Assuntos
Hipertensão Induzida pela Gravidez , Hipertensão , Pré-Eclâmpsia , Recém-Nascido , Gravidez , Humanos , Feminino , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/prevenção & controle , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Pressão Sanguínea , CorticosteroidesRESUMO
Hypertension is a common disorder of major clinical, public health and economic importance. It affects men and women of all ages, and the prevalence is increasing in most countries. Maintenance of blood pressure below 140/90 mm of Hg is recommended by most of the guideline available around the world. Various classes of drugs are being used in the treatment of hypertension. Losartan potassium and amlodipine are two different antihypertensive agents belonging to two different groups used commonly around the world in treating essential hypertension. Losartan potassium is non-peptide Angiotensin-II receptor antagonist. Amlodipine which is the third generation dihydropyridine group of calcium channel blocker. The aim of the study was to compare the efficacy and safety of amlodipine and losartan for the treatment of essential hypertensive patients (18-75 years). A non-randomized comparative observational study was conducted in the Department of Pharmacology and Therapeutics in collaboration with Department of Medicine, Sylhet, MAG Osmani Medical College, Sylhet, Bangladesh from July 2021 to June 2022. In this study non-randomization was in two groups. Group A received amlodipine 5mg daily at morning and Group B received losartan potassium 50mg daily at night. The study parameters were systolic blood pressure (SBP), diastolic blood pressure (DBP), ankle oedema, serum K+ level. The result of treatment outcome was compared between two groups. After treatment the reduction of SBP was 5.19±2.93mm of Hg versus 3.27±1.34mm of Hg (p<0.001); reduction of DBP was 1.7±0.70 mm of Hg versus 0.68 mm of Hg (p<0.001) and serum K+ level 4.22±0.27mmol/L versus 4.21±0.16mmol/L (p<0.719) in amlodipine and losartan group respectively. Amlodipine is more effective than losartan potassium in respect to treatment of essential hypertension. Regarding adverse events losartan potassium causes angioedema, hyperkalemia, headache, dizziness etc. The study concluded that amlodipine is superior to losartan potassium in treating essential hypertension.
Assuntos
Hipertensão , Mercúrio , Masculino , Humanos , Feminino , Losartan/uso terapêutico , Losartan/farmacologia , Anlodipino/uso terapêutico , Anlodipino/farmacologia , Bangladesh , Centros de Atenção Terciária , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/induzido quimicamente , Pressão Sanguínea , Resultado do Tratamento , Mercúrio/farmacologia , Mercúrio/uso terapêutico , Método Duplo-CegoRESUMO
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of anti-acquired immunodeficiency syndrome treatment regimen. In the present work, with the previously reported compound K-16c as lead, a series of novel 2,4,5-trisubstituted pyrimidine derivatives were designed based on the cocrystal structure of K-16c/RT, with the aim to improve the anti-human immunodeficiency virus type-1 (HIV-1) activities and metabolic stability properties. Compound 11b1 exhibited the most potent antiviral activity against wild-type (WT) and a panel of single mutant HIV-1 strains (EC50 = 2.4-12.4 nM), being superior to or comparable to those of the approved drug etravirine. Meanwhile, 11b1 exhibited moderate cytotoxicity (CC50 = 4.96 µM) and high selectivity index (SI = 1189) toward HIV-1 WT strain. As for HIV-1 RT inhibition test, 11b1 possessed excellent inhibitory potency (IC50 = 0.04 µM) and confirmed its target was RT. Moreover, the molecular dynamics simulation was performed to elucidate the improved drug resistance profiles. Moreover, 11b1 was demonstrated with favorable safety profiles and pharmacokinetic properties in vivo, indicating that 11b1 is a potential anti-HIV-1 drug candidate worthy of further development.
Assuntos
Síndrome de Imunodeficiência Adquirida , HIV-1 , Humanos , Anti-Hipertensivos , Simulação de Dinâmica Molecular , NucleosídeosRESUMO
The creation of a scleral flap during trabeculectomy can be complicated by a buttonhole, partial amputation at the limbus, and extensive thinning. In some cases, the procedure must be aborted to prevent more serious postoperative complications. This report describes a technique of converting complicated trabeculectomy into ab externo cyclodialysis. A 41-year-old patient with congenital glaucoma presented with a perforated scleral wall with the choroidal tissue exposed during the dissection of the partial-thickness scleral flap. By using a Barraquer cyclodialysis spatula through the scleral perforation, the choroid was separated from the sclera up to the scleral spur over 30° into the anterior chamber. The sclera and conjunctiva/Tenon were sutured with 10-0 nylon single sutures. Two months later, the intraocular pressure was reduced to 16 mmHg with no hypotensive topical medications. This case illustrates an alternative approach to managing a flap-related perioperative complication in trabeculectomy, which yielded good early results.
Assuntos
Glaucoma , Trabeculectomia , Humanos , Adulto , Trabeculectomia/efeitos adversos , Esclera/cirurgia , Câmara Anterior , Túnica Conjuntiva/cirurgia , Anti-Hipertensivos , Glaucoma/cirurgiaRESUMO
BACKGROUND: Polypharmacy is easily achieved in elderly patients with multimorbidity and it is associated with a higher risk of potentially inappropriate medication use and worse health outcomes. Studies have shown that deprescription is safe, however, some barriers have been identified. The aim of this study was to analyse Portuguese General Practitioners (GP) deprescription's attitudes using clinical vignettes. METHODS: Cross-sectional study using an online survey with 3 sections: demographic and professional characterization; two clinical vignettes with an elderly patient with multimorbidity and polypharmacy in which the dependency level varies; barriers and factors influencing deprescription. Frequencies, means, and standard deviations were calculated to describe the GPs. Analysis of the deprescription attitude, globally and for each drug, for each clinical vignette applying the McNeemar's test. RESULTS: A sample of 396 GP was obtained with a mean age of 38 years, most of them female. A statistically significant difference (p < 0.01) was observed in deprescribing according to the patient dependency level, with more GPs (80.4% versus 75.3%) deprescribing in the most dependent patient. A statistically significant difference was found for all drugs except for antihypertensive drugs. All medications were deprescribed more often in dependent patients except for anti-dementia drugs. More than 70% of the participants considered life expectancy and quality of life as "very important" factors for deprescription and more than 90% classified the existence of guidelines and the risks and benefits of medication as "very important" or "important". In the open question, the factors most reported by the GP were those related to the patient (52,9%). CONCLUSIONS: This is the largest study on this topic carried out in Portugal using clinical vignettes, with a representative sample of Portuguese GP. The level of dependence significatively influenced the deprescription attitude of Portuguese GPs. The majority of the GPs classified the quality of life, life expectancies, potential negative effects and the existence of guidelines as "very important" or "important" while deprescribing. It is important to develop and test deprescribing in real life studies to analyze if these attitudes are the same in daily practice.
Assuntos
Desprescrições , Clínicos Gerais , Humanos , Feminino , Idoso , Adulto , Estudos Transversais , Qualidade de Vida , Anti-Hipertensivos/uso terapêuticoRESUMO
BACKGROUND: Despite declining mortality in most countries and in Lithuania, ovarian cancer burden has remained high. Studies have indicated that antihypertensive medications use may help to improve ovarian cancer survival, however findings remain controversial. The aim of the study was to analyse the association between post-diagnosis antihypertensive medications intake and cancer-specific survival in ovarian cancer patients. METHODS: This retrospective cohort study included 588 ovarian cancer cases diagnosed between 2013 and 2015. Hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) were estimated using multivariable Cox proportional hazards models to assess associations between antihypertensive medications and ovarian cancer-specific mortality. RESULTS: In total, 279 (47%) patients died during the follow-up; 242 (87%) of them died due to ovarian cancer. The risk of ovarian cancer death was reduced in angiotensin-converting enzyme inhibitors (ACE inhibitors) users vs. non-users (HR 0.55, 95% CI: 0.36-0.83). Subgroup analysis showed better ovarian cancer survival in higher dose ACE inhibitors users (HR 0.46, 95% CI: 0.28-0.77, p for trend 0.002); the effect was also stronger in age 51-65 years, stage I-III, surgery or chemotherapy treatment, pre-diagnosis ACE inhibitor users' and pre-diagnosis hypertension subgroups. The risk of cancer-specific death was slightly lower among calcium-channel blocker and angiotensin-receptor blocker users and higher among beta-blocker users as compared to non-users, however chance and confounding could not be ruled out. We found no association between the use of centrally and peripherally acting antiadrenergic agents and diuretics and risk of ovarian cancer-specific mortality. CONCLUSIONS: Our findings imply that post-diagnosis use of ACE inhibitors may be associated with reduced ovarian cancer-specific mortality; however, further research is needed for the comprehensive assessment.
Assuntos
Anti-Hipertensivos , Neoplasias Ovarianas , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Anti-Hipertensivos/uso terapêutico , Estudos Retrospectivos , Neoplasias Ovarianas/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêuticoRESUMO
Purpose: High blood pressure (HBP) is the leading cause of mortality and years of disability, and its prevalence is increasing. Therefore, diagnosis and effective treatment of HBP is one of the main goals to prevent and reduce its complications, and pharmacological treatment is the cornerstone of hypertension management.Materials and Methods: The gradual introduction of different drug families has led to the development of new molecules that have improved efficacy and reduced adverse effects. Results: Current drugs include a large number that target key mechanisms of blood pressure regulation as well as those that contribute to hypertension-induced organ damage. Recently, new antihypertensive drugs have been introduced that not only aim to lower blood pressure but also provide additional protection against organ damage and metabolic disorders. Some of them were introduced for specific indications other than hypertension and other are based in a pharmacogenomic approach. Other routes of administration, such subcutaneous injection, are also being explored to improve protection and compliance.Conclusions: The main characteristics of each class of antihypertensive drug are summarised.
Assuntos
Hipertensão , Humanos , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Pressão SanguíneaAssuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Padrão de Cuidado , Hipertensão Pulmonar Primária Familiar , Hipertensão Pulmonar/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Quimioterapia CombinadaAssuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Padrão de Cuidado , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar Primária Familiar , Quimioterapia Combinada , Anti-Hipertensivos/uso terapêuticoRESUMO
PURPOSE: Visit-to-visit blood pressure variability is a strong predictor of the incidence of cardiovascular events and target organ damage due to hypertension. The present study investigated whether year-to-year blood pressure variability predicts the risk of hypertension in the Japanese general population. MATERIALS AND METHODS: This study analysed 2806 normotensive individuals who participated in our physical check-up program for five years in a row from 2008 to 2013. The average, standard deviation, coefficient of variation, average real variability, and highest value of systolic blood pressure in the five consecutive visits were determined and used as baseline data. The participants were followed up for the next 6 years with the development of 'high blood pressure', an average blood pressure level of ≥140/90 mmHg or the use of antihypertensive medications, as the endpoint. RESULT: During follow-up, 'high blood pressure' developed in 389 participants (13.9%, 29.5 per 1 000 person-years). The incidence increased across the quartiles of standard deviation and average real variability, while the average and highest systolic blood pressure had the most prominent impact on the development of 'high blood pressure'. Multivariate logistic regression analysis adjusted for possible risk factors indicated that the average, standard deviation, average real variability, and highest blood pressure, but not the coefficient of variation of systolic blood pressure, were significant predictors of 'high blood pressure'. CONCLUSION: Increased year-to-year blood pressure variability predicts the risk of hypertension in the general normotensive population. The highest blood pressure in the preceding years may also be a strong predictor of the risk of hypertension.
What is the context A relatively high blood pressure level recorded by chance is not usually examined further, especially in cases where the blood pressure values recorded in different opportunities were within normal levels.However, high blood pressure observed by chance may be a result of increased blood pressure variability.Increased blood pressure variability predicts incident hypertension in patients with diabetes, but clinical significance of increased blood pressure variability in the general population with normal blood pressure has not been studied.What is new The impact of blood pressure variability on the development of hypertension in the normotensive general population was investigated.The present study demonstrated that increased blood pressure variability was the significant predictor of the development of hypertension in the general population.What is the impact Increased year-to-year blood pressure variability as well as the highest blood pressure observed by chance in the preceding years is a strong predictor of the development of hypertension in the general normotensive population.