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1.
Endocrine ; 68(2): 253-254, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32346814
2.
Medicine (Baltimore) ; 98(40): e17359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577731

RESUMO

INTRODUCTION: The clinical and genetic characteristics of nephrogenic diabetes insipidus (NDI) were described via assessing 2 cases of NDI patients from a Chinese family. PATIENT CONCERNS: Two patients who manifest polyuria and polydipsia were admitted to hospital for definite diagnosis. DIAGNOSIS: Water deprivation-vasopressin tests showed that the patients may possess renal-origin diabetes insipidus. All the levels of thyroid-stimulating hormone, luteinizing hormone, follicle stimulation hormone, adrenocorticotropic hormone, prolactin, and growth hormone in both patients were normal. These results were certified that both patients possess a nephropathy-type diabetes insipidus. B-mode ultrasonography and urinalysis test demonstrated that the patient's diabetes insipidus is unlikely to originate from renal organic disease. Remarkably, by nucleotide sequencing, we found a novel mutation c.414_418del in arginine-vasopressin receptor 2 (AVPR2) was related to the disease of NDI. INTERVENTIONS: Two patients were treated with oral hydrochlorothiazide and indomethacin. In addition, low salt diet and potassium supplementation throughout the patients' treatment. OUTCOMES: The clinical symptoms of 2 patients were significantly reduced after targeted therapy. CONCLUSION: A mutation in AVPR2 was discovered to be associated with NID. It provides a new target for molecular diagnosis of NDI, enabling families to undergo genetic counseling and obtain prenatal diagnoses.


Assuntos
Diabetes Insípido Nefrogênico/genética , Receptores de Vasopressinas/genética , Grupo com Ancestrais do Continente Asiático , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/tratamento farmacológico , Humanos , Hidroclorotiazida/uso terapêutico , Indometacina/uso terapêutico
3.
Med Arch ; 73(3): 157-162, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31391706

RESUMO

Introduction: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). Aim: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results: SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Idoso , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Artérias , Diástole/efeitos dos fármacos , Combinação de Medicamentos , Hipertensão Essencial/tratamento farmacológico , Feminino , Humanos , Hidroclorotiazida/farmacologia , Hidroclorotiazida/uso terapêutico , Lisinopril/farmacologia , Lisinopril/uso terapêutico , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Sístole/efeitos dos fármacos , Valsartana/farmacologia , Valsartana/uso terapêutico
4.
Hypertension ; 74(3): 614-622, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327267

RESUMO

Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the ß-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways (KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2) with large effect size (-3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.


Assuntos
Afro-Americanos/genética , Anti-Hipertensivos/uso terapêutico , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Variação Genética/efeitos dos fármacos , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Estados Unidos
5.
Diabetes Care ; 42(4): 693-700, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30894383

RESUMO

OBJECTIVE: Sodium-glucose cotransporter (SGLT)-2 inhibitors lower clinic and ambulatory blood pressure (BP), possibly through their natriuretic action. However, it remains unclear whether this BP-lowering effect is dose dependent and different from that of low-dose hydrochlorothiazide. The purpose of this meta-analysis was to quantify the association of the dose with response of ambulatory BP to SGLT-2 inhibition and to provide comparative evaluation with low-dose hydrochlorothiazide. RESEARCH DESIGN AND METHODS: PubMed/MEDLINE, Embase, and Cochrane database of clinical trials from inception of each database through 22 August 2018. Randomized controlled trials (RCTs) reporting treatment effects of SGLT-2 inhibitors on ambulatory BP. We extracted data on the mean difference between the active treatment and placebo groups in change from baseline (CFB) of ambulatory systolic and diastolic BP. RESULTS: We identified seven RCTs (involving 2,381 participants) comparing SGLT-2 inhibitors with placebo. Of these, two RCTs included low-dose hydrochlorothiazide as active comparator. CFB in 24-h systolic BP between SGLT-2 inhibitor and placebo groups was -3.62 mmHg (95% CI -4.29, -2.94) and in diastolic BP was -1.70 mmHg (95% CI -2.13, -1.26). BP lowering with SGLT-2 inhibition was more potent during daytime than during nighttime. The CFB in ambulatory BP was comparable between low-dose and high-dose subgroups and was similar to that for low-dose hydrochlorothiazide. Eligible RCTs did not evaluate cardiovascular outcomes/mortality. CONCLUSIONS: This meta-analysis shows that SGLT-2 inhibitors provoke an average reduction of systolic/diastolic BP 3.62/1.70 mmHg in 24-h ambulatory BP. This BP-lowering effect remains unmodified regardless of the dose of SGLT-2 inhibitor and is comparable with BP-lowering efficacy of low-dose hydrochlorothiazide.


Assuntos
Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Neurology ; 92(13): e1435-e1446, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30814321

RESUMO

OBJECTIVE: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. METHODS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. RESULTS: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. CONCLUSIONS: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. CLINICALTRIALSGOV IDENTIFIER: NCT00468923. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Disfunção Cognitiva/epidemiologia , Hidroclorotiazida/uso terapêutico , Hipolipemiantes/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Cognição , Combinação de Medicamentos , Feminino , Humanos , Masculino
7.
Pediatrics ; 143(4)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30842257

RESUMO

OBJECTIVES: Clinicians prescribe antihypertensive medication to children with primary hypertension, but without data to define a particular choice as first-line therapy. A one-size-fits-all approach may not be appropriate for these patients. Our aim was to develop a personalized approach to hypertension treatment, using repeated ambulatory blood pressure monitoring (ABPM) in n-of-1 trials (single-patient randomized crossover trials). METHODS: Children undergoing hypertension management at a single pediatric referral center were offered participation in an n-of-1 trial with repeated ABPM to compare 3 commonly used medications. The medication producing the greatest blood pressure reduction, and without unacceptable side effects, was selected as the preferred therapy for the individual. RESULTS: Forty-two children agreed to participate; 7 were normotensive without medication; and 3 failed to complete one treatment cycle. Of the remaining 32 patients, lisinopril was preferred for 16, amlodipine for 8, hydrochlorothiazide for 4, and 4 had uncontrolled blood pressure on maximum doses of monotherapy. In conservative Bayesian analyses, the proportion of patients who preferred lisinopril was 49% (95% credible interval [CrI]: 32% to 69%), 24% (95% CrI: 12% to 41%) preferred amlodipine, and 12% (95% CrI: 4% to 26%) preferred hydrochlorothiazide. The preferred therapy for the majority (67%) of African American participants was lisinopril. Unacceptable side effects were reported in 24% of assessments for hydrochlorothiazide, 16% for lisinopril, and 13% for amlodipine. CONCLUSIONS: No single medication was preferred for more than half of hypertensive children. n of-1 trials with repeated ABPM may promote better informed and individualized decisions in pediatric hypertension management.


Assuntos
Anlodipino/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial/métodos , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Lisinopril/uso terapêutico , Medicina de Precisão , Centros Médicos Acadêmicos , Adolescente , Anti-Hipertensivos/uso terapêutico , Teorema de Bayes , Determinação da Pressão Arterial/métodos , Criança , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Masculino , Preferência do Paciente , Texas , Resultado do Tratamento
8.
BMJ Case Rep ; 12(2)2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30755424

RESUMO

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterised by the appearance of erythematous plaques and papules with overlying non-follicular pinpoint pustules. Drugs are the cause of AGEP in approximately 90% of cases. The most common causes include anti-infective agents (aminopenicillins, quinolones, antibacterial sulfonamides and terbinafine), antimalarials and diltiazem. To the best of our knowledge, to date there has only been one report of hydrochlorothiazide-induced AGEP. There has never been a case report of losartan-induced AGEP. Here, we present a case of AGEP that is the second case purportedly caused by hydrochlorothiazide.


Assuntos
Pustulose Exantematosa Aguda Generalizada/patologia , Anti-Infecciosos/efeitos adversos , Oftalmopatias/tratamento farmacológico , Hidroclorotiazida/efeitos adversos , Impetigo/tratamento farmacológico , Pustulose Exantematosa Aguda Generalizada/tratamento farmacológico , Administração Tópica , Idoso de 80 Anos ou mais , Anti-Infecciosos/uso terapêutico , Betametasona/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Oftalmopatias/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidroclorotiazida/uso terapêutico , Impetigo/patologia , Metoprolol/uso terapêutico , Resultado do Tratamento
9.
Heart Fail Rev ; 24(3): 343-357, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30645721

RESUMO

Blood pressure (BP) is a complex trait that is regulated by multiple physiological pathways and include but is not limited to extracellular fluid volume homeostasis, cardiac contractility, and vascular tone through renal, neural, or endocrine systems. Uncontrolled hypertension (HTN) has been associated with an increased mortality risk. Therefore, understanding the genetics that underpins and influence BP regulation will have a major impact on public health. Moreover, uncontrolled HTN has been linked to inter-individual variation in the drugs' response and this has been associated with an individual's genetics architecture. However, the identification of candidate genes that underpin the genetic basis of HTN remains a major challenge. To date, few variants associated with inter-individual BP regulation have been identified and replicated. Research in this field has accelerated over the past 5 years as a direct result of on-going genome-wide association studies (GWAS) and the progress in the identification of rare gene variants and mutations, epigenetic markers, and the regulatory pathways involved in the pathophysiology of BP. In this review we describe and enhance our current understanding of how genetic variants account for the observed variability in BP response in patients on first-line antihypertensive drugs, amlodipine and hydrochlorothiazide.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/genética , Variantes Farmacogenômicos/genética , Adulto , Anlodipino/farmacocinética , Anti-Hipertensivos/farmacocinética , Feminino , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Humanos , Hidroclorotiazida/farmacocinética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
10.
J Clin Lipidol ; 13(1): 148-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30293937

RESUMO

BACKGROUND: There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly. OBJECTIVES: We examined the relationship of early initiation of LLT with short- and long-term all-cause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2). METHODS: This was an in- and post-trial observational study. About 4257 hypertensive participants aged 65 to 84 years within Australian family practices were randomized to an angiotensin-converting enzyme inhibitor or a diuretic treatment group. After excluding participants with a prior history of CVD, the cohort was stratified into "LLT" and "no LLT" subgroups based on LLT status at randomization. RESULTS: At randomization, the participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg and estimated 5-year CVD risk of 18.7 ± 8.3%. In the overall study population, the association of LLT with long-term (11-years) all-cause and non-CVD mortality was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66-0.92, P = .003] and HR 0.70 [95% CI 0.54-0.90, P = .006], respectively). Magnitudes of the association of LLT with long-term mortality and the association with short-term mortality were similar; however, no statistically significant association with short-term mortality was observed. In the subgroup analysis by baseline 5-year CVD risk, LLT participants in the highest risk tertile had a substantially lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13-0.71, P for interaction .02) compared to those with lower estimated CVD risk. All analyses were adjusted for baseline and in-trial characteristics. CONCLUSION: Our study showed a strong association between LLT and reduced long-term all-cause mortality. Thus, our findings support recommendations of the use of LLT in patients over 65 years, particularly those with high CVD risk who were more likely to obtain additional benefits in the short term. The findings also suggested that mortality benefits of LLT for the elderly may take longer to become evident.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Enalapril/uso terapêutico , Hidroclorotiazida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Australásia/epidemiologia , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Números Necessários para Tratar , Prevenção Primária , Risco , Análise de Sobrevida , Fatores de Tempo
11.
J Pharm Biomed Anal ; 164: 373-381, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30439665

RESUMO

BACKGROUND: Therapy-refractory arterial hypertension is defined as a blood pressure (BP) in a subset of patients who fail to achieve BP control despite a three-drug regimen (including a diuretic). Various factors have impact on loss of therapy response. Drug-drug-interactions (DDIs) may cause altered pharmacokinetics (PK) of antihypertensive drugs. Upregulation of activity and expression of cytochrome P450 (CYP) enzymes can result in decreased plasma drug levels. Besides these PK considerations a significant problem could be nonadherence to drug therapy. In this regard Therapeutic Drug Monitoring (TDM) is a useful tool for detecting nonadherence. Therefore a LC-MS/MS-method for determination of Metoprolol (MET), Amlodipine (AML), Canrenone (CAN) and Hydrochlorothiazide (HCT) was developed. METHODS: An UHPLC-MS/MS method was developed and validated for simultaneous determination of MET, AML, CAN and HCT in plasma matrix. Extraction of serum samples consisted of simple protein precipitation using acetonitrile. Stable isotope labeled analogues for each antihypertensive were obtained for internal standardization and quantitative analysis ([2H7]-MET, ([13C6]-AML, [2H4]-CAN, [13C6]-HCT). Calibrators and quality controls were prepared in plasma matrix of normal individuals. Sample preparation: protein precipitation with acetonitrile and addition of internal standard-mix. RESULTS: All analytes were eluted within a runtime of 2.5 min. Linearity experiments were demonstrated in plasma over following concentration ranges: MET: 5-750 µg/l, AML: 1-50 µg/l, CAN: 10-500 µg/l, HCT: 5-500 µg/l (R2 > 0.993). Chromatographic separation was achieved using a C18 column (50 × 2.1 mm, 1.9 µm particle size) and an isocratic elution. LC-MS/MS analyses were performed on a triple quadrupole mass spectrometer using positive and negative electrospray ionization in selected reaction monitoring (SRM) mode. Ion transitions monitored for quantitation were m/z 268.2 → 74.1 for MET, m/z 409.1 → 238.0 for AML, m/z 341.2 → 91.0 for CAN and m/z 296.0 → 205.1 for HCT. For all analytes, inter- and intra-day precision (CV, %) varied between 1.7 and 14.0 and inter- and intra-day accuracy values ranged from -2.5 to 7.1%. The lower limits of detection and quantification were: 0.08 and 0.23; 0.05 and 0.15; 2.82 and 8.54; and 0.02 and 0.05 µg/l for MET, AML, CAN and HCT, respectively. Results of stability experiments were within the required range of +/- 15%. CONCLUSIONS: Although the level of recommendation of TDM of antihypertensive drugs in patients with refractory hypertension is not yet established, the present LC-MS/MS-method can serve as an effective tool for detection of PK-alterations/nonadherence and may help to monitor antihypertensive pharmacotherapy.


Assuntos
Anti-Hipertensivos/sangue , Monitoramento de Medicamentos/métodos , Resistência a Medicamentos , Hipertensão/tratamento farmacológico , Anlodipino/sangue , Anlodipino/farmacocinética , Anlodipino/uso terapêutico , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/uso terapêutico , Canrenona/sangue , Canrenona/farmacocinética , Canrenona/uso terapêutico , Isótopos de Carbono , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Deutério , Monitoramento de Medicamentos/instrumentação , Humanos , Hidroclorotiazida/sangue , Hidroclorotiazida/farmacocinética , Hidroclorotiazida/uso terapêutico , Hipertensão/sangue , Hipertensão/patologia , Limite de Detecção , Masculino , Metoprolol/sangue , Metoprolol/farmacocinética , Metoprolol/uso terapêutico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/instrumentação , Espectrometria de Massas em Tandem/métodos
12.
Clin Exp Nephrol ; 23(4): 455-464, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30426292

RESUMO

BACKGROUND: Tolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan. METHODS: Male PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ. Biochemical examinations of the plasma and urine were performed as well as histological and molecular (mRNA and protein expression) analyses. RESULTS: Groups treated with tolvaptan had significantly higher 24 h urine excretion, which was significantly reduced in the tolvaptan + HCTZ group after 2 weeks. Cyst size, pERK protein expression, and Cyclin D1 mRNA expression were all significantly reduced in both the tolvaptan and tolvaptan + HCTZ groups, indicating that HCTZ did not affect the beneficial functions of tolvaptan. Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group. The renal glomerular filtration rate was reduced in the tolvaptan + HCTZ group. Significantly lowered mRNA expression of neuronal nitric oxide synthase, prostaglandin E synthase 2 and renin were also found in the medulla, but not in the cortex. CONCLUSION: HCTZ reduces tolvaptan-induced polyuria without altering its beneficial effects on PKD. This novel therapeutic combination could potentially lead to better PKD treatments and improved quality of life for the affected patients.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Diuréticos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Doenças Renais Policísticas/tratamento farmacológico , Poliúria/tratamento farmacológico , Tolvaptan/uso terapêutico , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Aquaporina 2/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Expressão Gênica/efeitos dos fármacos , Taxa de Filtração Glomerular , Masculino , Óxido Nítrico Sintase Tipo I/genética , Doenças Renais Policísticas/fisiopatologia , Poliúria/induzido quimicamente , Prostaglandina-E Sintases/genética , RNA Mensageiro/metabolismo , Ratos , Renina/genética , Tolvaptan/efeitos adversos , Urina
14.
J Am Acad Dermatol ; 80(2): 460-465.e9, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29913261

RESUMO

BACKGROUND: Hydrochlorothiazide use has been associated with markedly increased risk for squamous cell carcinoma. No previous studies have investigated the association between hydrochlorothiazide use and the risk for Merkel cell carcinoma (MCC) and malignant adnexal skin tumors (MAST). OBJECTIVE: To examine the association between hydrochlorothiazide use and the risk for MCC and MAST. METHODS: Using Danish nationwide health registries, we identified all patients with incident MCC or MAST during 2004-2015 and matched the cases individually to cancer-free population controls by risk set sampling. Using conditional logistic regression, we estimated the odds ratios (ORs) and confidence intervals (CIs) associated with cumulative use of hydrochlorothiazide. RESULTS: The adjusted ORs for MCC and MAST associated with high use (≥50,000 mg) of hydrochlorothiazide was 2.3 (95% CI 1.1-4.8) and 3.6 (95% CI 1.9-7.0), respectively, which increased to 3.3 (95% CI 1.3-8.3) and 5.6 (95% CI 2.4-13.3), respectively, with highest use (≥100,000 mg). We found no increased risk for these tumors in analyses of drugs with similar indications as hydrochlorothiazide, except there was a tendency toward an increased risk for MCC associated with the use of furosemide (OR 1.9, 95% CI 0.9-4.0). LIMITATIONS: No data on sun exposure was available. CONCLUSION: Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.


Assuntos
Carcinoma de Célula de Merkel/induzido quimicamente , Hidroclorotiazida/efeitos adversos , Neoplasias de Anexos e de Apêndices Cutâneos/induzido quimicamente , Sistema de Registros , Neoplasias Cutâneas/induzido quimicamente , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/epidemiologia , Carcinoma de Célula de Merkel/patologia , Estudos de Casos e Controles , Dinamarca , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias de Anexos e de Apêndices Cutâneos/epidemiologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Razão de Chances , Prognóstico , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Análise de Sobrevida
15.
BMC Pharmacol Toxicol ; 19(1): 70, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413182

RESUMO

PURPOSE: High blood pressure (hypertension) is a relatively common condition that increases blood pressure in the arteries abnormally, causing problems such as heart disease and stroke. Blood pressure is a force that is felt through the walls of the blood vessels and has a direct relationship to the power of pumping the heart and vascular resistance to the blood flow. One of the lowing of blood pressure medications is hydrochlorothiazide (Hctz) which is used to treat high blood pressure and swelling from heart failure, liver damage, and other minor actions. PROCEDURES: This study explains the effectiveness of Hctz with the help of "fractal dimension". To perfect investigate the fractal dimension, we used the Hctz drug nanoparticle form then using MATLAB software, homogeneity levels or heterogeneity of Nano Hctz using SEM images were computed. RESULTS: We calculated histogram plot with SEM image by MATLAB software which that its standard deviation was eclose to zero and it can explain that the scattering of data is low and their amount is in one suffering. Fractal dimensions obtained from Matlab and SPSS software for normal distribution, correlation, standard deviation, mean, cumulative frequency and variance analysis were analyzed. CONCLUSIONS: In this research, the association between Hctz treatment effects with the point of view of the fractal dimension of the drug was demonstrated to prove the properties of the drug in the body. in the near future, drug fractal studies can improve the development of new drugs and treatments with minimal cost than clinical approaches by linking chemistry, mathematical sciences and pharmaceutical sciences.


Assuntos
Anti-Hipertensivos , Fractais , Hidroclorotiazida , Nanopartículas , Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Microscopia Eletrônica de Varredura , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Software
17.
J Clin Hypertens (Greenwich) ; 20(10): 1507-1515, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30251403

RESUMO

Left ventricular hypertrophy develops in 36%-41% of hypertensive patients and independently predicts cardiovascular events and total mortality. Moreover, drug-induced reduction in left ventricular mass (LVM) correlates with improved prognosis. The optimal thiazide-type diuretic for reducing LVM is unknown. Evidence regarding potency, cardiovascular events, sodium, and potassium suggested the hypothesis that "CHIP" diuretics (CHlorthalidone, Indapamide, and Potassium-sparing diuretic/hydrochlorothiazide [PSD/HCTZ]) would reduce LVM more than HCTZ. Systematic searches of five databases were conducted. Among the 38 randomized trials, a 1% reduction in systolic blood pressure (SBP) predicted a 1% reduction in LVM, P = 0.00001. CHIP-HCTZ differences in reducing LVM differed across trials (ie, heterogeneity), making interpretation uncertain. However, among the 28 double-blind trials, heterogeneity was undetectable, and HCTZ reduced LVM (percent reduction [95% CI]) by -7.3 (-10.4, -4.2), P < 0.0001. CHIP diuretics surpassed HCTZ in reducing LVM: chlorthalidone -8.2 (-14.7, -1.6), P = 0.015; indapamide -7.5 (-12.7, -2.3), P = 0.005; and all CHIP diuretics combined -7.7 (-12.2, -3.1), P < 0.001. The comparison of PSD/HCTZ with HCTZ had low statistical power but favored PSD/HCTZ: -6.0 (-14.1, +2.1), P = 0.149. Thus, compared to HCTZ, CHIP diuretics had twice the effect on LVM. CHIP diuretics did not surpass HCTZ in reducing systolic or diastolic blood pressure: -0.3 (-5.0, +4.3) and -1.6 (-5.6, +2.4), respectively. The strength of evidence that CHIP diuretics surpass HCTZ for reducing LVM was high (GRADE criteria). In conclusion, these novel results have demonstrated that CHIP diuretics reduce LVM 2-fold more than HCTZ among hypertensive patients. Although generally related to LVM, blood pressure fails to explain the superiority of CHIP diuretics for reducing LVM.


Assuntos
Clortalidona/farmacologia , Diurético Poupador de Potássio/farmacologia , Hidroclorotiazida/farmacologia , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Indapamida/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Clortalidona/administração & dosagem , Clortalidona/uso terapêutico , Diurético Poupador de Potássio/administração & dosagem , Diurético Poupador de Potássio/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/uso terapêutico , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Indapamida/administração & dosagem , Indapamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Tiazidas/farmacologia , Tiazidas/uso terapêutico
18.
Pak J Pharm Sci ; 31(4(Special)): 1659-1662, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30203756

RESUMO

To observe and analyze the clinical efficacy and ultrasound detection results of treatment of hypertensive patients with heart disease with valsartan combined with hydrochlorothiazide. The 160 hypertensive patients with heart disease who were treated in our hospital were selected as study subjects and randomly divided into study group and reference group, each with 80 patients. Where, the reference group was solely treated with valsartan, while the study group received hydrochlorothiazide treatment on this basis. The therapeutic effects of the two groups were observed and analyzed. Comparison of the overall treatment efficacy and incidence of adverse reactions between the two groups showed that the study group had more significant advantages than the reference group, P<0.05; in comparison of systolic blood pressure and diastolic blood pressure after treatment between the two groups, the study group had higher improvement degree than the reference group, P<0.05; ultrasonic ECG inspection showed that the study group was superior to the reference group with better recovery in indexes including left ventricular mass index, left ventricular posterior wall thickness, left ventricular ejection fraction, P<0.05. The combination of Valsartan and hydrochlorothiazide for hypertensive patients with heart disease can significantly improve the treatment effect and significantly reduce the incidence of adverse reactions. Therefore, it is worthy of popularization and application.


Assuntos
Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Valsartana/uso terapêutico , Idoso , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada/efeitos adversos , Ecocardiografia , Feminino , Cardiopatias/complicações , Cardiopatias/tratamento farmacológico , Humanos , Hidroclorotiazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Valsartana/efeitos adversos , Função Ventricular Esquerda/efeitos dos fármacos
19.
Drug Des Devel Ther ; 12: 2611-2616, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197501

RESUMO

Aim: The aim of this study was to evaluate the effects of canrenone compared to hydrochlorothiazide (HCTZ) added to angiotensin II receptor blockers (ARBs) on glycemia, lipid profile, potassium, aldosterone and renal function in patients with hypertension and type 2 diabetes mellitus. Patients and methods: The study enrolled 182 Caucasian patients with hypertension and type 2 diabetes mellitus. Patients were already taking ARBs and were randomized to canrenone, 50 mg once a day, or HCTZ, 12.5 mg once a day for 1 month. After the first month, patients not reaching an adequate blood pressure (BP) were up-titrated to canrenone 100 mg or HCTZ 25 mg once a day for 12 months. The following parameters were considered at 6 and 12 months: BP, body weight, body mass index (BMI), fasting plasma glucose (FPG), post-prandial glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin (HOMA-IR), lipid profile, potassium, plasma aldosterone, urine albumin excretion rate and estimated glomerular filtration rate (eGFR). Results: We observed a similar decrease in BP with both treatments. Canrenone led to a significant decrease in FPG, PPG and HOMA index compared to baseline, while there was a significant increase in the same parameters with HCTZ. HCTZ also worsened glycated hemoglobin (HbA1c), while canrenone did not change it. No variations in lipid profile were recorded with canrenone, while there was a worsening of total cholesterol (TC) and triglycerides (Tg) with HCTZ. Potassium levels were decreased and uric acid levels were increased by HCTZ, but not by canrenone that had a neutral effect on these parameters. We recorded a slight decrease in eGFR with HCTZ and an improvement with canrenone; creatinine and eGFR were improved by canrenone compared to HCTZ. Plasma aldosterone levels were decreased by canrenone and increased by HCTZ. Conclusion: Canrenone and HCTZ have a similar effect on BP; however, canrenone seems to improve metabolic parameters, while HCTZ worsens them.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Canrenona/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hidroclorotiazida/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
PLoS One ; 13(9): e0203166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30204768

RESUMO

BACKGROUND: Previous research has been highly suggestive that patients of African ancestry are less responsive to beta-blockers and angiotensin converting enzyme inhibitors. However, clinical practice within Ethiopia has continued to recommend all drugs for treatment of hypertension despite the lack of evidentiary support. Therefore this study aims to compare the effectiveness of the three major antihypertensive drugs currently prescribed in an Ethiopian health care setting to further the potential for evidence based prescribing practices. METHODS: A prospective, randomized, open label comparative study was used to determine the mean reduction in blood pressure (primary outcome) and assess cardiovascular events (secondary outcomes) among patients receiving one or more of three common antihypertensive drugs (i.e., nifedipine, hydrochlorothiazide, and enalapril) in routine clinical practice between November 2016 and April 2017. Patients were followed for three months. Analysis was based on an intention-to-treat approach. One way analysis of covariance was used to compare the difference in therapeutic effectiveness in reducing blood pressure. RESULT: A total of 141 patients were randomized to one of three recipient groups-nifedipine (n = 47), enalapril (n = 47) or hydrochlorothiazide (n = 47). Three months after randomization, 44 patients in each group completed the follow-up. Patients randomized to nifedipine had significantly higher mean reduction in systolic blood pressure than those randomized to enalapril(p = 0.003) or hydrochlorothiazide(p = 0.036). The mean reduction in systolic blood pressure was -37.35(CI:-40, -34.2) in the nifedipine group; -30.3(CI: -33.5, -27.1) in patients receiving enalapril; and -32.1(CI:-35, -29.3) in patients assigned hydrochlorothiazide. However, nifedipine did not have a significance difference in reduction of mean diastolic blood pressure compared than those receiving enalapril (p = 0.57) or hydrochlorthiazide (p = 0.99). CONCLUSION: This study revealed that amongst the three drugs nifedipine was found to be the most effective drug in reduction of systolic blood pressure. Hydrochlorothiazide and enalapril did not show a difference in reduction of mean blood pressure. Further, long term randomized trials are highly recommended to inform revision of Ethiopia-centric hypertension treatment guidelines.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/uso terapêutico , Enalapril/uso terapêutico , Etiópia , Feminino , Serviços de Saúde , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
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