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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120455, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624815

RESUMO

For determination of amlodipine besylate (AML) and olmesartan medoxomil (OLM) at the same time, four UV chemometric spectrophotometric techniques were created and tested in accordance with ICH standards. Method (I) was absorption subtraction method (ASM) using two wavelengths, one of which was of AML at 365 nm and the other was the isoabsorptive point of both drugs at 237 nm. Method (II) was ratio subtraction method (RSM) for determination of OLM at λmax = 254 nm by taking the ratio spectrum and subtracting the constant values using 10 µg/mL of AML as a divisor in combination with extended ratio subtraction method (ERSM) to determine AML at λmax = 239 nm using 10 µg/mL OLM as a divisor. Method (III) was dual wavelength method; the wavelengths used to determine OLM were 221 nm and 235 nm, while those used to determine AML were 246 nm and 259 nm. Method (IV) was the second order derivative (2D) spectrophotometric method at 219 nm for OLM and 227 nm for AML. The proposed approaches were used to achieve linearity in the concentration range of 2-25 µg/mL for both drugs. The approaches were found to be uncomplicated, reproducible, efficient, and cost-effective as well as they were successfully used to determine the cited drugs in both laboratory samples and commercial pharmaceutical formulations.


Assuntos
Anlodipino , Olmesartana Medoxomila , Espectrofotometria , Comprimidos
2.
Chemosphere ; 286(Pt 1): 131641, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34325263

RESUMO

The photolysis of amlodipine (AML) as a ubiquitous pollutant in natural water has been extensively studied. Montmorillonite (MMT), a major component of suspended particles in surface aquifers, plays key roles in the natural transportation and transformation of organic contaminants in the environment. However, literature has scarcely focused on whether and how suspended particles affect the phototransformation of AML. This study systematically investigated the phototransformation behavior of AML in MMT suspensions under simulated sunlight. The results obtained showed that MMT significantly enhanced the photolysis of AML. The photodegradation of AML in 0.05 g/L MMT suspension reached 92.2 % after 3 h irradiation under the simulated sunlight. The photodecomposition followed the pseudo-first-order kinetic with a rate constant of 0.803 h-1 in the presence of 0.05 g/L MMT, which is about 19 times larger than that in the absence of MMT (0.0421 h-1). Further mechanistic investigation suggested that MMT accelerated the photolysis of AML by the formation of surface complexes between cationic amino groups of AML and the negatively charged sites on MMT surface, which greatly facilitated light absorption and electron transfer for the production of cationic radical AML+·. Meanwhile, the hydroxyl radicals generated by irradiated MMT also played an important role in the photocatalytic degradation of AML. The probable photodegradation pathways of AML in MMT suspension further supported the proposed mechanisms. The toxicity evaluation of phototransformation products of AML with ECOSAR program indicated that photolysis could reduce its potential threats. These findings reveal an important and previously overlooked phototransformation mechanisms of AML in the presence of MMT clays, which is of importance in assessing the environmental fate of other similar organic contaminants.


Assuntos
Bentonita , Poluentes Químicos da Água , Anlodipino , Cinética , Fotólise , Luz Solar , Água , Poluentes Químicos da Água/análise
3.
Arch Argent Pediatr ; 119(6): e610-e615, 2021 12.
Artigo em Espanhol | MEDLINE | ID: mdl-34813241

RESUMO

Calcium channel blocker poisoning is a rare condition in the pediatric population. Signs and symptoms can be rapidly progressive and lead to cardiovascular collapse and death. Hemodynamic support with inotropics and vasopressors is usually not effective. The insulin/glucose therapy is an effective complement to the initial treatment, which is widely studied and used in different pathologies with hemodynamic compromise. The case of a pediatric patient with a history of highdose ingestion of amlodipine for suicidal purposes, with hemodynamic decompensation refractory to usual inotropic support treatment, is presented. From the insulin/glucose treatment, hemodynamic stability was achieved with a favorable evolution.


Assuntos
Overdose de Drogas , Pediatria , Anlodipino , Bloqueadores dos Canais de Cálcio , Criança , Overdose de Drogas/terapia , Glucose , Humanos , Insulina
4.
Ann Palliat Med ; 10(10): 10768-10778, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763438

RESUMO

BACKGROUND: Left ventricular (LV) hypertrophy predicts worse cardiac outcomes. Blood pressure lowering is associated with the reduction of LV hypertrophy. This study evaluated the effect of a calcium channel blocker, amlodipine, on LV hypertrophy in patients with hypertension. METHODS: Studies were identified by conducting a literature survey in electronic databases, and study selection was carried out according to precise eligibility criteria. Meta-analyses of mean change between the follow-up and baseline values of systolic/diastolic blood pressure (SBP/DBP) and LV hypertrophy indices were performed. Meta-regression analyses were performed to examine the factors affecting changes in these indices. RESULTS: Twenty-three studies [involving 737 patients; age 56.4 years, 95% confidence interval (CI): 53.5-59.2; females 34%, 95% CI: 25-44%; body mass index 26.4 kg/m2, 95% CI: 24.6-28.1] were included. Amlodipine treatment led to a significant reduction in SBP (-24.9 mmHg; 95% CI: -28.3 to -21.6; P<0.0001) and DBP (-14.8; 95% CI: -16.4 to -13.3; P<0.0001), without affecting the heart rate. Amlodipine treatment also significantly reduced the LV mass index. The mean difference (MD) between the follow-up and baseline LV mass index was -12.9; 95% CI: -15.4 to -10.4 (P<0.001). This decrease in LV mass index was positively associated with the follow-up duration [meta-regression coefficient (MC): 0.392; 95% CI: 0.050-0.733; P=0.026] and baseline LV mass index (MC: 0.139; 95% CI: 0.007-0.271; P=0.040). Amlodipine treatment significantly reduced the LV posterior wall thickness, which was also positively associated with the follow-up duration. There was no significant decrease in the LV end-diastolic diameter following amlodipine treatment. DISCUSSION: Amlodipine treatment in patients with hypertension significantly reduced the LV mass index and LV posterior wall thickness, without notably affecting the LV end-diastolic diameter. Since many of the included studies were non-randomized, open-label, or lacking appropriate comparability, we therefore performed pooled analyses of the changes from baseline, and a comparative account could not be carried out.


Assuntos
Anlodipino , Hipertensão , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Pessoa de Meia-Idade
6.
Kardiologiia ; 61(8): 14-22, 2021 Aug 31.
Artigo em Russo | MEDLINE | ID: mdl-34549689

RESUMO

Aim      To study the condition of coronary vasculature by data of coronarography (CG) in patients with chronic ischemic heart disease (IHD) and arterial hypertension (AH) associated with stage 2-4 chronic kidney disease (CKD) and to evaluate the effect of a 12-week complex treatment with perindopril or with a combination of perindopril/amlodipine on changes in vascular wall stiffness, endothelial function, and structure and function parameters in this patient category after coronary stenting.Material and methodsr This study included 87 patients with chronic IHD and AH associated with stage 2-3 CKD for whom CG was performed due to ineffectiveness of the antianginal therapy. The patients were divided into three subgroups: subgroup 1 included 28 patients who received a conservative treatment with perindopril 10 mg/day; subgroup 2 consisted of 25 patients who underwent coronary stenting and were prescribed perindopril; subgroup 3 consisted of 34 patients who underwent stenting and were prescribed the perindopril/amlodipine combination. The reference group included 47 patients with IHD and AH with preserved kidney function. Anatomic and functional parameters of the heart, arterial stiffness, pulse wave velocity, cardio-ankle vascular index, augmentation index, central aortic systolic and pulse pressure, endothelium-dependent vasodilation, plasma concentration of endothelin-1 (ET-1), and plasma concentration of nitric oxide metabolites were evaluated at baseline and after 12 weeks of treatment.Results In patients with IHD, AH, and stage 2-3 CKD, arterial stiffness was more pronounced than in patients with preserved kidney function. Concentrations of ET-1 were significantly higher and levels of nitric oxide were lower in CKD. Supplementing the complex therapy with perindopril resulted in a considerable hypotensive effect in all subgroups, improvement of the kidney function, and positive dynamics of arterial stiffness and endothelial function. Changes in these parameters were more pronounced in patients after coronary stenting than in patients receiving only a conservative treatment. The use of perindopril/amlodipine following stenting exerted the most significant angioprotective and cardioprotective effect.Conclusion      Patients with IHD and AH in combination with early CKD have pronounced impairment of the condition of arterial blood vessels and the heart. Addition of perindopril to the treatment not only exerted a hypotensive effect but also beneficially influenced mechanisms of progression of this combined pathology.


Assuntos
Doença das Coronárias , Hipertensão , Insuficiência Renal Crônica , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Doença das Coronárias/tratamento farmacológico , Combinação de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Perindopril , Análise de Onda de Pulso , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
7.
Lancet ; 398(10305): 1043-1052, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34469767

RESUMO

BACKGROUND: Treatment inertia is a recognised barrier to blood pressure control, and simpler, more effective treatment strategies are needed. We hypothesised that a hypertension management strategy starting with a single pill containing ultra-low-dose quadruple combination therapy would be more effective than a strategy of starting with monotherapy. METHODS: QUARTET was a multicentre, double-blind, parallel-group, randomised, phase 3 trial among Australian adults (≥18 years) with hypertension, who were untreated or receiving monotherapy. Participants were randomly assigned to either treatment, that started with the quadpill (containing irbesartan at 37·5 mg, amlodipine at 1·25 mg, indapamide at 0·625 mg, and bisoprolol at 2·5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). If blood pressure was not at target, additional medications could be added in both groups, starting with amlodipine at 5 mg. Participants were randomly assigned using an online central randomisation service. There was a 1:1 allocation, stratified by site. Allocation was masked to all participants and study team members (including investigators and those assessing outcomes) except the manufacturer of the investigational product and one unmasked statistician. The primary outcome was difference in unattended office systolic blood pressure at 12 weeks. Secondary outcomes included blood pressure control (standard office blood pressure <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects. Analyses were per intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12616001144404, and is now complete. FINDINGS: From June 8, 2017, to Aug 31, 2020, 591 participants were recruited, with 743 assessed for eligibility, 152 ineligible or declined, 300 participants randomly assigned to intervention of initial quadpill treatment, and 291 to control of initial standard dose monotherapy treatment. The mean age of the 591 participants was 59 years (SD 12); 356 (60%) were male and 235 (40%) were female; 483 (82%) were White, 70 (12%) were Asian, and 38 (6%) reported as other ethnicity; and baseline mean unattended office blood pressure was 141 mm Hg (SD 13)/85 mm Hg (SD 10). By 12 weeks, 44 (15%) of 300 participants had additional blood pressure medications in the intervention group compared with 115 (40%) of 291 participants in the control group. Systolic blood pressure was lower by 6·9 mm Hg (95% CI 4·9-8·9; p<0·0001) and blood pressure control rates were higher in the intervention group (76%) versus control group (58%; relative risk [RR] 1·30, 95% CI 1·15-1·47; p<0·0001). There was no difference in adverse event-related treatment withdrawals at 12 weeks (intervention 4·0% vs control 2·4%; p=0·27). Among the 417 patients who continued, uptitration occurred more frequently among control participants than intervention participants (p<0·0001). However, at 52 weeks mean unattended systolic blood pressure remained lower by 7·7 mm Hg (95% CI 5·2-10·3) and blood pressure control rates higher in the intervention group (81%) versus control group (62%; RR 1·32, 95% CI 1·16-1·50). In all randomly assigned participants up to 12 weeks, there were seven (3%) serious adverse events in the intervention group and three (1%) serious adverse events in the control group. INTERPRETATION: A strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting monotherapy. This trial demonstrated the efficacy, tolerability, and simplicity of a quadpill-based strategy. FUNDING: National Health and Medical Research Council, Australia.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bisoprolol/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Hipertensão/tratamento farmacológico , Indapamida/administração & dosagem , Irbesartana/administração & dosagem , Austrália , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Life Sci ; 285: 119965, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543638

RESUMO

Galangin is a natural flavonoid isolated from ginger, honey and propolis. AIMS: To investigate the effect of galangin on blood pressure, vascular changes, sympathoexcitation, oxidative stress and inflammation in rats treated with NG-nitro-l-arginine methyl ester (l-NAME). MATERIALS AND METHODS: Male Wistar rats (220-250 g) were given l-NAME (0.5 mg/mL in drinking water) to induce hypertension for 5 weeks. They were treated with vehicle, galangin (30 or 60 mg/kg), or amlodipine (10 mg/kg) for the final two weeks (n = 6/group). KEY FINDINGS: Galangin significantly reduced blood pressure and improved the impairment of endothelium-dependent vasodilation in hypertensive rats. Sympathoexcitation, including enhancement of contractile responses to electrical field stimulation, increases in intensity of tyrosine hydroxylase and plasma norepinephrine concentration in hypertensive rats, was attenuated by galangin treatment. Galangin also reduced systemic and vascular oxidative damage and increased plasma nitric oxide levels in the hypertensive groups. Aortic remodelling accompanied by aortic wall hypertrophy and fibrosis observed in hypertensive rats were alleviated by galangin treatment. Furthermore, galangin exhibited an anti-inflammatory effect by suppressing the upregulation of tumour necrosis factor receptor 1 (TNF-R1), phospho-nuclear factor kappa B (p-NF-κB) and vascular cell adhesion protein 1 (VCAM-1) in aortic tissue and reducing plasma tumour necrosis factor alpha (TNF-α) in l-NAME rats. In conclusion, galangin had antihypertensive effects that were relevant to attenuating endothelial dysfunction, sympathoexcitation and vascular remodelling. These effects might be contributed by antioxidant and anti-inflammatory capacities and modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Hipertensão/metabolismo , NF-kappa B/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Remodelação Vascular/efeitos dos fármacos , Anlodipino/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster , Ratos , Ratos Wistar
11.
Kardiologiia ; 61(7): 68-78, 2021 Jul 31.
Artigo em Russo | MEDLINE | ID: mdl-34397344

RESUMO

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.


Assuntos
Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Perindopril
12.
Nutrients ; 13(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34444956

RESUMO

Curcumin, a curcuminoid known as the main bioactive compound of turmeric, is used in foods, cosmetics, and pharmaceutical products. Amlodipine is a general antihypertensive drug used in combination with various other antihypertensive agents. To date, no studies have examined the effects of the co-administration of amlodipine with curcumin. In this study, the vasodilatory effects of curcumin, amlodipine, and the co-administration of curcumin with amlodipine on isolated rat aortic rings pre-contracted with phenylephrine were evaluated, and the hypotensive effects were evaluated using the tail cuff method. To measure blood pressure, male spontaneously hypertensive rats were divided into four groups, each containing six rats, as follows: amlodipine 1 mg/kg alone treated, amlodipine 1 mg/kg with curcumin 30 mg/kg treated, amlodipine 1 mg/kg with curcumin 100 mg/kg treated, and amlodipine 1 mg/kg with curcumin 300 mg/kg treated groups. Amlodipine and curcumin were intraperitoneally injected, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at 1, 2, 4, and 8 h after administration. The combined administration of curcumin and amlodipine induced a stronger vasorelaxant effect than amlodipine alone. However, co-administration did not significantly lower SBP and DBP compared to the single administration of amlodipine. The results of this study suggest that hypertensive patients taking amlodipine can consume curcumin or turmeric for food or other medical purposes without inhibiting the blood pressure-lowering effect of amlodipine.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Curcumina/administração & dosagem , Hipertensão/tratamento farmacológico , Vasodilatadores/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Masculino , Ratos , Ratos Endogâmicos SHR
13.
J Clin Hypertens (Greenwich) ; 23(9): 1706-1714, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34432358

RESUMO

Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post-exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p < .01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post-exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.


Assuntos
Hipertensão , Anlodipino/farmacologia , Animais , Pressão Sanguínea , Estudos Cross-Over , Eplerenona , Força da Mão , Humanos , Hipertensão/tratamento farmacológico , Músculo Esquelético , Ratos
14.
J Pharm Pharmacol ; 73(9): 1151-1160, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383955

RESUMO

OBJECTIVES: To study the effect of Zingiber officinale and Hibiscus sabdariffa on pharmacokinetics and pharmacodynamics of amlodipine. METHODS: Hypertension was induced in rats (SBP 173.2 ± 1.7 mmHg, mean, 1-24 h). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) of group-I (amlodipine treated), group-II (Z. officinale, and Z. officinale + amlodipine) and group-III (H. sabdariffa, and H. sabdariffa + amlodipine) animals were measured by "tail-cuff system". Pharmacokinetics of amlodipine with and without herbs (Z. officinale or H. sabdariffa) was also investigated. RESULTS: Z. officinale as well as H. sabdariffa decreased the SBP, DBP and MBP. Concurrent treatment with Z. officinale + amlodipine (SBP 129.4 ± 4.5) or H. sabdariffa + amlodipine (SBP 130.4 ± 3.9) showed higher decrease in BP (mean, 1-24h), than individually administered amlodipine (SBP 149.5 ± 2.4) or Z. officinale (SBP 150.2 ± 3.1) or H. sabdariffa (SBP 139.1 ± 1.2). These herbs also influenced the Cmax, AUC0-t, and Tmax of amlodipine. H. sabdariffa increased AUC0-t of amlodipine from 81.8 ± 14.7 to 125.0 ± 10.6 (ng h/mL). CONCLUSION: Simultaneous administration of Z. officinale or H. sabdariffa with amlodipine, improves its pharmacodynamic response.


Assuntos
Anlodipino/farmacocinética , Anti-Hipertensivos/farmacocinética , Pressão Sanguínea/efeitos dos fármacos , Gengibre , Interações Ervas-Drogas , Hibiscus , Hipertensão/fisiopatologia , Animais , Anti-Hipertensivos/farmacologia , Área Sob a Curva , Quimioterapia Combinada , Frequência Cardíaca , Hipertensão/tratamento farmacológico , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Ratos Wistar
15.
J Feline Med Surg ; 23(9): 812-822, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34428941

RESUMO

PRACTICAL RELEVANCE: Chronic kidney disease (CKD) is a highly prevalent disorder of senior cats. CKD is frequently diagnosed in association with hypertension, and the two conditions have an intermingled cause-and-effect relationship. Hypertensive target organ damage (TOD) to the eye, brain, heart and kidney significantly impacts the welfare of cats suffering from this comorbidity. Hypertension also drives proteinuria, which is an independent risk factor for progression and mortality in cats with CKD. Blood pressure monitoring and institution of effective antihypertensive treatment, where indicated, is therefore crucial in effective management of the feline CKD patient. Current guidelines recommend a target systolic blood pressure of <160 mmHg to minimise risk of TOD. Both amlodipine besylate and telmisartan are effective antihypertensive agents for use in these patients. CLINICAL CHALLENGES: Clinical signs of hypertension may not be apparent to owners of affected cats until severe hypertensive TOD is present. Despite this, blood pressure monitoring in cats with CKD is still infrequently performed, and hypertension likely remains underdiagnosed in this population. EVIDENCE BASE: This review is based upon evaluation of the currently available published literature, including relevant consensus statements. There is a large body of evidence supporting the association between hypertension and CKD in cats. However, significant aspects, such as the mechanisms behind this association, and effect of hypertension and antihypertensive treatment on mortality and progression of CKD, remain unclear. Further research is therefore required in order to improve understanding of these conditions.


Assuntos
Doenças do Gato , Hipertensão , Insuficiência Renal Crônica , Anlodipino/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Doenças do Gato/tratamento farmacológico , Doenças do Gato/epidemiologia , Gatos , Comorbidade , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/veterinária , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/veterinária
16.
Clin Exp Hypertens ; 43(8): 742-749, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34338579

RESUMO

Objectives: This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. Methods: The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for three years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. Results: In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, P < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Conclusions: Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.


Assuntos
Hipertensão , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Quimioterapia Combinada , Humanos , Hipertensão/tratamento farmacológico , Estudos Retrospectivos , Estações do Ano , Resultado do Tratamento
17.
J Clin Invest ; 131(18)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34351870

RESUMO

Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Doenças de Pequenos Vasos Cerebrais/etiologia , Hiperemia/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Anti-Hipertensivos/administração & dosagem , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Demência Vascular/tratamento farmacológico , Demência Vascular/etiologia , Demência Vascular/fisiopatologia , Modelos Animais de Doenças , Quimioterapia Combinada , Eplerenona/administração & dosagem , Eplerenona/uso terapêutico , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperemia/fisiopatologia , Losartan/administração & dosagem , Losartan/uso terapêutico , Masculino , Camundongos , Microvasos/efeitos dos fármacos , Microvasos/fisiopatologia , Canais de Potássio Corretores do Fluxo de Internalização/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120137, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34273891

RESUMO

Five simple, selective and accurate spectrophotometric methods have been applied and developed for first time for simultaneous determination of amlodipine besylate (AML) and celecoxib (CEL) in presence of one harmful impurity, 4-methylacetophenone (MAP), in their ternary mixture without prior separation. Those spectrophotometric methods were developed and called: dual wave length in ratio spectra (DWRS), successive ratio-derivative spectra (SDR), modified absorption factor method (MAFM), modified amplitude center method (MACM) and first derivative -zero crossing coupled with amplitude factor method (FDAF). These methods include various steps using zero /or ratio /or derivative spectra and some mathematical techniques. Linear calibration curves were constructed over the concentration range of 2-100, 10-200 and 0.5-20 µg/mL for AML, CEL and MAP, respectively. High sensitivity with low LOD values 0.583, 3.118 and 0.147 for AML, CEL and MAP, respectively were obtained. Moreover, validation of the proposed methods was achieved according to ICH guidelines and satisfactory results were obtained indicating that the developed methods can be used for quality control analysis of AML and CEL concerning its impurity. No significant difference was observed when the obtained results of the developed methods were statistically compared with the reported HPLC method.


Assuntos
Anlodipino , Celecoxib , Espectrofotometria
19.
J Avian Med Surg ; 35(2): 155-160, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34256545

RESUMO

Amlodipine is a calcium channel blocker shown to be effective in lowering blood pressure with minimal adverse effects in mammals. To provide a retrospective evaluation of amlodipine use in psittacine birds, medical records were reviewed for all avian patients prescribed amlodipine for treatment for the presumptive diagnosis of hypertension, based on clinical signs and indirect blood pressure measurements. Five birds were treated with amlodipine between 2010 and 2018. The median age was 33 years (range, 22-37 years) and 3/5 birds presented for ataxia or seizures. The median indirect systolic blood pressure at diagnosis was 243 mm Hg (range, 200-275 mm Hg). In 3/5 birds, amlodipine was the only drug prescribed, whereas, in 2/5 birds, enalapril was also prescribed in addition to amlodipine. In addition to the prescription of enalapril, blood pressure measurements were obtained indirectly, which are variables to be considered in this report. The initial median dose of amlodipine prescribed was 0.4 mg/kg (range, 0.1-0.4 mg/kg) PO q24h. In 3/5 birds, amlodipine administration was increased either in dose or frequency. Median follow-up time was 25 months (range, 2-55 months) after the initiation of amlodipine treatment. Owners in all 5 cases reported improvement of clinical signs by a median time of 2 months (range, 1-15 months). Three of 5 birds (60%) demonstrated a decreasing trend in blood pressure during the first 6 months after treatment with amlodipine was started (average, ≥20% decrease). Prospective, controlled studies are needed to investigate the efficacy of amlodipine in psittacine birds.


Assuntos
Hipertensão , Psittaciformes , Anlodipino/uso terapêutico , Animais , Aves , Hipertensão/tratamento farmacológico , Hipertensão/veterinária , Estudos Prospectivos , Estudos Retrospectivos
20.
J AOAC Int ; 104(5): 1442-1452, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34115124

RESUMO

BACKGROUND: Hypertension is a major health problem found in people throughout the world and numerous fixed-dose combination (FDC) products of telmisartan are available in the local market for its treatment. Several chromatography methods such as reversed-phase (RP)-HPLC and HPTLC methods have been published for estimation of FDC products of telmisartan with hydrochlorothiazide, atorvastatin, and amlodipine. No RP-HPLC method has been reported yet for synchronous estimation of FDC products of telmisartan, which would save analysis time, cost, and solvent. OBJECTIVE: A multipurpose RP-HPLC method has been developed for synchronous estimation of FDC products of telmisartan using the analytical quality by design approach based on risk- and design of experiment (DoE)-based define, measure, analyse, improve, control (DMAIC) principles. METHOD: The risk-based DMAIC principle was implemented by risk parameter identification and assessment as per the ICH Q9 guideline. The DoE-based DMAIC principle was applied by response surface analysis using a Box-Behnken design. The method operable design ranges were navigated and a control strategy was set for the development of the method as per the analytical target profile (ATP). RESULTS: Chromatographic separation was performed using Shimpack ODS C18 column and acetonitrile: 0.1% (v/v) triethylamine (pH 6.5), keeping a flow rate of 1.0 mL/min. The method was validated as per the ICH Q2 (R1) guideline. The developed method was applied for synchronous estimation of seven different anti-hypertensive products. CONCLUSIONS: The developed method is an eco-friendly and economical alternative to published chromatography methods for the analysis of anti-hypertensive products. Hence, the developed method can be used as a multipurpose RPLC method for quality control of anti-hypertensive products in the pharmaceutical industry. HIGHLIGHTS: A multipurpose RPLC method for synchronous estimation of antihypertensive products of telmisartan was developed, saving analysis time, cost, and solvent. The developed method was applied to the synchronous estimation of seven different anti-hypertensive products.


Assuntos
Anlodipino , Anti-Hipertensivos , Cromatografia Líquida de Alta Pressão , Humanos , Hidroclorotiazida , Controle de Qualidade
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