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A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective.
McNally, RJ, Morselli, F, Farukh, B, Chowienczyk, PJ, Faconti, L
British journal of clinical pharmacology. 2019;(12):2707-2713
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Abstract
Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide-type and thiazide-like diuretics as first-line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first-line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide-like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide-type diuretics are more widely used than thiazide-like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.
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Treatment and Prevention of Hypertensive Disorders During Pregnancy.
Leavitt, K, Običan, S, Yankowitz, J
Clinics in perinatology. 2019;(2):173-185
Abstract
This article reviews the pharmacology of the most commonly used antihypertensive medications during pregnancy; their mechanism of action; and the effects on the mother, the fetus, and lactation. Each class of antihypertensive pharmacologic agents have specific mechanisms of action by which they exert their antihypertensive effect. β-Adrenoreceptor antagonists block these receptors in the peripheral circulation. Calcium channel blockers result in arterial vasodilation. α-Agonists inhibit vasoconstriction. Methyldopa is a centrally acting adrenoreceptor antagonist. Vasodilators have a direct effect on vascular smooth muscle. Diuretics decrease intravascular volume. Medications acting on the angiotensin pathway are avoided during pregnancy because of fetotoxic effects.
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[New aspects of the pathomechanism of salt-sensitive hypertension].
Sulyok, E
Orvosi hetilap. 2019;(2):43-49
Abstract
This article shortly outlines the evolution of hypertonia from risk factors to end-organ damage. The pathogenetic role of salt intake is underlined and in the light of recent clinical and experimental observations, the importance of renal and extrarenal mechanism in the development of salt-sensitive hypertension is analysed. The generally accepted concept that the inefficient renal sodium excretion and the subsequent expansion of the extracellular space is the major factor in blood pressure elevation is challenged. Evidences have been provided that the retained sodium dissociates from the volume of extracellular space and, also from the blood pressure. It has been shown that the negatively charged macromolecules in the subcutaneous interstitium bind sodium ions in osmotically inactive form and store sodium reversibly. The local tissue hypertonicity induces monocytes/macrophages invasion and activation that causes increased expression of tonicity-responsive enhancer binding protein (TonEBP) and the secretion of vascular endothelial growth factor C that result in enhanced lymphangiogenesis. The expanded lymphatic system drains the excess sodium and volume back to the circulation. The reduction of buffer function of this system may contribute to the development or to worsening of hypertension. Similar buffer and barrier functions are attributed to the glycocalyx that covers the luminal surface of vascular endothelium. It is also recognised that the high sodium intake alone is an important pathogenetic factor in end-organ damage independent of hypertension. This may be accounted for by the induction and activation of Th17 cells as well as by the increased production of several pro-inflammatory and pro-fibrotic cytokines. Orv Hetil. 2019; 160(2): 43-49.
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[Development of therapeutic vaccine for life style-related diseases].
Nakagami, H
Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 2019;(5):270-274
Abstract
In the 18th century, Edward Jenner proposed the vaccine for smallpox as a first vaccine therapy based on the legend that a vaccinia prevents the infection with smallpox. Recently, the therapeutic target of vaccine will expand from infectious diseases to various diseases, such as amyloid β or tau vaccine for Alzheimer's disease. We are now going to develop a therapeutic vaccine to lifestyle-related diseases (i.e. high blood pressure), and aim to realize a novel therapy which will be injected once or twice per year from a daily medication. For this purpose, the appropriate choice of an antigen, carrier and adjuvants should be required to activate hormonal immunity by the vaccine, leading to efficient antibody production without toxicity, because the therapeutic target of our vaccine is an endogenous protein (i.e. hormone). The clinical advantage of this therapeutic vaccine is to improve the medical adherence and drug management because the multiple drug users are increased in particular old patients, so called polypharmacy. If the vaccine will take place of a part of medicine in future, it may give us a novel therapeutic option with several social benefits.
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[Sexual dysfunction and antihypertensive treatment: Involvement of the different therapeutic classes and what to do about the treatment of hypertension].
Bouhanick, B, Blacher, J, Huyghe, E, Colson, MH, Boivin, JM, Mounier-Vehier, C, Denolle, T, Fauvel, JP
Presse medicale (Paris, France : 1983). 2019;(11 Pt 1):1222-1228
Abstract
Erectile dysfunction (ED) is not routinely discussed with patients in cardiology practices whereas it may impact the ability of patients to stay on therapy. Most of the studies about ED and antihypertensive therapies have several methodological limitations. Diuretics and beta-blockers have been shown to have a deleterious effect on ED. ISRA inhibitors, calcium antagonists, vasodilator beta-blockers and alpha-blockers have been shown to have a neutral impact on ED. Angiotensin 2 inhibitors, nebivolol and alpha-blockers use has sometimes beneficial effect on ED. In case of ED due to antihypertensive treatment, drugs can be switched each other but careful attention in patients with a high cardiovascular risk is required.
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Reviewing the effects of thiazide and thiazide-like diuretics as photosensitizing drugs on the risk of skin cancer.
Kreutz, R, Algharably, EAH, Douros, A
Journal of hypertension. 2019;(10):1950-1958
Abstract
BACKGROUND Thiazide diuretics and particularly hydrochlorothiazide were recently linked to an increased risk of skin cancer, which was attributed to the photosensitizing properties of these drugs. Given the widespread use of thiazide diuretics, a potential skin cancer promoting effect would impose an important public health concern. OBJECTIVE To critically appraise in a narrative review, the association between use of thiazide and thiazide-like diuretics and risk of skin cancer. METHODS We evaluated chemical structures and photosensitizing potential of selected thiazide and thiazide-like diuretics. Moreover, we searched PubMed up to December 2018 for observational studies assessing the association between use of thiazide or thiazide-like diuretics and risk of skin cancer. Study quality was assessed for major methodological biases. RESULTS Commonly used thiazide and thiazide-like diuretics carry resonating structural components, such as sulfonamide groups that contribute to their photosensitizing activity. Overall, 13 observational (9 case-control, 4 cohort) studies assessed the association between use of different thiazide or thiazide-like diuretics and risk of several skin cancer types. Of those, nine studies showed positive associations ranging from 3% increased risk for bendroflumethiazide and basal cell carcinoma to 311% increased risk for thiazide diuretics and squamous cell carcinoma. All studies had important design-related methodological limitations including potential confounding by indication, detection bias, and time-window bias. CONCLUSION Commonly used thiazide and thiazide-like diuretics have photosensitizing potential, and some observational studies with important methodological limitations have linked their use to an increased risk of skin cancer. Well designed observational studies are needed to provide more solid evidence on this possible association.
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Protective measures of patients with cardiovascular diseases from exposure to heat waves: medicated and non-medicated.
Smirnova, MD, Svirida, ON, Ageev, FT
Terapevticheskii arkhiv. 2019;(1):101-107
Abstract
In conditions of climate warming with an increase in heat waves associated with an increase in cardiovascular morbidity and mortality, the particular interest is the effect of cardiovascular drugs on adaptation to high temperatures. The review reflects the results of European and domestic studies on the safety of therapy during long and short heat waves. Recommendations for the correction of therapy during this period are given. Self-control of blood pressure (SCAD) is a mandatory component of the therapy of arterial hypertension during heat waves. With the development of clinically significant hypotension, a reduction in the dose of antihypertensive drugs is necessary. It is recommended to start with a dose reduction and/or withdrawal of diuretics and nitrates. Not recommended the complete abolition of antihypertensive therapy because of the risk of hypertensive crises, characteristic of abnormal heat, as well as due to the increase in blood pressure when the weather changes and the temperature drops. With increasing blood pressure during heat waves, it is recommended to give preference to calcium channel antagonists, angiotensin converting enzyme inhibitors (ACE inhibitors) and selective beta-blockers. It is necessary to inform patients about the additional protective effect of statins in order to increase adherence to therapy. Patients taking diuretics require individual daily monitoring of fluid intake and body weight. An overview of recommendations on sanogenic behavior during heat waves is given. Details are considered rules for the use of air conditioning, methods of diagnosis of dehydration and drinking mode Keywords: heat waves, cardiovascular complications, preventive measures.
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Hypertension linked to allostatic load: from psychosocial stress to inflammation and mitochondrial dysfunction.
Mocayar Marón, FJ, Ferder, L, Saraví, FD, Manucha, W
Stress (Amsterdam, Netherlands). 2019;(2):169-181
Abstract
Although a large number of available treatments and strategies, the prevalence of cardiovascular diseases continues to grow worldwide. Emerging evidence supports the notion of counteracting stress as a critical component of a comprehensive therapeutic strategy for cardiovascular disease. Indeed, an unhealthy lifestyle is a burden to biological variables such as plasma glucose, lipid profile, and blood pressure control. Recent findings identify allostatic load as a new paradigm for an integrated understanding of the importance of psychosocial stress and its impact on the development and maintenance of cardiovascular disease. Allostasis complement homeostasis and integrates behavioral and physiological mechanisms by which genes, early experiences, environment, lifestyle, diet, sleep, and physical exercise can modulate and adapt biological responses at the cellular level. For example, variability is a physiological characteristic of blood pressure necessary for survival and the allostatic load in hypertension can contribute to its related cardiovascular morbidity and mortality. Therefore, the current review will focus on the mechanisms that link hypertension to allostatic load, which includes psychosocial stress, inflammation, and mitochondrial dysfunction. We will describe and discuss new insights on neuroendocrine-immune effects linked to allostatic load and its impact on the cellular and molecular responses; the links between allostatic load, inflammation, and endothelial dysfunction; the epidemiological evidence supporting the pathophysiological origins of hypertension; and the biological embedding of allostatic load and hypertension with an emphasis on mitochondrial dysfunction.
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ACE-inhibitor/calcium antagonist combination: is this the first-choice therapy in arterial hypertension?
Taddei, S
Minerva medica. 2019;(6):546-554
Abstract
The 2018 ESH/ESC guidelines indicate that the first-choice therapy in the majority of hypertensive patients should be a fixed combination of a drug that blocks the renin-angiotensin-aldosterone system and a calcium antagonist or a diuretic. Evidence from the meta-analysis of controlled clinical trials, however, indicates that the classes of drugs that block the renin-angiotensin-aldosterone system should not be considered equivalent as ACE inhibitors have been clearly shown to outperform AT-1 antagonists in preventing myocardial infarction and total mortality. Moreover, studies such as ASCOT and ACCOMPLISH demonstrate a superiority of the ACE-inhibitor/calcium antagonist association over beta-blocker/diuretic associations and especially towards the ACE-inhibitor/diuretic combination, whereas there is no scientific evidence of efficacy with respect to cardiovascular events on the part of AT-1 antagonist/calcium antagonist combinations. Drugs such as ramipril and amlodipine are undoubtedly the reference molecules within their respective classes as numerous controlled clinical studies have demonstrated their effectiveness on cardiovascular events. It is therefore obvious that the availability of a fixed combination with both molecules is a great opportunity for the therapy of the hypertensive patient, considering also the availability of studies that demonstrate its effectiveness on intermediate endpoints associated with high tolerability. So, in accordance with the 2018 ESH/ESC guidelines, the fixed combination ramipril/amlodipine represents a first choice therapy for hypertension.
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Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide.
Georgianos, PI, Agarwal, R
Diabetes care. 2019;(4):693-700
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Abstract
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.