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Thiazide Diuretics (thiazide + diuretic)
Selected AbstractsEmerging Insights in the First-Step Use of Antihypertensive Combination TherapyJOURNAL OF CLINICAL HYPERTENSION, Issue 2007Keith Norris MD The blood pressure (BP) goals set by hypertension management guidelines (<140/90 mm Hg in uncomplicated hypertension; <130/80 mm Hg in type 2 diabetes or kidney disease) are not being achieved in a high proportion of patients, partly because monotherapy is insufficient in many patients. In particular, patients with uncontrolled moderate or severe hypertension and/or associated cardiovascular risk factors remain at high risk for cardiovascular events and hypertensive emergency. In recognition of the urgency of treating moderate and severe hypertension, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) advocates the initial use of 2-drug therapies in patients with systolic BP levels >20 mm Hg above goal or diastolic BP level >10 mm Hg above goal. Regimens should usually include a thiazide diuretic and, for patients with diabetes or kidney disease, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Recently, clinical trial data have shown that first-step antihypertensive treatment of moderate and severe hypertension with carefully chosen fixed-dose combinations provides a high rate of BP goal achievement, a simplified dosing regimen, and superior tolerability compared with monotherapy. [source] Your Drug, My Drug, or Our Drugs: How Aggressive Should We Be With Antihypertensive Therapy?JOURNAL OF CLINICAL HYPERTENSION, Issue 2005Joseph L. Izzo Jr. MD In the prevention of hypertensive complications, especially stroke and kidney disease, "lower is better" because for each decrease of 20 mm Hg systolic or 10 mm Hg diastolic pressure in the population, cardiovascular risk is halved. Ideally, the goal for each patient should be to reach the lowest blood pressure that is well tolerated, a value that may be well below the arbitrary threshold value of 140/90 mm Hg. For the majority of "uncomplicated hypertensives," the question of single-drug therapy is essentially moot, because more than one agent is almost always required to optimally control blood pressure. In individuals who already have heart or kidney disease, there are compelling indications for the use of drugs that block the renin-angiotensin system, but the large outcome studies that spawned these recommendations are themselves combination trials. Thus, in virtually all patients, more than one drug is indicated. The best combinations take advantage of long durations of action and complementary mechanisms of action of the component and are not only able to effectively lower blood pressure, but also to favorably affect the natural history of hypertensive complications. Regimens,including fixed-dose combination products,that combine a thiazide diuretic or calcium antagonist with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker are most efficient. In summary, why would an astute clinician (or informed patient) be satisfied with the relatively limited effects of any single class of antihypertensive agents when better overall protection is possible? [source] Treatment of isolated systolic hypertension in diabetes mellitus type 2DIABETES OBESITY & METABOLISM, Issue 4 2006Ingrid Os Age-related arterial stiffness is more pronounced in diabetics compared to non-diabetics, which could explain the prevalence of isolated systolic hypertension (ISH, systolic blood pressure ,140 mmHg and diastolic blood pressure <90 mmHg) being approximately twice that of the general population without diabetes. Large-scale interventional outcome trials have also shown that diabetics usually have higher pulse pressure and higher systolic blood pressure than non-diabetics. Advanced glycation end-product formation has been implicated in vascular and cardiac complications of diabetes including loss of arterial elasticity, suggesting possibilities for new therapeutic options. With increasing age, there is a shift to from diastolic to systolic blood pressure and pulse pressure as predictors of cardiovascular disease. This may affect drug treatment as different antihypertensive drugs may have differential effects on arterial stiffness that can be dissociated from their effects on blood pressure. While thiazide diuretics are associated with little or no change in arterial stiffness despite a robust antihypertensive effect, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and calcium-channel blockers have been shown to reduce arterial stiffness. However, combination therapy is nearly always necessary to obtain adequate blood pressure control in diabetics. There are no randomized controlled trials looking specifically at treatment of ISH in diabetics. Recommendations regarding treatment of ISH in diabetes mellitus type 2 are based on extrapolation from studies in non-diabetics, post-hoc analyses and prespecified subgroup analysis in large-scale studies, and metaanalysis. These analyses have clearly demonstrated that blood pressure lowering in ISH confers improved prognosis and reduced cardiovascular and renal outcomes in both diabetics and non-diabetics. [source] Low-dose thiazide diuretics in and around diabetes,definitely yes, and how do they compare with other interventions?DIABETIC MEDICINE, Issue 2 2010J. K. Cruickshank No abstract is available for this article. [source] Risk factors for symptomatic hyponatraemia: the role of pre-existing asymptomatic hyponatraemiaINTERNAL MEDICINE JOURNAL, Issue 3 2007M. Bissram Abstract Background: Hyponatraemia is associated with substantial morbidity and mortality. Identification of the risk factors associated with the development of symptomatic hyponatraemia is important in determining preventive strategies. Methods: A retrospective analysis of the risks factors associated with the development of severe, symptomatic hyponatraemia requiring hospital admission over the past 3 years at our institution was carried out. Results: Forty-seven patients (26 women, 21 men) with a hospital admission serum sodium <134 mmol/L were identified. Of these patients, 31 (65.9%) had associated changes in the mental status that improved with the treatment of the hyponatraemia suggesting causality. The average admission sodium level of this cohort was 118.8 mmol/L. Symptomatic hyponatraemia was associated with volume depletion (32.6%), congestive heart failure (26%), syndrome of inappropriate antidiuretic hormone (26%), thiazide diuretic use (26%) and selective serotonin re-uptake inhibitor use (26%). In 21.7% of cases, the cause was multifactorial (congestive heart failure, syndrome of inappropriate antidiuretic hormone or medication use with volume depletion). In 11% of cases, patients were taking both thiazide diuretics and serotonin re-uptake inhibitors. Most importantly, 70.9% of all patients admitted with symptomatic hyponatraemia had pre-existing hyponatraemia that was untreated and believed to be asymptomatic (P < 0.05). This was the most common risk factor identified. We next investigated the prevalence of presumed asymptomatic hyponatraemia in the outpatient setting. Out of 27 496 patients analysed, 14% had serum sodium levels less than or equal to 134 mEq/L and 4% had values less than 130 mEq/L. Conclusion: Pre-existing asymptomatic hyponatraemia is a common finding and is associated with a high risk for the development of worsening hyponatraemia with altered mental status. [source] Non-prescription medicine use by outpatients of a hospital in north-central Trinidad living with hypertension, and the potential clinical risksINTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 5 2008Miss Rian Extavour Assistant Lecturer, principal investigator Objective To describe the reported use of non-prescription medicines (NPMs) and the reported frequency of use by outpatients living with hypertension; to identify potential drug-drug and drug-disease interactions between reported NPMs and either antihypertensives prescribed or hypertension. Setting Adult outpatient clinics of the Eric Williams Medical Sciences Complex Adult Hospital in Trinidad. Method Outpatients were interviewed about their use of NPMs using a structured instrument. Chi-squared test or Fisher's exact test was used to test for associations between NPM use and selected variables: age group, gender, education level, number of prescribed medicines, use of prescribed medicines and the presence of comorbidities. Combinations of NPMs and antihypertensive drugs or hypertension itself that may lead to undesirable interactions were identified. Key findings One hundred and fifty-five clients were interviewed (mean age 61 years; 46% men; 56% of East Indian descent). Of these, 82% were living with a cardiac condition and 60% with diabetes mellitus. In addition, 92% reported using NPMs to treat minor illnesses. Analgesic use was reported by 81%. Some 66% reported using paracetamol, 54% reported antitussives, 48% antacids, 47% antihistamines and 39% said they used sympathomimetic drugs. The majority (98%) of NPMs were used only when needed. Sixty per cent had at least one combination a with risk of interaction with NPMs and hypertension or antihypertensive medicines: 16% had risk of interactions between enalapril (or captopril) and antacids, 13% between angiotensin-converting enzyme (ACE) inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs), 12% between beta-blockers and NSAIDs and 12% between thiazide diuretics and NSAIDs. Thirty-nine per cent had a drug-disease interaction risk due to sympathomimetic drugs and 26% had one due to NSAID use. Conclusion Based on self-reports, outpatients living with hypertension in north-central Trinidad use NPMs when needed to treat minor illnesses, mainly paracetamol for pain. Non-prescription-antihypertensive interactions may arise due to ACE inhibitor/antacid combinations and NPM-hypertension interactions may result from use of sympathomimetics. Interactions may also arise as a result of the use of NPMs containing NSAIDs and sodium. [source] Indapamide, a Thiazide-Like Diuretic, Decreases Bone Resorption In VitroJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2001Agnes Lalande Abstract We recently showed that indapamide (IDP), a thiazide-related diuretic, increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. We showed that 10,4 M IDP and 10,4 M AZ, as well as 10,5 M pamidronate (APD), decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10,8 M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We investigated the mechanism of this antiresorptive effect of IDP; IDP decreased osteoclast differentiation as the number of osteoclasts developing in coculture of marrow and osteoblast-like cells was decreased markedly. We then investigated whether IDP affected osteoblast-like cells because these cells are involved in the osteoclast differentiation. Indeed, IDP increased osteoblast-like cell proliferation and alkaline phosphatase (ALP) expression. Nevertheless, it did not modify the colony-stimulating factor 1 (CSF-1) production by these cells. In addition, osteoblast-like cells expressed the Na+/Cl, cotransporter that is necessary for the renal action of thiazide diuretics, but IDP inhibited bone resorption in mice lacking this cotransporter, so the inhibition of bone resorption and osteoclast differentiation did not involve this pathway. Thus, we hypothesized that IDP may act directly on cells of the osteoclast lineage. We observed that resorption pits produced by spleen cells cultured in the presence of soluble osteoclast differentiation factor (sODF) and CSF-1 were decreased by 10,4 M IDP as well as 10,5 M APD. In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors. [source] Thiazide Diuretics Affect Osteocalcin Production in Human Osteoblasts at the Transcription Level Without Affecting Vitamin D3 ReceptorsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2000D. Lajeunesse Abstract Besides their natriuretic and calciuretic effect, thiazide diuretics have been shown to decrease bone loss rate and improve bone mineral density. Clinical evidence suggests a specific role of thiazides on osteoblasts, because it reduces serum osteocalcin (OC), an osteoblast-specific protein, yet the mechanisms implicated are unknown. We therefore investigated the role of hydrochlorothiazide (HCTZ) on OC production by the human osteoblast-like cell line MG-63. HCTZ dose-dependently (1,100 ,M) inhibited 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]- induced OC release by these cells (maximal effect, ,40,50% and p < 0.005 by analysis of variance [ANOVA]) as measured by ELISA. This effect of HCTZ on OC release was caused by a direct effect on OC gene expression because Northern blot analysis revealed that OC messenger RNA (mRNA) levels were reduced in the presence of increasing doses of the diuretic (,47.2 ± 4.0%; p < 0.0001 by paired ANOVA with 100 ,M HCTZ). HCTZ (100 ,M) also stimulated calcium (Ca2+) uptake (8.26 ± 1.78 pmol/mg protein/15 minutes vs. 13.6 ± 0.49 pmol/mg protein/15 minutes; p < 0.05) in MG-63 cells. Reducing extracellular Ca2+ concentration with 0.5 mM EDTA or 0.5 mM ethylene glycol-bis(,-amino ethyl ether)- N,N,N',N' -tetraacetic acid (EGTA) only partly prevented the inhibitory effect of the diuretic on OC secretion (maximal effect, ,22.5 ± 6.9%), suggesting that thiazide-dependent Ca2+ influx is not sufficient to elicit the inhibition of OC secretion. Because OC production is strictly dependent on the presence of 1,25(OH)2D3 in human osteoblasts, we next evaluated the possible role of HCTZ on vitamin D3 receptors (VDR) at the mRNA and protein levels. Both Northern and Western blot analyses showed no effect of HCTZ (1,100 ,M) on VDR levels. The presence of EGTA in the culture media reduced slightly the VDR mRNA levels under basal condition but this was not modified in the presence of increasing levels of HCTZ. The OC gene promoter also is under the control of transcription factors such as Yin Yang 1 (YY1) and cFOS. Western blot analysis revealed no changes in YY1 levels in response to HCTZ either in the presence or in the absence of 0.5 mM EGTA in the culture media. In contrast, HCTZ induced a dose-dependent increase in cFOS levels (p < 0.002 by ANOVA), a situation prevented by incubation with EGTA. These studies indicate that HCTZ inhibits OC mRNA expression independently of an effect on VDR, YY1, or extracellular Ca2+ levels but involves changes in cFOS levels. As OC retards bone formation/mineralization, the inhibition of OC production by HCTZ could explain its preventive role in bone loss rate. (J Bone Miner Res 2000;15:894,901) [source] Secondary Hypertension: Obesity and the Metabolic SyndromeJOURNAL OF CLINICAL HYPERTENSION, Issue 7 2008Gregory M. Singer MD The epidemic of obesity in the United States and around the world is intensifying in severity and scope and has been implicated as an underlying mechanism in systemic hypertension. Obese hypertensive individuals characteristically exhibit volume congestion, relative elevation in heart rate, and high cardiac output with concomitant activation of the renin-angiotensin-aldosterone system. When the metabolic syndrome is present, insulin resistance and hyperinsulinemia may contribute to hypertension through diverse mechanisms. Blood pressure can be lowered when weight control measures are successful, using, for example, caloric restriction, aerobic exercise, weight loss drugs, or bariatric surgery. A major clinical challenge resides in converting short-term weight reduction into a sustained benefit. Pharmacotherapy for the obese hypertensive patient may require multiple agents, with an optimal regimen consisting of inhibitors of the renin-angiotensin-aldosterone system, thiazide diuretics, ,-blockers, and calcium channel blockers if needed to attain contemporary blood pressure treatment goals. [source] Angiotensin-Converting Enzyme Inhibitors in the Treatment of Hypertension: An UpdateJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2007William B. White MD Angiotensin-converting enzyme inhibitors are an important treatment option for hypertension, especially when elevated blood pressure exists in the presence of diabetes mellitus, chronic kidney disease, or congestive heart failure. This article reviews some of the pathophysiologic mechanisms involved in patients with hypertension and these comorbidities and how they relate to the renin-angiotensin system (RAS). Inhibition of the RAS when utilized along with other antihypertensive medications has been particularly effective in hypertensive patients with type 2 diabetes, chronic kidney disease, and vascular disorders; consensus group guidelines have reflected this in their treatment recommendations. Clinical trial data demonstrate that the effectiveness of RAS blockers is enhanced by maximizing the daily dose and combining these medications with thiazide diuretics. [source] Queen Mary Utilization of Antihypertensive Drugs Study: side-effects of antihypertensive drugsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2005B. M. Y. Cheung PhD FRCP Summary Background and objective:, Effective prevention of cardiovascular events in hypertensive patients requires good control of blood pressure. Side-effects of antihypertensive drugs affect tolerability and compliance. Accordingly, we surveyed side-effects in the hypertension outpatient clinic. Methods:, A total of 228 patients (109 men, 119 women) were interviewed in April,May 2004 in the Queen Mary Utilization of Antihypertensive Drugs Study. Results:, The percentage of patients receiving no drug (life-style modification), one, two, three and over three drugs were 3, 30, 40, 22 and 6% respectively. The proportion of patients taking calcium channel blockers, , -blockers (BB), angiotensin-converting enzyme inhibitors, thiazide diuretics, , -blockers and angiotensin receptor blockers were 65, 64, 33, 24, 4 and 7% respectively. Blood pressure on treatment was 144 ± 21/82 ± 11 mmHg. Among patients on antihypertensive drug therapy, 34% reported adverse effects: dizziness (9%), ankle swelling (7%), headache (5%), fatigue (4%), chest discomfort (3%) and cough (3%). Fewer patients on BBs reported side-effects (OR 0·46, P = 0·008). The likelihood of experiencing side-effects was unrelated to sex, age, weight, BMI, years of treatment, number of drugs used, heart rate on treatment or compliance. Conclusions:, To achieve good blood pressure control, multiple drugs are used. Thiazides are underused whereas BBs are popular. The popularity of the latter may be related to its tolerability. [source] Antihypertensive drug therapy and the risk of lower extremity amputations in pharmacologically treated type 2 diabetes patients,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2004Joėlle A. Erkens PharmD Abstract Purpose The objective of this study was to determine the association between different antihypertensive drug therapies and lower extremity amputations (LEAs) in type 2 diabetes patients. Methods Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and data on hospitalisations for all 450,000 residents of eight Dutch cities. In a nested case-control study among 12,140 type 2 diabetes patients who used antihypertensive drugs, 26 cases with a first LEA and 94 controls without a LEA matched on age, sex and calendar time were identified. Logistic regression was used to estimate the relative risk of LEA and to adjust for potential confounding factors. Results Among type 2 diabetes patients who used antihypertensive drugs, subjects who used thiazide diuretics, alone or in combination, had a higher risk of LEA compared to subjects who used Angiotensin Converting Enzyme (ACE) inhibitor monotherapy (crude odds ratio (OR): 6.11 [95% confidence interval (CI): 1.32,28.27]). The use of thiazide diuretics was also associated with an increased risk of LEA when compared to the use of any non-thiazide antihypertensive drug (adjusted OR: 7.04 [1.10,45.30]). The increased risk of LEA associated with the use of thiazides compared to the use of non-thiazides depended on the duration of use (adjusted OR,365 days, 4.82 [0.61,38.34] and adjusted OR>365 days, 26.16 [1.02,674.02], p -trend,=,0.01). Conclusions Treatment with thiazide diuretics compared to treatment with other antihypertensive drugs was associated with excess amputations in type 2 diabetes patients. Due to several limitations of this study, our findings do not preclude the use of thiazides in type 2 diabetes mellitus patients as yet. Copyright © 2004 John Wiley & Sons, Ltd. [source] Hyponatremia in Heart Failure: Revisiting Pathophysiology and Therapeutic StrategiesCLINICAL CARDIOLOGY, Issue 6 2010Amir Kazory MD Hyponatremia is frequently encountered in patients with heart failure (HF), and its association with adverse outcomes is well-established in this population. While hyponatremia is an independent marker for severity of HF, it is not certain whether it has a causal impact on the progression of the disease. There are no universally accepted consensus guidelines regarding therapeutic strategies for HF-associated hyponatremia and volume overload; current societal guidelines do not address management of this complication. Whereas thiazide diuretics are known to induce or worsen hyponatremia in this setting through a number of mechanisms, loop diuretics can be considered a readily available first-line pharmacologic therapy. Consistent with pathophysiology of the disease and mechanisms of action of loop diuretics, available clinical evidence supports such an approach provided that patients can be closely monitored. Use of vasopressin receptor antagonists is an emerging therapeutic strategy in this setting, and the efficacy of these agents has so far been shown in a number of clinical studies. These agents can be reserved for patients with HF in whom initial appropriate loop diuretic therapy fails to improve serum sodium levels. Copyright © 2010 Wiley Periodicals, Inc. [source] | |||||||||||||||||||||||||