- any of a group of drugs commonly used as diuretics in the treatment of hypertension; they block the reabsorption of sodium in the kidneys
- 排尿促進の,利尿の / 利尿剤
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- Diuretics: a review and update.
- Roush GC, Kaur R, Ernst ME.Author information 1UCONN School of Medicine and St Vincent's Medical Center, Bridgeport, CT, USA.AbstractDiuretics have been recommended as first-line treatment of hypertension and are also valuable in the management of hypervolemia and electrolyte disorders. This review summarizes the key features of the most commonly used diuretics. We then provide an update of clinical trials for diuretics during the past 5 years. Compared to other classes of medications, thiazide diuretics are at least as effective in reducing cardiovascular events (CVEs) in patients with hypertension and are more effective than β-blockers and angiotensin-converting enzyme inhibitors in reducing stroke. Observational cohort data and a network analysis have shown that CVEs are lowered by one-fifth from chlorthalidone when compared to the commonly used thiazide, hydrochlorothiazide. Relative to placebo, chlorthalidone increases life expectancy. In those aged 80 years and older, the diuretic, indapamide, lowers CVEs relative to placebo. The aldosterone antagonist, eplerenone, lowers total mortality in early congestive heart failure. The benefit of eplerenone following acute myocardial infarction (MI) is limited to administration within 3 to 6 days post-MI. Aldosterone antagonists have been shown to lower the incidence of sudden cardiac death and to reduce proteinuria. In the setting of heart failure, long acting loop diuretics azosemide and torasemide are more effective in improving heart failure outcomes than the far more commonly used short acting furosemide. Evening dosing of diuretics appears to lower CVEs relative to morning dosing. In conclusion, diuretics are a diverse class of drugs that remain extremely important in the management of hypertension and hypervolemic states.
- Journal of cardiovascular pharmacology and therapeutics.J Cardiovasc Pharmacol Ther.2014 Jan;19(1):5-13. doi: 10.1177/1074248413497257. Epub 2013 Nov 15.
- Diuretics have been recommended as first-line treatment of hypertension and are also valuable in the management of hypervolemia and electrolyte disorders. This review summarizes the key features of the most commonly used diuretics. We then provide an update of clinical trials for diuretics during th
- PMID 24243991
- Pharmacologic inhibition of the renal outer medullary potassium channel causes diuresis and natriuresis in the absence of kaliuresis.
- Garcia ML, Priest BT, Alonso-Galicia M, Zhou X, Felix JP, Brochu RM, Bailey T, Thomas-Fowlkes B, Liu J, Swensen A, Pai LY, Xiao J, Hernandez M, Hoagland K, Owens K, Tang H, de Jesus RK, Roy S, Kaczorowski GJ, Pasternak A.Author information Departments of Ion Channels (M.L.G., B.T.P., J.P.F., R.M.B., T.B., B.T.-F., J.L., A.S., G.J.K.), Hypertension (M.A.-G., X.Z., L.-Y.P., J.X., M.H., S.R.), Drug Metabolism (K.O.), and Medicinal Chemistry (H.T., R. K.J., A.P.), Merck Research Laboratories, Rahway, New Jersey; and Safety and Exploratory Pharmacology, Merck Research Laboratories, West Point, Pennsylvania (K.H.).AbstractThe renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct, plays an important role in kidney physiology by regulating salt reabsorption. Loss-of-function mutations in the human ROMK channel are associated with antenatal type II Bartter's syndrome, an autosomal recessive life-threatening salt-wasting disorder with mild hypokalemia. Similar observations have been reported from studies with ROMK knockout mice and rats. It is noteworthy that heterozygous carriers of Kir1.1 mutations associated with antenatal Bartter's syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. Although selective ROMK inhibitors would be expected to represent a new class of diuretics, this hypothesis has not been pharmacologically tested. Compound A [5-(2-(4-(2-(4-(1H-tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one)], a potent ROMK inhibitor with appropriate selectivity and characteristics for in vivo testing, has been identified. Compound A accesses the channel through the cytoplasmic side and binds to residues lining the pore within the transmembrane region below the selectivity filter. In normotensive rats and dogs, short-term oral administration of compound A caused concentration-dependent diuresis and natriuresis that were comparable to hydrochlorothiazide. Unlike hydrochlorothiazide, however, compound A did not cause any significant urinary potassium losses or changes in plasma electrolyte levels. These data indicate that pharmacologic inhibition of ROMK has the potential for affording diuretic/natriuretic efficacy similar to that of clinically used diuretics but without the dose-limiting hypokalemia associated with the use of loop and thiazide-like diuretics.
- The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2014 Jan;348(1):153-64. doi: 10.1124/jpet.113.208603. Epub 2013 Oct 18.
- The renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct, plays an important role in kidney physiology by regulating salt reabsorption. Loss-of-function mutations in the human
- PMID 24142912
- 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8).
- James PA1, Oparil S2, Carter BL1, Cushman WC3, Dennison-Himmelfarb C4, Handler J5, Lackland DT6, Lefevre ML7, Mackenzie TD8, Ogedegbe O9, Smith SC Jr10, Svetkey LP11, Taler SJ12, Townsend RR13, Wright JT Jr14, Narva AS15, Ortiz E16.Author information 1University of Iowa, Iowa City.2University of Alabama at Birmingham School of Medicine.3Memphis Veterans Affairs Medical Center and the University of Tennessee, Memphis.4Johns Hopkins University School of Nursing, Baltimore, Maryland.5Kaiser Permanente, Anaheim, California.6Medical University of South Carolina, Charleston.7University of Missouri, Columbia.8Denver Health and Hospital Authority and the University of Colorado School of Medicine, Denver.9New York University School of Medicine, New York, New York.10University of North Carolina at Chapel Hill.11Duke University, Durham, North Carolina.12Mayo Clinic College of Medicine, Rochester, Minnesota.13University of Pennsylvania, Philadelphia.14Case Western Reserve University, Cleveland, Ohio.15National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.16at the time of the project,National Heart, Lung, and Blood Institute, Bethesda, Maryland17currently with ProVation Medical, Wolters Kluwer Health, Minneapolis, Minnesota.AbstractHypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
- JAMA : the journal of the American Medical Association.JAMA.2013 Dec 18. doi: 10.1001/jama.2013.284427. [Epub ahead of print]
- Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want
- PMID 24352797
- 小西賞受賞者 高血圧併用療法とCOPE Trial
- Effects of Hydrochlorothiazide on Oxidative Stress and Pulse Pressure in Hypertensive Patients with Chronic Stroke: The EMINENT Study
- Thiazide diuretics are mainly used to treat high blood pressure. A diuretic is a medicine which increases the amount of water that you pass out from your... ... What are the possible side-effects of thiazide diuretics? Side-effects are ...
- Thiazide diuretic A particular class of medication that encourages urine production. Mentioned in: Medullary Sponge Kidney ... Disclaimer All content on this website, including dictionary, thesaurus, literature, geography, and other ...
- thiazide diuretic, benzothiazide diuretic
- 利尿薬、利尿薬の作用部位、sodium-chloride symporter inhibitor。ギテルマン症候群
- Na+とCl-の共輸送体(NCCT)を阻害→Na+,Cl- の再吸収を阻害する
- チアジド系利尿薬の慢性使用により体液量が減少し、近位尿細管での再吸収が亢進するため (GOO.755) ？？
- チアジド系利尿薬自体のDCTでの作用による；NCCTを阻害すると細胞内のNa濃度低下、これにより側底膜でのNa+-Ca2+交換系が亢進することでCa2+の再吸収↑ (GOO.755) → つまり管腔側から受動的に引き込まれるということ。
- ループ利尿薬と同様の機序による (GOO.755)
- 長期間の使用における副作用：低カリウム血症、高尿酸血症、高脂血症、耐糖能低下、光線過敏症、脂質代謝障害。高カルシウム血症(YN.C-62) → (利尿薬参照。ループ利尿薬との違いはカルシウムを排泄するかどうか)
- 第二次世界大戦中、衛生状態の悪い兵士の間でシラミを介したバルトネラ属の感染症(塹壕熱、病原体はBartonella quintana)が流行していたが、この治療にサルファ剤が用いられていた。このサルファ剤が有する利尿作用に中臆して開発されたのがチアジド系利尿薬である。1957年にクロロチアジド、1959年に10倍の利尿作用を有するヒドロクロロチアジドが開発された。いずれも光線過敏症が副作用として知られている。日本では光線過敏症がより少ないと言われているトリクロルメチアジド(フルイトラン)がもっぱら用いられている。チアジド系利尿薬は日本では光線性白斑黒皮症と知られており、色素沈着と白斑を伴う。
- 参考：チアジド系利尿剤の副作用の歴史 日本医史学雑誌第58巻第2号(2012)p156