Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several new diuretics have recently been developed. This review summarises the published knowledge about some of them. Azosemide is a loop diuretic. The bioavailability is about 15% and it has a half-life of 2 to 3 hours. Renal and non-renal clearance are 1.32 and 5.4 L/h, respectively. Etozolin is also a loop diuretic. It is rapidly metabolised to the active metabolite, ozolinone. The gastrointestinal uptake of etozolin is almost complete. The plasma half-life of etozolin and ozolinone are 2 and 10 hours, respectively. The compounds are mainly eliminated as metabolites. Renal and liver impairment do not seem to change the pharmacokinetics. Fenquizone has properties similar to the thiazides. The plasma half-life is approximately 17 hours. Apparent volume of distribution averaged 686 L and renal clearance is 7.2 L/h. Indapamide acts predominantly on the proximal segment of the distal tubule and also has direct vasodilatory effects. Gastrointestinal uptake is at least 80%. The drug binds highly to carbonic anhydrases of red blood cells. Protein binding is about 80%, while terminal plasma half-life is 15 hours and the apparent volume of distribution 25 L. Renal clearance is 0.3 L/h and non-renal clearance 0.9 L/h. Several metabolites have been described, of which one major metabolite is pharmacologically active. Muzolimine is a loop diuretic. Its uptake is almost complete, but decreased substantially by food. The protein binding is about 65%, the apparent volume of distribution is about 1 L/kg and average terminal half-life 10 to 20 hours. Elimination is mainly non-renal, and non-renal clearance ranges between 0.5 and 1.32 L/h. The pharmacokinetics of the drug do not seem to be changed in cardiac failure. Terminal plasma half-life is essentially unchanged in patients with renal failure, except in those with very severe reduction of glomerular filtration rate. Piretanide is a loop diuretic which is about 6 times as potent as frusemide (furosemide). Its bioavailability is most likely complete in healthy subjects and in renal patients. Protein binding in healthy subjects is about 95%. The plasma half-life of the drug is about 1 hour and apparent volume of distribution averages about 17 L. Renal and non-renal clearance are about 6 L/h, although renal clearance is decreased in renal failure: this decrease is correlated with glomerular filtration rate. Non-renal clearance is unchanged in renal failure, as is the apparent volume of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of some newer diuretics. 331 32

Recent international guidelines on the detection, clinical assessment and management of patients with hypertension have highlighted a number of themes that should be incorporated into routine clinical practice. First, although antihypertensive therapy is having a major impact on reducing the incidence of coronary heart disease, cerebrovascular disease and heart failure, community surveys show that most hypertensive patients remain untreated or have suboptimal blood pressure control. Second, the guidelines have emphasised the importance of making an overall assessment of individual patients to gauge their absolute risk of a cardiovascular event; risk factors include not only blood pressure but also target organ damage, the presence of coexisting symptomatic vascular disease and the number of associated cardiovascular risk factors. Patients at the highest risk, especially those with diabetes, the elderly and patients with target organ damage, merit vigorous antihypertensive therapy, and such patients often require treatment with more than one drug to achieve target levels of blood pressure (< 135/80 mm Hg). An additional important theme in recent guidelines has been a move towards using lower dosages and therapies that provide 24-hour blood pressure control with once-daily administration. Since diuretics have been reaffirmed as evidence-based first-line therapy in a broad spectrum of patients with hypertension, especially the elderly, a new lower dosage sustained release formulation of indapamide has been developed (indapamide SR 1.5 mg). Recent multicentre European clinical trials have defined the efficacy and tolerability of indapamide SR 1.5 mg, both relative to other antihypertensive drugs and in key subgroups of patients. Indapamide SR 1.5 mg has an antihypertensive effect, maintained throughout the 24-hour administration interval, equivalent to that of immediate release indapamide 2.5 mg, but the new formulation has even less effect on circulating K+ levels. Indapamide SR 1.5 mg is at least as effective as amlodipine or hydrochlorothiazide. In patients with left ventricular hypertrophy (LVH), a comparative study of indapamide SR 1.5 mg and enalapril (the LIVE study) used a rigorous unique study design with blinded reading of echocardiograms to show that after 1 year the ACE inhibitor had no significant effect on LVH regression, whereas indapamide SR 1.5 mg produced significant reductions in left ventricular mass index. Diuretic-based therapy for hypertension has been reaffirmed in international guidelines as effective first-line therapy, especially in the elderly and patients with LVH. Indapamide SR 1.5 mg shows an improved efficacy-tolerability profile, with impressive 24-hour effects on blood pressure, important ancillary properties with regard to LVH and cardiovascular protection.
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PMID:Clinical implications of indapamide sustained release 1.5 mg in hypertension. 1049 30

Although recent trials have shown that antihypertensive treatment can bring about a reduction in stroke, coronary heart disease, heart failure and renal disease, the situation is no longer improving. This is due to the fact that the percentage of hypertensive patients with satisfactory blood pressure is still very poor. International guidelines on hypertension indicate the importance of assessing the absolute risk of patients and the use of a lower dose of drugs to improve the efficacy-tolerability profile. Diuretics used at lower dosage than in the past are effective in reducing morbidity and mortality and continue to be drugs of first choice in the treatment of hypertension. Indapamide sustained release (Natrilix SR) 1.5 mg has an antihypertensive effect equivalent to indapamide immediate release 2.5 mg with a 50% reduction in incidence of serum potassium levels <3.4 mmol/l. Natrilix SR has proved to have a neutral effect both on lipid and glucose profiles and to reduce microalbuminuria in diabetic hypertensive patients. Recent multicentre European clinical trials have shown that Natrilix SR decreases diastolic blood pressure to <90 mmHg in about 75% of patients treated for 1 year. In elderly patients with isolated systolic hypertension, Natrilix SR has been proven to be as effective as amlodipine 5 mg and significantly more effective than hydrochlorothiazide 25 mg. Natrilix SR produces regression of left ventricular hypertrophy which, in the Left ventricular hypertrophy: Indapamide Versus Enalapril study was greater than that induced by enalapril. Natrilix SR represents an appropriate choice not only as a first-line drug in many hypertensive patients but also in at-risk patients like the elderly, subjects with other cardiovascular risk factors, target organ damage, diabetes, or impaired renal function.
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PMID:Clinical role of Natrilix SR in the treatment of at-risk hypertensive patients. 1276 62