Fixed low-dose combination therapy for hypertension

Waeber, Bernard

doi:10.1007/s11906-996-0008-9

Cited by 9 publications

(8 citation statements)

References 47 publications

(48 reference statements)

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“…Although there are many drugs currently approved to treat hypertension, such as indapamide, metoprolol, enalapril, losartan, nifedipine [6], most of these drugs present serious adverse effects, inefficacy in term of blood pressure control, toxicity and warnings for hypertensive patients [7–10]. On the other hand, some traditional Chinese medicines (TCM), known for their good therapeutic performance and fewer side effects, are widely used for the prevention and treatment of hypertension disease [11–15].…”

Section: Introductionmentioning

confidence: 99%

Relaxation of Rat Aorta by Farrerol Correlates with Potency to Reduce Intracellular Calcium of VSMCs

Qin

Hou

Zhang

et al. 2014

IJMS

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Farrerol, isolated from Rhododendron dauricum L., has been proven to be an important multifunctional physiologically active component, but its vasoactive mechanism is not clear. The present study was performed to observe the vasoactive effects of farrerol on rat aorta and to investigate the possible underlying mechanisms. Isolated aortic rings of rat were mounted in an organ bath system and the myogenic effects stimulated by farrerol were studied. Intracellular Ca2+ ([Ca2+]in) was measured by molecular probe fluo-4-AM and the activities of L-type voltage-gated Ca2+ channels (LVGC) were studied with whole-cell patch clamp in cultured vascular smooth muscle cells (VSMCs). The results showed that farrerol significantly induced dose-dependent relaxation on aortic rings, while this vasorelaxation was not affected by NG-nitro-l-arginine methylester ester or endothelium denudation. In endothelium-denuded aortas, farrerol also reduced Ca2+-induced contraction on the basis of the stable contraction induced by KCl or phenylephrine (PE) in Ca2+-free solution. Moreover, after incubation with verapamil, farrerol can induce relaxation in endothelium-denuded aortas precontracted by PE, and this effect can be enhanced by ruthenium red, but not by heparin. With laser scanning confocal microscopy method, the farrerol-induced decline of [Ca2+]in in cultured VSMCs was observed. Furthermore, we found that farrerol could suppress Ca2+ influx via LVGC by patch clamp technology. These findings suggested that farrerol can regulate the vascular tension and could be developed as a practicable vasorelaxation drug.

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Section: Introductionmentioning

confidence: 99%

Relaxation of Rat Aorta by Farrerol Correlates with Potency to Reduce Intracellular Calcium of VSMCs

Qin

Hou

Zhang

et al. 2014

IJMS

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“…24 Largely through blockade of angiotensin II, ACE inhibitors decrease vasoconstriction, sympathetic activation, and aldosterone release, thus lowering total peripheral resistance and decreasing renal sodium and fluid retention. 25,26 In addition, ACE inhibitors promote preservation of bradykinin, a potent vasodilator that contributes to the antihypertensive effects of ACE inhibition. 27 Diuretics are believed to lower BP generally by stimulation of diuresis-natriuresis, resulting in reduction of plasma fluid, extracellular fluid volume, and sodium.…”

Section: Optimal Combinations Of Antihypertensive Drugs Typically Invmentioning

confidence: 99%

“…29,30 The blunting of this counterregulatory response with ACE inhibition, particularly the inhibition of aldosterone release, also enhances the antihypertensive efficacy of the diuretic. 26,28,29 Furthermore, the mild natriuretic effect of ACE inhibitors adds to the sodium-and fluid-volume reduction of diuretics. 29,30 Multiple studies have shown that adding a diuretic to an ACE inhibitor provides significant BP reduction compared to placebo 31,32 and adds significantly greater antihypertensive efficacy than component monotherapy, while reducing Thiazide-type diuretics for most; may consider ACEI, ARB, βB, CCB, or combination…”

Section: Optimal Combinations Of Antihypertensive Drugs Typically Invmentioning

confidence: 99%

“…Angiotensin II is a powerful vasoconstrictor that promotes sympathetic activation, aldosterone release, and renal salt and water reabsorption, among other effects that raise BP and increase risks for CVD 24 . Largely through blockade of angiotensin II, ACE inhibitors decrease vasoconstriction, sympathetic activation, and aldosterone release, thus lowering total peripheral resistance and decreasing renal sodium and fluid retention 25,26 . In addition, ACE inhibitors promote preservation of bradykinin, a potent vasodilator that contributes to the antihypertensive effects of ACE inhibition 27 …”

Section: Recommendations and Research Findings For Treating Stage 2 Hmentioning

confidence: 99%

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Treating Stage 2 Hypertension

Giles

Materson

2005

J of Clinical Hypertension

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H ypertension, or high blood pressure (BP), affects at least 65 million Americans-31% of all adults-and is a major independent risk factor for cardiovascular (CV) morbidity and mortality.1 A disproportionate number of individuals with high BP are older adults; approximately 81% of adults with high BP are 45 years of age and older, although this same age group represents about 46% of the population.1 Increasing age is associated with changing patterns of BP such that in patients with hypertension, systolic BP (SBP) continues to rise progressively in both men and women throughout adult life, while diastolic BP (DBP) tends to increase until approximately age 55 years, level off over the next decade, and either remain the same or decline somewhat thereafter. 1-4By age 75 years, almost all hypertensive patients have systolic hypertension. The National Health and Nutrition Examination Survey (NHANES) 2 has shown that many of these individuals have SBP of ≥160 mm Hg, a level that triples the risk of CV events. The Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) 4 defines stage 2 hypertension as BP ≥160/100 mm Hg. Unfortunately, BP control is particularly poor among older hypertensive patients, who are at highest risk for CV events. 5Controlling systolic hypertension is now recognized as the more important factor for CV and renal event risk reduction. This is due in part to the greater difficulty in achieving SBP control and the understanding that the majority of patients older than age 50 will reach DBP goal once SBP goal is achieved. 4 Starting at about age 50, SBP is the strongest predictor of CV disease (CVD) and premature death. 3,6 A meta-analysis of randomized, controlled clinical trials including more than one million individuals aged 40-69 years revealed that the absolute risk of CVD mortality doubled with each 20 mm Hg increase in SBP above 115 mm Hg. Nevertheless, a random survey of 2500 patients enrolled in a large health maintenance organization revealed that most hypertensive individuals continue to perceive DBP, rather than SBP, as a more important risk factor for CVD. 8The relationship between increasing levels of BP and all CV events is strong, continuous, and independent of other risk factors, including age and the presence of other CVDs. 4 Data from numerous randomized, controlled trials have proven that BP-lowering therapy is associated with substantial reductions in stroke, myocardial infarction R e v i e w P a p e r

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“…Today, multi-drug therapy is standard in a number of indications and even fixed combinations are no longer anathema. Guideline/consensus-sanctioned examples of the former include certain infectious diseases (tuberculosis [1], HIV [2], Helicobacter pylori [3]), hypertension [4,5] and more advanced stages of myocardial failure [5], rheumatoid arthritis [7], and bronchial asthma [8]. The main hope for a satisfactory treatment of acute ischemic stroke lies in development of a combination that covers more than one aspect of the multi-faceted pathophysiology [9].…”

Section: Introductionmentioning

confidence: 99%

Complementary Mode of Action of Rosiglitazone and Metformin in a Single Tablet for the Treatment of Diabetes mellitus Type 2

Petersen

2011

Arzneimittelforschung

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Summary As multi-drug preparations have come past the era of intuitive composition, their value is increasingly recognized. Improved treatment compliance is an accepted advantage, in particular in diseases without overt distress such as earlier-stage diabetes mellitus, type 2, but does not suffice for market authorization. For preparations composed of more than one active substance, the prevailing guidelines rule that each constituent must contribute to efficacy (or improve tolerability); effective and safe doses must be used and pharmacokinetic interactions between the active ingredients must be excluded or clearly defined. In the typical case, the combination must demonstrate enhanced efficacy, with a largely unchanged risk profile, or improvement of tolerability at constant efficiency. These requirements are convincingly met with a recently registered drug, Avandamet?, which is metformin HCl (CAS 1115-70-4) and a thiazolidinedione, rosiglitazone maleate (CAS 155141-29-0), in one tablet. By complementary actions, the two components cover both hepatic and peripheral sites of action to restitute insulin sensitivity. Acting on a variety of targets, rosiglitazone is able to overcome insulin resistance in patients with insufficient response to maximally dosed metformin. For example, adding rosiglitazone (8 mg/day) to an ongoing treatment with metformin (2.5 g/day) resulted in a drop of glycosylated hemoglobin by 1.2 %. Pharmacokinetics of the two constituents fall into the same range and are not altered by coadministration (range 3.4-4.3 h). As the tolerability profiles of the two drugs show little overlap, the drug combination is well tolerated; the risk of hypoglycemia is low (less than 3 %) and precautions and contraindications are largely those of the active ingredients. In sum, the combination of metformin and rosiglitazone in a single tablet displays an improved benefit/risk ratio with regard to its constituents. It is indicated for type 2 diabetes mellitus patients, particularly overweight patients, who are unable to achieve sufficient glycemic control at their maximally tolerated dose of metformin alone.

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Fixed low-dose combination therapy for hypertension

Cited by 9 publications

References 47 publications

Relaxation of Rat Aorta by Farrerol Correlates with Potency to Reduce Intracellular Calcium of VSMCs

Relaxation of Rat Aorta by Farrerol Correlates with Potency to Reduce Intracellular Calcium of VSMCs

Treating Stage 2 Hypertension

Complementary Mode of Action of Rosiglitazone and Metformin in a Single Tablet for the Treatment of Diabetes mellitus Type 2

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