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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olmesartan medoxomil is a new non-peptide angiotensin (A) II antagonist under development for treating hypertension. It is a pro-drug containing an ester moiety that, after oral administration, is rapidly cleaved to release the active form olmesartan (RNH-6270). In vitro, olmesartan is a highly potent, competitive and selective All AT1 receptor antagonist with almost no antagonistic activity on AT2 and AT4 receptors. Olmesartan produces selective insurmountable inhibition of All-induced contractions of the guinea-pig aorta and is much more potent than losartan in reducing maximal responses. In vivo, intravenous olmesartan produces a rapid and long-lasting inhibition of All-induced pressor responses in conscious rats. Oral olmesartan medoxomil also inhibits All-pressor response but onset of the action is slower compared with intravenous administration. Following oral administration, olmesartan has a faster onset but similar potency when compared with candesartan cilexetil, and clearly exceeds losartan in both respects. Oral olmesartan medoxomil exhibits dose-dependent antihypertensive effects in several rat and dog models, with the most marked effects seen in high plasma renin models, when compared with normal or low renin types. Haemodynamic studies in spontaneously hypertensive rats and normotensive dogs showed intravenous olmesartan selectively reduces renal vascular resistance, which suggests that vasodilatation in the renal vascular bed contributes most to the antihypertensive action of the drug. Long-term treatment with olmesartan medoxomil exhibits, beside antihypertensive effects, beneficial effects in animal models of various types of nephrosis and heart failure, and anti-atherogenic effects in hyperlipidaemic animals. Olmesartan medoxomil is worthy of clinical development in essential and renal hypertension, particularly where renal function is threatened by underlying diabetic disease.
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PMID:In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type AT1 receptor antagonist. 1145 Dec 12

The therapeutic profile of olmesartan medoxomil, which is a recently developed angiotensin II (A II) receptor blocker, has been compared with four commonly used antihypertensive therapeutic drugs (atenolol, captopril, felodipine and losartan) in five separate multicentre, randomised, double-blind, parallel-group, phase III trials. The trials were designed to compare the efficacy of individually optimised dosages of olmesartan medoxomil and the comparator agent. The primary efficacy variable in all trials was the mean change from baseline to week 12 in trough mean sitting diastolic blood pressure (DBP). Olmesartan medoxomil (10-20 mg once daily (o.d.)) showed similar efficacy to atenolol (50-100 mg o.d.), both in patients with mild-to-moderate hypertension and, when given together with hydrochlorothiazide (HCTZ) 25 mg o.d., in patients with moderate-to-severe hypertension. Olmesartan medoxomil (20-40 mg o.d.) was also similar in efficacy to felodipine (5-10 mg o.d.) in reducing BP in patients with mild-to-moderate hypertension. Compared with captopril (12.5-50 mg twice daily (b.i.d.)) and losartan (50-100 mg o.d.), in patients with mild-to-moderate hypertension, olmesartan medoxomil (5-20 mg o.d. and 10-20 mg o.d., respectively) was significantly superior in terms of lowering DBP from baseline to week 12. In terms of the secondary efficacy variable, which was mean change from baseline to week 12 in trough mean sitting systolic BP, olmesartan showed significant superiority to atenolol, captopril and losartan in patients with mild-to-moderate hypertension. In the longer term, compared with losartan, a lower percentage of olmesartan-treated patients required concomitant HCTZ after 12 weeks of therapy. Olmesartan was well tolerated in all studies.
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PMID:Antihypertensive efficacy of olmesartan compared with other antihypertensive drugs. 1196 29

Olmesartan medoxomil is a nonpeptide angiotensin II receptor antagonist which selectively and competitively inhibits the type 1 angiotensin II receptor without affecting other receptors regulating the cardiovascular system. In well designed randomised trials, olmesartan medoxomil was significantly more effective than placebo, and at dosages of 10 to 20 mg/day was at least as effective as atenolol 50 to 100 mg/day in reducing diastolic blood pressure (DBP). At dosages of 5 to 20 mg/day, olmesartan medoxomil was more effective than captopril 12.5 to 50mg twice daily at lowering seated DBP in patients with mild to moderate hypertension in a dose titration study. Reductions in seated DBP were greater with olmesartan medoxomil 10 to 20 mg/day than losartan 50 to 100 mg/day. Olmesartan medoxomil at 20 mg/day was more effective in lowering seated DBP than losartan 50 mg/day, valsartan 80 mg/day or irbesartan 150 mg/day, and was more efficacious than losartan 50 mg/day or valsartan 80 mg/day at reducing 24-hour ambulatory systolic blood pressure. Olmesartan medoxomil has shown no clinically important pharmacokinetic interactions with digoxin, warfarin or antacid (aluminium magnesium hydroxide). Adverse events were infrequent in clinical studies of olmesartan medoxomil and were similar to those attributed to placebo. With olmesartan medoxomil, the frequency of dizziness was higher than with placebo but similar to that occurring with losartan, valsartan and irbesartan.
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PMID:Olmesartan medoxomil. 1207 83

Olmesartan medoxomil is a new angiotensin II receptor blocker. In this randomized, double-blind, placebo-controlled study, the efficacy and safety of olmesartan medoxomil was assessed in 334 patients with moderate to severe essential hypertension. Patients were randomized to receive placebo; 5, 20, or 80 mg olmesartan medoxomil q.d.; or 2.5, 10, or 40 mg olmesartan medoxomil b.i.d. Ambulatory and cuff blood pressure were measured prior to and after 8 weeks of treatment. Treatment with olmesartan medoxomil resulted in a significant placebo-adjusted reduction of mean 24-hour ambulatory diastolic blood pressure of 9.6 mm Hg, 12.2 mm Hg, and 10.6 mm Hg in the 5-, 20-, and 80-mg q.d. groups, respectively. Corresponding reductions in mean ambulatory systolic blood pressure were 14.5 mm Hg, 16.5 mm Hg, and 15.4 mm Hg. Similar reductions of diastolic and systolic blood pressure were seen with b.i.d. dosing. The diastolic trough-to-peak ratios of the q.d. doses of olmesartan medoxomil ranged from 57%-70%, indicating 24-hour effectiveness. The safety profile of olmesartan medoxomil was similar to that of placebo. Olmesartan medoxomil appears to be a safe and effective once-a-day treatment for hypertension.
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PMID:Antihypertensive efficacy of olmesartan medoxomil, a new angiotensin II receptor antagonist, as assessed by ambulatory blood pressure measurements. 1236 70

The continued poor rates of blood pressure (BP) control to the recommended target BP of <140/90 mm Hg in patients with hypertension indicate a persistent need for improved antihypertensive therapy. Angiotensin II receptor blockers (ARBs) constitute the newest approved class of antihypertensive agents. As with angiotensin converting enzyme inhibitors, ARBs block the renin-angiotensin-aldosterone system, but do so through a more specific mechanism. Angiotensin converting enzyme inhibitors block the conversion of angiotensin I to angiotensin II, but angiotensin II may be produced by several alternate pathways. Angiotensin II receptor blockers, by contrast, inhibit the binding of angiotensin II to the angiotensin II type 1 (AT1) receptor, independent of the pathway of angiotensin II production. Comparative safety and efficacy trials indicate that ARBs are similar to other antihypertensive drugs in terms of BP-lowering effectiveness and have superior tolerability. Olmesartan medoxomil is the newest and one of the most effective of the ARBs. In controlled trials, it has been shown to provide 24-h BP control with antihypertensive efficacy at least as good as that of the calcium channel blockers amlodipine besylate and felodipine and the beta-blocker atenolol. In a comparative study, olmesartan medoxomil demonstrated significantly greater reductions in diastolic BP than did three other leading ARBs-losartan potassium, irbesartan, and valsartan. With the convenience of placebo-like tolerability and once-daily dosing, combined with excellent antihypertensive efficacy, olmesartan medoxomil may be a useful addition to our management of hypertension.
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PMID:Strategies to meet lower blood pressure goals with a new standard in angiotensin II receptor blockade. 1238 91

The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents. This randomized, double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate (amlodipine) in subjects with mild-to-moderate hypertension. Following a 4-week, single-blind, placebo run-in period, 440 subjects aged >/=18 years were randomized to the starting dose of olmesartan medoxomil (20 mg/day), amlodipine (5 mg/day), or placebo for 8 weeks. Subjects were evaluated by 24-h ambulatory blood pressure monitoring (ABPM) and by seated cuff blood pressure (BP) measurements at trough. The primary end point was the change from baseline in mean 24-h diastolic blood pressure (DBP) by ABPM at Week 8. Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure (SBP) at 8 weeks, change from baseline in mean seated trough cuff DBP and SBP measurements, and response and control rates for DBP <90 and <85 mmHg. Control rates for SBP <140 and <130 mmHg were also calculated. Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo. Mean reductions in ambulatory and seated BP were similar between the two active agents; however, in the olmesartan medoxomil group, significantly more patients achieved the SBP goal of <130 mmHg and the DBP goal of <85 mmHg. Both drugs were well tolerated at the recommended starting dose. Although amlodipine was associated with a higher incidence of oedema, this did not reach statistical significance. Olmesartan medoxomil is an effective antihypertensive agent, with BP-lowering efficacy at the starting dose similar to that of amlodipine, and is associated with more patients achieving the rigorous BP goals of SBP <130 mmHg and DBP <85 mmHg.
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PMID:Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension. 1276 6

Olmesartan medoxomil is a new angiotensin-II receptor antagonist for the treatment of hypertension. Olmesartan medoxomil is a pro-drug that is de-esterified to the active metabolite, olmesartan. Olmesartan has a dual method of elimination, with about 60% eliminated by the liver and the remainder by the kidney. In situations of impaired renal or hepatic function, the alternative excretion pathway can compensate for the compromised one. Olmesartan is not metabolized by the cytochrome P450 enzyme system and therefore has a low potential for metabolic drug interactions, a feature that may be of importance when treating patients on multiple drug regimens, such as the elderly. Olmesartan is well tolerated and has an excellent safety profile that is comparable to that of placebo. In addition, olmesartan provides 24-h blood pressure control with a once-daily dosing. In head-to-head studies, olmesartan delivered superior blood pressure reduction when compared with other angiotensin-II receptor antagonists at their recommended doses.
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PMID:Clinical efficacy of olmesartan medoxomil. 1292 7

Olmesartan medoxomil is a new angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension. Olmesartan medoxomil is a pro-drug that is converted to the active metabolite olmesartan. Olmesartan does not undergo further metabolism and does not interact with cytochrome P450 enzymes. Olmesartan is a potent ARB with high selectivity for the type 1 (AT(1)) receptor subtype and shows insurmountable antagonism against the AT(1) receptor in vascular tissues. This antagonistic mode, which could be attributed to tight binding of this drug to the receptor, would underlie the potent and persistent action of olmesartan medoxomil in vivo. In fact, oral administration of olmesartan medoxomil produces a potent and long-lasting antihypertensive action without inducing tachycardia. The preventive effects of olmesartan medoxomil on end-organ damage in the kidney, heart, and blood vessels have been demonstrated in various animal models. In clinical studies, olmesartan medoxomil is shown to be well tolerated and have an excellent safety profile that is comparable to that of placebo. Head-to-head comparisons with other ARBs (losartan, valsartan, irbesartan, and candesartan cilexetil) conducted in the United States and Europe have revealed that olmesartan medoxomil is superior to these other ARBs in lowering blood pressure. These facts suggest that olmesartan medoxomil would be beneficial for the treatment of hypertension and other end-organ diseases.
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PMID:[Pharmacological profiles and clinical effects of olmesartan medoxomil, a novel angiotensin II receptor blocker]. 1546 59

Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends starting treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in patients with diabetes, using two different antihypertensive agents. Searches of Medline, EMBASE, and BIOSIS databases identified four similarly designed, randomized, factorial studies comparing various doses of angiotensin II receptor blockers with hydrochlorothiazide as monotherapy and in combination. The methodology and results of these studies were compared. The primary efficacy end point in these studies was a decrease from baseline in mean diastolic BP after 8 weeks of therapy. All currently available angiotensin I receptor blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced significant systolic BP and diastolic BP reductions. Olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in absolute and placebo-corrected systolic BP/diastolic BP. For all angiotensin II receptor blocker/hydrochlorothiazide combinations evaluated, > or =63% of patients achieved a diastolic BP response (diastolic BP <90 mm Hg or > or =10-mm Hg reduction). In conclusion, the combination of an angiotensin II receptor blocker and hydrochlorothiazide produces more substantial BP responses than monotherapy with either component.
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PMID:Antihypertensive efficacy of angiotensin receptor blockers in combination with hydrochlorothiazide: a review of the factorial-design studies. 1547 Feb 86

Intensive blood pressure control is a desirable and obtainable goal in patients with hypertension, according to the most recent treatment guidelines from Europe and the US. Achieving target blood pressure depends on the efficacy of antihypertensive treatment and patient compliance. Olmesartan medoxomil, a non-peptidergic angiotensin AT1 receptor antagonist, has been shown to be effective and well tolerated. Continuation of initial treatment is higher with AT1 receptor antagonists than for any other class of antihypertensive drugs. Olmesartan medoxomil may also have end-organ protective effects that provide additional clinical benefit. Optimal blood pressure control may be achieved faster if initial treatment contains the most efficacious and well tolerated antihypertensive drug or drugs. The ongoing European study, known as OLMEBEST (Efficacy and safety of OLMEsartan: reduction of Blood pressure in the treatment of patients suffering from mild to moderate ESsenTial hypertension), will provide important information on the use of olmesartan medoxomil as an initial treatment for hypertension.
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PMID:The role of olmesartan medoxomil in the management of hypertension. 1556 46


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