Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 2002, the World Health Organization estimated that over 58% of cardiovascular disease in North America is due to 'both blood pressure and cholesterol higher than optimal'. Unfortunately, less than a third of patients with both conditions are identified, and fewer than one in ten reach the treatment goals for both factors. Adherence to treatment is notably improved when therapy is initiated simultaneously. Combination therapy of amlodipine besylate (Norvasc, Pfizer Ltd) with atorvastatin calcium (Lipitor, Pfizer Ltd), marketed as Caduet (Pfizer Ltd) is the first dual-therapy compound designed to treat hypertension and/or angina and dyslipidemia concurrently with a single daily pill in the full range of dosing combinations. Amlodipine/atorvastatin retains the safety and efficacy of its parent compounds whilst simplifying the management of these comorbid conditions, in what may be considered the first version of a polypill.
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PMID:Amlodipine/atorvastatin: the first cross risk factor polypill for the prevention and treatment of cardiovascular disease. 1535 Jan 69

National and international guidelines recommend the use of combination drugs as a first-line therapy for persons with stage 2 hypertension (blood pressure > or =160/100 mmHg). Although hypertension is common (30% of adults in the USA), its control to recommended blood pressure levels of under 140/90 mmHg remains low, at 36.8%. In the past, fixed-drug combinations included a diuretic with another antihypertensive drug. Recently, combinations of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers mostly with dihydropyridine calcium channel blockers have been developed and approved for the treatment of hypertension. One of these, olmesartan medoxomil in combination with amlodipine besylate has been shown to be effective and safe for the treatment of hypertension. In a large, randomized, placebo-controlled study (Combination of Olmesartan medoxomil and Amlodipine besylate in Controlling High blood pressure [COACH]) of 1940 patients, the high-dose combinations of olmesartan medoxomil and amlodipine besylate 40/10 mg/day reduced the sitting systolic and diastolic blood pressure by 29/19 mmHg from baseline (p < 0.001) and resulted in 54% of patients achieving blood pressure goals. It also decreased the pedal edema induced by amlodipine monotherapy 10 mg/day by 36.1%. This drug combination, besides being effective, is also safe and well tolerated.
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PMID:Amlodipine besylate/olmesartan medoximil fixed combination for the treatment of hypertension. 1967 66

This report includes a prespecified secondary analysis of the COACH study (Combination of Olmesartan medoxomil and Amlodipine besylate in Controlling High blood pressure) based on baseline hypertension severity and prior antihypertensive medication use and a post hoc efficacy analysis of the subset of patients with baseline mean seated systolic blood pressure (SeSBP) > or =180 mm Hg. The efficacy and safety of placebo, amlodipine (5 or 10 mg/d), olmesartan medoxomil (OM) (10, 20, or 40 mg/d), and all possible combinations of the drugs (12 treatment arms in total) were evaluated for 8 weeks. Primary end point was seated diastolic blood pressure (SeDBP) decrease at study end. Secondary end points included decrease in SeSBP and proportion of patients achieving blood pressure (BP) goal and prespecified BP targets. In each subgroup, > or =1 dosage combination of amlodipine + OM significantly reduced SeDBP and SeSBP compared with constituent monotherapies. Combinations produced the greatest mean BP reductions in patients with baseline SeSBP > or =180 mm Hg. More patients with stage 1 than stage 2 hypertension achieved BP goal. Prior antihypertensive medication use did not seem to affect efficacy. Subgroup categorization did not affect safety. After 8 weeks of treatment, the combination of amlodipine + OM is safe and efficacious, irrespective of baseline hypertension stage or prior antihypertensive medication use.
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PMID:Subgroup analyses of an efficacy and safety study of concomitant administration of amlodipine besylate and olmesartan medoxomil: evaluation by baseline hypertension stage and prior antihypertensive medication use. 1973 Mar 91

Amlodipine besylate (AML) is a long-acting calcium channel blocker used as an antihypertensive agent. Valsartan (VAL) is also used to treat hypertension, either alone or in combination with other agents. Two-component mixtures of AML and VAL were analyzed by HPLC and the ratio spectra of the first derivative spectrophotometric technique. The spectrophotometric method depends on the first derivative of the ratio-spectra by measurements of the amplitudes at 234.0 nm for VAL and 351.0 nm for AML. Calibration graphs were established for 0.5-20 microg/mL AML and 1-32 microg/mL VAL using the ratio spectra of the first derivative spectrophotometric method. In the HPLC method, an ACE 5 C18 (4.6 x 150 mm, 5 microm) RP column at 30 degrees C with the mobile phase methanol-acetonitrile-NaH2PO4.H2O buffer, including 5 mL/L triethylamine and adjusted to pH 3.0 (42 + 18 + 40, v/v/v) at 2.0 mL/min flow rate was used to separate both compounds with detection at 254.0 nm. Linearity was obtained in the concentration range of 0.5-500 microg/mL for AML and 5.0-900 microg/mL for VAL. The proposed methods have been extensively validated. These methods allow a number of cost- and time-saving benefits. They were successfully applied to the determination of AML and VAL in synthetic mixtures and in a pharmaceutical dosage form. There was no significant difference between the performance of the proposed methods regarding the mean and SD values. The proposed methods are simple, rapid, and suitable for QC applications.
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PMID:High-performance liquid chromatographic and first derivative of the ratio spectrophotometric determination of amlodipine and valsartan in their binary mixtures. 2062 91

Many patients with hypertension require more than one drug to control their blood pressure.1 Tribenzor (Daiichi Sankyo), recently approved by the FDA for treatment of hypertension, combines the calcium channel blocker amlodipine (Norvasc, and others), the angiotensin receptor blocker (ARB) olmesartan (Benicar) and the most commonly prescribed diuretic, hydrochlorothiazide (HCTZ). Tribenzor is not approved for initial therapy, but is recommended for patients not adequately controlled on any 2-drug combination of a calcium channel blocker, an ARB or a diuretic.
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PMID:Tribenzor for hypertension. 2081 2

The "manometric" way of considering the complex management of high blood pressure (HBP) must remain ancient history. The huge therapeutical armamentarium existing nowadays allows us to select the drug/s most appropriate for the comorbidities/particularities of each case. The BP level target, unanimously considered a very important element of HBP management, must not be the only one. The so-called pleiotropic effects of the different classes of antihypertensive drugs must always influence our way of thinking. Another important possibility to improve the therapeutical efficacy of the antihypertensive treatment is chronotherapy. The aim of the present study is to demonstrate the possibility of some benefic effects by imposing, by chronotherapy, a "normal" "dipping" status of the BP values. Among the surrogate end-points that can be used to demonstrate the benefits of this kind of HBP management we chose the structural and functional cardiac parameters, echocardiographically determined--using the criteria of the American Society of Echocardiography. We studied the evolution of these parameters of the left ventricle (LV) and we have evaluated them after 3 months of once-a-day morning (at awakening) administration, and respectively after 3 months of once-a-day administration in the evening (at bedtime) of: Prestarium (perindopril) cp 10 mg Tarka (cp 180 mg verapamil hydrochloride/2 mg trandolapril) Norvasc (amlodipine besilat) cp 10 mg as monotherapy, in 60 patients. We studied the anatomical parameters of the left ventricle (dimensions measured enddiastolically: the thickness of the interventricular septum, the thickness of the posterior wall, the internal diameter of the LV), the LV mass (which has a cutedge value for hypertrophy of the LV-LVH--of 134 g/m2 for men and 110 g/m2 for women) and the functional parameters, systolic as diastolic of the LV. We noticed a statistically significant reduction (p < 0.05) in all the 3 subgroups, of the functional parameters, these ones becoming similar to those in normotensive subjects only after the evening (at bedtime) administration of the studied drugs. The differences between the 3 subgroups for all the studied parameters, also in comparison with the normotensive subjects, have not been statistically significant after vesperal (at bedtime) administration of the studied drugs. It is, thus, possible that by an optimal treatment, chronotherapeutically "tailored", to obtain a normalisation of the anatomical and functional parameters of the LV and a significant improvement of the prognosis of these patients.
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PMID:Bedtime versus at awakening administration of BP lowering drugs--is it the way to success? 2117 17

The objective of the present study was to develop a tablet formulation of S-(-)-amlodipine besylate chiral separation drug and nebivolol hydrochloride for better management of hypertension, while reducing or avoiding undesirable adverse effects, which are often associated with administration of a racemic mixture of amlodipine. The composition containing the optically pure S-(-)- isomer of amlodipine 2.5 mg has calcium channel blocking activity and, nebivolol hydrochloride 5 mg has beta-receptor blocking activity.The study was also carried out to design a suitable dissolution medium for S-(-) - amlodipine besylate and nebivolol hydrochloride. Amlodipine besylate and nebivolol hydrochloride had maximum solubility in pH 1.2 and thus pH 1.2 was selected as the most suitable media for S-(-) - amlodipine besylate and nebivolol hydrochloride dissolution studies. The RSD below 2% indicated insignificant batch-to-batch variation. The accelerated stability study of the optimized formulation was performed as the ICH guidelines. The results indicated no change in optical rotation of S-(-) - amlodipine besylate. Hence, combination of two drugs can be formulated into the tablet by wet granulation technique having satisfactory release profile.
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PMID:Formulation and evaluation of s-(-)-amlodipine besylate and nebivolol hydrochloride tablets. 2224 46

Hypertension is associated with oxidative stress. Amlodipine besylate (AB) and benidipine hydrochloride (BH), which are Ca(2+) antagonists, have been reported to reduce oxidative stress. In this study, we examined the neuroprotective effects of AB and BH on oxidative stress-injured neural stem cells (NSCs), with a focus on the phosphatidylinositol 3-kinase (PI3K) pathway and the extracellular signal-regulated kinase (ERK) pathway. After treatment with H2O2, the viability of NSCs decreased in a concentration-dependent manner; however, co-treatment with AB or BH restored the viability of H2O2-injured NSCs. H2O2 increased free radical production and apoptosis in NSCs, whereas co-treatment with AB or BH attenuated these effects. To evaluate the effects of AB or BH on the H2O2-inhibited proliferation of NSCs, we performed BrdU labeling and colony formation assays and found that NSC proliferation decreased upon H2O2 treatment but that combined treatment with AB or BH restored this proliferation. Western blot analysis showed that AB and BH increased the expression of cell survival-related proteins that were linked with the PI3K and ERK pathways but decreased the expression of cell death-related proteins. To investigate whether the PI3K and ERK pathways were directly involved in the neuroprotective effects of AB and BH on H2O2-treated NSCs, NSCs were pretreated with the PI3K inhibitor, LY294002, or the ERK inhibitor, FR180204, which significantly blocked the effects of AB and BH. Together, our results suggest that AB and BH restore the H2O2-inhibited viability and proliferation of NSCs by inhibiting oxidative stress and by activating the PI3K and ERK pathways.
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PMID:Neuroprotective effects of amlodipine besylate and benidipine hydrochloride on oxidative stress-injured neural stem cells. 2444 Jul 75

Telmisartan (TL), Hydrochlorothiazide (HZ) and Amlodipine besylate (AM) are co-formulated together for hypertension management. Three smart, specific and precise spectrophotometric methods were applied and validated for simultaneous determination of the three cited drugs. Method A is the ratio isoabsorptive point and ratio difference in subtracted spectra (RIDSS) which is based on dividing the ternary mixture of the studied drugs by the spectrum of AM to get the division spectrum, from which concentration of AM can be obtained by measuring the amplitude values in the plateau region at 360nm. Then the amplitude value of the plateau region was subtracted from the division spectrum and HZ concentration was obtained by measuring the difference in amplitude values at 278.5 and 306nm (corresponding to zero difference of TL) while the total concentration of HZ and TL in the mixture was measured at their isoabsorptive point in the division spectrum at 278.5nm (Aiso). TL concentration is then obtained by subtraction. Method B; double divisor ratio spectra derivative spectrophotometry (RS-DS) and method C; mean centering of ratio spectra (MCR) spectrophotometric methods. The proposed methods did not require any initial separation steps prior the analysis of the three drugs. A comparative study was done between the three methods regarding their; simplicity, sensitivity and limitations. Specificity was investigated by analyzing the synthetic mixtures containing different ratios of the three studied drugs and their tablets dosage form. Statistical comparison of the obtained results with those found by the official methods was done, differences were non-significant in regard to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for TL, HZ and AM.
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PMID:Application and validation of superior spectrophotometric methods for simultaneous determination of ternary mixture used for hypertension management. 2659 Apr 80

Patients who are unable to receive oral medication (p.o.) are a major problem in outpatient settings, especially in home health care systems. Mucosal administration of drugs offers an alternative to the oral route, especially when the parenteral mode cannot be used. There are three main pathways of mucosal administration: sublingual/buccal, intranasal and rectal. We discuss the possibility of mucosal delivery of antihypertensive drugs. Perindopril arginine and Amlodipine besylate are registered in the EU as orodispersible tablets for oromucosal delivery, however, they are not available in all countries. For this reason, we describe other drugs suitable for mucosal delivery: Captopril and Nitrendipine in the sublingual system and Metoprolol tartrate, Propranolol and Furosemide by the transrectal route. Based on the published data and common clinical practice we discuss the use of mucosal delivery systems of all these antihypertensive drugs with special attention to their pharmacokinetics. We illustrate this mini-review with a case report of the prolonged-term use of mucosal delivery of sublingual Captopril and Nitrendipine combined with rectal Metoprolol tartrate and Furosemide in a patient with severe hypertension unable to receive medication p.o. This is also a report on the first human use of Furosemide-containing suppositories as well as prolonged-term transmucosal administration of these four drugs, describing a practical approach leading to successful control of severe hypertension with four antihypertensive drugs delivered via the mucosal route. The treatment was effective and without side effects; however, the long-term safety and efficacy of such therapy must be confirmed by randomized clinical trials.
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PMID:Mucosal delivery systems of antihypertensive drugs: A practical approach in general practice. 2976 68


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