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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past 4 years, six angiotensin II receptor antagonists (ARBs) were approved for treating essential hypertension. They differ with respect to dosing, metabolism, elimination, clinical efficacy, and investigational applications. Candesartan cilexetil is the only prodrug among the agents. Losartan is distinguished from other ARBs by cytochrome P450 (CYP) 3A4- and CYP2C9-mediated biotransformation to its active metabolite EXP-3174. No ARB requires dosage adjustment for renal impairment, but the initial dose of losartan should be reduced 50% in hepatically impaired patients. None of the drugs is significantly cleared by hemodialysis. Completion of continuing trials will elucidate the drugs' role in treating heart failure, cerebral stroke, and myocardial infarction.
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PMID:Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. 1067 91

Formerly, the incidence of primary aldosteronism (PA) among patients with hypertension was believed to be less than 1%. However, recent studies have suggested a much higher incidence of 6.59%-14.4% among such patients. These findings suggest that many cases of PA caused by small aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA) have not been properly diagnosed. To make a more accurate diagnosis in such cases, we developed a new diagnostic procedure for localization of PA, namely, adrenal venous sampling under continuous infusion of adrenocorticotropic hormone (ACTH) and administration of angiotensin II receptor blocker (AVS with ACTH and ARB). Here, we confirm the efficacy of this procedure in the case of a 37-year-old male suspected of having PA. The anticipated diagnosis of PA was based on the presence of hypokalemia, low plasma renin activity (PRA), elevated plasma aldosterone concentration (PAC) and left adrenal mass. However, AVS with ACTH and ARB revealed the presence of bilateral multiple adrenal microadenomas. In the new AVS method, neither ACTH nor the renin-angiotensin system (RAS) exert any influence on the plasma aldosterone level, and a more accurate aldosterone secretary state and a more accurate assessment of the aldosterone secretion of both adrenal glands can be recognized than by conventional AVS. Use of this new method should enable identification of additional cases of APA among patients diagnosed with essential hypertension.
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PMID:New diagnostic procedure for primary aldosteronism: adrenal venous sampling under adrenocorticotropic hormone and angiotensin II receptor blocker--application to a case of bilateral multiple adrenal microadenomas. 1204 27

This study evaluated a strategy to treat naive hypertensive patients, based on a single monotherapy followed, in uncontrolled patients, by a rationale choice for the second antihypertensive treatment. Subjects with essential hypertension, entered into the study if their BP measured with an OMRON 705CP was > 140/90 mmHg on two separate visits. Patients were allocated to single treatment in a balanced randomized design to receive either a "group 1" treatment (ACE inhibitor, beta-blocking drug or ARB) or a "group 2" treatment (calcium channel-blocking drug or thiazide diuretic). After one month of treatment at a standard dose, if BP was > 140/90 mmHg, first adaptation was a fixed combination therapy with one drug from "group 1" and one drug from "group 2". At 3 months, patients with BP < 140/90 mmHg were considered to have reached BP goal. Forty-eight patients entered the study with a mean age of 53 +/- 11 years. Initial SBP/DBP (mmHg) was 164 +/- 16/97 +/- 8. After 1 month, 40% achieved the target BP, 52% were uncontrolled with no side effects and 8% were uncontrolled and had side effects. After 3 months, 84% achieved BP goal and a fixed combination therapy was prescribed in 52% of the controlled patients. The initial monotherapy was maintained alone or in combination in 70% of the controlled patients. A strategy based on a single monotherapy followed, if necessary, by a rational choice for the second treatment in a fixed combination therapy is effective to achieve BP control in 84% of naive hypertensive patients.
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PMID:[Rational choice for second antihypertensive agent after failure of the first monotherapy: therapeutic strategy]. 1236 87

Renin angiotensin(RA) system is deeply involved in the pathophysiological conditions of essential hypertension. To inhibit RA system is supposed to be induced cardiovascular protective effect. ACEIs and ARBs are used as first choice of drugs in the treatment of hypertension. Clinical evidence shows that ACEIs have protective effects on heart, kidney and brain. Several large clinical trials suggest that ARBs have also protective effects on heart and diabetic nephropathy. Furthermore, recent study has demonstrated that an ARB prevents more cardiovascular morbidity and death than a beta blocker and is better tolerated in hypertensive patients with left ventricular hypertrophy. Now accumulated evidence indicates that ARBs are useful drugs in the treatment of hypertension.
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PMID:[Clinical application of ARB and ACEI]. 1239 95

Although vascular compliance, deltaV/deltaP, is abnormal in essential hypertension and can be improved by antihypertensive drug therapy, it is not clear whether drug-induced changes in compliance are attributable solely to lower achieved blood pressure (BP), and thus equally likely with different drugs possessing similar antihypertensive efficacy. Therefore, we used computerized arterial pulse waveform analysis (CAPWA) to measure capacitive (C1) and oscillatory (C2) components of arterial compliance in essential hypertensive subjects (n = 39) before, and 1 and 3 months after achieving normotensive BP values with administration of either dihydropyridine calcium channel antagonists (CaBl, n = 11), converting enzyme inhibitors (CEI, n = 9), angiotensin receptor blockers (ARB, n = 9), or beta-blockers (BBl, n = 10). Despite equivalent effects on BP (CABL: -19 +/- 4/-15 +/- 2 mm Hg; CEI: -12 +/- 3/-13 +/- 2 mm Hg; ARB: -10 +/- 3/-12 +/- 2 mm Hg; and BBl: -14 +/- 3/-12 +/- 2 mm Hg; P <.005 for each drug v pretreatment), CaBl, CEI, and ARB significantly increased arterial compliance (CaBl: %deltaC1 = 30.0 +/- 5.8, %Delta C2 = 43.7 +/- 23.3; CEI: %deltaC1 = 32.7 +/- 5.4, %deltaC2 = 26.7 +/- 7.1; ARB: %deltaC1 = 36.3 +/- 11.8, %deltaC2 = 43.6 +/- 23.1; P <.01 for CaBl, CEI, and ARB v pretreatment), but BBl did not (%deltaC1 = -3.9 +/- 7.6, %deltaC2 = -7.0 +/- 11.5, P = not significant v pretreatment, sig = 0.01 v other drugs). We conclude that for an equivalent effect on BP, arterial compliance improves after therapy with some, but not all antihypertensive drugs. We hypothesize that a greater clinical benefit may result from the preferential use of drugs that concomitantly improve arterial compliance.
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PMID:Differential effects of antihypertensive drug therapy on arterial compliance. 1246 Jul 7

Even well-conducted randomized controlled trials can only reduce uncertainty, not eliminate it. The trials presented in this article all have gaps, and like many studies, some raise more questions than answers. A summary of the current trials, however, can be presented as follows. For patients with essential hypertension who are at high risk for cardiovascular disease, the use of diuretic therapy (excluding simultaneous use of ACE or CCB) resulted in outcomes at least equivalent to the use of either ACE or CCB without diuretics. Naturally, the dilemma for clinicians is that these drugs are most often used in combination with thiazide diuretics, as indicated by the RENAAL trial where 80% of ARB were used with diuretics in patients with type II diabetes and known nephropathy. The increased risk of heart failure observed with ACE and CCB in that trial may be relevant only to patients in whom diuretics were not also used. The study does raise important awareness, however, that ACE or CCB use without diuretic therapy is no better than diuretic therapy, and may be associated with higher risk of certain outcomes. A substantial number of patients with essential hypertension might achieve adequate blood pressure control with diuretic monotherapy. If so, that certainly has important implications for the cost of medical care in this country. For African Americans with essential hypertension, ACE may have advantages as a component of therapy in comparison with CCBs or beta-blockers, although diuretics should probably be the cornerstone of therapy for them and supported by the Seventh Joint National Committee. For patients with proteinuric renal disease, whether associated with diabetes or hypertension, it should be considered inappropriate to use DHP CCB as monotherapy in any setting, whether as part of a clinical trial or in clinical practice. These drugs should not be considered as ethical placebo arms in trials, most especially in diabetic nephropathy, nor should they be used without an ACE or ARB in patients with proteinuric renal disease in the absence of documented contraindications or intolerance to ACE, ARB, or non-DHP CCB (which are now considered second-line agents for proteinuric renal disease, and are acceptable placebo or comparison arms in clinical trials). For patients with type I diabetes, ACE remain the cornerstone of therapy. Because of recent RENAAL and IDNT trial results, the greatest benefit for slowing progression of renal disease in type II diabetic nephropathy now belongs to ARBs. In contrast, however, the HOPE trial showed that ACE, specifically ramipril, had the greatest evidence for prevention of cardiovascular outcomes in patients with renal insufficiency, regardless of diabetic status. Cardiovascular outcomes were secondary end points in the RENAAL and IDNT trials, and with the exception of heart failure for losartan, no benefits on cardiovascular outcomes were statistically significant. Progression of renal disease has only been studied in a relatively small cohort of Israeli patients comparing enalapril with nifedipine. These gaps lead to a classic dilemma in medical decision-making. Because evidence has shown that patients with elevated serum creatinine (greater than or equal to 1.4 mg/dL) are just as likely to die from cardiovascular disease as they are to reach end-stage renal disease, which outcome should be the focus for clinicians, or for researchers? Using a strictly evidence-based approach, this question can only be answered by yet another large, long, randomized, controlled trial. Given the similarity of actions between the ARB and ACE, it is likely there is considerable overlap of both benefits and side-effects between the two, although ARB may have a lower incidence of cough and hyperkalemia. The decision of which antihypertensive agents to use will have to be tailored carefully to the needs of the patient and careful consideration of both medical and economic factors. Regardless of the choice between an ACE or ARB, however, post hoc analysis of clinical trials [21,47] and observational data clearly indicate that patients with chronic kidney disease, even if considered mild (ie, serum creatinine greater than or equal to 1.4 mg/dL) are at significantly greater risk of cardiovascular morbidity and mortality compared with those with better kidney function. As stated in a recent review by the authors of the HOPE trial [50], "the frequent practice of withholding ACE [or ARB] in patients with mild renal insufficiency is unwarranted," because not only are these patients precisely those who might benefit most from their use, but safety and tolerability are generally excellent. Based on the results of the AASK trial, the authors add the same for the use of ACE inhibitors in African Americans.
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PMID:What have we learned from the current trials? 1487 Oct 59

Immunization against components of the renin-angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel trade mark ) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel trade mark (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.
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PMID:Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects. 1510 32

Telmisartan (Micardis) is a potent, long-lasting, nonpeptide angiotensin II type-1 (AT(1)) receptor blocker (ARB) that is indicated for the treatment of essential hypertension. In receptor binding studies, telmisartan showed a high affinity and selectivity for the human AT(1) receptors compared with AT(2) receptors and a slower dissociation rate from the human AT(1) receptor than those of ARBs. In isolated aorta rings, telmisartan was shown to be an insurmountable antagonist of AII-induced contractions. The inhibitory effects of telmisartan on AII-induced contraction persisted even after wash-out procedures. In animal models such as spontaneous hypertension rats and renovascular hypertensive rats, telmisartan produced the consistent reduction of blood pressure. Furthermore, there were no rebound phenomenon and no tolerance to the drug developed in the repeated oral administration. Telmisartan has a longer terminal elimination half-life (about 24 h) than the other ARBs. In patients with mild-moderate hypertension, trough/peak ratios for telmisartan were above 80%. In Japanese patients with mild-moderate hypertension, telmisartan produced a significant reduction in blood pressure (effective rate: 76.0%) with a good safety profile. Therefore, telmisartan is expected to be effective in the treatment of hypertension, producing sustained 24-h blood pressure control.
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PMID:[Pharmacological and clinical profile of telmisartan, a selective angiotensin II type-1 receptor blocker]. 1522 20

Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus, Micardis HCT, PritorPlus] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management of patients with hypertension.
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PMID:Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension. 1872 41

In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease is interesting, because it was earlier believed that a certain high blood pressure was mandatory for preservation of the renal function. This appeared to be a completely wrong concept. The data regarding microalbuminuria suggest that patients with microalbuminuria should receive anti-hypertensive treatment, even patients with so-called normal blood pressure. This was confirmed in several trials and also included in the guidelines. Reducing blood pressure is important, but it appeared to be especially beneficial to block the renin-angiontensin system, and it is clear that albuminuria is a continuous variable and is also a risk factor. Earlier it was suggested to use ACE-inhibitors or ARBs. Now it is clear that it is possible to use a combination, with good theoretical background. In the history of hypertension, it was earlier believed that diastolic blood pressure was most important, but later on it was generally accepted that systolic is a better predictor and the goal for treatment and pulse pressure may be even better. Not only is microalbuminuria an important risk marker, but it is as well clear that regression of microalbuminuria is a good marker for a better prognosis in patients. Microalbuminuria is believed to be the strongest risk factor, but new studies actually suggest that a simple parameter such as self-rated health is crucial along with other factors. Regarding new developments, it is clear that new studies have led to several advancements in management in patients, for instance the Steno II study shows positive effect on mortality by multifactorial intervention. Similarly, the ADVANCE study also showed positive effect on mortality by more intensified anti-hypertensive treatment with an ACE-inhibitor. We are eagerly awaiting the results from glucose arm in the ADVANCE study, especially in the light of the ACCORD study showing increased mortality with too strict glycemic control with a goal of 6% in HbA1c.
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PMID:Twelve shifting paradigms in diabetic renal disease and hypertension. 1894 97


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