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Query: UMLS:C0010200 (cough)
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A number of new classes of antihypertensive drugs have become available in the recent years which appear to hold therapeutic potential for better management of hypertension. Losartan, an angiotensin II receptor antagonist, does not produce cough which is classically seen with ACE inhibitors. Fenoldopam, a dopamine D1-receptor agonist, has a rapid and short duration of action and is ideally suited by intravenous infusion for quick control of BP in hypertensive emergencies. Kentaserin, a serotonin (5-HT2A) receptor antagonist, has a long duration of action and can be given once daily. It has the added benefit of having antiplatelet effect. Monatepil, a dual alpha-receptor and calcium channel blocker, has potent antihypertensive effect, lowers serum cholesterol and also has antiatherosclerotic effect. Dual ACE and endopeptidase inhibitor, such as alatriopril, has a "broad spectrum" antihypertensive effect and may be effective in majority of hypertensive patients. Many other classes of antihypertensive drugs are still in the investigative stage, and their therapeutic potentials and safety need to be ascertained in long-term controlled clinical trials.
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PMID:New classes of antihypertensive drugs: therapeutic potentials. 1005 49

The importance of hypertension in the pediatric population is not as well-appreciated as in adults. This might well be related in part to the lower prevalence of high blood pressure in this age group. As with height and weight, blood pressure increases with age during childhood. 'High normal' blood pressure is a blood pressure above the 90th percentile and established hypertension a blood pressure above 95th percentile. The varying arm and thigh sizes of children and adolescents require blood pressure cuffs that are appropriately sized. A cuff that is too small will produce an artificially elevated blood pressure, while a cuff that is too large is not likely to obscure hypertensive levels of blood pressure. The use of an oscillometric device is more convenient for infants. The underlying causes of significant hypertension in the pediatric population differ considerably from those of adults: while the prevalence of hypertension in pediatrics is lower than in adults, clinically identifiable causes of hypertension account for a much higher proportion of hypertension in children. Children with chronic secondary hypertension will require drug therapy with converting-enzyme inhibitors, calcium-channel blockers, beta-blockers or diuretics. Therapy now tends to be initiated with converting-enzyme inhibitors because they are generally effective and have few side effects. Persistent cough sometimes develops on converting enzyme inhibitors. The term sartans denotes a new group of orally active antagonists of the angiotensin II receptor. Since sartans do not cause cough, these agents represent a promising treatment for patients who develop cough with converting enzyme inhibitors.
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PMID:[Arterial hypertension in childhood and adolescence]. 1006 29

The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the short-term and long-term regulation of arterial blood pressure, and fluid and electrolyte balance. The RAAS is a dual hormone system, serving as both a circulating and a local tissue hormone system (i.e., local mediator) as well as neurotransmitter or neuromediator functions in CNS. Control of blood pressure by the RAAS is exerted through multiple actions of angiotensin II, a small peptide which is a potent vasoconstrictor hormone implicated in the genesis and maintenance of hypertension. Hypertension is a primary risk factor associated with cardiovascular, cerebral and renal vascular disease. One of the approaches to the treatment of hypertension, which may be considered as a major scientific advancement, involves the use of drugs affecting the RAAS. Pharmacological interruption of the RAAS was initially employed in the late 1970s with the advent of the angiotensin converting enzyme (ACE) inhibitor, captopril. ACE inhibitors have since gained widespread use in the treatment of mild to moderate hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy. As the roles of the RAAS in the pathophysiology of several diseases was explored, so did the realization of the importance of inhibiting the actions of angiotensin II. Although ACE inhibitors are well tolerated, they are also involved in the activation of bradykinin, enkephalins, and other biologically active peptides. These actions result in adverse effects such as cough, increased bronchial reactivity, and angioedema. Thus, the goal of achieving a more specific blockade of the effects of angiotensin II than is possible with ACE inhibition. The introduction of the nonpeptide angiotensin II receptor antagonist losartan in 1995 marked the achievement of this objective and has opened new vistas in understanding and controlling the additional biological effects of angiotensin II. Complementary investigations into the cloning and sequencing of angiotensin II receptors have demonstrated the existence of a family of angiotensin II receptor subtypes. Two major types of angiotensin II receptors have been identified in humans. The type 1 receptor (AT1) mediates most known effects of angiotensin II. The type 2 receptor (AT2), for which no precise function was known in the past, has gained importance recently and new mechanisms of intracellular signalling have been proposed. This review presents recent advances in angiotensin II receptor pharmacology, molecular biology, and signal transduction, with particular reference to the AT1 receptor. Excellent reviews have appeared recently on this subject.
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PMID:Angiotensin II receptors-antagonists, molecular biology, and signal transduction. 1009 99

OBJECTIVE: To compare the blood pressure reduction induced by valsartan, a new angiotensin II receptor antagonist, with that induced by enalapril, an angiotensin converting enzyme (ACE) inhibitor in essential hypertension. METHODS: In total 189 adult outpatients with uncomplicated essential hypertension participated in this double-blind study. Patients were allocated randomly in equal numbers to be administered 80 mg valsartan or 20 mg enalapril daily for 12 weeks. Patients whose blood pressure had not been controlled adequately despite 8 weeks of monotherapy were administered additional therapy with 12.5 mg hydroclorothiazide (HCTZ) daily thereafter. Patients were assessed aftger 4, 8 and 12 weeks of therapy. The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Other variables analyzed included the change in sitting systolic blood pressure and percentage responses after 8 weeks of therapy. RESULTS: Valsartan and enalapril were both effective at lowering the blood pressure. Similar falls were induced in the two groups with a similar time course of blood pressure reduction. The mean decreases in SDBP after 8 weeks of therapy were 13.2 mmHg for valsartan and 12.0 mmHg for enalapril. There was no significant difference between the treatments [P = 0.475, 95% confidence interval of the estimated difference (SBP after therapy - SDBP before therapy) -3.5 to 1.6 mmHg]. After 8 weeks of therapy 60.6% had responded to valsartan and 52.6% to enalapril (P = 0.267). Both treatments were tolerated well. Three patients administered enalapril and one patient administered valsartan discontinued their treatment because it made them cough. CONCLUSION: The data show that 80 mg valsartan is as effective as 20 mg enalapril in the treatment of moderate hypertension and that it is tolerated well.
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PMID:Valsartan, a new angiotensin II antagonist; blood pressure reduction in essential hypertension compared with an angiotensin converting enzyme inhibitor, enalapril. 1023 13

There is a sexual dimorphism in blood pressure: men tend to have higher blood pressures than women with functional ovaries, whereas ovariectomy or menopause tends to abolish the sexual dimorphism and cause women to develop a "male" pattern of blood pressure. Synthetic estrogens and progestins, found in oral contraceptives, tend to elevate blood pressure, whereas naturally occurring estrogens, used in postmenopausal hormone replacement therapy, lower it or have no effect. Women are more likely than men to be aware of their hypertension, to be treated with antihypertensive drugs, and to have their blood pressure controlled. Antihypertensive therapy induces similar blood pressure reductions in men and women. However, men experience larger reductions in total cardiovascular risk with successful treatment of high blood pressure, because their absolute risk of coronary events at baseline is so much higher. Special considerations that can dictate antihypertensive treatment choices for women include increased vulnerability to the adverse effects of some drugs, including angiotensin-converting enzyme inhibitor-induced cough, calcium channel blocker-induced edema, and minoxidil-induced hirsutism. Beta-adrenergic blockers tend to be less effective in women than in men, and diuretics are particularly useful in women because they protect against hip fracture. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are contraindicated during pregnancy or if pregnancy is planned because of the risk of fetal developmental abnormalities.
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PMID:The Sexual Dimorphism of High Blood Pressure. 1034 60

In this review angiotensin II receptor antagonists (Angiotensin antagonists are discussed on the efficacy and safety in the treatment of essential hypertension. Angiotensin antagonists are more complete renin angiotensin system blockade, and are potent as ACE inhibitors, but they have rarely troublesome dry cough specific to ACE inhibitors. Angiotensin antagonists have demonstrated an excellent tolerability profile. Angiotensin antagonists will have potentially greater protection from end-organ damage, since they have provided end-organ protection in animal experiments. These agents will be considered for first-line therapies in very near future.
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PMID:[Comparison with other antihypertensive drugs, especially with ACEI]. 1036 54

Valsartan is a specific angiotensin II receptor antagonist with high selectivity for the AT(1) receptor subtype. After oral administration of single or repeated once-daily doses, valsartan 40-80 mg inhibits the pressor response to angiotensin II for 24 hours. In patients with mild-to-moderate hypertension, efficacy of valsartan appears to be independent of age, sex, and race, and is at least equivalent to that of calcium antagonists, ACE inhibitors, or thiazide diuretics. Response rate to valsartan 160 mg o.d. is significantly greater than after receiving losartan 100 mg o.d. Valsartan has additive effects with other antihypertensive drugs and combination therapy is effective in severe hypertension and in hypertension with renal insufficiency, where renal function is well maintained. Valsartan has good tolerability with a side-effect profile indistinguishable from placebo and superior to that of comparable drugs. Valsartan does not cause cough or adverse metabolic effects; first dose hypotension and rebound hypertension on abrupt withdrawal have not been encountered. Valsartan has clear clinical advantage in the management of hypertension. Its impact on prognosis in patients with a high risk of cardiovascular morbidity and mortality is under evaluation.
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PMID:Clinical advantage of valsartan. 1044 90

The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) includes recommendations for the assessment of overall cardiovascular risk and the need for active antihypertensive drug therapy. Once the decision to initiate antihypertensive drug therapy has been made, JNC-VI recommends one of three paths for the choice of initial therapy: one path for patients with uncomplicated hypertension, another for those with well-defined indications for certain drugs and a third path for patients with various concomitant conditions in which one or another drug has favorable effects. At this time, the place for the newest class of antihypertensive drugs, the angiotensin II receptor antagonists, remains uncertain. Currently, they are considered reasonable alternatives for patients who have a compelling need for an angiotensin-converting enzyme (ACE) inhibitor but develop a cough while taking this medication. When data from ongoing trials become available, angiotensin II receptor antagonists may prove to be a good choice for initial therapy in many patients because of the favorable side effect profile of this class of drugs.
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PMID:Angiotensin II receptor antagonists in the treatment of hypertension. 1050 47

Losartan is the first orally active angiotensin II receptor type 1 antagonist for a new class of cardiovascular therapeutic agent. Losartan is converted to an active metabolite (E3174) after oral administration in humans and rats. Both losartan and E3174 contribute to the net angiotensin II receptor blockade and produce anti-hypertensive effect. Losartan not only blocks the vasoconstrictive effect of angiotensin II but also inhibits its mitogenic effect; thus losartan is expected to protect against end-organ-damage-related hypertension and chronic heart failure. Unlike angiotensin-coverting-enzyme inhibitor, losartan does not elicit adverse effects of cough and angioneurotic edema by its blockade of angiotensin II receptor. It is also expected to reduce proteinuria in nephropathy. In addition to its blockade of angiotensin II receptor, losartan blocks thromboxane A2 receptor and facilitates excretion of uric acid, although therapeutic importance of these effects are under investigation. In summary, losartan, an angiotensin II type 1 receptor antagonist is a new class of antihypertensive agent and its therapeutic potentials are not merely reduction of blood pressure but total protection from end-organ damage resulting from activation of both the systemic and local renin-angiotensin system.
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PMID:[Pharmacological characteristics and clinical application of losartan, an orally active AT1 angiotensin II receptor antagonist]. 1052 59

Valsartan (Diovan) is an antihypertensive drug belonging to the family of angiotensin II receptor antagonists. At a dose of 40 mg/d, its antihypertensive effect is inconsistent. At 80 mg/d its effect on blood pressure, its adverse effects, and its contraindications (mainly pregnancy and renal artery stenosis) are similar to those of angiotensin-converting enzyme (ACE) inhibitors, except that coughing is rarer with valsartan than with ACE inhibitors. Valsartan has no demonstrated advantage over losartan, another angiotensin II antagonist. Valsartan has not been shown to prevent complications of arterial hypertension, and its use is, therefore, less well validated than that of diuretics and beta-blockers.
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PMID:Valsartan. Just a second-line antihypertensive drug. 1058 70


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