Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Accupril Canadian Clinical Evaluation and Patient Teaching (ACCEPT) study was a multicenter, 6-month, open-label, postmarketing surveillance study where the efficacy and safety of quinapril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in a general population of patients with essential hypertension. Participating physicians followed their normal office procedures for the initiation of quinapril therapy (a dose of 10 mg QD in the majority of cases). The dose was titrated to blood pressure response, generally at 2-week intervals, for a maintenance dose of 10 mg QD to 20 mg QD in most cases (86% at 6 months) and not to exceed 40 mg QD. The use of concomitant antihypertensive medications was left to the discretion of the physician. By random assignment, physicians obtained patient informed consent on either a detailed form that listed possible quinapril side effects or a less specific form, which did not list particular side effects. The purpose of using two different forms was to assess any potential association between the frequency of adverse-event reporting and patient's awareness of quinapril side effects. The patients also received an educational package that provided general information on hypertension and lifestyle modifications known to reduce cardiovascular risk factors. An intent-to-treat analysis included data from 3742 patients in whom the median age was 56 years and the median duration of hypertension was 5 years. The demographic characteristics of these patients were similar to those identified in Canadian hypertensive patients in a recent population-based survey. Nearly 80% of the ACCEPT study patients had more than one cardiovascular risk factor, in addition to hypertension. Among 2979 patients receiving quinapril at 3 months, 77% were stabilized. Among 2517 patients continuing to receive quinapril at 6 months, 84% were stabilized. Greater declines in both diastolic and systolic blood pressures were evident among patients who continued to receive quinapril as part of an antihypertensive regimen than among those who discontinued quinapril treatment. Blood pressure responses to quinapril were similar in newly diagnosed patients and those with a history of hypertension. A total of 980 patients (26.2%) reported one or more adverse events. Cough was most frequently reported and was deemed as definitely related to quinapril therapy by the treating physician in 3.6% of cases. Serious adverse events occurred in 55 patients (1.5%) and were assessed as possibly related to quinapril in only three patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A postmarketing surveillance evaluation of quinapril in 3742 Canadian hypertensive patients: the ACCEPT Study. Accupril Canadian Clinical Evaluation and Patient Teaching. 785 44

Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo. Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose. Adverse events were recorded continuously. After 12 weeks of treatment, moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo (-12.2/-9.9 mm Hg vs -1.6/-4.3 mm Hg, P < 0.001). Metabolic parameters were not affected by treatment with moexipril: mean levels of triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose remained unchanged throughout the study. Fibrinogen, an independent cardiovascular risk factor, increased after placebo (+35.0 mg/dl) and decreased after treatment with moexipril (-33.6 mg/dl), the difference, however, was not statistically significant. Moexipril was well-tolerated by postmenopausal women using HRT. The most frequent adverse events included headache (21.3%), cough (12.8%) and rhinitis (10.6%) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups. This study indicates that moexipril is effective and well tolerated in the treatment of hypertensive, postmenopausal women and can safely be co-administered to HRT.
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PMID:Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women. 1037 52

Hypertension is a very common condition and the most important risk factor for the occurrence of cardiovascular events. The hyperactivity of the renin-angiotensin-aldosterone system is considered a cardiovascular risk factor in subjects with essential hypertension. The intrinsic vascular abnormality in which the renin-angiotensin-aldosterone system is clearly the milieu for the development of the pathologic changes in blood vessel walls is one of the causes of the establishment of hypertension. Many drugs with different mechanisms of action have been used for the treatment of hypertension and its vascular complications. Nevertheless, the utilities of many drugs are limited by their adverse effects. Continuous research in the search for new pharmacological agents for the treatment of hypertension has led to the development of angiotensin II receptor type AT1 blockers. The most important functions mediated by AT1 receptors include: vasoconstriction, induction of the production and release of aldosterone, renal reabsorption of sodium, cardiac cellular growth, proliferation of vascular smooth muscle, increase of peripheral noradrenergic action and the central activity of the sympathetic nervous system, stimulation of vasopressin release, and inhibition of renin release from the kidney. The angiotensin II receptor type AT1 blockers inhibit the interaction of angiotensin II with its AT1 receptor. These agents lower blood pressure without producing cough as a side effect since, unlike the angiotensin-converting enzyme inhibitors they do not influence the levels of bradykinin or substance P. Hence, these drugs are suitable for the treatment of hypertensive patients who require therapy with a drug blocking the effect of angiotensin-converting enzyme but cannot use angiotensin-converting enzyme inhibitors due to cough as a side effect.
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PMID:Role of angiotensin II AT1 receptor blockers in the treatment of arterial hypertension. 1462 77

N-alpha-Tosyl l-arginine methyl ester [TAME]-esterase appears to be an important biochemical marker, which displays potent contractile properties on bronchial tissues and aorta in vitro. TAME-esterase induced contractions have been shown to be mediated via a nitric oxide-cyclic GMP pathway. TAME-esterase has also been described to be a possible new cardiovascular risk factor among smokers. TAME-esterase has been reported to be an enzyme, which is involved during the sequence of events leading to the activation of the kinin-kallikrein system. Use of aprotinin (a kallikrein inhibitor) as well as aspirin and indomethacin (prostaglandin inhibitors) have shown that there is an inter-dependent relationship between the kinin-kallikrein system and the cyclo-oxygenase pathway involved during the sequence of reactions leading to TAME-esterase induced contractions. Our findings also lend support to the concept of calcium antagonism whereby verapamil, and nifedipine, mimicked in reversible fashion the effects of Ca2+ withdrawal on muscle excitability during TAME-esterase induced contractions on rat aorta in vitro. We concluded that the effects of captopril, an ACE inhibitor, on TAME-esterase induced contractions could thus be due to the degradation of bradykinin by the enzyme kininase being blocked. This paper proposes an integrated model of possible biochemical-pharmacological pathways, which involve events leading to TAME-esterase induced contractions. We hypothesize that TAME-esterase induced cough through sensitization of airway sensor nerves in hypertensive patients taking angiotensin-converting enzyme inhibitors can be inhibited by aprotinin.
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PMID:Aprotinin suppresses ACE-inhibitor cough triggered by TAME-esterase. 1532 12

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.
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PMID:Candesartan cilexetil in cardiovascular disease. 1550 Apr 28

Targeting the renin-angiotensin-aldosterone system (RAAS), specifically the effector peptide angiotensin II (Ang II), represents a major opportunity for slowing the progression of cardiovascular disease (CVD) and, in turn, reducing the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme (ACE) and selective blockade of Ang II AT1 receptors are two approaches through which the pathophysiological effects of Ang II can be targeted. Numerous clinical studies have established the benefits of ACE inhibitors (ACE-Is) in lessening the morbidity and mortality burden of CVD. There are, however, tolerability concerns associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at the AT1 receptor level, Ang II receptor blockers (ARBs) provide a more specific and complete blockade of the deleterious effects of Ang II and tend to have more favourable tolerability. A number of clinical trials have shown that ARBs are not only associated with positive outcomes across the CVD continuum but mat also have a role in the prevention or delay of diabetes (a major cardiovascular risk factor). Ongoing trials are aiming to define the place of such agents in lessening morbidity and mortality from CVD.
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PMID:Clinical evidence for the cardiovascular benefits of angiotensin receptor blockers. 1696 48

Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system.
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PMID:[Menopause: Hypertension and vascular disease]. 2939 43