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)

Delapril, a new angiotensin converting enzyme (ACE) inhibitor discovered in the laboratory of Takeda Chemical Industries, Ltd., is the result of drug design based on the structure-activity relationships of ACE inhibitors. Delapril is an antihypertensive agent with a relatively long duration of action and no SH moiety in its structure. Following administration, it is converted into two active metabolites. Delapril effectively lowered blood pressure in 73% of 1,008 patients with hypertension during clinical trials in Japan. Efficacy rates were 73% for essential hypertension, 85% for renal hypertension, and 80% for renovascular hypertension. Excellent hypotensive response was observed in all age groups, from young to elderly patients. Side effects during administration of delapril, based on subjective evidence, were reported in 80 out of the 1,008 cases (7.9%). The main symptoms included orthostatic dizziness (1.7%), dizziness (1.3%), and nausea (1.1%). Dry cough, which has attracted attention in recent years as a side effect of ACE inhibitors, was reported at a low incidence of 1.1%. In a double-blind, controlled study in patients with mild to moderate essential hypertension in which captopril served as a positive control, delapril showed superior hypotensive effect and greater safety. Data derived from the Japan Study Group on Delapril indicate that this ACE inhibitor has excellent hypotensive effects and a high level of safety. It is suitable as a first-line drug in both monotherapy and combined therapy.
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PMID:Clinical evaluation of delapril in Japan. Report from the Japan Study Group on Delapril. 200 47

ACE-inhibitors have long been considered to be connected with only a few side-effects. Their use in clinical practice has shown that a considerable number of patients develop a dry, non-productive cough, resistant to treatment. The cause is hitherto unknown, but ACE-inhibition has been proved to alter the cough reflex. Non-smokers seem to cough more often than smokers, and females more often than males. Registration of side-effects in 28 patients treated for arterial hypertension in general practice in the years 1985-1988 is presented.
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PMID:[Side effects in 28 patients treated with angiotensin converting enzyme (ACE) inhibitor in arterial hypertension in general practice]. 240 13

In a double-blind, randomized, cross-over study in 23 diabetic patients, insulin treated (N = 11) or noninsulin treated (N = 12), with mild to moderate hypertension, the hypotensive effects of captopril and atenolol were compared. Five patients had overt diabetic nephropathy. All patients received 50 mg twice daily of either drug. Treatment periods lasted 6 weeks and were preceded and separated by a placebo period. Two patients dropped out, one because of intermittent claudication during atenolol, one with cardiac arrhythmia during placebo. Blood pressure was reduced from 165 +/- 5/96 +/- 1 to 154 +/- 5/89 +/- 2 mmHg (mean +/- SEM: P less than 0.01) during captopril and from 171 +/- 5/98 +/- 1 to 159 +/- 6/89 +/- 2 mmHg (P less than 0.01) during atenolol. These antihypertensive effects are not significantly different. There was a wide inter- and intraindividual variation in hypotensive response to both drugs, which may have important consequences for treatment strategies. No consistent differences between insulin and noninsulin treated patients were seen. Parameters of glycemic control did not change during any therapy, neither in insulin treated nor in non-insulin treated patients. Albuminuria and renal function did not change. During captopril treatment one patient complained of a non-productive cough. Two patients experienced a severe hypoglycemic reaction during atenolol. No other major side-effects were seen. In conclusion, this study showed equal hypotensive effectivity of 100 mg captopril and 100 mg atenolol daily in hypertensive diabetics, without evident effect on glycemic control.
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PMID:A comparison of the hypotensive effects of captopril and atenolol in the treatment of hypertension in diabetic patients. 265 75

1 The long-term effect of the converting-enzyme inhibitor captopril was investigated in 76 patients with various forms of severe hypertension, most cases being resistant to a standardised triple therapy (100 mg hydrochlorothiazide or 80-500 mg frusemide; 320 mg propranolol; and 200 mg hydralazine). 2 In each of the three groups examined (essential, renovascular, and renal parenchymatous hypertension) captopril led to a prompt and sustained reduction in systolic and diastolic blood pressure. Up to an observation time of 2 1/2 years patients with renovascular hypertension showed a more pronounced fall in mean diastolic blood pressures than those with essential hypertension. About 90% of all patients required a diuretic and a substantial percentage of patients needed propranolol as a third drug. 3 The most frequent side effects were skin manifestations, taste disturbances, dizziness, and non-productive cough. Serious adverse effects were rare and included one case of leucopenia and one of the nephrotic syndrome, both of them reversed after withdrawal of captopril. Further analysis showed that side effects occurred mainly in patients with impaired kidney function receiving relatively high dosages of captopril (greater than 200 mg/day). 4 Our results show that captopril is a very potent blood-pressure-lowering agent in severe hypertension, especially in cases with renovascular hypertension.
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PMID:Long-term experience with captopril in severe hypertension. 675 7

This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.
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PMID:Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. 771 81

For the treatment of hypertension, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic action and are expected to cancel out each other's adverse side effects. However, the long-term outcome of this combination antihypertensive therapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypertensive therapy with an ACE inhibitor, lisinopril, and a thiazide diuretic, trichlormethiazide. A total of 466 patients with essential hypertension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combination therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The average maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were observed. The incidence of cough was not significantly different between the monotherapy group (13.1%) and the combination therapy group (11.3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the combination therapy group. Fasting blood glucose was significantly reduced in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined antihypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.
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PMID:Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension. 948 36

Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system. The incidence of dry cough associated with two of these therapies, the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril, was assessed in a multicentre, randomised, parallel-group, double-blind, placebo-controlled, 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough. Patients received either telmisartan 80 mg, lisinopril 20 mg, or placebo once daily. Cough incidence, measured at each visit by a self-administered symptom assessment questionnaire, was significantly higher with lisinopril (60%) than with telmisartan (15.6%) or placebo (9.7%). A visual analogue scale demonstrated a similar trend for cough frequency. Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo.
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PMID:The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Telmisartan Cough Study Group. 1034 43

In the conventionally treated group of patients with chronic myelogenous leukemia (CML) the prognosis has been significantly improved by interferon-alpha (IFN-alpha). Several side effects in association with IFN-alpha treatment have been reported. Here we present the first case of a CML patient with reversible pulmonary artery hypertension (PAH) during IFN-alpha therapy. The patient received IFN-alpha-2b (up to 10 million U/day) for 6 months until he started to complain of dyspnea on exertion and an afebrile non-productive cough. An echocardiography and right heart catheterization showed signs of right heart failure with PAH (80 mmHg). A reduced carbon monoxide diffusion capacity and partial respiratory insufficiency were noted. Inflammatory markers were not elevated and pulmonary infiltrates could not be detected. Respiratory infections, thromboembolic causes or autoimmune diseases were carefully ruled out. IFN-alpha was suspected as causative agent, because experimental investigations in sheep showed that IFN-alpha can stimulate the thromboxane cascade which resulted in transient PAH. A reduced pulmonary diffusion capacity had been observed secondary to PAH. After discontinuation of IFN-alpha, our patient's clinical status improved rapidly. After 6 months the pulmonary artery pressure had returned to near normal values (35 mmHg) and the pulmonary diffusion capacity was normal. It took one year until the electrocardiogram reverted to the pre-IFN-alpha pattern. PAH should be included in the differential diagnosis of patients treated with IFN-alpha who complain of exertional dyspnea in the absence of inflammatory signs.
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PMID:Pulmonary artery hypertension during interferon-alpha therapy for chronic myelogenous leukemia. 1144 36

Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10, respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.
Hypertension 2001 Aug
PMID:Iron supplementation inhibits cough associated with ACE inhibitors. 1175 45

The CORD trials tested ramipril and losartan in patients with hypertension. CORD A randomised 4016 patients with blood pressure (BP) <160/100 mm Hg, who had been treated with an ACEI for >3 months. The patients discontinued ACEI and switched to losartan. After 1 month the BP decreased to 7.7/4.7 mm Hg (p<0.001) and after 1 year to 13.8/8.7 mm Hg (p<0.001). CORD B compared ramipril and losartan in 3813 patients with hypertension who were not being treated with an ACEI or ARB. The patients were randomised to ramipril (n=1926) or losartan (n=1887). After 1 year the BP decreased in the ramipril group to 21.8/13.7 mm Hg (p<0.001) and in the losartan group to 22.0/13.3 mm Hg (p<0.001). No significant differences were found between the groups. No differences were in serious adverse events. Dry cough was more frequently after ramipril (33 vs 4, p<0.001).
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PMID:CORD: COmparison of Recommended Doses of ace inhibitors and angiotensin II receptor blockers. 1929 39


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