Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety of 738 high-risk patients treated with enalapril under various clinical programs was evaluated. High risk was defined as the presence of a collagen vascular disease; a renal disease, including renovascular hypertension; or either hypertension or refractory cardiac failure with serum creatinine greater than or equal to 1.7 mg/dl at baseline. Essential hypertension was the primary diagnosis in most of these patients. Treatment with enalapril in these patients usually continued without interruption for the length of the particular protocol. The incidence of adverse reactions resulting in discontinuation of treatment was comparable to that observed with other standard antihypertensive therapies in patients with milder forms of disease. No enalapril-related neutropenia, proteinuria, dysgeusia or ageusia were reported in these high-risk patients. The incidence of discontinuation due to rash was less than 0.5%. Resolution and/or improvement of captopril-related adverse effects was observed in many patients crossed over to treatment with enalapril. In patients with collagen vascular diseases and those with severe impairment of renal function (serum creatinine greater than or equal to 3.0 mg/dl), the incidence of discontinuation due to adverse experiences or death as well as the profile of reported adverse experiences was similar to those for the total group of high-risk patients. The data suggest that enalapril is efficacious and well tolerated by the high-risk patients.
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PMID:High-risk patients treated with enalapril maleate: safety considerations. 253 44

We studied 11 patients affected by mild essential hypertension during chronic therapy with enalapril (E). After a pharmacological wash-out the patients were treated with E once a day (10-20 mg) for 4 weeks. Before and after the treatment period the patients were studied by means of the isotonic exercise stress test on the cycloergometer with increments of 25 W every 2 min and by means of the Sustained Handgrip test (SHG) at 70% of maximal capacity for 1 min. During the study period E reduced the blood pressure at rest in all patients without untoward effects. During the isotonic test and particularly during SHG, E reduced systolic and diastolic blood pressure (BP) and the product systolic BP x heart rate. The treatment did not influence the time length of the isotonic exercise stress test. Our results suggest that E does not increase the MVO2 at rest and during different types of exercise: this can be very important because many patients affected by hypertension suffer from ischemic heart disease. E is utilized also in patients with heart failure, some of whom have an hypertensive or ischemic cardiomyopathy.
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PMID:[Influence of chronically-administered enalapril on isotonic and isometric exercise in patients with moderate grade hypertension]. 255 75

Short term angiotensin converting enzyme inhibition may induce a transient salt and water retention in patients with hypertension or heart failure. To verify the glomerular and tubular effects of short term converting enzyme inhibition, thirteen patients with mild to moderate essential hypertension (WHO I-II) were treated orally either with perindopril (4 mg o.d.) or captopril (25 mg b.i.d.) for one week. Both drugs reduced supine mean blood pressure significantly (p less than 0.01) (perindopril from 126 +/- 11 to 108 +/- 7 mmHg, mean +/- SD, and captopril from 132 +/- 12 to 121 +/- 16). Plasma volume (radio-iodinated albumin space) was unchanged while mean extracellular fluid volume (inulin space) increased although not significantly (from 5.05 +/- 1.32 l/sqm to 5.71 +/- 2.21 with perindopril and from 4.96 +/- 2.6 to 5.6 +/- 1.7 with captopril). Sodium clearance decreased (from 1.4 +/- 0.6 to 1.1 +/- 0.5 ml/min 1.73 sqm with perindopril, p less than 0.05, and from 0.97 +/- 0.44 to 0.88 +/- 0.51 with captopril, n.s.). In 9 patients (6 on captopril and 3 on perindopril) extra-cellular fluid volume increased simultaneously with reduction in glomerular filtration rate and in proximal tubule sodium re-absorption as well as an increase in distal tubule sodium reabsorption. In these patients the changes in proximal and distal tubule sodium reabsorption were significantly (p = 0.05) different from those of the patients with no extra-cellular fluid expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Volume of the extracellular liquid and renal function during short-term administration of angiotensin converting enzyme inhibitors in essential hypertension]. 267 Jun 57

Renin plays a major role in the control of blood pressure and water and electrolyte metabolism and it is clear that blocking of this system is particularly effective in the treatment of essential hypertension and heart failure. A large number of converting enzyme inhibitors have been synthesized. Converting enzyme inhibitors are remarkably active in heart failure and they reduce microalbuminuria and possibly maintain glomerular function. Blocking of the renin-angiotensin system by converting enzyme inhibitors is not accompanied by hypotension or reflex stimulation of the sympathetic nervous system. Converting enzyme inhibitors represent a major therapeutic advance in the field of cardiovascular and renal disease but the long-term effects of decreased angiotensin II levels are unknown. There are other ways to inhibit the renin-angiotensin system. The recent discovery of orally-active non-peptide angiotensin II antagonists opens a range of fascinating prospects. Another approach consists in inhibiting the reaction of renin on angiotensinogen, which is remarkably selective. Although it is too early to know whether these new approaches will be less active, more active or as active as current converting enzyme inhibitors, they may constitute a progress in relation to currently available treatments.
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PMID:New therapeutic prospects of renin-angiotensin system inhibition. 269 Nov 25

Baroreceptor reflex plays an important role in the pathophysiology of essential hypertension. Experiments in dogs could demonstrate that after complete denervation of sinoaortic and cardiopulmonar baroreceptors a long-lasting hypertension with labile blood pressure behavior occurred. The sympathetic tone was enhanced significantly when studied in denervated rats. In patients with essential hypertension no comparable conditions to the "neurogenic hypertension" of animals exist. Therefore, studies in patients after orthotopic heart transplantation are of interest because those patients develop severe hypertension even if cyclosporine is not administered. Preliminary results reported here support a participation of baroreceptors in hypertension of transplanted patients. A further reason of essential hypertension is found on baroreceptor resetting. Changed ion concentrations and/or wall thickness of the respective blood vessels could be the cause. The sympathetic system influences the renin-angiotensin-system and baroreflex activity by central and peripheral mechanisms. It, for example, attenuates Ang-II and the baroreflex via central actions. Converting-enzyme-inhibitors (CEI) act in part as peripheral vasodilators without affecting the heart rate significantly. This effect is possibly due to lacking Ang-II that is able to increase the sensitivity of baroreceptors. In the past it has been shown that the inhibition of tissue-converting enzyme is more responsible for the antihypertensive effects of CEI than that of plasma-converting enzyme. The cardioprotective effects of CEI are suggested to be an important advantage in the treatment of hypertension and heart failure. These cardioprotective actions are partly due to accumulated bradykinin, just as are the hypotensive effects of CEI. The interactions between CEI and the sympathetic system should be differentiated into pre- and postsynaptic actions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Influence of baroreceptors on hypertension, pharmacotherapy with conversion enzyme inhibitors]. 269 53

A fall in blood pressure occurs, in most patients, within a few hours of a single dose of an angiotensin converting enzyme (ACE) inhibitor. While a serious fall in pressure is unusual in previously untreated essential hypertension, some patients are at risk of severe first-dose hypotension. These include those with treated heart failure, severe hypertension on polypharmacy, 'renin-dependent' renovascular hypertension and the occasional elderly patient. In such groups of patients the incidence of severe, symptomatic first-dose hypotension approaches 10%. This effect is not specific for ACE inhibitor therapy and may well occur as frequently with other drugs in such patients. First-dose hypotension may not be accompanied by tachycardia, possibly as a result of a parasympathomimetic action that may contribute to the first-dose effect. It is generally not possible to predict patients at risk, although plasma renin and angiotensin II concentrations show a modest positive correlation with the initial fall in blood pressure. The maximum initial hypotensive effect of ACE inhibitors is not clearly dose related but the duration of effect may be. Therefore such drugs should be started at minimum effective dosage. High-risk patients should be observed closely for at least 6 h. Symptomatic hypotension usually responds to supine rest although infusion of angiotensin II, atropine and occasionally saline may be required.
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PMID:Angiotensin converting enzyme inhibitors in the clinic: first-dose hypotension. 282 78

New method for measuring plasma and urinary Na-K-ATPase inhibitor (ATPI) was developed. Plasma and urine were extracted with reversed phase cartridge column and sample was reconstituted by assay buffer. Na-K-ATPase inhibitory activity of sample was monitored by continuously recording the absorbance of NADH at 340 nm, which coupled to the dephosphorylation of ATP. Ouabain was used for standards of Na-K-ATPase inhibition and this standard showed good linearity ranged 5-100 nmol/ml. Using this new method, P-ATPI and U-ATPI were quantitatively evaluated and paradoxical Na-K-ATPase stimulating phenomenon which observed in conventional method (Hamlyn et al) was diminished. Adopting of this new method for measuring plasma(P-) and urinary(U-)ATPI, and radioimmunoassay for P- and U-digitalis-like substance(DLS)--using crossreactivity to anti digoxin antibody--, these substances were estimated in patients with essential hypertension (EHT), chronic heart failure(CHF), primary and idiopathic hyperaldosteronism(HA), hyperthyroidism(BA) and chronic renal failure(CRF). In EHT, U-DLS, P-DLS, U-ATPI, P-ATPI were significantly higher than those of control(C). In CHF and BA, U-DLS and -ATPI were also significantly higher than those of C. In HA, U-ATPI, DLS distributed in wide range, and a few patients showed high levels of U-DLS and -ATPI. In CRF, P-DLS and -ATPI levels were significantly higher than those of C in prehemodialytic state but P-ATPI was significantly decreased after hemodialysis. From these results it is suggested that 1) DLS and ATPI might contribute to the etiology of hypertension. 2) Volume expansion stimulates the secretion of DLS and ATPI. 3) Stimulatory effect of volume expansion and inhibitory effect of mineralocorticoid may be responsible for wide distribution of these factors in HA. 4) DLS and ATPI are not the same substances.
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PMID:[Endogenous digitalis-like substance and Na-K-ATPase inhibitor in cardiovascular and renal disease]. 283 14

The results of large epidemiological studies dealing with the prognosis and unfavourable outcome of essential hypertension, clearly show that the pharmacological reduction of the elevated blood pressure of hypertensive patients significantly reduces the risk of at least some major cardiovascular complications. Satisfactory antihypertensive efficacy reflects, nevertheless, merely a minimal requirement for a modern antihypertensive drug. Additional pharmacological properties, which counteract the typical concomitant diseases like CHD, heart failure and other cardiovascular complications would be desirable. In this respect, the oral CE-inhibitors captopril and enalapril offer an exciting new approach to the treatment of arterial hypertension. As the most predictive international studies on prevention of hypertension were conducted before CE-inhibitors were available, the present review evaluates the pharmacological profile of this new class of antihypertensive compounds in the light of previously available baseline drugs, including the calcium channel antagonists. Until now, captopril and enalapril have been the best investigated and documented representatives. Besides new experimental results concerning the molecular mechanism of these drugs, clinical and experimental approaches to verify protective effects on the cardiovascular and the renal system are addressed. These offer a rational basis for the preferential treatment of hypertensive patients with reduced renal function, diabetes and chronic heart failure. In addition, some distinct advantages of enalapril over captopril, resulting mainly from the long-term reduction of high blood pressure, are discussed.
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PMID:[Differential therapeutic topics in antihypertensive therapy. What can angiotensin-converting enzyme inhibitors accomplish?]. 285 Jun 83

During 10 years of clinical use involving almost 3 million patient-years, acebutolol has become established as a remarkably safe and well-tolerated beta-blocking agent, effective in treating essential hypertension and cardiac arrhythmias. The existence of a long-lived active metabolite (diacetolol) confers a 24-hour duration of action, which permits effective use of a once-daily regimen, particularly for hypertension. Acebutolol has low lipid solubility and low protein binding; the former property reduces the risk of central side effects, and the latter means that displacement interactions with other drugs are unlikely. Because acebutolol and its metabolite normally have both renal and hepatic excretion pathways, an alternative pathway is available should either be compromised through disease. Acebutolol is cardioselective, and clinical use has borne out the low incidence of bronchospasm in patients with impaired lung function. The possession of intrinsic sympathomimetic activity (ISA) leads to only modest reductions in cardiac output, which in turn reduces the chance of excessive bradycardia and the likelihood of precipitating heart failure. A combination of selectivity and ISA may be responsible for the low incidence of tiredness and cold extremities observed with acebutolol compared with other beta blockers. The unique pharmacologic and pharmacokinetic profile of acebutolol confers several therapeutic advantages and may be responsible for the generally low level of side effects experienced in clinical use.
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PMID:Acebutolol: ten years of experience. 285 85

The role of serotonin in the pathogenesis of hypertension is interesting, and its investigation is much in vogue at present. This study compared the hypotensive effect of ketanserin, a specific 5-hydroxytryptamine receptor antagonist, with metoprolol in essential hypertension. On a double-blind basis, one treatment group (19 patients on ketanserin) was compared with another (21 patients on metoprolol). There was a significant reduction in diastolic blood pressure with both ketanserin and metoprolol (P less than 0,001). Side-effects were insignificant. One patient on metoprolol and 2 on ketanserin complained of dizziness. The dose of ketanserin was 40 mg twice a day and that of metoprolol 100 mg twice a day. Ketanserin does not appear to cause abnormal haematological values or biochemical adverse effects. It can be given to hypertensive patients with cardiac failure or bronchial asthma without adverse effects and may improve the peripheral vascular status of a hypertensive patient.
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PMID:A comparative study of ketanserin and metoprolol in essential hypertension. 293 40


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