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)

Adverse effects of converting enzyme inhibitors are either substance-specific (neutropenia, proteinuria, skin rashes, taste disturbances) or due to the converting enzyme inhibition (hypotension, functional renal insufficiency, hyperkalemia, cough, angioedema). They are rare nowadays because of better knowledge of the pharmacokinetics and -dynamics of the converting enzyme inhibitors, resulting in lower dosage, and because of identifying patients at high risk. The dosage must be adjusted according to renal function, in order to prevent accumulation and toxicity. In addition to patients with renal insufficiency, patients at high risk are those with a stimulated renin-angiotensin-aldosterone system, i.e. patients with renovascular hypertension or heart failure. Patients with collagen vascular disease, for example, systemic lupus erythematosus or scleroderma, should not be considered for long-term therapy with converting enzyme inhibitors because of the increased risk of neutropenia. Life-threatening angioedema may develop, mainly during the first few hours after drug administration.
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PMID:[Angiotensin-converting enzyme inhibition: side effects and risks]. 285 Jun 87

Angiotensin-converting enzyme (ACE) inhibitors are a new class of drugs, whose main indications are the treatment of hypertension and of heart failure. Data obtained with captopril, the first orally active ACE inhibitor, affords an understanding of the rationale of their therapeutic use based on the knowledge of their mechanisms of action, efficacy, contraindications and precautions, dosage and frequency of administration, side-effects, interactions and advantages. ACE inhibitors appear to exert their haemodynamic effect mainly by inhibiting the renin-angiotensin-aldosterone system, but also by modulating sympathetic nervous system activity and by increasing prostaglandin synthesis. Therefore they act both on vasoconstrictor and volume factors, since they cause vasodilation (the main effect) and mild natriuresis without affecting the heart rate and contractility and, probably, favourably influencing renal, coronary and cerebral circulation. So far it appears that ACE inhibitors can be usefully employed in the treatment of heart failure, in which they reduce both pre- and after-load, and mainly of hypertension. In the past captopril has been used to treat only severe and or resistant hypertension and some secondary forms, like renal parenchymal and renovascular hypertension, but now it seems that captopril is useful also to treat mild to moderate essential hypertension. Their efficacy in reducing blood pressure is similar to that of thiazide diuretics and of beta-blockers, the two drugs now considered of first choice and they exert their hypotensive action without the development of pseudotolerance or tolerance. ACE inhibitors seem, at the moment, contraindicated in pregnancy and in hyperkalaemic syndromes and must be used with caution in patients with collagen disease (mainly associated with renal failure), with severe bilateral renal artery stenosis (and with severe artery stenosis of a solitary kidney) and with severe sodium depletion. It is now established that captopril has a flat dose response curve and that it must be given (twice daily) at a dose not exceeding 150 mg/day. The same pharmacological approach must be used with future ACE inhibitors in order to establish the right posology and the frequency of administration. In this respect enalapril seems to be a promising ACE inhibitor with a prolonged action (at least 24 hours). The exact posology of ACE inhibitors might be crucial, since it has been shown that the side-effects of captopril (skin rashes, fever, taste disturbances, proteinuria and neutropenia) are dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin-converting enzyme inhibitors in hypertension: a review. 300 82

Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE) and has been widely studied in the treatment of patients with mild to moderate essential hypertension, severe hypertension not responsive to conventional diuretic/beta-adrenoceptor blocker/vasodilator regimens, and patients with chronic congestive heart failure refractory to treatment with a diuretic and digitalis. In patients with mild or moderate essential hypertension, titrated low doses of captopril used alone or in conjunction with a diuretic are similar in efficacy to usual doses of hydrochlorothiazide, chlorthalidone, or beta-adrenoceptor blocking drugs, as well as to the other ACE inhibitors. In addition, captopril improved well-being to a greater extent than methyldopa or propranolol in a study designed specifically to determine the effect of treatment on the quality of life of patients with mild or moderate essential hypertension. The earlier demonstrated efficacy of captopril, used with a diuretic and often also with a beta-adrenoceptor blocking drug, in the treatment of severe hypertension refractory to conventional 'triple therapy' has been confirmed in more recent trials which illustrate the generally marked antihypertensive effect of captopril-containing regimens in such patients. Results of initial trials in patients with scleroderma are promising, with control of hypertension and stabilization of renal function in these patients when treated at an early stage of the disease. Several comparative and long term trials of captopril in patients with chronic congestive heart failure refractory to treatment with a diuretic/digitalis regimen clearly demonstrate that initial haemodynamic improvement is maintained and correlates with clinical benefit. A tendency for overall clinical response to captopril to be better than the response to prazosin, hydralazine, nisoldipine or enalapril has been reported. Results of a multicentre comparison with digoxin and placebo indicate that captopril is a suitable alternative to digoxin in patients with mild to moderate heart failure who are receiving maintenance diuretic therapy. The tolerability of captopril has now been studied in many thousands of patients involved in formalized trials and the early impression of poor tolerability can no longer be justified. The use of generally lower dosages of captopril in patients with normal or slightly impaired renal function has resulted in a generally low incidence of rash (0.5 to 4%), dysgeusia (0.1 to 3%), proteinuria (0.5%), neutropenia (0.3% during first 3 months) and symptomatic hypotension (0.1 to 3%). Cough is an infrequent but troublesome effect resulting from ACE inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Captopril. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. 306 99

Thirty-eight patients with advanced breast cancer were treated with oral 4-demethoxydaunorubicin in a continuous weekly schedule at a dose of 15 mg/m2/week. Subjective toxicity consisted of mild nausea (grade 1) in 52% with more severe GI side effects (grade 2) in 15%. Three patients developed grade 1 alopecia and there were no episodes of cardiac failure. Significant neutropenia (grade 2/3) only occurred in patients with marrow involvement or widespread bone disease. There was one CR and 5 PRs, an overall response rate of 15.7% (95% confidence limits 6-31%). In addition 6 patients had disease stabilization for at least 6 months. Fourteen patients progressing on 4-demethoxydaunorubicin have received adriamycin 60 mg/m2 21 days. There have been 5 PRs in this group indicating possible non-cross-resistance between these two agents.
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PMID:A phase II study of oral weekly 4-demethoxydaunorubicin in advanced breast cancer. 347 4

Captopril is the first angiotensin-converting enzyme inhibitor for oral administration. In combination with continued digitalis and diuretic therapy it has been demonstrated to be effective in the management of severe heart failure refractory to optimal digitalis, diuretic and, in many patients, vasodilator treatment. Most studies to date have been open trials of several weeks or months duration, but a number of patients have received continued treatment, with sustained benefit, for up to 1 year or more. A placebo-controlled trial in a limited number of patients with less severe heart failure has confirmed the results of open trials. Captopril administration improves cardiac performance as a result of a reduction in systemic vascular resistance (afterload) and the various determinants of left ventricular filling pressure (preload). Improvements in exercise tolerance and functional classification, with associated reduction of clinical symptomatology, occur with simultaneous decreases in myocardial oxygen consumption. At present, captopril is worthy of a trial in patients refractory to more traditional medical management. Whether it should be considered a 'first-line' agent after failure of optimal digitalis and diuretic therapy, and before instituting other vasodilator therapy, is less clear. In patients with severe or resistant heart failure, a response to captopril is usually accompanied by a general improvement in the quality of life. The effect of captopril treatment on 1- and 2-year survival rates in patients with severe heart failure appears similar to that reported for other vasodilators. Most patients tolerate captopril treatment well, but hypotension, reduced renal function, skin rash, dysgeusia, and neutropenia have been reported.
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PMID:Captopril: an update review of its pharmacological properties and therapeutic efficacy in congestive heart failure. 621 82

A total of 16 children with Shwachman's syndrome were studied over a period of 17 years. Eight cases were detected in autopsy at 6 to 15 months; all had died of cardiac failure due to myocardial lesions. The left ventricles showed necrosis of myofibres in large areas and the pancreas was atrophic and replaced by adipose tissue. The other eight patients included two siblings of deceased cases. Only one of these showed transient cardiac failure and no significant nutritional deficiencies were found. They had steatorrhoea due to failure of the exocrine pancreas and either constant (6 cases) or cyclic (2 cases) neutropenia. The steatorrhoea improved with age. Pyogenic infections, mainly otitis media were frequent during the first three years of life. Measurements of humoral and cell-mediated immunity were normal, but in addition to low numbers of neutrophils, the neutrophilic chemotaxis was depressed in all seven patients tested. Skin lesions, hepatic inflammation, and growth tended to improve with age. The family data of the patients is consistent with an autosomal recessive trait inheritance.
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PMID:Frequent myocardial lesions in Shwachman's syndrome. Eight fatal cases among 16 Finnish patients. 648 83

Nineteen out of 62 evaluable patients with advanced breast cancer achieved an objective tumour response to mitoxantrone (31%) given in a dose of 12-14 mg/m2 by i.v. infusion repeated at 3-weekly intervals. The response rate in patients who had received no prior chemotherapy for advanced disease was 35%, compared with 22% in previously treated patients. Median duration of response was 10 months. Responses were seen in three out of nine patients who failed to respond to adriamycin. Neutropenia was dose limiting and eight out of 65 patients evaluable for toxicity had a neutropenic infection. Two patients developed readily reversible cardiac failure and two more developed physiological features of cardiac impairment, all after prolonged treatment. Other toxicities were mild and the drug was well tolerated; severe alopecia occurred in only one patient. Nine patients treated with a combination of mitoxantrone, vincristine and methotrexate all developed leukopenia with a mean white blood count of 1400/mm2 (range 200-2400) although no episodes of neutropenic infection were seen and the combination was otherwise well tolerated. Mitoxantrone is an active, well tolerated drug in the treatment of advanced breast cancer and merits further evaluation.
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PMID:Mitoxantrone (Novantrone) as single agent and in combination chemotherapy in the treatment of advanced breast cancer. 666 33

Sixty-five patients with advanced breast carcinoma were treated with mitoxantrone, an anthracenedione with structural similarities to adriamycin. The series included 26 patients who had received no prior chemotherapy. Treatment was given in a dose of 12-14 mg/m2 by IV infusion, repeated every 3 weeks. Sixty-two patients were evaluable for response, but all were evaluable for toxicity. One (2%) achieved a complete response and 18 (29%) a partial response (overall response rate 31%). The response rate in patients who had received no prior chemotherapy was 35%, vs 22% in previously treated patients. The median duration of response was 10 months (range 3.5-18.5 months). Two responders had previously failed to respond to adriamycin, and a third responder subsequently failed to respond to adriamycin. Neutropenia was the most frequently seen toxicity, with a WBC of less than 2,000/mm3 seen in 26 patients (40%), eight of whom (12%) had a neutropenic infection. Thrombocytopenia (less than 100,000/mm3) occurred in 12 patients (18%), but in three of these only after at least 6 months of treatment. Two patients developed readily reversible cardiac failure after prolonged treatment (11-13 months). Other toxicities were in general mild, and the drug was well tolerated: severe alopecia occurred in only one patient. Mitoxantrone is an active well-tolerated agent in the treatment of advanced breast carcinoma, but the risk of neutropenia requires careful supervision. The long-term risk of cardiotoxicity cannot yet be fully assessed.
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PMID:Mitoxantrone: an active new agent in the treatment of advanced breast cancer. 669 66

Familial cases of childhood congestive cardiomyopathy with X linked recessive inheritance and abnormalities of heart muscle mitochondria have been previously reported. We report here three families with possible X linked congestive cardiomyopathy and specific mitochondrial abnormalities. The heart disorder presented as endocardial fibroelastosis with neonatal death in two brothers in one family, and as heart failure and death in infancy in two brothers in the other two families. In one family a maternal uncle may also have been affected. Pyodermia and neutropenia was reported in one of the boys. Electron microscopy of heart muscle after necropsy showed increased numbers of mitochondria and abnormal mitochondrial crystal condensations and paracrystalline inclusions in all sibships. Barth's syndrome has been mapped to Xq28 and includes cardiomyopathy, skeletal muscle myopathy, neutropenia, and mitochondrial abnormalities similar to those found in the three families reported here. Since the clinical picture differed in the three families, they may represent more than one entity.
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PMID:Possible X linked congenital mitochondrial cardiomyopathy in three families. 848 69

Attempting to develop a new active, convenient regimen, we initiated a phase I study of paclitaxel (Taxol; Bristol-Myers squibb Company, Princeton, NJ) combined with epirubicin (Farmitalia Carlo Erba, Milan, Italy) in patients with metastatic breast cancer. In addition to standard eligibility criteria, patients with chemotherapy-naive metastasis and at least one measurable lesion had to have left ventricular ejection fractions of at least 50%; the metastatic relapse had to have occurred more than 6 months after adjuvant treatment. Anthracycline-pretreated patients could not have received cumulative doses of more than 300 mg/m2 doxorubicin, 450 mg/m2 epirubicin, or 70 mg/m2 mitoxantrone. An intravenous bolus dose of epirubicin was followed by a 3-hour paclitaxel infusion, with courses repeated every 3 weeks. To date, seven dose levels have been investigated and 31 patients have been treated, 19 of whom had already received anthracyclines. Grades 3 and 4 neutropenia occurred in 37% and 19% of 123 courses, respectively, with five episodes of febrile neutropenia. Grade 2 or 3 neurotoxicity has been observed in 42% of patients and cardiac toxicity in four patients (13%), all of whom had already received anthracyclines. One patient experienced transient myocardial ischemia, one had an asymptomatic decrease in ejection fraction, and two patients had clinical heart failure that required treatment. Dose-limiting toxicity was reached at dose level 5 (paclitaxel 200 mg/m2 plus epirubicin 60 mg/m2), with two of three patients experiencing febrile neutropenia. Reducing the epirubicin dose to 50 mg/m2, however, allowed the paclitaxel dose to be escalated to 250 mg/m2. At this dose level, only one of six patients experienced febrile neutropenia. At a preliminary response evaluation (dose levels 1 to 6), 11 patients (44%) had partial responses, 12 patients (48%) had stable disease, and disease progressed in two patients. We conclude that the combination paclitaxel/epirubicin is safe for patients with metastatic breast cancer and, at this early evaluation, shows promising antitumor activity. Additional patients will be treated at dose level 5 to confirm whether dose-limiting toxicity occurs at this step. Indeed, we took into consideration that dose-limiting toxicity observed at this particular dose level in two of three patients might be due to hazard, since paclitaxel dose escalation up to 250 mg/m2 was further possible in association with 50 mg/m2 epirubicin.
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PMID:Phase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety. 862 32


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