Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) inhibitors are useful first-line drugs in the therapy of mild and moderate hypertension. Adverse reactions to this drug class are rarely serious. Hypotension, cough, rash, and taste disturbance are uncommon; reduced glomerular filtration and hyperkalemia occur infrequently; angioedema is rare and neutropenia is extremely rare. Quinapril is a new ACE inhibitor that is converted to biologically active quinaprilat in the liver. This ACE inhibitor has a rapid onset of action and inhibits local tissue converting enzyme systems in kidney, heart, and brain, as well as in the circulating renin-angiotensin system. Clinically significant adverse effects of quinapril occur at low rates. In 1,771 patients receiving quinapril, the reported incidence of the first occurrence of orthostatic hypotension was comparable to that seen in patients receiving placebo. In other studies, headache was reported by up to 4.7% of patients receiving quinapril, which is comparable to reported incidences of headache in patients receiving other ACE inhibitors. Other adverse events reported at rates greater than 1% include cough with associated rhinitis and bronchitis, dizziness, and somnolence. Such adverse events have only rarely led to the withdrawal of patients from clinical studies of quinapril.
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PMID:Adverse effects of angiotensin-converting enzyme inhibitors in antihypertensive therapy with focus on quinapril. 154 39

Angiotensin-converting enzyme (ACE) inhibitors have been available for about 10 years for the treatment of various forms of hypertension. Essential hypertension responds particularly well to the administration of this group of drugs, especially when combined with diuretics. A pronounced fall in blood pressure can be achieved in renovascular hypertension with high plasma renin levels; when ACE inhibitors were administered in diagnosed renal artery stenosis there was a significant rise in plasma renin activity on the affected side. Renoparenchymatous hypertension and hypertension in diabetes mellitus can also be improved by the long-term administration of ACE inhibitors, and the progression of renal failure in these disorders seems to be slowed down. Side effects such as neutropenia, exanthema, hearing disorders and pronounced hypotension with an acute deterioration in renal function are substance- and dose-dependent; regular monitoring of the patients greatly reduces their occurrence.
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PMID:Angiotensin-converting enzyme inhibition in renal and hypertensive disorders. 225 21

Angiotensin-converting enzyme (ACE) inhibitors are being increasingly prescribed for the treatment of hypertension and heart failure. Not only are they efficacious but the incidence of serious adverse events with ACE inhibitors is similar to that with placebo. 'First-dose hypotension' mainly affects the renin-dependent patient. Neutropenia and agranulocytosis have been reported rarely for the nonsulfhydryl compounds. Comparative safety data are provided for captopril, enalapril, and quinapril, a new nonsulfhydryl ACE inhibitor that has been investigated extensively in over 2,000 patients. Results show that the proportion of patients reporting associated adverse events was lower with quinapril (11%) than with captopril (17%) or enalapril (15%). Similarly, there was a lower proportion of patients withdrawn due to adverse events with quinapril.
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PMID:The safety of ACE inhibitors for the treatment of hypertension and congestive heart failure. 267 Feb 22

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

This investigation was performed in two groups of adult patients, 10 with type I and 10 with type II diabetes mellitus, all with arterial hypertension (160 to 200 mm Hg systolic and 95 to 120 mm Hg diastolic). Captopril, 50 mg twice a day, was administered for 12 weeks and was effective as monotherapy in 16 patients. Mean arterial pressure (+/- s.d.) in type I patients changed from 121.4 +/- 9.6 to 100.2 +/- 10.1 after 4 weeks and to 102.0 +/- 3.8 mm Hg after 12 weeks; in type II patients it changed from 132.8 +/- 5.7 to 123.9 +/- 13.5 after 4 weeks and to 109.1 +/- 11.1 mm Hg after 12 weeks. The differences were statistically significant. In only 4 patients was it necessary to add a thiazide after the first month of therapy. No significant change was induced by captopril in urine output, osmolar clearance, free water clearance inulin, and PAH clearances. No significant change was observed in serum and urine Na+, Cl-, Ca++ and Mg++, whereas a statistically significant reduction was found in the renal clearances of K+ and PO4-. No important change in serum aldosterone was found, while plasma renin activity was increased, as expected. No alterations in urine protein, glucosaminoglycans, gamma GT, and N-acetyl-beta-glucosaminidase were observed during follow-up. All patients maintained good metabolic control of their disease. No neutropenia and orthostatic hypotension were seen. Captopril appears to be an effective and safe drug for lowering blood pressure in diabetic patients, without affecting renal function, electrolyte balance and the metabolic control of diabetes.
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PMID:Captopril in the treatment of hypertension in type I and type II diabetic patients. 353 66

Our retrospective study showed inhibition of the renin-angiotensin system was associated with better outcomes in patients with advanced pancreatic cancer receiving gemcitabine. The primary objective of this phase I study was to determine the recommended dose of candesartan in combination with gemcitabine in normotensive patients with advanced pancreatic cancer. Candesartan was given orally at an escalating dose (4, 8, 16, and 32 mg) q.d. daily, and gemcitabine was given 1000 mg/m(2) 30 min i.v. on days 1, 8, and 15, repeated every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicities, grade 2 hypotension, abnormal creatinine or potassium, and grade 3 or 4 other non-hematological toxicities. A standard "3+3" phase I dose-escalation design was used. A total of 14 patients (candesartan 4 mg, three patients; 8 mg, three patients; 16 mg, six patients; 32 mg, two patients) were enrolled. One of six patients at 16 mg showed DLT of grade 4 neutropenia and two of two patients at 32 mg showed DLT of grade 2 hypotension. Response rate and disease control rate were 0% and 79%, respectively. Progression-free survival and overall survival were 7.6 and 22.9 months, respectively. Candesartan 16 mg is the recommended dose in combination with gemcitabine in the treatment of advanced pancreatic cancer. (UMIN CTR: UMIN000002152).
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PMID:Phase I trial of gemcitabine and candesartan combination therapy in normotensive patients with advanced pancreatic cancer: GECA1. 2251 32

Hypertension (HT) is considered to be a potential risk factor for cardiovascular diseases and has been directly related to pathologies such as obesity and dyslipidemias. Angiotensin-converting enzyme inhibitors (ACEIs) blocked the renin-angiotensin-aldosterone cascade diminishing the production of angiotensin II and the level of bradykinin, produced by the kallikrein-kinin system. Although ACEIs are effective therapeutics in regulating HT, they present several side-effects that can be due to their mechanism of action (as hypotension, cough, dizziness, light-headedness or hyperkalemia) to specific drug molecular structure (skin rash, neutropenia and tasting disorders) or due to associated pathologies in the patients (it has been considered a possible nephrotoxic effect when ACEIs are administered in combination with angiotensin receptor blockers, in patients that present comorbidities as diabetes, acute kidney injury or chronic kidney disease). Therefore, it is necessary the searching for new products with ACEI activity that do not produce side effects. Interestingly, species of the plant genus Salvia have been found to possess hypotensive effects. In the present study, we analyzed the effects of the ethanolic extract of Salvia hispanica L. seeds (EESH) on the expression of genes involved in pathways regulating HT. Administration of EESH to hypertensive rats inhibited the angiotensin-converting enzyme (ACE) activity along with a decrease in Ace and elevation of Agtr1a and Nos3 gene expression, as compared to that in healthy rats. Moreover, these results were similar to those observed with captopril, an antihypertensive drug used as a control. No significant change in the expression of Bdkrb2 gene was observed in the different groups of rats. To conclude, our results demonstrate that EESH regulates blood pressure (BP) in hypertensive rats through transcriptionally regulating the expression of genes that participate in different pathways involving ACE.
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PMID:Ethanolic Extract of Salvia hispanica L. Regulates Blood Pressure by Modulating the Expression of Genes Involved in BP-Regulatory Pathways. 3285 88