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)

To date, more than 5000 patients have had experience with enalapril. Over 1000 subjects have been exposed to the drug for more than one year and approximately 600 for over two years. In controlled trials, 2249 subjects, who included normal volunteers and patients with hypertension and congestive heart failure, have received enalapril alone or concomitantly with hydrochlorothiazide or other antihypertensive agents. There have been no deaths attributed to enalapril. The incidence of serious adverse experiences in controlled trials was similar to placebo, and was not higher in the elderly. The incidence of adverse experiences was not dose-related. Drug discontinuation due to adverse experiences was 3.5%, similar to placebo, and approximately half that of control drugs. Serious laboratory adverse experiences were rare. Enalapril attenuated the adverse metabolic effects of hydrochlorothiazide, particularly hypokalaemia. Skin rash occurred in approximately 1.0% of patients. One case of transient taste loss occurred on enalapril, and one on enalapril in combination with hydrochlorothiazide. Neutropenia and agranulocytosis were not encountered. Mean white blood cell counts did not change overall. Most patients (approximately equal to 80%) show no change or an improvement in renal function on enalapril. Discontinuation of concomitant hydrochlorothiazide usually normalized renal function. Enalapril is well tolerated in renal insufficiency. Azotaemia may occur in bilateral renovascular hypertension. Proteinuria was rarely seen and often improved on enalapril. Compassionate use protocols have been available to patients either resistant or intolerant to captopril. Of 68 patients admitted for captopril-related skin rashes, only five recurred on enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Overall tolerance and safety of enalapril. 610 Aug 72

Captopril (Capoten; Squibb) is a specific orally active antagonist of peptidyl-dipeptide carboxyhydrolase, the enzyme which converts angiotensin I to angiotensin II and which inactivates bradykinin. Captopril therefore reduces blood pressure in a variety of animal models of hypertension. In 96 studies on 1570 patients, captopril has been shown to be superior to placebo and equivalent to either propranolol or a diuretic in the treatment of essential hypertension. In the management of severe treatment-resistant hypertension, the response to captopril (alone or in combination with a diuretic and/or propranolol) was better than the response to standard triple therapy. Captopril, with digitalis and a diuretic, also improved the haemodynamic and clinical status of patients with refractory congestive heart failure. Side-effects include skin rashes (15%), proteinuria (1,1%, or 0,4% of patients with no prior renal disease) and the nephrotic syndrome (0,9%, or 0,3% of patients with no prior renal disease). Nearly all patients with the nephrotic syndrome in whom renal biopsies were performed were found to have membranous glomerulopathy. Neutropenia (total white cell count less than 1,000/microliter) was found in 33 of over 6,000 patients (0,4%), but in all cases there were other possible causes for this. Captopril is the first of an important group of antihypertensive and afterload-reducing drugs; its major indications are likely to be in the treatment of refractory severe hypertension or congestive heart failure.
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PMID:Captopril--an overview. 621 58

To study the value of low-dose captopril (6.25 and 12.5 mg) and a diuretic combination, the blood pressure and heart rate of 17 patients with moderate-to-severe hypertension were monitored for 6 hours (hospital) or 3 hours (office) after the single low-dose or larger (25, 50, 100 and 150 mg) captopril dosage. All patients had preserved renal function and were taking an oral diuretic (hydrochlorothiazide or furosemide) for at least 4 weeks. The supine and upright acute blood pressure lowering with 6.25 mg was not different from the larger captopril doses; none produced persistent or profound hypotension. There was no deterioration of renal function, new or persistent increase in proteinuria, neutropenia or agranulocytosis acutely or during 17 +/- 2 weeks of follow-up. Low-dose captopril (6.25 or 12.5 mg three times daily) normalized the supine blood pressure of 35% of these patients acutely. We suggest that in hypertensive patients already taking a diuretic, a lower starting dose of captopril than the recommended 25 mg three times daily may be desirable.
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PMID:Low-dose captopril titration in patients with moderate-to-severe hypertension treated with diuretics. 634 35

Short-term results of this double-blind control trial (previously reported) in patients with initial diastolic blood pressures (DBP) in the range of 92-109 mm Hg indicated that doses of 12.5 or 25 mg captopril (C) three times daily (t.i.d.) and 37.5 mg twice daily (b.i.d.) had similar antihypertensive effectiveness as 50 mg t.i.d. After 7 weeks of C, the addition of hydrochlorothiazide (H) to two-thirds of the patients enhanced the antihypertensive response. This report presents the results of unchanged and uninterrupted treatment for 9.5 months in 46 patients taking C alone, and for 7.8 months in 94 patients taking C plus H or H alone. With C alone, reductions in DBP averaged 8.3, 11.0, 15.1, and 17.5 mm Hg with the 12.5, 25, 37.5, and 50 mg doses respectively. The response to the 12.5 mg dose only was significantly less than the 50 mg dose. With H alone, the reduction in DBP averaged 10.6 mm Hg and with C plus H reductions averaged 15.6, 18.1, 16.8, and 18.7 mm Hg with the 12.5, 25, 37.5, and 50 mg doses of C, respectively. Reductions in DBP with C plus H regimens were significantly different from H alone. There was no waning of effectiveness from short to long term except for the 12.5 mg dose of C alone. During the long-term phase, two patients developed rash and one lost the sense of taste. Neutropenia in one patient probably was not drug-related. There were no terminations for elevated DBP greater than 104 mm Hg on two successive visits.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Low-dose captopril for the treatment of mild to moderate hypertension. 635 29

Most forms of hypertension require life-long treatment; thus, it is important to determine the continuing effectiveness and safety of any new therapeutic agent. While participating in various investigational studies, 7103 hypertensive patients received captopril, of whom 4397 were treated for 3 months to 4 years. The 4-year patients included 2498 with mild or moderate essential hypertension (diastolic pressure less than 120 mm Hg), 893 with severe essential hypertension, and 517 with renovascular hypertension. Repeated examinations of these long-term therapy patients, the majority of whom also were receiving a diuretic, indicated no drug tolerance to the combination, i.e., there was continuing control of the blood pressure without significant increases in dosage or addition of other drugs. Side-effects occurring during the first few months of captopril administration (rash, taste disturbances, and, rarely, neutropenia) were not a problem during prolonged therapy. A few patients (70/7,103, or 1.0%) developed proteinuria, usually reversible and seldom associated with any deterioration of renal function. The proteinuria occurred most often in patients who had preexisting renal disease and were receiving high doses of the drug. There were no significant changes in key biochemical parameters. A total of 230 patients discontinued treatment for failure to maintain adequate blood pressure reduction, and 397 for side-effects. The estimated 4-year cumulative frequency of drug discontinuance for side-effects was 11.6% (life table method), which compares favorably with other classes of antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Long-term antihypertensive therapy with captopril. 635 30

To determine the usefulness of neutrophil values in diagnosing neonatal sepsis among infants at risk of neutropenia, we evaluated the pattern of sequential absolute total and immature neutrophil counts and the immature to total neutrophil (I:T) proportion over the first 5 days of life in infants with sepsis (n = 13), asphyxia neonatorum (n = 12), or delivered of mothers with pregnancy-induced hypertension (PIH) (n = 20), comparing values to references ranges previously reported by us. Neutropenia was initially present in 67% and 50% of infants with asphyxia and those whose mothers had PIH, respectively, and persisted through the first 3 postnatal days. In contrast, infants with sepsis were less likely to be neutropenic initially (38%), and neutropenia did not persist after 36 hours of age. Elevated values for the total immature neutrophil count and I:T proportion were much more likely to occur in infants with sepsis (46% and 61%, respectively) than in infants of mothers with PIH (4% and 12%) or those with asphyxia (13% and 22%). The importance of considering the perinatal history as well as the differential neutrophil count in the evaluation of neonatal neutropenia is demonstrated.
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PMID:Neutropenia in high-risk neonates. 650 53

The effects on the neonate of severe maternal hypertension originating before the thirty-sixth week of gestation were determined by comparing data obtained on 28 preterm infants born of hypertensive mothers with data from 28 gestational age-matched controls. All hypertensive mothers had diastolic blood pressure greater than or equal to 110 mm Hg, proteinuria, and systemic symptoms of their disease; over half had thrombocytopenia and significant elevations of LDH and SGOT. All hypertensive mothers had been treated intravenously with magnesium sulfate, and 79% received other antihypertensive agents. When compared to control infants, the infants of hypertensive mothers had a significantly higher incidence of somatic growth retardation, microcephaly, thrombocytopenia, leukopenia, neutropenia, low Apgar scores, delayed adaptation, patent ductus arteriosus, hypotonia, and gastrointestinal hypomotility. Apgar scores, platelet count, WBC count, neutrophil count, and weight percentile correlated with the severity of maternal platelet and enzyme abnormalities. The occurrence of gastrointestinal hypomotility, hypotonia, and patent ductus arteriosus may be related to transplacental passage of maternally administered drugs.
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PMID:Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy. 705 37

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Absolute neutropenia lasting longer than 72 hours after birth occurred in four very low birth weight neonates with a maternal history of severe pregnancy-induced hypertension, and was treated with recombinant granulocyte colony-stimulating factor for 3 days. Absolute neutrophil counts increased nearly four-fold within 48 hours; maximal values were recorded on the ninth day after the infusion was started. Total leukocyte counts subsequently decreased but remained in the normal range. It appears that recombinant human granulocyte colony-stimulating factor promotes a rapid increase in circulating neutrophils in these patients despite the possible presence of a circulating preeclampsia-associated inhibitor of neutrophil production.
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PMID:Effect of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia. 753 9

The evaluation of a neutropenia first must document its etiology. Besides the particular etiological aspects in the newborn, neutropenia in a child may be 1) acquired, 2) constitutional, part of a complex genetic disease, 3) constitutional, isolated. Primary acquired neutropenia, also called benign chronic neutropenia, is the most frequent cause of chronic neutropenia in children; it is usually well tolerated and has a frequent favorable outcome in 12-14 months. Many complex genetic diseases include a neutropenia, among which several immunologic disorders that must be ruled out before considering the diagnosis of isolated constitutional neutropenia. Infantile agranulocytosis is the main primary constitutional neutropenia. It may be sporadic or hereditary (autosomal recessive or dominant inheritance) and is present at birth. It is profound, usually < 0.5 G/l (< 500/mm3) and exposes to severe pyogenic and fungal infections. In the neonatal period neutropenia must primarily suggest a bacterial infection, although other etiologies have to be known, particularly neonatal neutropenia caused by passive transfer of maternal antibodies and neutropenia related to gravidic maternal hypertension. The treatment of severe chronic neutropenia is directed towards the prevention of infections. It includes prophylactic antibiotherapy, the most commonly used one being the trimetroprim-sulfamethoxazole association, and granulocyte colony stimulating factor (G-CSF). G-CSF has considerably improved the condition of patients; it is usually well tolerated, but secondary effects have been reported (hypersplenism, glomerulonephritis, osteoporosis, vasculitis), and a potential leukemogenic risk has been evoked.
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PMID:[Acquired and constitutional neutropenia in children]. 784 76


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