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)

Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adverse effects of alpha 1-adrenergic blocking drugs. 791 78

The purpose of this study was to evaluate the effects of the alpha 1-blocking agent terazosin on blood pressure (BP) and blood lipids in a large, variant population of patients with hypertension. A total of 16,917 patients with hypertension were evaluated at 2214 primary and community care facilities; 7808 of these patients had not been treated previously for hypertension; 3928 were switched to terazosin from another antihypertensive agent; and 5181 received terazosin in addition to an agent that had not controlled their hypertension. Terazosin produced highly significant reductions in systolic (-18.2 +/- 0.2 mm Hg) and diastolic (-13.2 +/- 0.1 mm Hg) BP when used as monotherapy (mean dose, 3.1 mg; range, 2 to 10 mg) without causing a significant increase in heart rate. Equal antihypertensive efficacy was demonstrated in men, women, blacks, and whites of all ages, with particular benefit to elderly patients (> or = 65 years of age) with systolic hypertension. Comparative studies indicated that terazosin had equal antihypertensive efficacy in combination with diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Patients who had not responded to monotherapy with one of these classes of antihypertensive drugs showed significant reductions of BP after terazosin, in the following average doses, was added to diuretics, 3.1 mg; beta-blockers, 3.4 mg; calcium channel blockers, 3.3 mg; and ACE inhibitors, 3.4 mg. Terazosin produced highly significant reductions in blood levels of total cholesterol (-5.0%), triglycerides (-6.1%), and low-density lipoprotein cholesterol (-7.6%) without change in high-density lipoprotein cholesterol when used as monotherapy. Similar favorable effects on blood lipid levels were demonstrated when terazosin was used in combination with all other classes of antihypertensive drugs. The greatest reductions in blood cholesterol (-9.2%) were observed among patients with hyperlipidemia (total cholesterol > or = 240 mg/dL). Terazosin maintained its antihypertensive efficacy and was well tolerated by patients with a variety of concomitant diseases, including congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, benign prostatic hyperplasia, diabetes, and obesity. Adverse effects occurred in 17.9% of patients and caused 2.2% to drop out of the study. The most frequent adverse effects were dizziness (4.8%), headache (2.5%), and asthenia (2.4%). Only 0.4% suffered syncope and 0.2% impotence. These data demonstrate the usefulness of terazosin as monotherapy or add-on therapy for treatment of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha 1-blockade for the treatment of hypertension: a megastudy of terazosin in 2214 clinical practice settings. 792 16

During normal pregnancy, serum transaminase levels remain within normal limits. An elevated level observed in a pregnant woman always signals a disease process, most often of hepatic origin, but in certain cases, of muscular origin. During the last three months of pregnancy and in the immediate post partum period a large number of liver diseases can cause elevated transaminase levels, depending upon the clinical presentation. In everyday practice, a complete liver battery together with specialized consultation is required for all pregnant women with raised transaminase levels. Toxaemia gravis may be evident in patients with severely raised blood pressure, especially if seizures occur. Epigastric or subcostal pain should suggest hepatic involvement. Hypertension may however be absent and epigastric or left shoulder pain may be the only clinical signs. Acute liver steatosis is 20 to 50 times more rare than toxaemia and may cause nausea and vomiting. Certain non-specific signs such as asthenia, anorexia, polyalgia, abdominal pain, diarrhoea and fever, together with pruritus should suggest acute hepatitis. A 25-fold increase in transaminase level is commonly encountered. The risk of fulminating hepatitis is less than 1/1000 but should always be entertained. All drugs should be stopped and careful research for recent xenobiotic contamination (drugs, infusions, alphamethyldopa, etc.) should be undertaken. Viral hepatitis requires serovaccination of the newborn at birth. Herpetic hepatitis is rare but requires rapid diagnosis (liver biopsy) and treatment with acyclovir in addition to cesarean section and treatment of the newborn at birth. Rare cases of hepatitis E may occur after a stay in North Africa, the Middle-East, Southeast Asia or Mexico. Chronic cases with or without temporary pruritus suggest infectious hepatitis B or C although, in chronic hepatitis C, serum transaminase levels often return to normal during pregnancy. Rare cases of asymptomatic elevations of serum transaminase levels can reveal subclinical chronic hepatitis.
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PMID:[Significance of elevated transaminase levels at the end of pregnancy]. 802 21

An open randomized study was conducted in mild to moderate hypertensive patients to evaluate, over a 3 months treatment period, the efficacy and tolerability of carvedilol 25 mg OD and to compare, in case of insufficient results with 25 mg, the efficacy and tolerance of carvedilol 50 mg and carvedilol 25 mg coadministered with diuretics. Mean office blood pressure (sitting) of the 91 patients who completed the study according to the protocol was reduced from 161/100 to 147/91 mm Hg after 4 weeks of treatment carvedilol 25 mg OD. Continuation of carvedilol 25 mg produced no further reduction in blood pressure. Increasing carvedilol to 50 mg OD or addition of diuretics further reduced blood pressure. Ambulatory blood pressure measurements showed a significant reduction in both SBP and DBP after 3 months treatment in the three groups, as well as with respect to the circadian profile of blood pressure and heart rate. Large differences between ambulatory and office blood pressure were observed: 37% of the patients diagnosed as mild to moderate hypertensives according to office blood pressure before treatment had mean daytime DBP < 90 mm Hg and 39% mean daytime SBP < 140 mm Hg. Twenty-eight percent of the patients experienced adverse events; they occurred mainly at the beginning of treatment; less than 5% of participants withdrew due to adverse events. The most frequent adverse events were fatigue, vertigo and asthenia. This study showed that carvedilol is safe and effective in the treatment of mild to moderate hypertension and that there is a high prevalence (nearly 40%) of low ambulatory blood pressure means in a population labelled as mild to moderate hypertensive.
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PMID:Carvedilol in the treatment of mild to moderate hypertension: experience with ambulatory blood pressure monitoring. 805 82

Nineteen patients treated by continuous ambulatory peritoneal dialysis (CAPD) were studied according to clinical outcome parameters: insomnia, asthenia, pruritus, arterial hypertension, anorexia, nausea and/or vomiting, anemia, and rate of hospitalization. Using clinical scores, three groups were defined: poor clinical outcome (P), intermediate (I), and good (G). The quantity of treatment by PD was evaluated monthly with urea kinetic tests (weekly Kt/V, weekly urea clearance/1.73 m2 of body surface area (BSA), index of dialysis by Teehan), and with the weekly creatinine clearance/1.73 m2 of BSA. The metabolic index was analyzed: normalized protein catabolic rate (NPCR), serum albumin (Alb) and prealbumin, and reabsorption of glucose. There was good correlation between clinical scores and quantity of dialysis. The Alb was lower in group P. Group G was differentiated from group I and from group P by quantification tests and NPCR, with lower levels as follows: weekly Kt/V = 2.06, urea clearance 70 L/week/1.73 m2, index of dialysis = 0.87, and creatinine clearance = 60 L/week/1.73 m2. We conclude that the qualitative clinical approach is not sufficient to predict deleterious signs, and the quantitative approach is predictive of the good clinical outcome and good nutritional status. We think that levels proposed to now are insufficient, and we suggest the following: weekly urea clearance > 70 L, weekly Kt/V > 2, weekly creatinine clearance > 60 L, and index of dialysis > 0.85.
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PMID:Quantification of adequacy of peritoneal dialysis. 839 69

Ninety-two patients with diagnosis of lone atrial fibrillation (AF) were retrospectively identified by our in-hospital records. Among the 92 patients, 62 were males and 30 females. Mean age was 50 +/- 15 years (range 13-81). In 30% of the patients mild to moderate systemic hypertension was present. None had thyroid dysfunction. At the time of our first clinical observation, AF showed the following characteristics: recurrent AF in 58% of the cases (53 patients), chronic AF in 16% of the cases (15 patients) and first episode of AF in 26% of the cases (24 patients). Patient's symptoms were: palpitation in 73% of the cases, dyspnea in 24%, asthenia in 22%, chest pain in 19%, dizziness in 19% and syncope in 9% of the cases. In 9% of the subjects AF was asymptomatic. Recurrent AF presented with more than one episode per day in 12% of the cases, one per week in 16% of the cases, one-two episodes in 1 month in 8% of the cases and between two and six episodes in 1 year in 33% of the cases. Cross-sectional echocardiography, evidenced a higher prevalence of left atrial enlargement in patients with chronic AF (7/15 cases = 47%) either compared to subjects with recurrent AF (5/53 cases = 9%, p < 0.005) or compared to subjects with a first episode of AF (3/24 cases = 11%, p < 0.05). Echocardiographic signs of left ventricular dysfunction (left ventricular enlargement or hypokinesia) were found in 27% of the patients with chronic AF and in 8% of the other two groups (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Idiopathic atrial fibrillation: clinical-instrumental characterization and thromboembolic risk]. 852 35

This study investigated the anti-hypertensive efficacy and tolerability of once-daily losartan potassium (50 mg titrated to 100 mg), an angiotensin II receptor antagonist, compared with once daily felodipine extended release (ER) (5 mg titrated to 10 mg), a calcium channel blocker, after 12 weeks of therapy in elderly hypertensive patients. Following a 4-week, single-blind, placebo baseline period, qualifying patients were randomly allocated to 12 weeks of double-blind treatment with losartan potassium or felodipine ER. After 6 weeks, patients with a 24 h post-dose sitting diastolic blood pressure > or = 90 mm Hg had their dose doubled for the remaining 6 weeks. At 6 weeks, there was a greater BP response for felodipine ER than losartan potassium in elderly patients with mild to moderate hypertension. However, after 12 weeks of therapy, losartan potassium reduced BP as effectively as felodipine ER with no differences in mean BP reduction or anti-hypertensive response category between treatment groups. In this study, both treatments were well tolerated; felodipine ER was associated with a numerically higher incidence of headache and oedema while the incidence of asthenia was numerically higher in losartan-treated patients.
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PMID:Randomised, double-blind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension. 855 92

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
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PMID:Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. 921 Oct 87

Losartan is a novel orally active nonpeptidal antihypertensive agent that specifically blocks the angiotensin II type 1 receptor. This paper compares the short- and long-term safety and tolerability of losartan with those of placebo. Approximately 3800 patients with mild-to-severe essential hypertension were enrolled in 16 double-masked and 4 open clinical trials worldwide. Of these, approximately 2900 were treated with losartan either alone or in combination with other antihypertensive drugs. These trials included patients with diabetes mellitus (n = 133). An additional 5 trials enrolled hypertensive patients with compromised renal function (n = 115) or heart failure (n = 220). Losartan dosages primarily ranged from 10 to 150 mg once daily, with most patients receiving 50 to 100 mg per day. Hypertension trials generally lasted 12 weeks. The most frequently reported adverse events were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups. Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo. The overall incidence of clinical and laboratory adverse events in the losartan- and placebo-treated groups was similar among patients with hypertension and either diabetes mellitus, renal impairment, or heart failure. The data suggest that losartan can be safely administered in hypertensive patients with concomitant illnesses. It can be considered for first-line therapy and is suitable as an alternative therapy in patients already experiencing side effects with other agents.
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PMID:Clinical safety and tolerability of losartan. 937 6

Zolmitriptan (Zomig, formerly 311C90) at doses of 0.5-50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses > or = 2.5 mg. In the clinical pharmacology studies, the overall incidence of subject exposures experiencing at least one adverse event was 52% with zolmitriptan 2.5 mg (28% with placebo). In placebo-controlled studies, the overall incidence of patients with at least one adverse event was dose-dependent for zolmitriptan over the 1-15 mg dose range, e.g. 42% and 46% with 1 and 2.5 mg, respectively and 58% with 5 mg (29% with placebo). Only four serious adverse events attributable to zolmitriptan were reported. In a long-term study, during which 2,058 outpatients treated a total of 31,579 migraine attacks with either one or two zolmitriptan 5 mg doses over a period of up to 1 year, the number of attacks associated with at least one adverse event was similar after one (26%) and two (24%) doses. The majority (59%) of the adverse events reported in this study (59%) occurred within 2 h of dosing, were predominantly mild (59%) or moderate (35%) in intensity, of < or = 4 h duration (58%), required no further action (94%). In placebo-controlled studies, the percentage of patients who reported severe adverse events was similar with zolmitriptan 2.5 mg (4%) and placebo (5%). The most frequently reported adverse events with zolmitriptan in the placebo-controlled clinical studies were asthenia, heaviness (other than chest or neck), dry mouth, nausea, dizziness, somnolence, paresthesia and warm sensations. The type and severity of the adverse events was not influenced by gender (although the frequency of reported adverse events was higher in females, as was the case in the placebo group), age, presence of aura prior to the attack, association of migraine with menstruation, concurrent medication, or by the addition of a second zolmitriptan dose. Zolmitriptan showed a similar tolerability profile in the long-term study, in which a low withdrawal rate due to adverse events of 8% was observed. Zolmitriptan was not associated with an increased frequency of central nervous system-related adverse events in a comparative study of sumatriptan, despite pre-clinical and neurophysiological evidence of a dual peripheral and central action of zolmitriptan. Moreover, zolmitriptan doses of 5-20 mg produced no statistically significant effects on objective assessments of psychometric function. Zolmitriptan had no clinically significant effects on blood pressure (even in patients with controlled mild to moderate hypertension or impaired renal function), ECGs (e.g. there was no evidence of ischemic events) or clinical chemistry, hematological or urinalysis measurements. In summary, zolmitriptan is well tolerated, particularly at the recommended dose of 2.5 mg. Zolmitriptan has a well-defined dose-response with 2.5 mg proving highly effective and optimizing the benefit/risk ratio of treatment. Thus, zolmitriptan is well suited as an acute oral treatment for migraine in the outpatient setting.
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PMID:Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on > 3000 subjects treated with zolmitriptan. 939 16


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