Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.
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PMID:Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 208 13

The long acting angiotensin-converting enzyme inhibitor enalapril was compared with the calcium channel blocker nifedipine as sustained-release formulation in 136 patients with mild to moderate hypertension. This multicentre study was carried out in a double-blind, double-dummy fashion by 28 cardiologists in private practice. After a 2-week placebo period, patients were randomly allocated to 2 treatment groups; the first group received enalapril 20 mg daily (n = 68), and the second group received sustained-release nifedipine 20 mg twice daily (n = 68). The duration of treatment was 12 weeks. In both groups, hydrochlorothiazide 25 mg was added at week 4 if diastolic blood pressure remained greater than 90 mm Hg. At week 8, if the target diastolic pressure of less than 90 mm Hg was not achieved, the dosage of hydrochlorothiazide was increased to 50mg. The clinical characteristics of the patients in each group were comparable. After 4 weeks of treatment, the reduction in supine diastolic blood pressure was similar in both groups (12.1 mm Hg in the enalapril group vs 10.3 mm Hg in the nifedipine group). Moreover, although the difference between the groups was more noticeable after 12 weeks of treatment (16.3 vs 13.9 mm Hg, respectively), it did not reach significance. The number of patients experiencing clinical adverse effects was significantly greater in the nifedipine group than in the enalapril group [33 (48.5%) vs 18 (26.5%), respectively]. The most common complaints of patients administered nifedipine included swollen ankles, flushing and headaches, whereas complaints in the enalapril group included cough, asthenia, and epigastralgia. Three patients were withdrawn from the study because of side effects in the enalapril group and 10 were withdrawn from the nifedipine group. These results indicate that enalapril and sustained-release nifedipine are equally effective in controlling mild to moderate hypertension. However, enalapril was much better tolerated in this study.
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PMID:Comparative efficacy and safety of enalapril and sustained-release nifedipine in patients with mild to moderate hypertension. The Enalapril vs Nifedipine French Study Group. 218 26

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension. 244 53

51 hypertensive outpatients, whose diastolic blood pressure exceeded 100 mmHg after a 2-week period on atenolol alone (100 mg once daily) participated in this long-term study. They received, in addition to atenolol, the vasodilator cadralazine (ISF 2469; 10 to 30 mg once daily) for a standard period of 24 weeks, according to an open design. Cadralazine caused a progressive and important decrease in both systolic and diastolic blood pressure, from 173/111 mmHg (end of atenolol alone) to 154/99 mmHg (12th week, p less than 0.01/p less than 0.01; mean dose, 24.5 mg/day). At this time a diuretic was added as a third-step drug in 15/51 initial patients (29%), and final blood pressure in all patients was 150/96 mmHg (p less than 0.01/p less than 0.01), with positive results in 88% of the cases. During cadralazine treatment, heart rate was always significantly lower than before atenolol alone; the most common side effects, many of which were already present during treatment with atenolol alone, included headache, asthenia, dizziness, palpitation and flushing, and tended to disappear spontaneously as therapy progressed. Routine laboratory tests did not show important changes; sodium excretion was not reduced. In conclusion, the therapeutic efficacy of cadralazine, its low or absent salt and water retention effects, its good tolerability, and the high compliance obtained with once daily administration allowed the use of this vasodilator as a second-step drug for long-term treatment of hypertension.
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PMID:Cadralazine, a new vasodilator, in addition to a beta-blocker for long-term treatment of hypertension. 285 65

Right-sided valvular heart disease is a common complication of metastatic carcinoid tumors. On the contrary, left valve involvement is a rare finding. In our report we describe a patient in whom the subsequent involvement of right and left heart valves was documented by 2D and Doppler echocardiography. The patient was a 46-year-old woman who, in the last three years, complained of face flushing, postprandial diarrhea and shooting epigastric pain lasting for hours. She came at our observation for increasing dyspnoea, peripheral edemas and asthenia. 2D-echocardiography and Color Doppler revealed a severe tricuspid regurgitation and a turbulent blood flow across the pulmonary valve. An Angiographic examination confirmed the severe tricuspidal regurgitation and disclosed a mild pulmonary stenosis. These findings were associated with high 5 hydroxyndole acetic acid (5-HIAA) urinary excretion and the presence of a liver metastasizing ileal carcinoid tumor. Some months later, a new 2D echo-Doppler examination showed thickening and reduced motion of the posterior mitral leaflet, associated with regurgitation and an aortic insufficiency without evident structural valvular abnormalities. Even if carefully investigated no right-to-left shunt was found.
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PMID:[Left valvular involvement in carcinoid: description of a case]. 805 18

Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in pemphigus in India because it is relatively free from the side effects seen with heavy doses of daily oral steroids. One hundred forty-six pemphigus patients treated with DCP were observed for side effects of this regimen. One hundred forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a period of 60-90 minutes on 3 consecutive days. Five hundred mg of cyclophosphamide was added on first day of the pulse and 50 mg given orally daily in the intervening period. DCP was repeated every 4 weeks and continued for 6 months after subsidence of the disease (no new lesions). Flushing over the face was the most common event recorded during the adiministration in 78 subjects followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along thighs, breathlessness, seizure and unilateral limb edema were observed in one patient each. Generalized weakness/malaise was the most troublesome delayed side effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty-six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%) complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%) had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%) had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1). Thirteen of eighteen diabetics had an increase in blood sugar requiring higher doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed hypertension. Pulse therapy is not absolutely free from side effects. Hypertension and diabetes occur less frequently as compared to conventional steroid therapy. Generalized weakness, flushing, headache and taste alteration occur exclusively with pulse therapy.
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PMID:Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy. 1468 52

Fixed combinations of calcium channel blockers and angiotensin converting enzyme inhibitors represent an alternative to diuretic-based combination therapy. The aim of the present study was to compare the antihypertensive efficacy of the combination enalapril 10 mg/nitrendipine 20 mg (E/N) vs losartan 50 mg/hydrochlorothiazide 12.5 mg (L/H), assessed by 24-h ambulatory blood pressure monitoring. This multicentre, double-blind, parallel study included 97 hypertensive patients (office diastolic blood pressure (DBP) 90-109 mmHg and daytime DBP > 85 mmHg). After a 2- to 3-week period of single-blind placebo, they were randomized to receive double-blind treatment with E/N (n = 48) or L/H (n = 49) for a 4-week period. The primary outcome measure was the difference in 24-h DBP reduction between treatments from randomization to the end of the double-blind period. Secondary efficacy variables included differences in 24-h systolic (S) BP reduction, daytime, night-time and office SBP and DBP reduction, proportion of responders and controlled patients, trough-to-peak ratio and smoothness indexes. Safety was assessed by the proportion of patients with adverse events and the detection of laboratory abnormalities. No significant differences were observed in the primary outcome measure. The group receiving E/N tended to show greater reductions in most measures (24 h, daytime and office SBP and DBP) and higher BP control rates, but only the difference in the rate of office SBP control (< 140 mmHg) reached statistical significance (42.2 vs 22.4%; P = 0.048). The trough-to-peak ratios and smoothness indexes were similar in both groups. The incidence of adverse events related to the treatment was 27.1% (95% CI 14.5-39.6%) in E/N-treated patients and 14.3% (95% CI 4.5-45.8%) in the L/H group, but differences were not significant. The kind of event more frequently observed were flushing and headache in E/N, and dizziness and asthenia in L/H; all observed adverse events were mild. We conclude that E/N and L/H have a similar antihypertensive efficacy, assessed by office or ambulatory blood pressure monitoring. E/N achieved a significantly higher office SBP control rate, but this was accompanied by an apparently higher proportion of mild adverse events.
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PMID:Comparison of the antihypertensive effects of the fixed dose combination enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg, assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive patients. 1497 17

Chronic heart failure (CHF) is an increasingly common cardiovascular disorder. Many patients who have CHF report moderate to marked decreases in the frequency of sexual activity, and up to 75% of patients report erectile dysfunction (ED). There are few controlled clinical data on the efficacy and safety of sildenafil citrate in men who have ED and CHF; thus, we evaluated these parameters in patients who had stable CHF. This was a double-blind, placebo-controlled, flexible-dose study. Men who had ED and stable CHF were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function. Secondary outcomes included the 5 functional domains of the International Index of Erectile Function, 2 global efficacy assessment questions, intercourse success rate, the Erectile Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction Checklist. By week 12, patients who received sildenafil (n = 60) showed significant improvements on questions 3 and 4 compared with patients who received placebo (n = 72; p <0.002). Larger percentages of patients who received sildenafil reported improved erections (74%) and improved intercourse (68%) compared with patients who received placebo (18% and 16%, respectively). Intercourse success rates were 53% among patients who received sildenafil and 20% among those who received placebo. Patients who received sildenafil were highly satisfied with treatment and their sexual life compared with patients who received placebo. Sixty percent of patients who received sildenafil and 48% of patients who received placebo developed adverse events, including transient headache, facial flushing, respiratory tract infection, and asthenia. The incidence of events related to cardiovascular effects was low. Sildenafil is an effective and well-tolerated management of ED in men who have mild to moderate CHF.
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PMID:Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure. 1561 91

Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, increases progression-free survival in patients with advanced neuroendocrine tumours. Patients with neuroendocrine tumours and symptomatic carcinoid have inferior health-related quality of life than those without symptoms. We aimed to evaluate the effect of everolimus on symptomatic control of neuroendocrine tumours. Fifteen patients with metastatic neuroendocrine disease pre-treated with depot octreotide received combination everolimus and octreotide (midgut = 8, pancreatic = 3, other = 4). Reasons for initiation of everolimus were progressive disease (PD) by response evaluation criteria in solid tumours (n = 5), worsening syndromic symptomology (n = 5), or both (n = 5). Symptomatic and objective response and toxicity were evaluated using standard criteria. 7/10 patients who were syndromic had improvements in symptomology, with a mean duration of symptom control 13.9 months (range 1-39). All 10 symptomatic patients had non pancreatic neuroendocrine (pNET) primaries, and with everolimus, 6/10 had reduced stool frequency, 3/7 had a reduction of asthenia, and 5/7 had reduced frequency and severity of flushing. Sixty percent of patients experienced any grade toxicities, including the following: 40% grade 1/2 stomatitis, 7% grade 3/4 stomatitis, 20% grade 1/2 rash, 13% diarrhoea, and one case of pneumonitis. In this cohort of 15 patients, we demonstrated that 70% of non pNET individuals with common carcinoid syndrome symptoms resistant to depot octreotide had improvement in these symptoms on institution of everolimus, with meaningful durations of symptom control. Although this data is observational, to our knowledge, this represents the largest analysis of carcinoid syndrome control with combined everolimus and octreotide.
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PMID:Symptomatic Control of Neuroendocrine Tumours with Everolimus. 2624 86