Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Calcium antagonists are potent vasodilators and are widely used in the treatment of hypertension and angina pectoris. The currently available compounds belong to three classes: (1) dihydropyridines (e.g. nifedipine, amlodipine and felodipine), (2) phenylalkylamines (e.g. verapamil) and (3) benzothiazepines (e.g. diltiazem). The three classes differ in their pharmacological profile and safety. For example, verapamil and diltiazem lower heart rate, while dihydropyridines increase it or leave it unchanged. With most of the latter compounds, a marked activation of the sympathetic nervous system has been noted. Most compounds exhibit negative inotropic effects, particularly the first-generation molecules, which is disadvantageous in patients with impaired left-ventricular function. The most common side effects of these drugs are flushing, headache and edema. With verapamil, constipation may represent a problem in certain patients. Hence, in spite of a large number of calcium antagonists available, there remains a need for new compounds with enhanced efficacy and improved tolerability. A new compound should lack any negative inotropism, avoid any increase in sympathetic outflow or heart rate and exhibit a high degree of vascular selectivity. Furthermore, a low incidence of side effects, particularly ankle edema and optimal pharmacokinetics allowing once-daily dosing would be desirable. Mibefradil is a new calcium antagonist with promising pharmacological and clinical properties. The compound has a high bioavailability, lacks negative inotropic effects at therapeutic concentrations, does not exhibit reflex tachycardia during vasodilation and actually slightly decreases heart rate. It is a potent direct vasodilator efficacious in hypertension and chronic angina pectoris, elicits endothelium-dependent relaxations and facilitates the effects of nitric oxide in vascular smooth muscle. The drug is a particularly efficacious vasodilator in intramyocardial coronary arteries which may be important for its anti-ischemic effects and the lack of steal in the coronary circulation. Furthermore, mibefradil has antiproliferative properties in human vascular smooth muscle cells in culture. As a unique property, mibefradil blocks T-type calcium channels and hence represents a new class of calcium channel blockers. In patients with hypertension, mibefradil has a high efficacy in controlling blood pressure. The drug does not cause constipation and has a low incidence of ankle edema. A large trial is under way to further delineate the properties of this new calcium antagonist in patients with heart failure.
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PMID:Comparative pharmacological properties among calcium channel blockers: T-channel versus L-channel blockade. 957 Apr 24

Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.
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PMID:Diversity and intensity of adverse events in the treatment of hypertension with barnidipine. 966 May 24

Optimal treatment of hypertension requires the use of effective antihypertensive drugs. Calcium channel blockers are widely used in the treatment of hypertension and appear to be particularly efficacious in ethnic Chinese patients. The aim of this open-label study was to prospectively investigate the efficacy and tolerability of three dihydropyridine calcium channel blockers in sequence, using the same protocol for each. After 2 weeks of placebo treatment, 73 males and 45 females (mean age, 45 +/- 10 years; mean weight, 67 +/- 10 kg) with essential hypertension (diastolic blood pressure, 95 to 115 mm Hg) were treated with amlodipine (n = 41), felodipine (n = 38), or isradipine (n = 39) for 8 weeks, with dose titration after 4 weeks. Mean seated systolic and diastolic blood pressure decreased by 23/17, 30/17, and 20/15 mm Hg after 8 weeks of treatment with amlodipine, felodipine, and isradipine, respectively. These reductions were all statistically significant. Blood pressure was controlled (defined as diastolic pressure < 90 mm Hg at the final visit or a decrease from baseline of > or = 10 mm Hg) in 85%, 74%, and 74% of patients receiving amlodipine, felodipine, and isradipine, respectively. There were no significant changes in heart rate, plasma lipid levels, or serum biochemistry markers with any of the three treatments. No serious adverse events occurred, but mild adverse effects, including headaches, flushing, tachycardia, dizziness, and edema, were reported; 1 (2%), 6 (16%), and 5 (13%) patients receiving amlodipine, felodipine, and isradipine, respectively, withdrew from the study (P < 0.05). The results of this study indicate that all three drugs are highly effective in lowering blood pressure and are well tolerated in Chinese patients with mild-to-moderate hypertension.
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PMID:Amlodipine, felodipine, and isradipine in the treatment of Chinese patients with mild-to-moderate hypertension. 991 9

Preclinical studies indicate that dihydropyridine-type calcium channel antagonists modulate dopamine neurotransmitter function and can reduce cocaine-reinforced behaviors. Amlodipine, a long-acting dihydropyridine-type calcium channel antagonist related to isradipine and nifedipine, was administered in open label fashion for 12 weeks to 26 cocaine-dependent patients. In subjects expressing cocaine craving, craving significantly declined during the course of the 12 weeks. Five individuals reported flushing, headache, fatigue, nocturia, nausea, and lightheadedness. No conclusions regarding efficacy can be made due to the small number of subjects and the open-label design.
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PMID:Amlodipine treatment of cocaine dependence. 1043 93

Hypertension developing after liver transplantation during immunosuppression with cyclosporine A reflects an unusual hemodynamic transition from peripheral vasodilation to systemic and renal vasoconstriction. Although dihydropyridine calcium channel blockers are often administered for their efficacy in promoting vasodilation, some liver transplant recipients report marked symptomatic intolerance to these agents. In the present study we examined systemic and renal responses to isradipine using systemic (thoracic bioimpedance) and renal hemodynamic measurements in 15 liver transplant recipients studied at the time of initial diagnosis of posttransplant hypertension and after 3 months of treatment. Circadian blood pressure patterns were examined by overnight ambulatory blood pressure monitoring before and during antihypertensive therapy. During isradipine administration, blood pressure decreased from 151 +/- 3/91 +/- 2 to 130 +/-3/81 +/- 2 mm Hg (P < .01) without change in renal blood flow (406 +/- 43 to 425 +/- 52 mL/min/1.73m2, P = NS) or renal vascular resistance index (25,674 +/-3312 to 20,520 +/- 2311 dynes x sec x cm(-5)/m2, P = NS). Pre-treatment differences in systemic vascular tone persisted during treatment and predicted the tendency for symptomatic tachycardia and flushing, predominantly in those with hyperdynamic circulations. Twice daily dosing of isradipine was associated with partial and significant restoration of the nocturnal decrease in blood pressure (systolic blood pressure decreased 5.5%, normal 13%), usually absent early after transplantation. Our results demonstrate the ability of hemodynamic measurements to predict the symptomatic response to antihypertensive therapy in the posttransplant setting.
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PMID:Hypertension after liver transplantation: a predictive role for pretreatment hemodynamics and effects of isradipine on the systemic and renal circulations. 1077 26

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.
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PMID:Treatment of hypertensive children with amlodipine. 1104 Nov 59

Calcium antagonists (calcium channel blockers) are widely used in the treatment of hypertension and other cardiovascular diseases. The results of a large number of clinical trials have demonstrated that calcium antagonists are as efficacious as other classes of antihypertensive agents in decreasing blood pressure in the elderly patients. Large clinical trials have shown the effectiveness of calcium antagonists (with long duration of action) in reducing cardiovascular and cerebrovascular morbidity and mortality in elderly hypertensive patients. The calcium antagonists are a chemically, pharmacologically and therapeutically heterogeneous group of agents. Among themselves, they differ in vasoselectivity, effect on cardiac conduction, sympathetic activation, adverse effect profile, ability to protect against target organ damage, suitability for patients with co-morbid conditions, and pharmacodynamic characteristics. The calcium antagonists can be used as single agents or in combination with other antihypertensive drugs. These drugs should not be used as first-line drugs in treating high blood pressure in patients with heart failure, since drugs in other classes provide more benefits. The dihydropyridine calcium antagonists should not be used in post-myocardial infarction patients or in patients with unstable angina; however, non-dihydropyridines may be used in such patients. The adverse effects of dihydropyridines include peripheral and ankle edema, flushing and headache. The short-acting preparations of the older calcium antagonists are no longer used, because of the potential for adverse cardiovascular outcome.
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PMID:The use of calcium antagonists in the therapy of hypertension in the elderly. 1462 75

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

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy. In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.
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PMID:Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension. 1513 92

As a drug class, calcium channel blockers encompass a heterogeneous group of compounds with distinctive structures and pharmacologic characteristics. These agents are widely used in the treatment of hypertension, chronic coronary ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding to increased cardiovascular risk associated with calcium channel blocker use has been silenced by an array of outcomes trials that show these drugs to be both safe and effective in reducing hard cardiovascular end points. The most common side effects associated with calcium channel blockers are vasodilatory in nature and include a non-volume-dependent form of peripheral edema, flushing, and headache. Despite the sometimes discomforting side effects seen with calcium channel blocker therapy, their robust blood pressure-lowering effect makes them an important component of most multidrug regimens used for blood pressure control.
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PMID:Pharmacotherapy review: calcium channel blockers. 1640 90


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