UMLS:C0016382 - FACTA Search

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)

The antihypertensive effects of the regular immediate release formulation of verapamil (verapamil IR) and the newer sustained release formulation of verapamil (verapamil SR) were compared in Hispanic patients with untreated essential hypertension. Verapamil IR was given in 3 divided doses (80 or 160mg 3 times daily) and verapamil SR was given either as a single daily dose of 240mg or as 240mg every 12 hours. With both formulations there was a significant reduction in systolic (SBP) and diastolic blood pressure (DBP); a greater lowering of BP was observed with verapamil 480 mg/day than with 240 mg/day. With verapamil SR 480 mg/day, 91% of patients had reductions in SBP and DBP greater than 20 and 15mm Hg, respectively. In addition, 83% of patients reached normotension. With the lower dose (240mg once daily), 83% of patients had decreases in DBP greater than 10mm Hg and 73% of patients achieved normotension. Comparable effects were achieved with verapamil IR. With verapamil IR there was a more rapid fall in BP which peaked 3 to 4 hours postdose, whereas with verapamil SR a more gradual and sustained BP reduction was observed. Only small changes in heart rate (HR) were observed with verapamil IR and verapamil SR. For verapamil SR, the mean increase in HR was 5 beats/min (to 80 beats/min) and the mean decrease in HR was 13 beats/min (to 62 beats/min). Both verapamil SR and verapamil IR prolonged the PR interval of the ECG. An equal degree of PR prolongation was observed with 240 and 480 mg/day. The incidence of side effects (headache, palpitations, dizziness and flushing) was dose dependent, decreased with continuous treatment and was much higher with verapamil IR than with verapamil SR. Steady-state plasma verapamil concentrations were monitored. Compared with verapamil IR, verapamil SR produced a more gradual rise and a more sustained elevation of plasma verapamil and norverapamil concentrations. Comparable trough verapamil concentrations (Cmin) were observed with verapamil IR (98 micrograms/L) and SR (81 micrograms/L); morning Cmin verapamil concentrations were higher than daytime Cmin values. The normalised area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) were 10 to 20% greater for verapamil IR than SR. The 2-fold increase in oral dose produced a 2.2- and 2.4-fold increase in AUC for verapamil IR and SR, respectively, associated with a 20% reduction in metabolism to norverapamil. Fasting increased the rate and extent of absorption of verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative efficacy, safety and pharmacokinetics of verapamil SR vs verapamil IR in hypertensive patients. 128 70

The effects of calcium antagonists on psychological well-being, cognitive function, activity and physical symptoms in hypertensive patients are reviewed. Effects on these aspects of quality of life appear to differ according to whether a dihydropyridine calcium antagonist such as nifedipine is employed or verapamil, which is a phenylalkylamine derivative. Nifedipine has been associated with a self-assessment of impaired cognitive function in 2 clinical trials. Nifedipine was also associated with more symptomatic complaints than both atenolol and verapamil in different studies. The problems with nifedipine centred on oedema, flushing and palpitations. Verapamil was associated with constipation. Compared with other classes of antihypertensive drugs, the position of calcium antagonists with respect to the maintenance of patients' quality of life is presently unclear. Verapamil has been associated with improved quality of life compared with propranolol (a beta-blocker) and nifedipine. Verapamil appears to have similar effects on quality of life as atenolol and the angiotensin converting enzyme (ACE) inhibitor, captopril. The position of nifedipine remains unclear.
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PMID:Quality of life in the treatment of hypertension. The effect of calcium antagonists. 128 77

The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37 degrees C and 6 days at 4 degrees C were 80.3 +/- 5.2 and 31.6 +/- 2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0 +/- 3.9% (P less than 0.001) after 6 h of warm ischemia, while this inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 microM of verapamil, 21.2 +/- 5.8% (P less than 0.001) after 6 h of warm ischemia and 25.2 +/- 3.3% (P less than 0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 mM of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 microM of verapamil followed by incubation for 6 h at 37 degrees C. In the livers that were flushed and stored at a warm temperature for 6 h, verapamil reduced the increase of tissue lipid peroxidation product (P less than 0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is thought that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.
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PMID:Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver. 208 35

The complementary antihypertensive effects of the beta-blocker/calcium antagonist combination has to be weighed against their additive and potentially detrimental negative inotropic, chronotropic, and dromotropic effects inherent in both classes of drugs. We reviewed the main adversity, particularly electrophysiological and hemodynamic effects, of combined treatments with beta-blockers and the calcium antagonists verapamil, diltiazem, and nifedipine. In patients with coronary artery disease, a different picture emerged between the verapamil and nifedipine combination with a beta-blocker. Verapamil was more often associated with conduction problems (up to 9%) and dyspnea or heart failure (up to 8%). These problems had rarely been reported with nifedipine but ankle edema (up to 11%), flushing (up to 11%), and headaches (up to 7%) predominated. The cardiovascular unwanted effects led to withdrawal in 5-8% for the verapamil/beta-blocker or nifedipine/beta-blocker combination. Although there was little cardiac adversity with the nifedipine/beta-blocker combination, the intravenous administration of verapamil in patients on beta-blockers is contraindicated and the oral verapamil/beta-blocker combination should not be sought in patients with impaired left ventricular function and when conduction disturbances are likely to occur. In treating hypertensive patients without overt coronary artery disease, there is no argument against the use of the nifedipine/beta-blocker combination but there is a need for definitive studies of the verapamil/beta-blocker combination.
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PMID:Review of the cardiovascular adversity of the calcium antagonist beta-blocker combination: implications for antihypertensive therapy. 241 10

From a hemodynamic point of view, the calcium antagonists represent an interesting way of treating hypertension, because they reduce total peripheral resistance without compromising cardiac output. Blood flow is also maintained during muscular exercise. Verapamil and diltiazem induce slight reduction in heart rate, but this is compensated by increase in stroke volume. Verapamil and diltiazem also prolong atrioventricular conduction time, in contrast to the dihydropyridines. Most clinical data are available for verapamil, diltiazem, and nifedipine. In patients with mild-to-moderate hypertension, these compounds seem as effective as diuretics and beta-blockers. They do not induce disturbances in glucose metabolism, serum uric acid, or serum potassium, and unwanted disturbances in blood lipids have not been described. The dihydropyridines may safely be combined with beta-blockers, but the combination of either verapamil or diltiazem with a beta-blocker should be avoided (because of the high risk of bradycardia). The calcium antagonists seem particularly useful in patients with the combination of hypertension and angina pectoris or peripheral vascular diseases or chronic obstructive lung diseases or diabetes. They are also effective in hypertensive crises. They may also be tried as a first line drug in patients with mild and moderate essential hypertension, particularly when diuretics or beta-blockers are contraindicated. Temporary side effects due to vasodilatation (headache, flushing, and palpitations) are seen frequently, particularly on the dihydropyridines. Edema is the most frequent serious side effect of the dihydropyridines, and constipation is most common with verapamil. At this point, few long-term data are available and it is not known whether the calcium antagonists will give better or worse results, with respect to morbidity and mortality, than the beta-blockers, diuretics, or other more recent antihypertensive agents.
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PMID:Clinical use of calcium antagonists in hypertension: update 1986. 245 35

In coronary heart disease, beta-blockers are beneficial because they limit the increase in heart rate and blood pressure during exercise, and calcium antagonists are useful because they reduce myocardial oxygen demand. Many different pharmacological combinations of a beta-blocker and a calcium antagonist are possible, and beta-blockade may ameliorate reflex tachycardia induced by peripheral vasodilatation due to calcium antagonists, therefore enhancing the benefit. Studies have shown that combination therapy with propranolol and nifedipine, verapamil or diltiazem has greater antianginal efficacy based on symptomatic and objective assessment than either agent alone. A similar result has been reported for nifedipine or verapamil combined with atenolol. In combination, atenolol and nifedipine did not depress cardiac output or change the left ventricular ejection fraction (LVEF) at rest. During exercise atenolol alone resulted in a reduced LVEF response in most patients but the combination did not adversely affect left ventricular function. Nifedipine alone did not significantly change LVEF. When verapamil was combined with atenolol, resting ejection fraction fell, indicating a deterioration in cardiac function. Nifedipine and propranolol combined do not change heart rate significantly. Verapamil and atenolol both reduce resting heart rate and their combination has a greater effect; a combination of propranolol and diltiazem also reduces heart rate to a similar extent. Caution is therefore warranted when prescribing the latter 2 combinations. An increase in side effects can be expected with combination regimens compared with monotherapy; but with the nifedipine-atenolol combination the calcium antagonist can alleviate beta-blocker-induced effects by its vasodilator effect, and beta-blockers may ameliorate nifedipine-induced palpitations and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-blockers and calcium antagonists in angina pectoris. The potential role of combination therapy. 289 3

The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

Calcium channel blocking drugs are a chemically heterogenous group, so it might be expected that their effects on vascular smooth muscle, cardiac contractility, and conduction tissue may differ. However, the majority of adverse reactions are predictable from their pharmacological actions and may be conveniently grouped in the following categories: 1) vasodilatation, 2) negative inotropic effects, 3) conduction disturbances, 4) gastrointestinal effects, 5) metabolic effects, and 6) drug interactions. Vasodilatory symptoms, namely, dizziness, headaches, flushing sensation, and palpitation, are more likely with nifedipine. Peripheral edema is also common with nifedipine, but the mechanism is uncertain. For a given degree of vasodilation, the greatest negative inotropic effect is seen with verapamil first, diltiazem second, and nifedipine last. Calcium channel blocking drugs are contraindicated in hypertensive patients with second and third degree heart block, sick sinus syndrome, and severe heart failure. Verapamil and diltiazem have a significant effect on cardiac conduction, whereas nifedipine, in therapeutic doses, does not. Local gastrointestinal symptoms, such as nausea and constipation, are common with verapamil. None of the calcium channel blocking drugs have been reported to adversely affect lipid or protein metabolism. However, nifedipine, verapamil, and diltiazem in high doses may inhibit liberation of insulin. The significance of this finding needs to be explored further in hypertensive diabetics. Serum digoxin levels have been shown to increase after administration of verapamil and nifedipine, but there is no evidence that this change has any clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Side effects of calcium channel blockers. 328 Apr 92

The efficacy and electrophysiologic effects of adenosine and verapamil in termination of paroxysmal supraventricular tachycardia (SVT) were compared in 18 patients (age 18-48 years, mean 33 +/- 9 years) with recurrent sustained and inducible SVT. Ten patients had atrioventricular nodal reentrant tachycardia (AVNRT) and 8 had atrioventricular reentrant tachycardia involving a retrograde accessory pathway (cycle length of SVT 280-360 msec; mean 315 +/- 20 msec). Each patient served as his own control. After induction of SVT, adenosine was administered first (6 mg i.v. bolus). If the tachycardia was not terminated, a bolus of 12 mg was given. Ten minutes later, verapamil (5 mg i.v. over 30 sec) was administered after reinduction of SVT. If the tachycardia was not terminated, a 5 mg dose was repeated every 5 minutes upto 20 mg. Adenosine terminated the SVT in 16 cases (6 mg - 7 patients, 12 mg - 9 patients). Verapamil was effective in 11 patients (5 mg - 6 patients, 10 mg - 4 patients, 15 mg - 1 patient, 20 mg - nil). The overall efficacy of adenosine (89%) was significantly greater than that of verapamil (61%; p < 0.05). Adenosine terminated the tachycardia more quickly than verapamil (mean 24 +/- 11 sec versus 142 +/- 40 sec; p < 0.01). Termination of tachycardia by both drugs was related to antegrade block of the atrioventricular node in all patients except one with AVNRT in whom adenosine blocked the retrograde fast pathway. Ventricular premature beats were seen transiently in 5 patients following adenosine. Transient side effects such as flushing, burning and chest pain were frequently observed with adenosine and correlated with the termination of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative clinical and electrophysiologic effects of adenosine and verapamil on termination of paroxysmal supraventricular tachycardia. 782 34

Ninety patients, 50 males and 40 females, and their ages ranged between 42 and 70 years, with severe hypertension were treated by either sublingual verapamil tablets 40 mg (30 patients) or 80 mg (30 patients) or sublingual nifedipine capsules 10 mg (30 patients). Blood pressure and heart rate were measured before and 15, 30, 60, 90 and 120 mins after administration of the drugs. - Results showed that sublingual verapamil 40 mg caused significant drop of blood pressure after 60 min (200 +/- 11.6 / 127 +/- 8.7 to 177 +/- 13.8 / 95.4 +/- 11.8, P <0.05) and in 10/30 patients blood pressure was less than 150/90 mmHg. Verapamil 40 mg decreased heart rate in 16 patients, elevated in 5 patients and unchanged heart rate in 9 patients. Verapamil 80 mg caused significant reduction of blood pressure after 30 min (201 +/- 16 / 129 +/- 7.5 to 182 +/- 13 / 105 +/- 10.7, P <0.05) and the blood pressure was dropped to less than 150/90 mmHg in 18/30 patients. Sublingual verapamil 80 mg caused significant decrease in heart rate in 21/30 patients and peak decrease was recorded at 90 min (92.6 +/- 7.2 beats/min to 82 +/- 9, P <0.05). It alleviated headache in 8 patients including 2 patients with migraine. Sublingual nifedipine caused significant drop of elevated blood pressure at each time intervals and the peak drop was at 60 min (from 199 +/- 13.8 / 126 +/- 13.2 to 142.8 +/- 15 / 80. 9 +/- 9, P <0.05). In 22/30 patients blood pressure dropped to less than 150/90 mmHg after 60 min. Nifedipine elevated heart rate in 22/30 patients and peak elevation was at 30 min (from 91.6 +/- 7.8 to 105.6 +/- 6.1 beats/min, P <0.05). It caused headache in 8 patients and flushing in other 2 patients. Therefore, as compared to sublingual verapamil, sublingual nifedipine caused rapid lowering of elevated blood pressure and elevation of heart rate in most of the patients treated. The differences in proportions of patients whom blood pressure was dropped to less than 150/90 mmHg between nifedipine group and verapamil 40 mg group and between verapamil 80 mg and verapamil 40 mg groups were significant (P <0.05). - It might be concluded that sublingual verapamil caused significant lowering of blood pressure in hypertensive patients, decreased heart rate in most of the treated patients and alleviated headache in symptomatic hypertensive patients.
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PMID:Efficacy of sublingual verapamil in patients with severe essential hypertension: comparison with sublingual nifedipine. 1033 9

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