Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.
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PMID:Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study. 135 85

Celiprolol is a third generation beta blocking drug with intrinsic vasodilator effect. We evaluated the effect of this drug at a fixed dose of 400 mg daily in 20 patients with coronary artery disease and stable angina having 2 to 40 episodes of pain a week. All patients had positive exercise stress test with greater than 1 mm ST depression. Compared to the 1 month baseline placebo phase, patients after 3 months of treatment with celiprolol had less episodes of angina (2.4 vs 7.2 a week, p less than 0.001), higher angina threshold (667 vs 337 sec, p less than 0.025), higher ischemia threshold (614 vs 401 sec, p less than 0.001) and were able to perform more work (3937 vs 2403 kgm/min. p less than 0.01). 9 patients had no pain during exercise. A decrease in blood pressure, heart rate and double product was evident in the stress tests of the active phase. Adverse effects included headache (4 patients), sweating (1) and fatigue (1) not requiring modification of drug dose. No adverse effects were seen in 13 patients. Thus, celiprolol is effective to decrease angina during daily life and increase exercise tolerance in patients with chronic stable angina pectoris.
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PMID:[Celiprolol in the treatment of chronic stable angina]. 168 95

Felodipine, a dihydropyridine calcium-channel antagonist, significantly reduces systolic and diastolic blood pressure (BP) in patients with hypertension and has been associated with beneficial hemodynamic effects in patients with chronic stable angina pectoris or congestive heart failure (CHF). In hypertensive patients, felodipine does not appear to significantly affect glomerular filtration rate, creatinine clearance, glucose tolerance, or plasma lipoprotein concentrations. Studies comparing felodipine with other agents as monotherapy in mild to moderate hypertension have demonstrated felodipine to be at least as efficacious as hydrochlorothiazide (HCTZ) and HCTZ plus amiloride hydrochloride in combination. Comparisons of felodipine with other agents as adjuncts to beta-blocker or diuretic therapy have shown felodipine to be at least as effective as HCTZ, propranolol hydrochloride, prazosin hydrochloride, and nifedipine. Evaluations of patients with chronic stable angina are limited, and additional studies are needed before felodipine can be recommended for the routine management of angina pectoris. Similarly, additional studies are essential to delineate the role of felodipine, if any, in the management of CHF. In the management of hypertension, felodipine 5-40 mg/d significantly reduces systolic and diastolic BP. Although some patients may be controlled throughout the entire dosing interval when felodipine is administered bid, many patients will require more frequent dosing to obtain adequate BP control. Adverse effects associated with felodipine are similar to those of other dihydropyridine calcium-channel antagonists and include peripheral edema, headache, dizziness, flushing, and fatigue. A potentially clinically important drug interaction was observed when felodipine was administered concomitantly with theophylline aminopropanol; significant decreases in theophylline concentrations were noted. In summary, felodipine appears to be safe and effective for the management of hypertension when used alone or in combination with other antihypertensive agents. The efficacy of felodipine in the management of chronic stable angina pectoris and CHF requires further investigation.
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PMID:Felodipine: a new dihydropyridine calcium-channel antagonist. 176 37

Amlodipine is a dihydropyridine calcium antagonist that has unique pharmacokinetic properties. The drug is absorbed gradually after oral administration and so produces a gradual vasodilatation, reducing the incidence of side effects such as reflex tachycardia and headache, which can be troublesome with other calcium antagonists. Amlodipine also has a long elimination half-life, which makes it suitable for use on a once-daily basis. Controlled clinical studies have confirmed that a suitable dose regimen of amlodipine for use in angina is to start with 5 mg daily and increase this to 10 mg daily if required to control symptoms. Exercise testing carried out 24 hours post dose has confirmed that once-daily doses of amlodipine provide good anti-anginal and anti-ischaemic efficacy for a full 24 hours, a vital aspect of any therapy for ischaemic heart disease. Amlodipine has been shown to have comparable anti-anginal efficacy to the beta-blocker nadolol taken once daily and the calcium antagonist diltiazem taken 3 times daily. When added to the treatment regimen of patients with uncontrolled chronic stable angina despite treatment with nitrates, beta-blockers or both, amlodipine produces improved anti-anginal efficacy. Amlodipine has also been shown to be consistently effective in patients with vasospastic angina. There has been no evidence of tolerance to the anti-anginal effects of amlodipine in formal clinical trials involving treatment for up to 26 weeks.
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PMID:The efficacy of amlodipine in the management of ischaemic heart disease. 183 71

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.
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PMID:Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. 185 72

The efficacy of nicorandil was compared with atenolol in 37 patients with chronic stable angina using a randomized, placebo-controlled, parallel study design. After a single-blind placebo phase, patients were randomized to receive nicorandil or atenolol using a double-dummy technique. Patients took nicorandil 10 mg twice daily or atenolol 50 mg once daily for the first 3 weeks, and if no adverse effects were encountered they took nicorandil 20 mg twice daily or atenolol 100 mg once daily, for the final 3-week phase. Treadmill exercise tests were performed at the end of each treatment phase immediately before and 2 hours after the morning dose of medication. Groups were demographically similar. Placebo exercise times were 7.06 (0.60) minutes (mean +/- standard error of the mean) in the nicorandil group and 6.81 (0.47) minutes in the atenolol group. After 6 weeks, improvements in exercise time were before dosing: +1.47 (0.40) minutes with nicorandil (p less than 0.005) and +1.33 (0.29) minutes with atenolol (p less than 0.001). Improvements after therapy was administered were +2.45 (0.41) minutes with nicorandil (p less than 0.001) and +2.37 (0.43) minutes with atenolol (p less than 0.0001). Whereas, the predose peak exercise double product (heart rate X systolic blood pressure mm Hg/100) was reduced with atenolol (-43.6 units; p less than 0.001), an increase (+7.56 units; difference not significant) was noted with nicorandil. One patient taking atenolol and 5 taking nicorandil developed persistent headaches. One subject with severe 3-vessel coronary artery disease had fatal myocardial infarction within 3 days of starting nicorandil, 10 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of nicorandil and atenolol in stable angina pectoris. 214 5

Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.
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PMID:Pharmacology and therapeutic effects of nicorandil. 215 May 92

The rationale for intermittent nitrate therapy is based on the pathophysiology of nitroglycerin tolerance and the diurnal pattern of symptoms encountered in patients with chronic stable angina. Nitrate tolerance was first observed as tolerance to headache in industrial toxicology. When long-acting nitrates for chronic stable angina became available, similar tolerance was observed but not thought to indicate tolerance to a haemodynamic or therapeutic effect. Subsequently, Needleman and coworkers (J Pharmacol Exp Ther 1973; 187: 324) defined in vitro the phenomenology of vascular smooth muscle tolerance to nitroglycerin-induced relaxation and reversibility was demonstrated. More recently, a potential molecular explanation for nitrate tolerance has been proposed: sulfhydryl group depletion in smooth muscle cells resulting in reduced formation of S-nitrosothiols on nitrate exposure with resultant reduced activation of cyclic GMP. In vivo, other mechanisms, including fluid retention and neurohumoral responses to vasodilation may also be important. The first demonstration that nitrate tolerance affected the therapeutic efficacy of long-acting nitrates was reported by Parker and coworkers in 1982 (Circulation 1987; 76: 572-6). This landmark study was not given much credence at the time because it appeared to be in conflict with earlier reports. However, in the past 6 years development of tolerance has been demonstrated with a variety of oral nitrates, transdermal nitroglycerin and intravenous nitroglycerin. When plasma concentrations are held constant, tolerance to antianginal effects is demonstrable within 24h, but varies markedly in severity from individual to individual.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intermittent nitrate therapy in angina pectoris. 250 Oct 96

The anti-anginal effect of sustained release diltiazem, isosorbide-5-mononitrate (IS-5-MN) and their combination has been evaluated in 25 patients in 4 blinded treatment periods of 2 weeks each. The number of anginal attacks during each treatment period was reduced from a mean of 23 during placebo to 15 during diltiazem and 15 during combination therapy, but it was not significantly changed after IS-5-MN-20. A similar pattern was seen for nitroglycerin consumption and number of angina-free days. Maximal exercise capacity was also significantly improved following diltiazem and the drug combination, and it was not changed after IS-5-MN. ST segment depression was less pronounced after diltiazem and the combination compared to IS-5-MN. There was no difference in exercise capacity or ST segment change between diltiazem and the combination. The PR interval was slightly prolonged after diltiazem, but this was of no clinical importance. Adverse effects of diltiazem treatment were rare. Headache was common following IS-5-MN (13 patients) and the combination (11 patients). Thus, sustained-release diltiazem was of value in the treatment of chronic stable angina pectoris, whereas IS-5-MN was not effective, either as a single therapy or in combination with diltiazem. The reason for the inefficacy of IS-5-MN is not known, but the development of tolerance and an inadequate dose are possible explanations.
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PMID:Effects of diltiazem and isosorbide-5-mononitrate, alone and in combination, on patients with stable angina pectoris. 250 59

The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time. 251 15


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