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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical response to felodipine, in addition to a beta-blocker, was evaluated and compared with placebo in this double-blind cross-over study. Twenty patients with exertional angina pectoris completed the study. Felodipine reduced the number of angina attacks and the Glyceryl Trinitrate (GTN) consumption. The median exercise capacity was increased 33% after 4 weeks' felodipine treatment compared with placebo. At maximal exercise, systolic blood pressure and rate pressure product were reduced by felodipine while no change was seen in heart rate or ST-depression. Felodipine reduced both supine and erect blood pressure. The mean supine blood pressure at rest was 138/82 mm Hg after four weeks' placebo treatment compared with 114/71 mmHg after felodipine 5-10 mg b.i.d. Felodipine has overall a modest but significant anti-anginal benefit when combined with a beta-blocker.
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PMID:The effects of felodipine in angina pectoris. 211 11

To investigate the antianginal efficacy and tolerability of felodipine, a new dihydropyridine calcium antagonist, 20 patients with stable exertional angina, not completely controlled by beta-blocker monotherapy, entered a randomized, double-blind, placebo-controlled, crossover study. Patients on standard beta-blocker therapy, who had at least 3 weekly anginal episodes and a reproducible exercise test (stopped for angina and ECG signs of ischaemia) at the end of 2 weeks placebo treatment, were eligible for the study. They were randomized to one sequence of treatment: felodipine 5 mg twice daily for 2 weeks followed by placebo for a further 2 weeks, or vice versa. Beta-blocker treatment was unchanged throughout the study. A treadmill test was carried out at the end of each crossover period, 2-4 h after drug administration. The number of anginal attacks and nitroglycerin consumption was recorded on a diary card. At rest, felodipine significantly (P less than 0.05) reduced standing systolic but not diastolic blood pressure. Heart rate was not modified by the active treatment. At ischaemic threshold and at peak exercise, heart rate, systolic blood pressure and rate-pressure product remained unchanged. Exercise duration was increased by felodipine (P less than 0.01) and maximal ST change was reduced (P less than 0.01). Time to 1 mm ST depression was prolonged non-significantly by felodipine (basal 5.7 +/- 1.5, felodipine 7.4 +/- 2.0, placebo 6.6 +/- 1.5 min). The number of patients who stopped exercise due to angina and ST change was 20/20 at baseline, 16/20 with placebo and 10/20 with felodipine. Felodipine significantly reduced weekly anginal episodes (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Felodipine in chronic stable angina: a randomized, double-blind, placebo-controlled, crossover study. 228 20

The effects of single oral doses of 10 mg felodipine and four beta-blockers (100 mg metoprolol, 5 mg pindolol, 80 mg propranolol, and 10 mg timolol) were evaluated alone and in combination in a 10-way crossover, double-blind, placebo-controlled trial in 10 healthy male volunteers randomized to the medication sequence according to a latin square design. Adverse effects were recorded from spontaneous complaints and investigator observations. Heart rate (HR), PR interval, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured supine, standing, and after treadmill exercise, before and 2 h after drug administration. The adverse effects experienced with felodipine were as expected for a vasodilator. Seven subjects mentioned complaints voluntarily on the combinations while three experienced side effects receiving felodipine or beta-blocker alone. Felodipine increased resting HR significantly. Timolol produced a greater depression of exercise heart rate than the other beta-blockers, indicating that the dose given was not equivalent to that of the other beta-blockers. Pindolol was ineffective in preventing the increase in supine HR produced by felodipine. Felodipine did not alter PR interval at any level of activity, but rate-corrected supine PR interval was prolonged slightly by felodipine. Metoprolol and timolol significantly prolonged standing PR interval. All beta-blockers prolonged exercise PR interval. Felodipine/beta-blocker combinations did not prolong PR interval more than beta-blockers alone. Prolonged PR interval was the result of reduced HR and direct inhibition of atrioventricular (AV) conduction. Only timolol and the timolol/felodipine combination lowered supine systolic blood pressure significantly. Timolol and all beta-blocker/felodipine combinations reduced exercise SBP significantly.
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PMID:Tolerance and cardiovascular effects of single dose felodipine/beta-blocker combinations in healthy subjects. 244 12

The antianginal properties and the duration of action of two doses of felodipine, a dihydropyridine calcium antagonist with a vascular:myocardial potency ratio approximating 100:1, were investigated in 15 patients suffering from disabling effort angina pectoris with reproducible exercise tolerance. Felodipine (5 mg, 10 mg) and placebo were administered once in the morning on three different days, with a 24 h interval between them, according to a double-blind 3 x 3 latin square design, 5 times replicated. Symptom-limited cycloergometric exercise tests were performed 3 and 12 h after administration. Duration of exercise to ST segment depression of 1 mm and to peak exercise was increased (all P less than 0.01) by both doses of felodipine in comparison with placebo. Twelve hours after administration, the 10-mg dose induced a significant improvement in the exercise time and a smaller ST segment depression (all P less than 0.01) in comparison with the 5-mg dose. The relationship between ST segment depression and the pressure-rate product during exercise was favourably influenced by the 10-mg dose at 3 and 12 h after intake, and by the 5-mg dose only at 3 h after intake. These findings suggest an increase in coronary blood flow induced by felodipine. Apart from mild headache there were no other unwanted effects. In conclusion, felodipine improves exercise tolerance and reduces electrocardiographic ischaemia for up to 12 h after single oral administration in patients with effort angina. Increasing the dose from 5 mg to 10 mg produces a more prolonged effect, with increased exercise tolerance 12 h after intake.
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PMID:Increased exercise tolerance and reduced electrocardiographic ischaemia 3 and 12 hours after oral felodipine in effort angina. 270 68

On rat aorta, diltiazem (0.2 microM) caused parallel shifts in the Ca2+ concentration-response curves (K+-depolarized preparations). In aged (greater than 19 months) rats, this shift (0.57 log units) was smaller than in young (2 months) rats (1.04 log units) indicating an age-related reduction in the potency of diltiazem. Felodipine (10 nM), like diltiazem (1 microM) in a previous study, depressed the maximum response to noradrenaline more in preparations from aged rats (40% reduction) than from young rats (14% reduction). This increase in the effect of felodipine or diltiazem vs. noradrenaline reflected a reduction in the alpha-adrenoceptor reserve for noradrenaline. Accordingly, the depression in the maximum responses to other spasmogens (5-HT or K+) by 1 microM diltiazem was not increased by age (5-HT, young 59%, aged 49% reduction; K+, young 65%, aged 70% reduction). This aging can have two opposing influences on the effects of Ca2+ entry blocking drugs on rat aorta - a decrease in potency, yet an increase in effectiveness against spasmogens with a reduced receptor reserve.
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PMID:Influence of age on calcium entry blocking drugs in rat aorta is spasmogen-dependent. 292 Jul 74

We studied the effects of adding felodipine to beta-adrenoceptor blockade on haemodynamics and exercise capacity in 14 patients with stable angina pectoris using a placebo controlled double-blind crossover protocol. Felodipine reduced supine and standing systolic pressure by 13% (P less than 0.01) and 14% (P less than 0.01) respectively and increased supine heart rate 7.4% (P less than 0.05). Felodipine at a plasma concentration of 15.5 +/- 3.0 nmol l-1 increased exercise duration by 16% (P less than 0.01) but failed to attenuate the degree of ST segment depression during exercise. The mean daily number of episodes of angina (0.53 +/- 0.16 on placebo vs 0.37 +/- 0.11 on felodipine) and mean daily GTN consumption (0.51 +/- 0.07 on placebo vs 0.36 +/- 0.12 on felodipine) were not significantly reduced (0.1 less than P greater than 0.05). These findings suggest that felodipine may provide useful additional benefits in patients with hypertension or angina pectoris, who are already receiving beta-adrenoceptor blockers.
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PMID:Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris. 310 5

The newer dihydropyridine calcium antagonists are structurally related to nifedipine, but may provide greater vascular selectivity and wider clinical utility. Five new dihydropyridines-nisoldipine, nicardipine, nimodipine, felodipine and nitrendipine-are reviewed with regard to their preclinical pharmacology, haemodynamic effects and clinical indications. Nisoldipine is a potent arterial vasodilator with minimal electrophysiological and negative inotropic effects. Although data are still preliminary, the drug has shown some efficacy in both exertional angina and essential hypertension. The dosing interval is not yet clearly established, but may be twice daily. Utility in congestive heart failure awaits confirmation, but preliminary studies are promising. Nicardipine is an especially potent peripheral, cerebral and coronary arterial vasodilator that causes 10-fold less myocardial depression in animals than nifedipine, and may provide important cardioprotective effects during ischaemia. Human haemodynamic studies have confirmed nicardipine's lack of negative inotropism, its ability to reduce coronary and peripheral vascular resistance, and its lack of effect on cardiac conduction. Several controlled trials have documented its efficacy in exertional angina, vasospastic angina, and essential hypertension. Nicardipine's potential as an antiatherosclerotic agent is currently under investigation. Nimodipine is undergoing a unique clinical development programme aimed at cerebrovascular disorders. In almost all species, nimodipine selectively increases cerebral blood flow and reverses cerebral artery spasm without altering cerebral oxidative metabolism or systemic blood pressure. In humans, a large, double-blind, placebo-controlled trial in subarachnoid haemorrhage showed that nimodipine significantly reduced the severity of neurological deficits associated with delayed cerebral vasospasm. Several uncontrolled trials with larger numbers of patients support these results. Nimodipine has also proved useful in reducing cerebral artery spasm during intracranial surgery, and in the prophylactic treatment of migraine headaches. A preliminary study of nimodipine in acute stroke showed promising results in limiting neurological disability. Felodipine is a very potent systemic arterial vasodilator with negligible myocardial depressant activity. It is also a renal artery vasodilator. Unlike the other new dihydropyridines, felodipine prolongs the A-H interval on electrophysiological testing, but only to about 50% of that observed with verapamil. Felodipine is undergoing clinical trials in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:'Second generation' dihydropyridine calcium antagonists. Greater vascular selectivity and some unique applications. 331 91

The effects, as monotherapy, of felodipine ER 10 mg o.m. and nifedipine SR 20 mg b.d. were compared in a double-blind, randomized, placebo-controlled, three-way cross-over trial in 43 patients with stable exercise-induced angina pectoris. The exercise tests were performed at the end of dosage interval (i.e. 24 h after felodipine ER, 12 h after nifedipine SR) and at the expected peak time of 3 h post dose. Felodipine and nifedipine improved exercise duration by 66 and 50 s, respectively, (P < 0.001) compared with placebo at the end of the dosing interval. Time to the end of exercise showed no statistically significant difference between the two calcium antagonists. The onset of anginal pain and time to 1 mm ST depression were significantly more delayed by felodipine ER than nifedipine SR (22 s and 19 s, respectively, P < 0.05). Both felodipine and nifedipine decreased the pain score and rate pressure product at the highest comparable work load. Overall tolerability was good for both drugs.
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PMID:24 h anti-anginal and anti-ischaemic effects with once daily felodipine. A double-blind comparison with nifedipine, twice daily, and placebo in patients with stable exercise induced angina pectoris. 774 87

The effects of the new dihydropyridine Ca-antagonist felodipine (CAS 72509-76-3) (3 x 10(-9) mol/l - 10(-6) mol/l) on intracellular action potentials of the rabbit sinus node and atrium were studied. Results were compared to the effects of nifedipine (10(-8) mol/l - 3 x (-10) mol/l). Additionally, rate-dependent effects of both substances on AV nodal conduction time were assessed. The data demonstrate a concentration-dependent reduction of sinus nodal automaticity due to depression of phase 4 automaticity concomitant with a reduction of the maximum upstroke velocity of the sinus action potential by both substances. Felodipine was about one half order of magnitude more potent than nifedipine. Both substances exerted little effects on action potentials in atrial cells. Felodipine and nifedipine led to a concentration and frequency-dependent ("use-dependent") retardation of AV nodal conduction. Again felodipine was about one half order of magnitude more potent than nifedipine.
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PMID:Effects of dihydropyridine calcium-antagonists on intracellular action potentials of rabbit sinus node, atrium and atrioventricular node. Comparison of felodipine with nifedipine. 805 68

Calcium entry through L-type calcium channels is essential for contraction of both arterial smooth muscle and the myocardium, and is important in cardiac conduction. First-generation calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac function at doses producing therapeutic arterial dilatation. Such agents may cause deterioration in patients with left ventricular dysfunction, and their combination with a beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agents has focused on obtaining a higher degree of vascular selectivity. Felodipine is a highly vascular selective calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally. Isradipine and nicardipine are also vascularly selective calcium entry blockers. Hemodynamic studies in patients with hypertension, coronary artery disease, congestive heart failure, or in patients receiving beta-adrenergic blockade, show that felodipine can produce profound arteriolar dilatation without the negative effects of left ventricular systolic performance. Furthermore, felodipine alone or when added to a beta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of dihydropyridine calcium entry blockers in hypertension and angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their effect from inhibition of cardiac performance. As some of these patients, most commonly the elderly, have concomitant left ventricular dysfunction, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients with heart failure indicate that felodipine and amlopidine may improve hemodynamics, reduce neurohormonal activation, and increase exercise tolerance, but final conclusions must await the randomized clinical trials now underway.
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PMID:Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: focus on felodipine. 857 48


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