Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to high pressure causes a significant depression of synaptic transmission. We examined the effects of various Ca-channel blockers and their interaction with high pressure on excitatory neuromuscular junction currents (EJCs) of lobster abdominal muscles. Reduced [Ca2+]o to half of normal concentration or exposure to 40-60 microM CdCl2, 10-20 microM NiCl2 and 1 microM omega-conotoxin decreased EJCs by 50%. Nifedipine, Nitrendipine and Bay K-8644 were ineffective. Either Ca-blockers or reduced [Ca2+]o, enhanced EJC suppression exerted by high pressure. The data suggest that high pressure primarily affects Ca2+ inflow at the presynaptic terminals through N-type voltage-gated Ca-channel.
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PMID:Interaction of Ca-channel blockers and high pressure at the crustacean neuromuscular junction. 185 59

Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way cross-over study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with beta-adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine-ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total exercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics. 188 25

The effects of antihypertensive drugs, such as nifedipine, chlorpromazine, reserpine and thiopental on mean arterial blood pressure (ABP), mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were studied in 43 patients with systemic hypertension and intracranial hypertension due to hemorrhagic cerebrovascular diseases and other causes. These drugs are commonly used in neurosurgical practice for the treatment of systemic hypertension. Nifedipine, chlorpromazine and reserpine reduced the mean ABP, raised the mean ICP and decreased the CPP. The effects of these drugs on mean ICP and CPP were more pronounced in patients with severely increased ICP (more than 40 mmHg) than in patients with moderately increased ICP (20-40 mmHg). Thiopental reduced both mean ABP and ICP, whereas the CPP was unchanged from the preadministration level. During thiopental administration, however, respiratory depression was observed, and hence, intubation and ventilation were required. We suggest that, in the treatment of systemic hypertension in patients with increased ICP, barbiturates are more desirable than agents with calcium channel or alpha-adrenergic blocking actions, despite the problem of respiratory control.
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PMID:Effects of antihypertensive drugs on intracranial hypertension. 195 Feb 24

Calcium entry blockers are now widely used in the treatment of cardiovascular diseases. Nifedipine is established for the treatment of perioperative hypertension during anesthesia. Previous animal experiments have demonstrated that calcium entry blockers potentiate the neuromuscular response induced by nondepolarizing blocking drugs. Occasional observations in patients have led to the suggestion that this phenomenon may be of clinical significance. The interaction of nifedipine with nondepolarizing muscle relaxants in patients was assessed in a prospective clinical study. PATIENTS AND METHODS. Atracurium or vecuronium was administered for muscular relaxation in 44 patients anesthesized with isoflurane in nitrous oxide/oxygen. Monitoring included checks on noninvasive blood pressure, heart rate, pharyngeal temperature, tidal volume, end-tidal CO2 and neuromuscular transmission with a Datex ABM 100 Relaxograph ("train of four"). In the first study protocol atracurium was given to the patients after the intubation dose of 0.5 mg/kg in equal repetition doses of 0.2 mg/kg whenever T1 reached 25%. In 12 patients with the second repetition dose 1 mg nifedipine was injected i.v. The duration of neuromuscular depression with nifedipine until T1 reached 25% again was compared with the duration without nifedipine in the same patient. In the second protocol, constant neuromuscular blockade was accomplished in 11 patients by administration of atracurium or vecuronium at a constant perfusion rate at a level of 75% twitch depression. After 15 min of stable neuromuscular blockade 1 mg nifedipine was injected. In the third study protocol, 1 mg nifedipine i.v. was given at the end of anesthesia when the patients began to breathe spontaneously (T1 was at least 25%). RESULTS. In each patient there was a significant prolongation of neuromuscular blockade from 29 min +/- 6 min up to 40 min +/- 8 min when nifedipdine was given with the second repetition dose (P less than 0.001). During continuous relaxation with constant neuromuscular depression nifedipine increased the neuromuscular blockade from 75% up to 90% +/- 4% (P less than 0.05). In patients with spontaneous breathing and fading but still existing neuromuscular blockade nifedipine injection resulted in hypoventilation. The cardiovascular effects of 1 mg nifedipine, although significant, attained no clinically relevant values. CONCLUSIONS. Our results confirm previous assumptions of synergistic effects of neuromuscular blocking drugs and nifedipine in patients. This synergistic effect includes both duration and intensity of neuromuscular blockade. In the postoperative period patients may be endangered by nifedipine therapy if recovery from the neuromuscular depression is not complete.
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PMID:[Potentiation of nondepolarizing muscle relaxants by nifedipine iv in inhalation anesthesia]. 197 Apr 60

A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05). Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.
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PMID:Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris. 272 45

The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine. 201 12

Diltiazem and Nifedipine could be synergic. The aim of this study was to investigate the benefits of their association. Eighteen patients, 15 men and 3 women, average age 61 +/- 6 years, with stable angina on effort, were studied. Eight patients had single vessel disease and 10 patients had multivessel disease. The patients underwent a randomised double-blind trial with 4 successive treatment periods each lasting one week: placebo; 360 mg/day of Diltiazem; 60 mg/day of Nifedipine; 180 mg/day of Diltiazem with 30 mg/day of Nifedipine. The benefits were evaluated clinically, by exercise stress testing and with drug plasma concentrations at the end of each sequence. The results at the end of the 3 treatment periods were significantly better than with placebo. Diltiazem was significantly better than Nifedipine with respect to the development of angina during exercise testing (1 patient compared with 7 patients) and to maximum load (118.3 +/- 33.3 watts compared with 105.9 +/- 35.4 watts) (p less than 0.05). The association of the two drugs did not give better results than Diltiazem alone. Compared with placebo, the total duration of exercise testing and the duration of 1 mm ST depression were significantly longer during the 3 treatment sequences but there were no significant differences between each of them. Secondary effects were significantly more common with Nifedipine (7 patients) and with the drug association (9 patients) than with Diltiazem alone (3 patients) or placebo (1 patient). Plasma concentrations of Diltiazem were 328 +/- 35 ng/l with the 360 mg/day dosage and 137 +/- 52 ng/l with the 180 mg/day dosage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of effects of diltiazem, nifedipine and their combination on exercise stable angina]. 202 Dec 84

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group. 224 50

Nifedipine may be effective in the treatment of stable angina by both decreasing myocardial oxygen demand and increasing myocardial oxygen supply. To determine the mechanism of action of nifedipine and its dose-response relation, 14 patients with stable angina were treated with nifedipine 10, 20 and 30 mg 4 times daily as single-agent therapy in a double-blind, randomized, placebo-controlled crossover trial. Treatment was continued for 1 week on each dose regimen and efficacy was determined using an exercise test at the end of each phase. Compared to placebo, a significant decrease of systolic blood pressure at peak exercise occurred with the nifedipine 20- and 30-mg regimens (p less than 0.05), accompanied by an increase in heart rate on the 10- and 20-mg regimens (p less than 0.005). There was no significant effect on the rate-pressure product compared to placebo at any exercise time on any of the nifedipine regimens. The times to onset of ST-segment depression and to angina were delayed significantly by all 3 dose regimens compared to placebo (p less than 0.02). There was a significant decrease in the magnitude of ST-segment depression at all exercise times by all dosage schedules of nifedipine compared with placebo (p less than 0.05), although there were no significant differences among the 3 dosage schedules. Data indicate that since nifedipine was effective in improving manifestations of myocardial ischemia during exercise without altering the double product at submaximal or maximal exercise, its beneficial mechanism of action may have been due to enhancing blood flow to ischemic zones or to favorably altering determinants of myocardial oxygen demand, which were not measured.
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PMID:Effects of nifedipine on myocardial perfusion during exercise in chronic stable angina pectoris. 218 49

Since not all patients tolerate beta-blockers, the efficacy of nifedipine and isosorbide dinitrate was evaluated alone and in combination in patients with stable angina pectoris. The study was a randomized double-blind crossover design with patients titrated to maximally tolerated doses of both drugs. Phases included isosorbide dinitrate alone, nifedipine alone, and isosorbide dinitrate plus nifedipine in combination, with efficacy determined by stress testing. Eleven men and one woman patient with a mean age of 60 years and a mean of five anginal episodes/week completed the study. Patients were in New York Heart Association (NYHA) classes I, II, and III. With nifedipine alone compared with isosorbide dinitrate alone, patients had fewer angina attacks/week (p less than 0.02), exercised longer before experiencing angina (p less than 0.03), and had less ST segment depression during (p less than 0.03) or after (p less than 0.05) exercise. When patients received isosorbide dinitrate plus nifedipine, only time to onset of angina during exercise (p less than 0.05) was significantly different from the response with isosorbide dinitrate alone. Analysis of variance between nifedipine and isosorbide dinitrate plus nifedipine was not significant. Diastolic blood pressure with isosorbide dinitrate plus nifedipine (p less than 0.04) was lower than with isosorbide dinitrate alone. No significant differences in systolic blood pressure were noted between the treatment groups. The drugs alone and in combination were relatively well tolerated. Nifedipine alone may be superior to isosorbide dinitrate alone. The combination of isosorbide dinitrate plus nifedipine demonstrated no advantage over nifedipine alone compared with isosorbide dinitrate alone.
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PMID:Nifedipine and isosorbide dinitrate alone and in combination for patients with chronic stable angina: a double-blind crossover study. 220 Feb 53


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