Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Nifedipine (1.5-3.0 x 10(-5) M) potentiated the (sub)tetanic tension during 10-50 Hz indirect or direct stimulation of the rat diaphragm preparation; the twitch contractions were not potentiated. 2. The effect was antagonized in high Ca2+ (5-10 x normal) solutions. 3. A comparison with the twitch potentiators caffeine (1.0 x 10(-3) M), quinine (1.4 x 10(-5) M) and phenytoin (2.0 x 10(-5) M), showed that only phenytoin, a putative Ca-antagonist, caused a nifedipine-like frequency-dependent potentiation, indicating a Ca-antagonistic rather than an unspecific effect. 4. A similar (sub)tetanic potentiation was found in a K(+)-free solution. 5. The slow development of the potentiation during repetitive stimulation is in accordance with an effect on the slow Ca channels known to be present in mammalian skeletal muscle. 6. A delay of the fatigue-inducing accumulation of K+ in the T tubules, which may occur during a nifedipine-induced reduction of a Ca2(+)-stimulated K+ efflux, as well as in a K(+)-free solution, may explain the effect.
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PMID:Selective potentiation of subtetanic and tetanic contractions by the calcium-channel antagonist nifedipine in the rat diaphragm preparation. 205 26

Despite decreasing cardiac mortality rates in the elderly since 1968, rates of health care service use by persons over age 65 years have progressively increased. The growing availability of potent and effective cardiovascular drugs, together with the high prevalence of untoward side effects in the elderly, make it important that we consider the influence of age on cardiovascular response to the calcium entry blockers. The age-related structural, functional, pharmacokinetic, and pharmacodynamic changes that occur in elderly patients suggest that careful monitoring, adjustment, and frequent reassessment of the medical regimen should be performed to minimize untoward effects. Nifedipine, diltiazem, and verapamil are all well absorbed orally, are extensively protein bound, and are metabolized by the liver. The age-associated attenuation in rates of hepatic metabolism and hepatic blood flow contribute to the decreased clearance and prolonged elimination half-lives of these drugs in the elderly. Advanced age can be associated with increased susceptibility to sinoatrial depression, fatigue, constipation, hypotension, and peripheral edema after calcium entry blockade, even at modest doses. It would be prudent, therefore, to administer these agents at lower doses and at less frequent intervals.
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PMID:Use of calcium entry blockers in elderly patients. Special considerations. 268 81

A randomized cross-over trial was undertaken on 21 occupationally active persons who had a stable mild or moderate hypertension with the purpose of comparing the effect of a beta-adreno-receptor blocking agent (atenolol) with that of a calcium channel inhibitor (nifedipine). The doses recommended by the manufactures were used. Atenolol (100 mg) given once a day resulted in a marked hypotensive effect at rest as well as during exercise, the compliance was satisfactory, and the hemodynamic changes were not reflected in unfavourable side effects during muscular exercise or in the subjects own personal assessment of fatigue during the exercise tests which ranged in energy expenditure from about three to six times the resting level. However, unfavourable, modest side effects occurred in two subjects during atenolol medication to the extent that they wanted to terminate the study. Nifedipine therapy with doses of 10 mg, three times a day, resulted in a modest, but statistically insignificant reduction in arterial blood pressure, which contrasts with previous published results. It is suggested that the modest effect is caused or related to the poor compliance and a daily dose that was quantitatively too small. No unfavourable side effects were seen during muscular efforts when the subjects were on nifedipine medication.
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PMID:Working ability and exercise tolerance during treatment of a mild hypertension. I. Comparison between a beta-adreno-receptor blocking drug and a calcium antagonist. 286 20

A randomised double blind parallel group study was performed to compare the efficacy and acceptability of slow release nifedipine (maximum dose 40 mg twice a day) with those of atenolol (maximum dose 100 mg once a day) as single agents for the treatment of essential hypertension. Of 410 patients recruited almost exclusively from general practices in 22 centres in the United Kingdom 210 received nifedipine and 200 atenolol. Both drugs significantly reduced blood pressure, and control--a reduction of the diastolic pressure to less than 95 mm Hg--was obtained in about 65% of patients. Those who received nifedipine had more pronounced reductions in systolic pressure than those who received atenolol. One hundred and forty nine patients who failed to respond adequately to either atenolol or nifedipine in low doses were given both drugs once daily for eight weeks in a fixed combination capsule that contained atenolol 50 mg and nifedipine 20 mg. All patients showed further reductions in blood pressure, although those who were taking beta atenolol before the combination capsule had more pronounced reductions in systolic pressures. Twenty six patients (12%) were withdrawn because of adverse effects while taking nifedipine compared with 19 (10%) taking atenolol. Flushing and oedema were more common after the calcium antagonist, whereas diarrhoea and dyspepsia were more common after atenolol. The frequencies of headaches, dizziness, fatigue, and dyspnoea were equally distributed between the two groups. When the fixed combination capsule was taken side effects such as flushing and oedema continued. Nifedipine was more effective than atenolol in lowering systolic blood pressure, although neither drug used alone controlled the pressure of more than two thirds of the patients studied. When used in a fixed combination slightly better control of blood pressure was achieved with a lower dose of each drug.
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PMID:Nifedipine and atenolol singly and combined for treatment of essential hypertension: comparative multicentre study in general practice in the United Kingdom. Nifedipine-Atenolol Study Review Committee. 289 83

Seventeen post-myocardial infarction patients experiencing angina on effort performed 6 different exercise tests until they reached symptom-limited maximal level, 3 after placebo and 3 after oral administration of 10 mg of the Calcium antagonist, nifedipine, in a randomized, double blind, cross-over controlled study. Four of the tests were conventional bicycle and treadmill tests with stepwise increasing load. In 2 of the tests an isometric exercise of carrying a weight averaging 6 kg and corresponding to about 30% of maximal grip strength was added to the treadmill walking. When the exercise was stopped because of moderately severe angina, the product of heart rate and systolic blood pressure did not show any statistically significant difference between the tests. However, in the treadmill plus isometric test the work time was shorter and the slope of the treadmill was less than in the treadmill test. The difference was caused partly by non-cardiac factors, namely fatigue of the hand muscles. In routine exercise tests of coronary patients the addition of an isometric to a dynamic load did not give substantially more information than dynamic exercise alone. Nifedipine caused a modest increase of exercise tolerance in all tests, the increase being greatest in the treadmill plus isometric test. The increase in exercise tolerance was seen also in patients receiving beta-blocking agent.
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PMID:Assessment of exercise tolerance of cardiac patients by bicycle, treadmill and treadmill plus isometric exercise with and without nifedipine. 344 98

In 93 patients with hypertension uncontrolled by bendrofluazide 5 mg plus atenolol 100 mg daily, the effects of adding nifedipine (up to 60 mg/day, n = 31), prazosin (up to 20 mg/day, n = 31), or hydralazine (up to 200 mg/day, n = 31) were compared in a 6 month open random parallel group study. The three drugs did not differ significantly as regards antihypertensive effect, withdrawal rate, total number of side effects, or effect on serum biochemical variables. The pattern of side-effects differed. Headache, flushing and oedema were common with nifedipine, tiredness and drowsiness with prazosin, and headache with hydralazine. Nifedipine is an acceptable third-line antihypertensive drug which may have some advantage over hydralazine and prazosin.
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PMID:Comparison of nifedipine, prazosin and hydralazine added to treatment of hypertensive patients uncontrolled by thiazide diuretic plus beta-blocker. 367 Dec 50

A controlled multicentre trial was organised to compare the effects of 20 mg Nifedipine tablets (N) and 2,5 mg Indapamide tablets (I) during a 4 months' treatment period after a placebo period, in 59 patients with moderate essential hypertension (n = 59). The results of blood pressure measurements of 18 patients treated by nifedipine (1 tablet twice daily) and 22 patients treated by indapamide (1 tablet every morning) were compared. The systolic blood pressure, after 10 minutes recumbency, fell from 165 +/- 10 mmHg to 148 +/- 13 mmHg (p less than 0.01), and the diastolic pressure from 104 +/- 6 mmHg to 86 +/- 7 mmHg (p less than 0.01) in the patients treated with nifedipine. In the indapamide group, the SBP fell from 164 +/- 13 mmHg to 152 +/- 15 mmHg (p less than 0.01) and the DBP from 100 +/- 4 mmHg to 87 +/- 6 mmHg (p less than 0.01). There were no significant changes of heart rate with either drug; plasma creatinine, potassium and uric acid concentrations were also unchanged. There was a higher incidence of headaches and tiredness in the nifedipine group, whilst patients treated with indapamide complained more often of muscular cramps. Flushing was observed in nearly a quarter of the patients in both groups. These results confirm that both nifedipine and indapamide induce significant and persistant falls in systolic and diastolic blood pressure. Although the fall was greater with nifedipine than with indapamide, the difference was not statistically significant. The tolerance was satisfactory in both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative effects of nifedipine and indapamide in the treatment of arterial hypertension]. 393 9

Calcium-entry blockers were administered in an attempt to protect myocardium during cardiac arrest due to ventricular fibrillation in mechanically ventilated dogs. An intravenous injection of verapamil, nifedipine, or lidoflazine was administered prior to successively prolonged episodes of ventricular fibrillation, during which no thoracic compression was performed. It is of interest that ventricular defibrillation was more easily obtained after treatment with the three drugs. As previously observed in this model, nine control dogs developed electromechanical dissociation (EMD) after 120 seconds of ventricular fibrillation. In contrast, six of the 11 dogs treated with 0.3 mg/kg of verapamil recovered mechanical systole after 120 seconds of ventricular fibrillation (p less than 0.05). Nifedipine administration also postponed the onset of EMD in three of four dogs. However, lidoflazine postponed the onset of EMD in only one of the eight dogs. The later onset of EMD after administration of verapamil or nifedipine in this model was attributed to myocardial protection by calcium-entry blockers during ventricular fibrillation. Decreased energy utilization during cardiac arrest was considered to be the principal protective mechanism. These observations indicate calcium-entry blockers, and especially verapamil and nifedipine, can be valuable drugs during cardiac resuscitation for ventricular fibrillation.
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PMID:Electromechanical dissociation after ventricular fibrillation: prevention with calcium-entry blockers. 608 70

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.
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PMID:Update on calcium-channel blocking agents. 635 66

Ten men with stable angina not completely relieved by full doses of propranolol (mean 218 mg/day) were administered an oral dose of 10 mg of nifedipine or placebo on alternate mornings in a double-blind fashion. Patients had been trained in a protocol that precipitated angina after 3-6 minutes of bicycle exercise. On test days, with propranolol continued, bicycle exercise to angina or fatigue was performed before nifedipine or placebo administration, and hourly thereafter for 8 hours. Mean exercise duration was greater 1 hour after nifedipine than after placebo by 123 seconds (372 +/- 21 vs 249 +/- 16 seconds, p less than 0.001). By the fifth hour, the increase in exercise time was reduced to 93 seconds (p less than 0.001), and a significant, though further diminished, difference of 57 seconds was still present at 8 hours (p less than 0.01). Nifedipine lowered resting systolic blood pressure by 20 mm Hg (p less than 0.001) without appreciably changing heart rate. We conclude that nifedipine is a very effective and reasonably long-acting antianginal supplement to propranolol.
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PMID:The additive antianginal action of oral nifedipine in patients receiving propranolol: magnitude and duration of effect. 711 88


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