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

Exercise myocardial-thallium scintigraphy plays a fundamental role in the diagnosis of coronary artery disease. Once exercise is not always feasible, pharmacological stress became a possible alternative. The authors review the mechanism of action, administrations protocols, indications and side effects of the drugs used for this purpose: dipyridamole, adenosine and dobutamine. Dipyridamole causes coronary hyperemia by increasing the interstitial levels of endogenous adenosine. Perfusion defects result from the mismatch of coronary reserve in different coronary territories. The drug administration is classically performed with a 0.142 mg/kg/min dosage e.v. for 4 minutes, total of 0.56 mg/kg. It is possible to use a greater dose of 0.84 mg/kg e.v. for 10 minutes, increasing sensitivity without loss of specificity for diagnosis of coronary artery disease. Oral dipyridamole protocols with 300 and 400 mg were used with similar results for sensitivity and specificity. The oral protocol has the disadvantage of delayed onset and longer action. Including several dipyridamole studies, 87% was obtained for sensitivity and 84% for specificity, in the diagnosis of CAD. Dipyridamole scintigraphy has been applied to myocardial infarction risk stratification, cardiac risk evaluation of patients proposed to noncardiac surgery and therapeutic efficacy evaluation of reperfusion techniques (angioplasty and surgery). The secondary effects of dipyridamole are frequent, however mild and well tolerated. They occur in half the patients, the most frequent, facial flushing (2%), dizziness (5%), nausea (4%), vomiting (1%), headaches (11%) and chest pain (26%). Some important complications were reported although rare: myocardial infarction, ventricular fibrillation and bronchospasm.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Role of pharmacologic stimulation with myocardial perfusion scintigraphy in the evaluation of patients with ischemic cardiopathy]. 129 Jun 55

The purpose of this study was to evaluate the significance of increased Tl-201 uptake by the lungs after oral dipyridamole testing. In conjunction with myocardial perfusion scintigraphy, intravenous dipyridamole has been recently approved as an alternative to exercise for the evaluation of coronary artery disease in patients who cannot adequately exercise, and it will largely replace oral dipyridamole testing. This study contributes to the understanding of the significance of increased lung thallium uptake during pharmacologic stress testing. Oral dipyridamole, 400 mg, was administered to 192 patients undergoing Tl-201 imaging for clinical indications. Mild adverse effects occurred in 31% of patients (chest pain, nausea, headache, or flushing). Dipyridamole had minimal hemodynamic effects. The lung/heart thallium activity ratio was determined in 152 patients. These were subdivided into four groups according to the presence or absence of ischemia, transient myocardial perfusion defect, or scar as indicated by a fixed myocardial perfusion defect. In 61 patients without transient myocardial perfusion defect or fixed myocardial perfusion defect (group 1), the lung/heart thallium activity ratio was 0.39 +/- 0.01 (mean +/- SEM). In 31 patients without transient myocardial perfusion defect but with fixed myocardial perfusion defect (group 2), the lung/heart thallium activity ratio was higher, 0.44 +/- 0.02 (P less than 0.05). In 27 patients with transient myocardial perfusion defect but no fixed myocardial perfusion defect (group 3) and in 33 patients with both transient myocardial perfusion defect and fixed myocardial perfusion defect (group 4), the lung/heart thallium activity ratio was 0.51 +/- 0.03 and 0.52 +/- 0.03, respectively, both significantly higher than either group 1 or group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Significance of increased Tl-201 uptake by the lungs in patients undergoing oral dipyridamole-thallium myocardial imaging. 161 45

Dipyridamole is a well known anti-aggregating agent characterized by poor water solubility as well as scant and variable bioavailability. Recently, the compound was complexed with beta-cyclodextrin forming a molecular encapsulation resulting in better oral absorption and stronger biological activities in animals. In the present study, a randomized double blind cross-over comparison between dipyridamole-beta-cyclodextrin complex (dip-beta-CD) and dipyridamole was performed in 12 healthy subjects after single (75mg) and multiple oral treatments (75mg TID). Dip-beta-CD showed better bioavailability and less interindividual variability than dipyridamole either after single or multiple doses. In particular, dip-beta-CD had a greater AUC and Cmax, and a smaller Tmax even at the steady state. In addition, 100% of the subjects receiving a single dose of dip-beta-CD, as compared to 66.7% of those treated with dipyridamole, had plasma levels superior to 1 microgram/ml (which is the supposed anti-aggregating threshold level). In contrast, 0 and 33.03% of the subjects showed plasma levels superior to 2.5 micrograms/ml (which might cause the appearance of side-effects) on the 7th day of the multiple treatment with dip-beta-CD and dipyridamole, respectively. In fact, the subjects presenting higher levels after uncomplexed dipyridamole also complained of headache and/or dizziness on occasion. No adverse side effects were reported for dip-beta-CD.
 ...
PMID:Pharmacokinetics of dipyridamole-beta-cyclodextrin complex in healthy volunteers after single and multiple doses. 181 37

Dipyridamole (DP) blocks nucleoside salvage by inhibiting uptake at the cell membrane. At the usual oral doses DP has no cytotoxic activity, but when combined with an antimetabolite, it results in synergistic cell kill in vitro. In this study, 45 patients with advanced solid tumors were treated with oral DP and i.v. or i.m. methotrexate (MTX) to define the toxicity of this combination. The DP dose was 75 mg b.i.d. in the first 16 patients, 150 mg b.i.d. in the next 2, and 75 mg q.i.d. in the remaining 27 patients. MTX was given weekly at an initial dose of 10-30 mg/m2 and increased weekly by 5-10 mg/m2 to the maximum tolerable dose (MTD) or a maximum of 60 mg/m2; thereafter that dose was given every other week. DP levels ranged from 2.76 to 11.46 microM, with a mean of 5.67 microM in four patients taking 75 mg q.i.d. The combination of oral DP and MTX was generally well tolerated and did not appear to result in any more myelotoxicity or mucositis than that expected for MTX alone. One patient experienced severe headaches related to DP, ten patients experienced grade 3 or 4 neutropenia and/or thrombocytopenia, and four patients had grade 3 mucositis. Although this trial was not designed as a phase II study, one partial remission was observed in a patient with metastatic pleomorphic adenoma of the parotid gland and seven patients showed significant improvement.
 ...
PMID:Oral dipyridamole and methotrexate in human solid tumors: a toxicity trial. 264 13

The anti-anginal effect of a controlled-release (Durules) formulation of isosorbide-5-mononitrate (5-ISMN) 60 mg, Imdur, once daily was evaluated in a randomised double-blind, placebo-controlled, crossover study with a placebo run-in period. Each period lasted for 2 weeks. A total of 70 patients (58 men and 12 women) with stable exertional angina pectoris on beta-blockade, mean age 59 years (range 39-71), were included. Exercise testing was performed on a bicycle ergometer 3 hours after the dose at the end of each period. Anginal attacks and intake of sublingual nitroglycerin tablets were noted. Imdur in combination with a beta-blocker significantly increased the total exercise capacity, the time and total work until the onset of chest pain and at 1 mm ST-depression compared with beta-blockade alone. The attack rate and the nitroglycerin consumption were significantly decreased. Headache was the only significant side-effect. In conclusion, the addition of Imdur once daily to beta-blockade significantly increased the anti-anginal effect.
 ...
PMID:Anti-anginal efficacy of a controlled-release formulation of isosorbide-5-mononitrate once daily in angina patients on chronic beta-blockade. 289 64

Dipyridamole thallium-201 imaging, using single-photon emission computed tomography, was evaluated for its safety and diagnostic efficacy in 109 patients with angiographically documented coronary artery disease and 35 normal subjects. The most common side effects after the intravenous administration of dipyridamole thallium-201 (0.56 mg/kg) included chest pain in 41 patients, dizziness in 20 patients, headache in 16 patients, and ST segment depression > or = 1 mm in 15 patients. Aminophylline was required to reverse the side-effects in 46 patients, and 45 of the 46 patients experienced complete relief of symptoms. Of the 109 patients with coronary artery disease, 104 had abnormal dipyridamole thallium images. The per patient sensitivity was 95%. Of the 35 normal subjects, 27 had normal thallium images. The per patient specificity was 77%. The sensitivity and specificity for the individual vessels were 84% and 87% for the left anterior descending artery, 67% and 97% for the left circumflex artery, and 89% and 85% for the right coronary artery, respectively. Dipyridamole thallium-201 imaging is a relatively safe noninvasive method and is an effective alternative to exercise thallium-201 scintigraphy for the diagnosis of coronary artery disease.
 ...
PMID:Diagnosis of coronary artery disease using dipyridamole thallium-201 imaging. 763 92

Zidovudine delays the progression of infection and prolongs the survival of human immunodeficiency virus (HIV)-infected patients, but these benefits are limited by dose-related toxicity and the cost of the drug. Dipyridamole, in micromolar concentrations, acts synergistically with zidovudine, reducing the anti-HIV 95% inhibitory concentration of zidovudine 5- to 10-fold in vitro. We sought to establish a well-tolerated dose of dipyridamole for use in combination with zidovudine and to detect clinically significant pharmacokinetic interactions. Both objectives are essential for planning studies of the efficacy of the zidovudine-dipyridamole combination. Eleven asymptomatic HIV-infected subjects (median CD4+ cell count, 311 cells per mm3), 10 of whom had been on zidovudine at 500 mg/day for at least 6 months, were admitted to the study. Zidovudine pharmacokinetics were measured on day 1. Dipyridamole was then begun at 600 mg/day (subjects 1 to 3) or 450 mg/day (subjects 4 to 11), and zidovudine and dipyridamole pharmacokinetics were measured on day 5. All subjects given 600 mg of dipyridamole per day developed headache or nausea, or both. Six of eight subjects given dipyridamole at 450 mg/day developed headache or mild nausea that resolved after a median of 2 days. The area under the zidovudine concentration-time curve was not significantly different on day 1 in comparison with that on day 5 (P = 0.11). Symptoms were significantly correlated with the maximum zidovudine concentrations, which were achieved when dipyridamole was dosed concomitantly (p = 0.03). Total (free and protein-bound) dipyridamole trough concentrations were near those demonstrating synergy with zidovudine against HIV in vitro. Dipyridamole was highly protein bound, with a median free/total dipyridamole ratio of 0.7%; the percent free/total dipyridamole ratio was inversely correlated with alpha 1 acid glycoprotein concentrations (r2 =0.66). Results of the study indicate that adjustment of the zidovudine dose was not required to achieve equivalent zidovudine concentrations when zidovudine was administered in combination with dipyridamole at the doses studied. In the short study described here, the zidovudine-dipyridamole combinations was well tolerated in asymptomatic HIV-infected subjects after the occurrence of mild transient symptoms.
 ...
PMID:Effect of dipyridamole on zidovudine pharmacokinetics and short-term tolerance in asymptomatic human immunodeficiency virus-infected subjects. 806 34

The use of pharmacologic stress testing for detecting and assessing ischemic heart disease (IHD) is reviewed. Methods of diagnosing IHD are designed to emulate conditions that increase myocardial oxygen demand in order to identify areas of ischemia and atherosclerotic lesions and to evaluate their functional or anatomical importance. Diagnostic methods can be divided into functional assessment with stress testing and anatomical assessment with coronary angiography. Physical stressors, such as exercise or atrial pacing, or pharmacologic stressors, such as vasodilators or beta-adrenergic-receptor agonists, can be used in stress testing. Electrocardiography, thallium planar scintigraphy, echocardiography, and other techniques are used to evaluate the response to stress testing. Unlike exercise stress testing, pharmacologic testing does not require physical exertion. Adenosine, dipyridamole, and dobutamine are the principal agents used in pharmacologic stress testing. Adenosine and dipyridamole mediate coronary artery vasodilation. Adenosine, a direct agonist, has a rapid onset and short duration of action. Dipyridamole, the only agent with approved labeling for use in stress testing, inhibits adenosine indirectly. Dobutamine increases cardiac output and heart rate as well as promoting coronary artery vasodilation. Clinical trials show that all three drugs can be used safely and effectively in patients after acute myocardial infarction or before vascular surgery and in individuals with risk factors for or symptoms of IHD. The sensitivity and specificity of pharmacologic stress testing for detecting IHD are at least as high as those of exercise testing. Minor adverse effects, including chest pain, headache, and facial flushing, are common, but major adverse effects are rare. Pharmacologic stress testing can be used in patients who cannot undergo exercise testing and offers a noninvasive alternative to coronary angiography.
 ...
PMID:Pharmacologic stress testing: experience with dipyridamole, adenosine, and dobutamine. 816 Jun 85

Dipyridamole-induced coronary hyperemia with 201Tl myocardial perfusion scintigraphy can detect ischemic regions in individuals unable to perform adequate exercise, but it has several limitations. Symptom-limited exercise supplementation to intravenous dipyridamole can potentially overcome them, but the safety and diagnostic accuracy for this combination has not been established. Between 1987 and 1991, 441 consecutive patients were assessed for combined symptom-limited exercise test preceded by i.v. dipyridamole. Clinical records could not be obtained for 37 patients, and 40 patients were not exercised because they were unable; therefore 384 patients (mean age 58 +/- 9.8 yr, 278 men) underwent symptom-limited exercise preceded by 0.56 mg/kg of dipyridamole and followed by planar 201Tl perfusion scintigraphy. Following dipyridamole infusion, systolic blood pressure fell by 10 +/- 14 mmHg and heart rate increased by 8 +/- 11 bpm. Adverse effects were experienced by 77 people (dizziness in 44; headache in 11; nausea in 9; syncope in 2 and chest pain in 11). Exercise heart rate was 69% +/- 16% of predicted maximum and ST shift was -0.9 +/- 0.9 mm. Following exercise, seven patients required aminophylline (four after dizziness, two after headache, one after chest pain), which was uniformly successful. There were no episodes of prolonged chest pain, MI, death or serious arrhythmia. Safety was maintained for people with severe triple coronary artery disease, the elderly (> 70 yr) and those with significant pulmonary disease. Sensitivity was 95% for at least one with > 70% luminal stenosis and 94% for at least one with > 40% luminal stenosis. Specificity was 28% and 53% respectively. The addition of a symptom-limited exercise test to i.v. dipyridamole is safe for all groups of patients referred for 201Tl study.
 ...
PMID:Safety and clinical utility of combined intravenous dipyridamole/symptom-limited exercise stress test with thallium-201 imaging in patients with known or suspected coronary artery disease. 825 87

Dipyridamole stress 201Tl scintigraphy is widely used in the investigation of myocardial ischaemia. We report our experience of adverse effects observed during this diagnostic procedure. A prospective study was undertaken of 435 consecutive patients (mean age 59 years; 273 males) referred to two nuclear medicine departments for assessment of myocardial perfusion was undertaken. Patients were monitored prior to and following the infusion of dipyridamole. All symptomatic, haemodynamic and electrocardiographic changes were documented. No deaths occurred in this series. Adverse events were observed in 174 (40%) patients. Of these, three patients experienced 'major' adverse events (0.6%) requiring hospitalization (myocardial infarction = 1; chest pain = 1; simple partial seizure = 1). 'Moderate' adverse events occurred in 39 (8.9%) patients and required intravenous aminophylline to reverse effects (ST segment abnormalities = 26; nausea = 7 headache = 3; chest pain = 2; bronchospasm = 1; protracted vomiting = 1; diarrhoea = 1). 'Minor' adverse events were experienced by 132 (30.3%) patients and did not require aminophylline. Sixty per cent of our patients experienced no ill effects from dipyridamole given as an exercise substitute in conjunction with 201Tl imaging. The rest had symptoms which were mostly mild, although a few patients found the experience unpleasant. Only one patient experienced a life-threatening episode.
 ...
PMID:Safety of intravenous dipyridamole thallium myocardial perfusion imaging: experience in 435 patients. 847 71


1 2 Next >>