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)

Patients who had survived a stroke or transient ischaemic attacks (TIA) were admitted to a trial of low-dose aspirin (50 mg) alone, sustained release dipyridamole (400 mg/day) alone, or a combination of the two agents, and results compared with a placebo over 24 months. This low-dose aspirin regimen produced in pairwise comparisons a significant risk reduction of 18% for stroke, 13% for stroke and/or death but no reduction in all cause mortality. The sustained release dipyridamole produced a significant risk reduction of 16% for stroke, 15% for stroke and/or death but no significant reduction of mortality. In combination, aspirin and dipyridamole produced a risk reduction of 37% in stroke, 24% in stroke and/or death, and no reduction in mortality. Similar findings were found in TIA, which was a secondary endpoint. These results are highly significant in comparison with placebo. As expected, there were enhanced reports of alimentary side-effects in the aspirin groups and also enhanced bleeding. Dipyridamole was associated with a slight increase in headache, which resolved in most patients if therapy was continued. The conclusions are that 50 mg/day of aspirin alone or 400 mg/day of sustained release dipyridamole alone are equally effective in stroke and TIA prevention. When used in combination the effects were additive and were significantly more effective than the single agents.
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PMID:Secondary stroke prevention with low-dose aspirin, sustained release dipyridamole alone and in combination. ESPS Investigators. European Stroke Prevention Study. 978 30

Dipyridamole is used for secondary prophylaxis in ischemic stroke and as a vasodilator agent in myocardial scintigraphy. An important side effect to administering dipyridamole is headache. The aim of the current study was to investigate the effects of dipyridamole on cerebral blood flow, large artery diameter, and headache induction. Twelve healthy subjects were included in this single-blind placebo-controlled study in which placebo (0.9% NaCl) and dipyridamole 0.142 mg/kg x min were administered intravenously over 4 minutes 1 hour apart. Blood flow velocity in the middle cerebral artery (Vmax) was recorded by transcranial Doppler and regional cerebral blood flow in the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and 133Xenon-inhalation. Blood pressure, heart rate, and pCO2 were measured repeatedly. Headache response was scored every 10 minutes on a verbal scale from 0 to 10 (10 = worst). Dipyridamole caused a decrease in pCO2 (P < 0.001). pCO2 corrected rCBFmca was 41.7 +/- 6.9 mL/100 g x min after placebo versus 41.2 +/- 6.9 after dipyridamole (P > or = 0.05). pCO2 corrected Vmca decreased 8.4% +/- 11.7 (P < 0.001) after dipyridamole, indicating a mean 5.6% +/- 6.7 (P = 0.005) relative increase of the arterial diameter. After dipyridamole the median peak headache score was 2 (range 0 to 7) compared with 0 (range 0 to 3) after placebo (P = 0.02). Dilatation of the middle cerebral artery outlasted the headache response. In conclusion, dipyridamole causes a modest pCO2 independent dilatation of the MCA, which is time-linked to the onset, but not to the cessation, of headache.
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PMID:Dipyridamole dilates large cerebral arteries concomitant to headache induction in healthy subjects. 1099 59

Dipyridamole, an inhibitor of nucleoside transport, increases the activity of 5-fluorouracil in a dose-dependent manner. The purpose of the present study was to determine whether dipyridamole with 5-fluorouracil and leucovorin gave an improved therapeutic outcome. Sixty patients entered in the present pilot study had previously received 5-fluorouracil (450 mg/m2) and leucovorin (100 mg/m2), every week, and relapsed during this treatment, which ended at least 6 weeks prior to study entry. Dipyridamole was administered at three different dosing schedules (DS) and methods of administration in three groups of patients. DS I: dipyridamole, 30 mg/m2 in normal saline solution, in 90 min iv infusion, followed by leucovorin, 100 mg/m2 iv push, followed by 5-fluorouracil, 450 mg/m2 in normal saline solution, in 60 min iv infusion, dipyridamole tablets (75 mg) every 12 hrs, continuously during the time of chemotherapy. DS II: dipyridamole, 50 mg/m2 in normal saline solution, in 90 min iv infusion, and the rest was the same as DS I. DS III: without oral dipyridamole, patients received dipyridamole (50 mg/m2) iv in the same manner as in DS I and II. Treatment was continued until tumor progression or unacceptable toxicity. All patients (n = 60) entered in the present study were assessable for response and toxicity. No complete response was observed. No patient at DS I responded, whereas 2 patients at DS II and 3 at DS III had a partial response (P <0.1). Stable disease was found with DS I (n = 1), DS II (n = 8) and DS III (n = 9) (P <0.01). More patients progressed at DS I (n = 19) than at DS II (n = 10) and DS III (n = 8) (P <0.0007). The median duration of response was 11 weeks (range, 8-16). Time to progression was 17 weeks for DS I, 15 weeks (range, 10-19) for DS II, and 14 weeks (range, 11-21) for DS III (P = 0.43). Median survival did not differ significantly between DS I (29 weeks; range, 14-48), DS II(31.5 weeks; range, 17-63) and DS III (36 weeks; range, 16-58) (P = 0.2). Neutropenia was most severe with DS I (grade 2, P<0.01) and DS II (grade 1, P<0.05) and nausea/vomiting with DS I (grade 0, P < 0.0005, grade 1, P <0.0002, grade 2, P <0.02) and DS III (grade 3, P<0.0009). Diarrhea was most severe in DS II (grade 3, P <0.005). Mucositis was increased in DS II (grade 0, P <0.008), anorexia in DS II (grade 0, P <0.032) and fatigue in DS I (grade 0, P <0.003). More patients in DS I than with the other two DS experienced headache (P <0.044). According to the response achieved at DS III (15% partial response and 45% stable disease) and the toxicity which was well tolerated mainly in this DS (except for nausea and vomiting grade 3, P <0.009), it can be stated that DS III is the appropriate dose and the simplest schedule of administration (administration of dipyridamole during therapy only). In conclusion, it appears that dipyridamole might still have a role in enhancing the clinical activity of drugs involved in the inhibition of the thymidylate synthetase biochemical pathway and its activity in combination with these agents (5-fluorouracil + leucovorin) as frontline treatment should therefore be explored in future phase II studies.
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PMID:Leucovorin + 5-fluorouracil plus dipyridamole in leucovorin + 5-fluorouracil-pretreated patients with advanced colorectal cancer: a pilot study of three different dipyridamole regimens. 1176 78

Dipyridamole inhibits phosphodiesterase 5 (PDE5) and adenosine re-uptake. The most prominent side-effect is headache. We examined the migraine-generating effects of dipyridamole as well as the cerebral blood velocity response in a single-blind study, including 10 patients with migraine without aura and 10 healthy subjects. Dipyridamole 0.142 mg/kg per min was administered intravenously. Headache intensity was scored on a verbal rating scale along with pain characteristics and accompanying symptoms. Blood velocity in the middle cerebral artery (V(mca)), blood pressure and heart rate were recorded repeatedly. Headache was induced in all migraine patients and in eight of 10 healthy subjects (P = 0.47) with no significant difference in headache intensity (P = 0.53). However, five patients but only one healthy subject experienced the symptoms of migraine without aura, according to ICHD-2 criteria, within 12 h (P = 0.14). Four patients reported photophobia after dipyridamole compared with no healthy subjects (P = 0.087). V(mca) decreased (P < 0.001) during and after dipyridamole infusion with no difference between groups (P = 0.15) coinciding with initiation, but not cessation of immediate headache. Thus, dipyridamole induces symptoms of migraine and an initial decrease in V(mca) in migraine patients, but not significantly more than in healthy subjects. This relatively low frequency of migraine induction, compared with nitric oxide donors and sildenafil, is probably due to the less specific action of dipyridamole on the cGMP signalling pathway as well as a possible bidirectional effect of adenosine on migraine induction.
Cephalalgia 2006 Aug
PMID:Dipyridamole may induce migraine in patients with migraine without aura. 1688 28


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