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  • 1
    ISSN: 1432-1041
    Keywords: 5-isosorbide-mononitrate ; Headache ; haemodynamics ; vasodilation ; peripheral arteries ; cranial arteries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale. A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery. It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 77-79 
    ISSN: 1432-1041
    Keywords: methysergide ; methylergometrine ; 5-HT antagonism ; migraine therapy ; human temporal artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Methylergometrine, the main metabolite of methysergide, has 40-times greater 5 HT antagonistic potency than methysergide in isolated segments of human temporal artery. It is suggested that methylergometrine is the “active” drug when methysergide is used in migraine prophylaxis, and that the two compounds should be compared in prophylactic trials in migraine.
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  • 3
    ISSN: 1432-1041
    Keywords: Flunarizine ; nimodipine ; cerebral artery ; temporal artery ; in vitro pharmacology ; migraine ; cerebral ischaemia ; arterial contraction ; arterial relaxation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of the calcium entry blockers flunarizine and nimodipine on isolated human cerebral and temporal arteries has been studied. Flunarizine induced only weak relaxation of precontracted temporal arteries in contrast to the response seen in cerebral arteries. Nimodipine invariably induced strong relaxation of both types of vessel. The effect of the calcium entry blockers on potassium (K+)-, noradrenaline (NA)- and 5-hydroxytryptamine (5-HT)-induced contraction was also examined. In general, the K−-induced contraction was inhibited by both calcium entry blockers, nimodipine being more potent than flunarizine, the cerebral artery being more sensitive. The response to K+ consisted of two phases; the second, slowly developing phase of contraction was more sensitive to either blocker than the initial, fast phase of contraction. Flunarizine was significantly more potent in inhibiting NA-induced contraction of the human cerebral than of the temporal artery, and there was no difference in its action on 5-HT-induced contraction of either artery. The same pattern was found for nimodipine, which was more potent in every aspect. Both calcium entry blockers induced a parallel shift in calcium-induced contraction studied by application of calcium to vessels preincubated in calcium free medium. Flunarizine was more potent on cerebral than on temporal arteries and there was no difference between the two vessels in this action of nimodipine. However, the latter was more potent than flunarizine in preventing calcium-induced contraction. The clinical implications of the two agents are discussed in relation to cerebrovascular disorders.
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  • 4
    ISSN: 1432-1041
    Keywords: nitroglycerin ; ergotamine ; ergotism ; arteries ; peripheral blood pressure ; human artery contraction ; migraine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ergotamine was used to induce arterial contraction in vitro (measurement of isometric tension in segments from 3 human temporal arteries) and in vivo (peripheral systolic blood pressure measured by strain gauge plethysmography in 5 migrainous patients). In both these models of ergotism, the directly acting vasodilator nitroglycerine (NTG) effectively relieved the ergotamine-induced arterial contractions. A case of ergotism treated succesfully with NTG infusion is reported. The diagnosis was based on history and measurement of peripheral systolic blood pressure by strain gauge plethysmography. The latter technique was also used to monitor the response to treatment for 20 h. Blood levels of ergotamine during ergotism were in the therapeutic range. Possible explanations for this finding are discussed.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 235-240 
    ISSN: 1432-1041
    Keywords: ergotamine ; pharmacokinetics ; migraine ; plasma drug levels ; i.v. administration ; i.m. administration ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2–3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with an initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90–155 min). The mean total plasma clearance was 11.0 ml kg−1 min−1, and the volume of distribution (Vdβ ) was 1847.6 ml kg−1. Individual t1/2β showed a positive linear correlation with the individual Vdβ . The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3–60.8%).
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 47-50 
    ISSN: 1432-1041
    Keywords: Nitroglycerin ; Headache ; tolerance ; nitric oxide ; arterial responses ; ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nitroglycerin-(NTG)-induced headache and dilatation of the radial artery were followed in a double blind, randomized, placebo-controlled, cross-over study in 6 healthy volunteers. NTG 0.5 μg · kg−1 · min−1 or saline were infused IV for 7 h, and subsequently the infusion rate was doubled for 10 min. The radial artery diameter was measured repeatedly with high frequency ultrasound and pain was scored using a 10 point verbal scale. After 5 min of NTG infusion both headache and the arterial diameter differed significantly from baseline, and no further significant change occurred. The intensity of the headache was mild to medium (median headache score 3, range 1–7). The mean dilatation of the radial artery was 36%. The dilatation in each individual, was stable over time, both during NTG and placebo, and it did not change with the double infusion rate. The headache score in each individual was more fluctuan. No tolerance either to the NTG-induced headache or arterial dilatation was observed.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 61-66 
    ISSN: 1432-1041
    Keywords: ergotamine ; pharmacokinetics ; blood/plasma concentration ratio ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ergotamine tartrate 0.5, 0.25 and 0.125 mg was administered i.v. to 6 volunteers in a cross-over study. Its pharmacokinetic characteristics were evaluated from plasma concentration-time data determined by HPLC. The clearance and volume of distribution were independent of the dose. The ratio between blood and plasma ergotamine concentrations in 4 subjects ranged from 0.41–0.67, indicating the lack of binding to blood cells. Ergotamine was found to be a high clearance drug, average 2.21/min/70kg body wt. suggesting extrahepatic clearance. A possible transient decrease in liver blood flow caused by ergotamine did not seem to affect the linearity of its kinetics.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 75-77 
    ISSN: 1432-1041
    Keywords: methysergide ; methylergometrine ; first-pass metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy men were given 1.0 mg methysergide maleate intravenously and 2.7 mg methysergide maleate orally in a cross-over study. The systemic availability of methysergide was only 13%, most probably due to a high degree of first-pass metabolism to methylergometrine. We also found evidence of extrahepatic clearance of methysergide. After oral administration the plasma concentrations of the metabolite were considerably higher than those of the parent drug and the area under the plasma concentration curve (AUC) for methylergometrine was more than ten times greater than for methysergide. Our findings may be relevant to the treatment of migraine if methylergometrine contributes to the effect of methysergide. Methylergometrine had a significantly longer elimination half-life than methysergide (223±43 min vs 62.0±8.3 min and 174±35 min vs 44.8±8.1 min in the oral and intravenous studies respectively).
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  • 9
    Publication Date: 1986-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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  • 10
    Publication Date: 1985-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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