Tolerability of sumatriptan: Clinical trials and post-marketing experience
ABSTRACT Through December 1998, sumatriptan had been used to treat more than 236 million migraine attacks world-wide. In clinical trials alone, more than 88000 migraine patients had treated more than 300000 migraine attacks with sumatriptan, and 2000 normal healthy volunteers had been exposed to the drug. This paper describes the safety and tolerability profile of sumatriptan in three sections: adverse events reported in clinical trials, special issues, and spontaneous post-marketing reports of adverse reactions. Data from the extensive clinical trials programme coupled with information from nearly 10 years of experience in clinical practice demonstrate that sumatriptan is generally well-tolerated, with an acceptable benefit-risk ratio when used properly. Significant cardiovascular and cerebrovascular events are rare but have been observed. This fact highlights the need for careful patient selection and vigilant adherence to the prescribing recommendations for sumatriptan. The wealth of clinical trials and post-marketing information for sumatriptan may be useful in guiding prescribing decisions for members of this class of drugs.
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- "The development (Humphrey et al., 1990) and clinical use of sumatriptan (Ferrari, 1998) initiated a cascade of mechanistic and therapeutic advances that has included several other triptans that all share the property of being serotonin (5-HT 1B/1D ) agonists (Goadsby, 2000). The search for novel non-vasoconstrictor treatments of acute migraine continues because of the potential safety bene®ts (Welch et al., 2000) such a strategy would offer, and the considerable mechanistic insight that would be generated if it were clear that non-vascular medicines were effective. "
ABSTRACT: There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperitoneally), and prepared for physiological monitoring. The superior sagittal sinus (SSS) was stimulated electrically, and linked units were recorded in the trigeminocervical complex. Post-stimulus histograms were constructed to analyse the responses and the effect of drug administration. Blood was sampled from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3-100 microg/kg) had a dose-dependent inhibitory effect on SSS-evoked trigeminal activity. The maximal effect (80 +/- 6% reduction in probability of firing) was seen at 100 microg/kg. The neuronal inhibitory effect of GR79236 could be inhibited by the selective adenosine A1 receptor antagonist DPCPX (300 microg/kg; P < 0.05). SSS stimulation increased cranial CGRP levels from 33 +/- 2 pmol/l (n = 6) to 64 +/- 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 microg/kg; P < 0.01). The selective low efficacy adenosine A1 receptor agonist, GR190178 (30-1000 microg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion. In this model of trigeminovascular nociception, adenosine A1 receptor activation leads to neuronal inhibition without concomitant vasoconstriction, suggesting a novel avenue for the treatment of migraine and cluster headache.Brain 07/2002; 125(Pt 6):1392-401. · 10.23 Impact Factor
Article: This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the author's clinical recommendations. Stereotactic Radiosurgery for the Management of Brain Metastases[Show abstract] [Hide abstract]
ABSTRACT: A 50-year-old man with a history of locally advanced non-small-cell lung cancer pre - sents with moderately severe headaches and mild numbness of the right arm. He is functionally independent and has no coexisting medical conditions. His neurologic examination is normal except for some diminished sensation in the right arm. Mag- netic resonance imaging (MRI) of the brain reveals a single lesion, 2.5 cm in diameter, in the left parietal region, with a moderate amount of edema. Additional testing shows no evidence of extracranial disease. He is treated with dexamethasone, with rapid improvement of his symptoms. His physicians recommend whole-brain radia- tion therapy followed by stereotactic radiosurgery.
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ABSTRACT: IGRAINE is a common, chronic, incapac- itating neurovascular disorder, characterized by attacks of severe headache, autonomic nervous system dysfunction, and in some patients, an aura involving neurologic symptoms. 1,2 Recent ad- vances in basic and applied clinical neuroscience 3 have led to the development of a new class of selective se- rotonin (5-hydroxytryptamine (5-HT)) receptor ago- nists that activate 5-HT 1B and 5-HT 1D (5-HT 1B/1D ) re- ceptors and are known as the triptans; these agents have changed the lives of countless patients with mi- graine. Despite such progress, migraine remains un- derdiagnosed and the available therapies underused. 4 In this article, we review the current understanding of the epidemiology, pathophysiology, and treatment of migraine.