Risk of ischemic complications related to the intensity of triptan and ergotamine use

Heijden, E A Wammes-van der; Rahimtoola, H.; Leufkens, H.G.M.; Tijssen, C.C.; Egberts, Toine C. G.

doi:10.1212/01.wnl.0000240128.76399.fa

Cited by 100 publications

(69 citation statements)

References 36 publications

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“…In recognition of the vasodilatory properties of CGRP, as well as concerns regarding the cardiovascular liabilities of the currently available ergot and triptan migraine treatments (MaassenVanDenBrink et al, 1998;Wammes-van der Heijden et al, 2006), multiple groups have conducted preclinical studies of the cardiovascular effects of CGRP receptor antagonism. There has been particular interest in the potential effect of CGRP receptor antagonism in the setting of myocardial ischemic injury, given that CGRP is stored in perivascular peripheral nerve terminals of sensory C-fibers in the heart and is released from activated peripheral nerve endings during myocardial ischemia (Franco-Cereceda and Liska, 2000).…”

Section: Introductionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide Receptor Antagonism Does Not Affect the Severity of Myocardial Ischemia during Atrial Pacing in Dogs with Coronary Artery Stenosis

Regan

Stump²,

Kane³

et al. 2008

J Pharmacol Exp Ther

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Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide that also has potent vasodilator activity. There are conflicting preclinical reports regarding the effect of CGRP receptor antagonism in the setting of myocardial ischemia. The present study was conducted in a canine model in which regional myocardial ischemia was reproducibly evoked by serial periods of atrial pacing (80 beats per min above baseline rate) in the presence of a 40% stenosis of the left anterior descending (LAD) coronary artery. Ischemia severity was quantitated by changes in unipolar epicardial electrograms (EG) recorded in the area of ischemia. In validation studies, the calcium entry blocker diltiazem reduced ischemia severity (before versus after treatment: ⌬EG, 1.92 Ϯ 0.23 versus 0.54 Ϯ 0.24 mV; p Ͻ 0.05) and tended to increase LAD flow (7.7 Ϯ 0.7 versus 9.4 Ϯ 1.4 ml/min; p ϭ 0.10), whereas the coronary constrictor serotonin increased ischemia severity (before versus after treatment: ⌬EG, 2.11 Ϯ 0.44 versus 4.90 Ϯ 1.46 mV; p Ͻ 0.05) concomitant with a reduction in LAD flow (9.1 Ϯ 1.1 versus 5.4 Ϯ 1.5 ml/min; p Ͻ 0.05). A 30 g/kg/min i.v. infusion test dose of the CGRP receptor antagonist CGRP was validated by demonstrating complete block of the depressor effects of exogenous i.v. 0.03 to 0.3 g/kg CGRP. This dose of CGRP , administered either intravenously or intra-atrially, had no effect on ischemia severity or paced LAD flow, indicating no intrinsic effect of CGRP receptor antagonism on the severity of acute myocardial ischemia. Likewise, the administration of a hemodynamically active dosing regimen of CGRP (0.03 g/kg/min i.v.) had no effect on paced coronary flow or ischemia severity, suggesting no major role of CGRP in regulating ischemic blood flow.Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide widely distributed throughout the central and peripheral nervous systems (Brain and Grant, 2004). CGRP has been proposed to play a role in the pathophysiology of migraine based upon correlative changes in circulating CGRP concentrations during spontaneous and nitrate-induced migraine and during migraine treatment with triptans, as well as the provocation of headache with exogenous CGRP infusion in migraineurs (Edvinsson, 2007;Goadsby, 2008). Clinical studies demonstrating efficacy with two CGRP receptor antagonists, the parenteral agent olcegepant (BIBN4096BS) (Doods et al., 2000;Olesen et al., 2004) and the orally available MK-0974 (telcagepant) (Ho et al., 2008;Salvatore et al., 2008), have confirmed CGRP to be an important mediator of migraine.CGRP also possesses direct and potent vasorelaxant properties (Brain and Grant, 2004). In recognition of the vasodilatory properties of CGRP, as well as concerns regarding the cardiovascular liabilities of the currently available ergot and triptan migraine treatments (MaassenVanDenBrink et al., 1998;Wammes-van der Heijden et al., 2006), multiple groups have conducted preclinical studies of the cardiovascular effects of CGRP receptor antagonism. There has been parti...

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Section: Introductionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide Receptor Antagonism Does Not Affect the Severity of Myocardial Ischemia during Atrial Pacing in Dogs with Coronary Artery Stenosis

Regan

Stump²,

Kane³

et al. 2008

J Pharmacol Exp Ther

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“…One exception is patients with known cardiovascular disease or significant cardiovascular risk factors because of the medication's vasoconstricting properties and the risk for ischemia. 3 Healthy patients who take these medications as prescribed are at low risk for developing adverse events. However, patients who experience refractory headaches may inadvertently overuse these agents in an attempt to reduce their pain and disability.…”

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confidence: 99%

Ischemic Colitis Related to Sumatriptan Overuse

Hodge

Hodge²

2010

The Journal of the American Board of Family Medicine

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Background: Serotonin-1 5-hydroxytryptamine (5-HT 1) receptor agonists are first line agents for migraine headaches. Patients with refractory headaches may use supratherapeutic doses of these medications. Described is a case of ischemic colitis related to overuse of sumatriptan.Case: A 35-year-old woman presented with severe abdominal pain without diarrhea or hematochezia. For several days prior she had been self-treating a refractory migraine headache with frequent doses of sumatriptan. She is a nonsmoker and took no oral contraceptives or other serotonin agonists. A computed tomography scan of the abdomen revealed left-sided colitis. A colonoscopy with biopsy confirmed ischemic colitis and excluded inflammatory bowel disease (IBD).Discussion: Previously published case reports have suggested an association between 5-HT 1 receptor agonists and ischemic colitis. These reports have been dismissed because the patients were taking oral contraceptives, serotonin agonists, or had other comorbidities. This healthy patient lacked risk factors for ischemia, is the youngest to be reported, and is the first without hematochezia.Conclusion :

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“…Though alternatives such as progesterone-only oral contraceptives have not demonstrated any increased risk of stroke, further research is warranted. 71 While triptan use in migraine patients has been shown to be generally safe, 23,25 ergotamine use should be avoided in patients with migraines, both as a treatment for migraine and for other disorders. Patients with migraines and stroke should avoid triptans as well.…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular Disease and Migraine

Star

Biller

2015

Headache and Migraine Biology and Management

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Risk of ischemic complications related to the intensity of triptan and ergotamine use

Abstract: In general practice, triptan overuse does not increase the risk of ischemic complications. Overuse of ergotamine may increase the risk of these complications, especially in those simultaneously using cardiovascular drugs.

Cited by 100 publications

References 36 publications

Calcitonin Gene-Related Peptide Receptor Antagonism Does Not Affect the Severity of Myocardial Ischemia during Atrial Pacing in Dogs with Coronary Artery Stenosis

Calcitonin Gene-Related Peptide Receptor Antagonism Does Not Affect the Severity of Myocardial Ischemia during Atrial Pacing in Dogs with Coronary Artery Stenosis

Ischemic Colitis Related to Sumatriptan Overuse

Cerebrovascular Disease and Migraine

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