Sumatriptan (Imitrex) for Migraine ================================== þ Imitrex Nasal Spray - 20 mg single-dose units (also 5 mg but 20 mg is standard) - $27/dose retail price (6/97) ------------------------------------------------- Date sent: Sun, 18 May 1997 08:36:16 -0500 Send reply to: "EMED-L is a list for hospital based emergency medicine practitioners." From: "Donald Dixon, MD, FACEP" Subject: Sumatriptan and arrhythmias To: Multiple recipients of list EMED-L Has anyone had any experience with sumatriptan (Imitrex) and ischemic chest pain and arrhythmias? A CASE: 45 yo female, nonsmoker, negative family Hx of CAD developed chest tightness with radiation to arm while traveling through our area. Driven by son the ED she presented to triage anxious, hyperventilating and obviously in distress. She then became unresponsive and was rushed back to the resuscitation room, found to be in ventricular fibrillation and countershocked into sinus rhythm. EKG #1 showed ? atrial strain pattern but no ischemic changes. EKG #2 (30 minutes later) was normal in all respects. All labs including CPK isos were normal with the exception of a K+ of 2.8. ABGs: pH 7.39, pO2 534 pCO2 32 BE 0 while being "assisted" with BVM post arrest. Stat cardiac echo revealed ? LV wall motion abnormality so patient was taken to cath lab. Normal cath with clean coronary arteries. Because patient had been travelling ? of PE was raised. Normal VQ (don't know why they didn't just do PAgram in cath lab). The patient had no history of any symptoms suggestive of prior arrhythmia or ischemia. Longterm meds were Synthroid (after partial thyroidectomy for Graves) and Fiorinal for migraines. However, the patient had been started on oral sumatriptan two week prior to arrest. It is unclear whether she took any on the day of arrest (she is a little amnestic about the hour or two prior to event) but the son mentioned she had complained of a "mild" headache while traveling. ABSTRACTS: Title Vasospasm-induced myocardial infarction with sumatriptan. Author Mueller L; Gallagher RM; Ciervo CA Address Department of Family Practice, University Headache Center, Moorestown, NJ 08057, USA. Source Headache, 1996 May, 36:5, 329-31 Abstract Sumatriptan, a 5-hydroxytryptamine1, (5-HT1) receptor agonist is an effective abortive agent for migraine headaches. A common side effect in 3% to 7.9% of patients is chest pain. Although most cases of chest pain are not thought to be of cardiac origin, its mechanism is not entirely understood. Rare examples of electrocardiogram changes consistent with transient ischemia have been reported. Isolated instances of angina, arrhythmia, myocardial infarction, and death have been temporally associated with sumatriptan administration. In most cases, it is unclear whether underlying cardiovascular disease existed or contributed to this adverse event. We report the history of a 56-year-old female patient with migraine who experienced a myocardial infarction shortly after using sumatriptan, despite having had a normal cardiovascular evaluation. As she had a normal cardiac catheterization after the event, we find it probable that sumatriptan induced coronary vasospasm and myocardial infarction. Title Chest symptoms after sumatriptan: a two-year clinical practice review in 735 consecutive migraine patients. Author Visser WH; Jaspers NM; de Vriend RH; Ferrari MD Address Department of Neurology, University Hospital, Leiden, The Netherlands. Source Cephalalgia, 1996 Dec, 16:8, 554-9 Abstract OBJECTIVES: To assess, in clinical practice, the (i) incidence, (ii) within-patient consistency, and (iii) clinical spectrum of chest symptoms (chest symptoms) after subcutaneous (sc) and oral sumatriptan, and (iv) to identify risk factors for chest symptoms. Design: Two-year retrospective survey with mailed self-administered questionnaire. Setting: Neurology outpatient clinic of university hospital. SUBJECTS: Migraine patients with or without aura (n = 869). MAIN OUTCOME MEASURES: Incidence, within-patient consistency and characteristics of chest symptoms; demographic and clinical characteristics of patients. RESULTS: There were 735 (85%)respondents. Sumatriptan was used by 453 patients, during 25 months (median), for 28000 attacks (median: 33 attacks/patient). Of sumatriptan users, 41% (sc) and 24% (oral) had chest symptoms in all attacks, 39% (sc) and 58% (oral) in none, and the remaining in some attacks. Because of chest symptoms, 10% discontinued sumatriptan. Chest symptoms mostly consisted of heavy arms and chest pressure, started within 5 (sc) to 30 (oral) min, and lasted 30 (sc) to 60 (oral) min. Compared with patients without chest symptoms, patients with chest symptoms more often were females and younger, and went to rest immediately after sumatriptan administration (all p < 0.001); they also tended to have lower body mass indices, more severe attacks and less efficacy of sumatriptan (all 0.001 < p < 0.05). Patients with chest symptoms had no higher incidence of cardiovascular symptoms or risk factors. CONCLUSIONS: Chest symptoms are frequent, within-patients consistent, but rarely important, adverse events of (notably sc) sumatriptan. The risk of chest symptoms is patient-dependent and not related, even opposite, to cardiovascular disease. This contradicts the hypothesis that chest symptoms after sumatriptan are caused by cardiac ischemia. Patient acceptance of chest symptoms is improved by pre-advising on the risk and nature of chest symptoms. Title Augmented contraction of the human isolated coronary artery by sumatriptan: a possible role for endogenous thromboxane. Author Maassen VanDenBrink A; Bax WA; Ferrari MD; Zijlstra FJ; Bos E; Saxena PR Address Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands. Source Br J Pharmacol, 1996 Nov, 119:5, 855-62 Abstract 1. The antimigraine drug, sumatriptan, contracts the human coronary artery and, in some patients, elicits chest symptoms (e.g. pressure and pain), particularly after subcutaneous administration. We studied the effects of the thromboxane A2 (TxA2) analogue, U46619 and endothelin-1 on contractile responses to sumatriptan in the human isolated coronary artery as well as the role of endogenously produced TxA2 and endothelin-1 in contractions evoked by sumatriptan. 2. In the presence of U46619 (1 and 3 nM), mean concentration-response curves to sumatriptan in the human coronary artery were shifted vertically due to the initial contraction by U46619, but when this initial contraction was subtracted from the response to sumatriptan, no significant augmentation was observed. However, analysis of the degree of augmentation in individual arterial segments revealed that the augmentation was variable and related inversely to the Emax of sumatriptan in the absence of U46619 (r = 0.78 and 0.81 for 1 and 3 nM, respectively; P < 0.05). 3. Treatment with the TxA2 receptor antagonist, SQ30741 (100 nM), or incubation of vessel segments with aspirin (10 microM), significantly reduced responses to sumatriptan; in aspirin-treated vessel segments, SQ30741 failed to decrease further the contractions to sumatriptan. The decrease in Emax of sumatriptan by both SQ30741 and aspirin correlated significantly with the Emax of sumatriptan without SQ30741 (r = 0.74; P < 0.01) or aspirin (r = 0.94; P < 0.01). In aspirin-treated vessel segments, responses to sumatriptan were significantly augmented in the presence of U46619 (3 nM; P < 0.05). 4. The specificity of SQ30741 was demonstrated by its ability to antagonize coronary artery contractions to U46619 (pA2: 7.54 +/- 0.30), but not endothelin-1. Similarly, incubation with aspirin (10 microM) did not affect contractile responses to endothelin-1, but significantly reduced TxA2 production in coronary artery segments as judged by a decrease in thromboxane B2 (TxB2) from 4.77 +/- 0.98 to 1.38 +/- 0.36 ng g-1 2 h-1. 5. Endothelin-1 (1 nM) did not significantly augment contractions to sumatriptan; there was also no relationship between the degree of augmentation and the control Emax of sumatriptan in the absence of endothelin-1. Furthermore, unlike SQ30741 or aspirin, a high concentration (100 nM) of the non-selective ETA/ETB receptor antagonist, SB 209670, failed to affect contractile responses to sumatriptan. However, SB 209670 potently antagonized coronary artery contractions induced by endothelin-1 with a pA2 of 8.84 +/- 0.32. 6. Compared to control vascular segments, endothelial denudation did not reduce TxA2 production (with endothelium = 2.56 +/- 1.38 vs. without endothelium = 12.32 +/- 4.94 ng TxB2 g-1 2 h-1), suggesting that the production of TxA2 is not confined to the endothelium. The sumatriptan-induced contractions were also unaffected by endothelial denudation. 7. The results of the present study suggest that endogenously produced TxA2 enhances contractions to sumatriptan in the human isolated coronary artery. Such a mechanism may play a role in causing chest symptoms after sumatriptan by potentiating coronary vascular contraction by sumatriptan in vivo. Regards, **************************************** Donald Dixon, MD, FACEP - donauw@dwave.net Director, Emergency Medical Education Wausau Hospital, Wausau, WI ****************************************