Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, a new nasal spray formulation of dihydroergotamine was developed which facilitates at-home treatment of migraine. We studied the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the acute treatment of classic and common migraine in two, identical, double-blind, randomized, placebo-controlled trials. Of the 229 patients enrolled, 206 (102 dihydroergotamine nasal spray, 104 placebo) were included in the intent-to-treat analyses; 182 treated two headaches and 24 treated one headache. Based on both the patients' and physicians' ratings, dihydroergotamine nasal spray was significantly superior to placebo for reducing the severity of headache pain in both studies, and in relieving nausea in Study 2. The onset of significant efficacy with dihydroergotamine nasal spray compared to that with placebo for both severity of headache pain and relief of nausea occurred at 1 hour in Study 2 and at 3 hours in Study 1. Dihydroergotamine nasal spray was also significantly superior to placebo for the relief of headache pain in both studies. Based on the physicians' global evaluations of treatment efficacy for headache pain, 71% of the dihydroergotamine-treated patients in Study 2 and 59% of their counterparts in Study 1 were considered to be responders. The dihydroergotamine-treated patients had less newly-occurring vomiting than the placebo-treated patients. The majority of adverse events reported by the dihydroergotamine-treated patients were nasopharyngeal. The results demonstrate the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine attacks.
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PMID:Efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine. Dihydroergotamine Nasal Spray Multicenter Investigators. 777 72

The effectiveness of dihydroergotamine administered by home subcutaneous injection by the patient or family for severe headache attacks was assessed retrospectively in 51 patients. Average follow-up was 21 weeks. Twenty-one patients had intermittent migraine attacks, 27 had transformed migraine with chronic daily headache, and 3 had chronic tension-type headache. Of the 51 patients taught home injection, 35% had an excellent overall response, 18% had a good response, 12% had a poor response but continued to use dihydroergotamine, and 35% had discontinued dihydroergotamine use. Side effects were the main reason for stopping dihydroergotamine. These included nausea or vomiting or both, limb pain or numbness or both, chest or throat tightness or both, and soreness at the injection site. Thirty-three patients (65%) continued to use dihydroergotamine at the end of the follow-up period. In patients who previously required injections from medical personnel for headache crises and in whom home injection of dihydroergotamine was effective, a dramatic reduction occurred in hospital emergency room and physician office utilization. Dihydroergotamine use by home injection can be an effective treatment for a significant proportion of patients with severe migraine including patients with transformed migraine and medication overuse.
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PMID:Effectiveness of subcutaneous dihydroergotamine by home injection for migraine. 898 85

Dihydroergotamine mesylate (DHE), an ergot alkaloid, has been extensively utilized and studied in the treatment of episodic and chronic migraine. This article reviews the pharmacokinetics, pharmacodynamics, and clinical efficacy and safety of DHE, particularly in comparison to ergotamine tartrate (ET), a similar ergot alkaloid with a long history of use in the treatment of migraine. Structural differences between these 2 compounds account for clinically important distinctions in their pharmacokinetic, pharmacodynamic, and adverse event profiles. DHE is a significantly less potent arterioconstrictor than is ET, which makes it a potentially much safer drug. In addition, DHE is associated with a markedly lower incidence of medication-withdrawal headache, nausea, and vomiting than is ET. The safety and efficacy data presented here are derived from clinical trials and case series involving DHE administered by intravenous infusion, intramuscular or subcutaneous injection, or intranasal spray.
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PMID:Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine. 1707 49

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms.
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PMID:DHE in the pharmacotherapy of migraine: potential for a larger role. 1707 53

Orally inhalable dihydroergotamine (iDHE), before the US Food and Drug Administration in 2013 for consideration for approval for acute treatment of episodic migraine in adults, is a user-friendly formulation of an older medication. Dihydroergotamine (DHE) has a heterogeneous receptor profile, central penetration, and persistent receptor binding that may account for its clinical prolonged benefits in acute treatment of migraine. The same features may result in the ability of DHE to reverse central sensitization and allodynia and to maintain efficacy deep into attacks. These characteristics make DHE particularly useful in treating migraine upon awakening, prolonged migraine and status migrainosus, menstrually related migraine, and for bridging patients out of medication-overuse headache/chronic migraine. The inhalable formulation has helpful pharmacokinetics, with a lower maximal serum concentration than intravenous DHE which may account for minimal nausea, and less binding to the potentially toxic serotonin2B receptor. The inhaler itself is designed for delivery of reproducible aliquots of intrapulmonary DHE with only nominal need for patient coordination. The inhalable form allows for bypassing the gastrointestinal tract in the setting of migraine nausea or vomiting, and greatly reduces first-pass effect. No drug-related serious adverse events were reported during the Phase 3 study of iDHE. Product taste and nausea were the most common side effects in both the Phase 3 regulatory trial and in the safety extension trial. Limitations for use of iDHE are those for any ergot or triptan, ie, contraindication in the setting of vascular disease. In addition, iDHE is metabolized by the cytochrome P450 3A4 liver enzymatic system. Inhalable DHE provides the promise of a new formulation of a valued medication with important clinical features, useful deep into attacks in a variety of situations.
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PMID:Orally inhaled dihydroergotamine: a review. 2402 2