Pharmacodynamic
Pharmacokinetics
Oral bioavailability is poor and it is not available in oral form in the US. DHE is available as a nasal spray and in ampules for subcutaneous, intramuscular and intravenous injection. Efficacy is variable in the nasal spray form with relative bioavailability of 32% compared to injection. Contraindications
Contraindications for DHE include: pregnancy, renal or hepatic failure, coronary, cerebral, and peripheral vascular disease, hypersensitivity reactions, sepsis, and uncontrolled hypertension. History
Dihydroergotamine (DHE) is a semi-synthetic form of ergotamine approved in the US in 1946. Society and culture
Brand names
Brand names of DHE include Diergo, Dihydergot, D.H.E. 45, Ergont, Ikaran, Migranal, Orstanorm, and Seglor, among others. European Union
In 2013 the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that medicines containing ergot derivatives no longer be used to treat several conditions involving problems with memory, sensation or blood circulation, or to prevent migraine headaches because the risks (increased risk of fibrosis and ergotism) were said to be greater than the benefits in these indications. References
External links
"Dihydroergotamine". Drug Information Portal. U.S. National Library of Medicine. "Dihydroergotamine mesylate". Drug Information Portal. U.S. National Library of Medicine.
Microscopic polyangiitis is an ill-defined autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation. Signs and symptoms
Clinical features may include constitutional symptoms like fever, loss of appetite, weight loss, fatigue, and kidney failure. A majority of patients may have blood in the urine and protein in the urine. Rapidly progressive glomerulonephritis may occur. Because many different organ systems may be involved, a wide range of symptoms are possible in MPA. Purpura and livedo racemosa may be present. Cause
While the mechanism of disease has yet to be fully elucidated, the leading hypothesis is that the process is begun with an autoimmune process of unknown cause that triggers production of p-ANCA. These antibodies will circulate at low levels until a pro-inflammatory trigger—such as infection, malignancy, or drug therapy. The trigger upregulates production of p-ANCA. Then, the large number of antibodies make it more likely that they will bind a neutrophil. Once bound, the neutrophil degranulates. The degranulation releases toxins that cause endothelial injury. Most recently, two different groups of investigators have demonstrated that anti-MPO antibodies alone can cause necrotizing and crescentic glomerulonephritis. Diagnosis
Laboratory tests may reveal an increased sedimentation rate, elevated CRP, anemia and elevated creatinine due to kidney impairment. An important diagnostic test is the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) with myeloperoxidase specificity (a constituent of neutrophil granules), and protein and red blood cells in the urine. In patients with neuropathy, electromyography may reveal a sensorimotor peripheral neuropathy.