Headache Meds

• Ergotamine alkaloids: Ergotamine, Dihydroergotamine


  • Bind to serotonin (5-HT1) receptors and dopamine receptors, leading to vasoconstriction, structurally similar to serotonin
  • Contraindicated with Angina and PVD
• Ergotamine

  • Sublingual, oral, rectal
  • Most effective when used in early stage of migraine
  • Can lead to rebound headaches so must exercise daily and have weekly dosage limits
• Dihydroergotamine

  • IV or intranasal
  • Limited to severe cases of migraines
• Triptans

  • Serotonin agonist at receptors (1B and 1D) on small peripheral nerves that innervate intracranial vasculature (intracranial and extra cerebral blood vessels), leading to vasoconstriction in vasculature of brain
  • Meninges: block release of inflammatory chemicals
  • Brainstem: inhibit pain impulses and may act on central pain perception
  • Bad taste, pain/pressure in chest/neck/throat/jaw, dizziness, increased BP, hypertensive crisis, MI
  • Contraindicated in uncontrolled HTN, stroke, PAD, ischemic CAD, use w/ MAO-A inhibitors (or within 2 wk of d/c) OR ergotamine meds OR w/ another 5-HT agonist
• CGRP Monocloncal antibodies

  • Human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) or to the CGRP receptor and antagonizes CGRP receptor function
  • Injection site rxn, hypersensitivity
  • Contraindicated in hypersensitivity to active ingredient, no data on pregnancy/lactation
  • Subcutaneous mostly, IV eptinezumab, most are monthly injections, injection/infusion every 3 months for eptinezumab and fremanezumab
  • For migraine prophylaxis
• CGRP Antagonists

  • Antagonist at CGRP receptor
  • Nausea, fatigue and xerostomia in ubrogepant, weight loss/anorexia in atogepant
  • Guidelines for initiating acute migraine tx include → contraindications to use of triptans or failure to respond to/tolerate at least 2 oral triptans
  • For acute tx of migraine for ubrogepant, prophylaxis for atogepant, both for rimegepant
• 5-HT1F Agonist

  • Highly selective 5-HT1F agonist, decrease activation and sensitization of trigeminal nerve system within meninges, act both centrally and peripherally
  • Does NOT activate 5-HT1B in peripheral vessels or induce vasoconstriction
  • Dizziness, sedation, paresthesia, hallucinations, euphoria, n/v, bradycardia (also tachycardia reported), increased BP, risk of serotonin syndrome (alone or with serotonergic drugs
  • Oral, do NOT drive or operate machinery at least 8 hours after a dose, controlled substance
  • Acute migraine tx, may reseve for pt who can't use triptans or failed 2 triptans
• What meds are available for headaches

  • NSAIDs, Acetaminophen
  • Ergotamine alkaloids
  • Triptans: Sumatriptan (Imitrex), -triptan ending
  • CGRP Monoclonal antibodies: -mab ending
  • CGRP Antagonists: Ubrogepant (Ubrelvy), Rimegepant, Atogepant
  • 5-HT1F Agonist: Lasmiditan