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Basic Science
Pharmacology
11 notes available
1 Last Minute Review 2 Neuropharmacology Principles 3 Antiepileptic Drugs 4 Movement Disorder Pharmacology 5 Neuromuscular Pharmacology 6 Headache Pharmacology 7 Pain & Anesthesia Pharmacology 8 Psychopharmacology 9 Stroke & Vascular Pharmacology 10 Immunotherapy & MS Pharmacology 11 Antimicrobials & CNS Infections
Basic Science › Pharmacology

Headache Pharmacology

Headache Pharmacology

What You'll Learn

  • Acute migraine agents: triptans (5-HT1B/1D), gepants (CGRP antagonists), ditans (5-HT1F), DHE, and their contraindications
  • Preventive migraine therapies: beta-blockers, topiramate, valproate, amitriptyline, CGRP monoclonal antibodies, onabotulinumtoxinA
  • Indications for starting preventive therapy (≥4 migraine days/month, significant disability, medication overuse)
  • Medication overuse headache thresholds and management (triptans >10 d/mo, analgesics >15 d/mo)
  • Cluster headache acute (high-flow O2, sumatriptan SC) and preventive (verapamil, lithium) treatments
  • Trigeminal neuralgia pharmacology: carbamazepine first-line, oxcarbazepine, surgical options
  • Indomethacin-responsive headache syndromes (hemicrania continua, paroxysmal hemicrania, primary cough/exertional)
HighYield Pearls
  • Triptans (5HT1B/1D agonists): CONTRAINDICATED in CAD, uncontrolled HTN, hemiplegic migraine, basilar migraine, recent stroke/TIA, peripheral vascular disease, vasospastic angina, pregnancy (relative); SC sumatriptan is the fastest-onset triptan and the go-to for cluster headache; 24h gap required from DHE.
  • Gepants (CGRP-receptor antagonists — ubrogepant, rimegepant, zavegepant, atogepant): NO vasoconstriction and no triptan-like CAD/stroke contraindication → useful when triptans are contraindicated; rimegepant and atogepant double as preventives; no serotonin syndrome risk. Use clinical caution in active/unstable vascular disease — pivotal trials often excluded unstable CV disease; long-term high-risk safety data remain limited.
  • Ditans (lasmiditan, 5HT1F agonist): NO vasoconstriction and no triptan-like CAD/stroke contraindication; Schedule V; mandatory 8-hour driving restriction after each dose due to sedation/dizziness. Use clinical caution in active/unstable vascular disease (limited data).
  • DHE and ergots: Non-selective ergot for status migrainosus (IV protocol); CONTRAINDICATED with triptans (24h gap), in pregnancy, CAD, uncontrolled HTN, and with CYP3A4 inhibitors. AVOID opioids and butalbital — high medication-overuse-headache (MOH) risk and inferior efficacy.
  • ED/status migrainosus — MENU of options (not all-at-once): dopamine-antagonist antiemetic (metoclopramide or prochlorperazine; pretreat with diphenhydramine for akathisia/dystonia), NSAID (IV ketorolac), IV fluids when needed, IV magnesium in selected patients (aura/menstrual), IV valproate in selected non-pregnant patients (avoid in pregnancy and significant hepatic disease), DHE protocols, occipital nerve block. Antiemetics are effective MONOTHERAPY for acute migraine in the ER.
  • Oral preventives: Propranolol/metoprolol (β-blockers); topiramate → cognitive slowing, kidney stones, weight loss, cleft lip/palate (AVOID in pregnancy); valproate → teratogen (neural tube defects, AVOID in pregnancy); amitriptyline (covers tension-type + migraine, anticholinergic + cardiac conduction risk); venlafaxine and nortriptyline as alternatives; candesartan (ARB); memantine off-label for chronic migraine.
  • CGRP-targeting preventives (erenumab, fremanezumab, galcanezumab, eptinezumab; oral atogepant/rimegepant): FIRST-LINE options for migraine prevention per AHS 2024 position statement — do not require failure of oral preventives as a biologic rule (though insurance step therapy may lag). Erenumab → constipation and possible HTN; use caution in Raynaud’s; AVOID in pregnancy. OnabotulinumtoxinA (PREEMPT protocol, 155–195 U q12 weeks) is approved ONLY for CHRONIC migraine (≥15 headache days/month).
  • Cluster headache: Acute = 100% O2 + SC sumatriptan; prophylaxis = verapamil HIGH-DOSE (baseline + serial ECGs for PR prolongation/AV block), galcanezumab (episodic cluster), GON block as bridge, lithium for chronic cluster.
  • MOH (medication overuse headache): Triptans/ergots/opioids/combination analgesics >10 days/month OR simple analgesics >15 days/month for >3 months → management = withdraw offender, bridge therapy, start preventive.
  • Pregnancy & pediatrics: Pregnancy acute migraine → acetaminophen ± metoclopramide first; sumatriptan may be considered with caution when needed (best pregnancy safety data among triptans); AVOID ergots, valproate, topiramate. Pediatric prevention = amitriptyline or topiramate (CHAMP trial — both not superior to placebo, but still used). AVOID serotonergic combos (triptan + MAOI; caution with SSRI/SNRI — serotonin syndrome risk small but recognized).
🔍 Quick ReferenceMechanism · Adverse effects · Use / pregnancy
Mechanism
  • Triptans (sumatriptan, rizatriptan, eletriptan) → 5-HT1B/1D agonists → cranial vasoconstriction + inhibit trigeminal nociceptive transmission
  • Gepants (ubrogepant, rimegepant, atogepant, zavegepant) → small-molecule CGRP RECEPTOR antagonists
  • Ditans (lasmiditan) → selective 5-HT1F agonist — NO 5-HT1B activity → NO vasoconstriction
  • CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) → monoclonal antibodies vs CGRP ligand (all except erenumab) or CGRP receptor (erenumab)
  • DHE / ergots → non-selective 5-HT1B/1D + alpha-adrenergic + dopaminergic agonist
  • OnabotulinumtoxinA (PREEMPT) → blocks SNAP-25 → inhibits release of acetylcholine and CGRP from peripheral trigeminal nociceptors
  • Topiramate → Na+ channel block, AMPA/kainate antagonism, GABA potentiation, carbonic anhydrase inhibition
  • Valproate → ↑ GABA, Na+ channel block, T-type Ca²+ inhibition
  • Verapamil → non-dihydropyridine L-type Ca²+ channel blocker — cluster prophylaxis of choice
  • Antiemetics (metoclopramide, prochlorperazine) → D2 dopamine receptor antagonists
Adverse effects / contraindications
  • CAD, uncontrolled HTN, hemiplegic/basilar migraine, recent stroke → triptans and DHE CONTRAINDICATED (use gepant or ditan)
  • Cognitive slowing + kidney stones + weight loss + metabolic acidosis + cleft lip/palate + oligohidrosis → topiramate
  • Teratogen — neural tube defects, ↓ IQ, hepatotoxicity, pancreatitis, hyperammonemia, thrombocytopenia → valproate (AVOID in pregnancy)
  • Anticholinergic effects + QT prolongation + orthostasis + weight gain → amitriptyline / TCAs
  • Constipation + injection-site reaction + possible HTN + Raynaud’s caution → erenumab (CGRP-R mAb)
  • Sedation, dizziness, 8-hour driving ban, Schedule V → lasmiditan (ditan)
  • PR prolongation / AV block — ECG-monitored uptitration → high-dose verapamil (cluster)
  • Tremor, polyuria, polydipsia, hypothyroidism, nephrogenic DI, narrow therapeutic index → lithium (chronic cluster)
  • Akathisia and acute dystonia in ER → metoclopramide / prochlorperazine (pretreat with diphenhydramine)
  • Serotonin syndrome (clonus, hyperreflexia, autonomic instability) → triptan or DHE + MAOI; caution with SSRI/SNRI
  • Neck/jaw/chest tightness (“triptan sensations”) → triptans — usually benign
  • MOH from butalbital, opioids, combination analgesics → AVOID in routine acute treatment
Use / pregnancy / pearls
  • Fastest-onset triptan / cluster headache acute therapy → SC sumatriptan (with 100% O2)
  • Longest-half-life triptan — menstrual migraine mini-prophylaxis → frovatriptan
  • Acute migraine when triptans are contraindicated (CAD, recent stroke, etc.) → gepant or lasmiditan (no vasoconstriction, no triptan-like CV contraindication; still use caution in active/unstable vascular disease)
  • Status migrainosus / ED — MENU (not all-at-once): dopamine-antagonist antiemetic (+ diphenhydramine), NSAID (ketorolac), IV fluids, magnesium (selected), IV valproate (selected non-pregnant; avoid in hepatic disease), DHE protocols, occipital nerve block
  • Chronic migraine (≥15 headache days/month) prevention → onabotulinumtoxinA PREEMPT 155–195 U q12 weeks (NOT episodic)
  • Cluster prophylaxis → high-dose verapamil (ECG monitoring), galcanezumab (episodic), GON block as bridge, lithium for chronic
  • Acute migraine in pregnancy → acetaminophen ± metoclopramide first; sumatriptan may be considered with caution when needed (best pregnancy safety data); AVOID ergots, valproate, topiramate; NSAIDs avoid in 3rd trimester
  • Migraine prevention in pregnancy → non-pharm first; if needed — propranolol or amitriptyline (lowest risk)
  • Oral preventive that is also acute (dual-use gepant) → rimegepant (q-other-day prevention) and atogepant (daily prevention)
  • MOH thresholds → triptans/ergots/opioids/combos >10 d/mo; simple analgesics >15 d/mo
  • Pediatric migraine prevention → amitriptyline or topiramate (CHAMP trial — placebo non-inferior, but still used)
  • CYP450 interactions → valproate inhibits glucuronidation (↑ lamotrigine); topiramate induces OCP metabolism; rizatriptan dose ↓ with propranolol
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