sumatriptan

MECHANISM: Selective agonist at 5-HT1B (vasoconstriction of intracranial/meningeal vessels) and 5-HT1D (presynaptic inhibition of trigeminal nerve terminals, reducing release of CGRP, substance P, and neurogenic inflammation). Also inhibits transmission in the trigeminal nucleus caudalis (central pain pathway).

INDICATIONS: Acute (abortive) treatment of migraine with or without aura, and acute cluster headache (SC or intranasal; 100% O2 is also first-line for cluster). NOT for prophylaxis. Most effective when taken early in the attack.

ROUTES: Oral, intranasal, subcutaneous (fastest onset, ~10 min). Short half-life (~2 h), so headache recurrence is common and a second dose can be given after the minimum interval stated on the label.

ADVERSE EFFECTS: Chest/neck/jaw tightness or pressure ("triptan sensations"), from coronary vasospasm or non-cardiac mechanisms; paresthesias, flushing, dizziness, fatigue; injection-site reactions (SC); rare MI, arrhythmia, stroke. Medication-overuse headache with frequent use (generally ≥10 days/month for triptans).

CONTRAINDICATIONS: Coronary artery disease, Prinzmetal (vasospastic) angina, prior MI or stroke/TIA, peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine, and use within 24 h of ergotamines or another triptan. Contraindicated with or within 2 weeks of an MAO inhibitor (relevant for sumatriptan, which is metabolized by MAO-A). Avoid in pregnancy only if risk outweighs benefit (data are fairly reassuring, but it is not first-line).

INTERACTIONS: Serotonin syndrome is a theoretical/rare risk when combined with SSRIs, SNRIs, MAOIs, or other serotonergic drugs (the FDA warning exists, but the actual risk appears low). Ergot alkaloids can cause additive vasoconstriction.

BOARD PEARLS: - Migraine pathophysiology: trigeminovascular activation, CGRP release, neurogenic inflammation, vasodilation. Aura is linked to cortical spreading depression. - Abortive therapy: NSAIDs, triptans, ergots, gepants (ubrogepant, rimegepant; CGRP receptor antagonists, no vasoconstriction, so usable in CAD), ditans (lasmiditan, a 5-HT1F agonist, also non-vasoconstrictive), antiemetics (metoclopramide). - Prophylaxis: propranolol, topiramate, amitriptyline, valproate, and CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab). - Vignette pattern: a patient with migraine who develops chest tightness after a triptan, or who has known CAD, so avoid the triptan and consider a gepant or ditan. - Cluster headache: unilateral periorbital pain with autonomic features (lacrimation, rhinorrhea, Horner-like signs), in clusters. Treat acutely with high-flow O2 or SC/intranasal sumatriptan. Verapamil is the prophylactic of choice. - Other triptans (rizatriptan, zolmitriptan, eletriptan, naratriptan, etc.) share the mechanism and contraindications.