🤕 Triptan Acute Migraine Abortive Therapy Simulator

Migraine Onset — Cranial Vasodilation & Trigeminal Activation

Dilated meningeal vessels and firing trigeminal fibers drive throbbing pain.

• ~14%: Migraine prevalence (of adults worldwide)
• 4–72 h: Attack duration untreated (per episode)
• +30–60%: Vessel dilation (meningeal artery diameter)
• ↑↑: CGRP release (neuropeptide surge)

The trigeminovascular cascade

Trigeminal fibers release CGRP, dilating meningeal vessels.

Neurogenic inflammation

Plasma proteins leak, sensitizing pain-sensing nerve endings.

Central sensitization risk

Delay lets brainstem neurons become hyperexcitable.

Early Triptan Dosing — The Golden Hour

Dosing within an hour of onset gives triptans their best chance to work.

• <1 h: Optimal dosing window (from pain onset)
• ~14%: Sumatriptan oral bioavailability (first-pass metabolism)
• ~2 h: Time to peak plasma (oral tablet)
• ~10 min: Subcutaneous onset (faster route)

Why timing matters

Early dosing beats a vessel wall that is not yet fully dilated.

Formulation choices

Oral, nasal spray, and injection trade speed for convenience.

Absorption during nausea

Gastric stasis during attacks slows oral absorption.

5-HT1B/1D Receptor Agonism

Triptans mimic serotonin, binding receptors on vessels and nerve terminals.

• 5-HT1B/1D: Primary receptor targets (Gi-coupled GPCRs)
• ~2.5 h: Sumatriptan half-life (plasma clearance)
• 2 sites: Receptor location (vascular smooth muscle + nerve)
• ↓ cAMP: Signal effect (via Gi inhibition)

5-HT1B on vessels

Receptor activation contracts vascular smooth muscle directly.

5-HT1D on nerve terminals

Presynaptic binding blocks CGRP and substance P release.

Selectivity matters

Cranial selectivity limits broader cardiovascular side effects.

Vasoconstriction & Neurogenic Inflammation Block

Vessel diameter falls back toward baseline as inflammatory signaling quiets.

• up to 90%: Vessel diameter recovery (toward baseline)
• ↓ sharply: CGRP suppression (presynaptic block)
• 10–15 min: Onset of relief (SC route) (fastest formulation)
• ~70–80%: Response rate, early dose (pain relief at 2 h)

Mechanical relief

Smaller vessel diameter reduces pulsatile stretch on nerve endings.

Inflammatory quieting

Reduced CGRP lowers plasma protein leakage around vessels.

Dose-timing dependence

Late dosing yields slower, weaker constriction response.

Attack Resolution — Pain-Free Outcome

Early, adequate dosing gives the best odds of a pain-free two-hour outcome.

• ~50–60%: Pain-free at 2 h (early dose) (clinical trial data)
• ~30–40%: Recurrence rate (within 24 h)
• 2 of 3: Consistent response (attacks, same patient)
• ~20–30%: Late-dose response (lower efficacy)

What determines success

Early timing and adequate dose drive resolution probability.

Recurrence risk

Headache can return as drug levels decline within a day.

Missed-window outcomes

Skipped or delayed dosing leaves the attack largely unresolved.