Sumatriptan

Mechanism

💊 Common Business Names

Imitrex, Imigran, Sumigran, Formigran, Amigran.

🔬 Pharmacological Group

Selective agonist of the 5-HT type 5-HT_1B/1D receptor. Indole derivative (Triptan).

Mechanism of Action

Sumatriptan exerts a selective action on the cranial microvasculature and dural nerve endings:

• Selective agonist of 5-HT_1B and 5-HT_1D receptors: It has an extremely low affinity for other serotonin receptors (5-HT₂, 5-HT₃, 5-HT₄) or adrenergic and dopaminergic receptors.
• Integrated Trigeminal-Vascular Mechanism:
  1. Selective Cranial Vasoconstriction (5-HT_1B pathway): Expressed in the smooth muscle cells of the medium-caliber meningeal and intracranial blood vessels. Its G_i protein-coupled activation reduces intracellular cAMP and induces direct vasoconstriction of overdilated meningeal arteries during the migraine attack.
  2. Presynaptic Neuromodulatory Inhibition (5-HT_1D pathway): Located in the primary afferent nociceptive endings of the trigeminal nerve that innervate the dura mater. Its stimulation inhibits the exocytosis and release of proinflammatory and vasodilator peptides such as Substance P and CGRP, mitigating neurogenic dural edema.
  3. Inhibition of Second Order Transmission: Reduces central pain processing in the caudal trigeminal nucleus of the brain stem.

Pharmacokinetics

Key Pharmacokinetics

Indicators and dose

Dosage and Adjustment

• Adults (Treatment of Acute Migraine Attack):
  • Oral Route: 50 mg to 100 mg per dose administered as soon as possible after the onset of headache. If the pain recurs, the intake can be repeated after a minimum of 2 hours. Maximum daily oral dose: 200 mg/day.
  • Subcutaneous route (autoinjector): 6 mg before the crisis. If the pain returns, a second dose can be administered a minimum of 1 hour after the first. Maximum daily subcutaneous dose: 12 mg/day.
  • Intranasal Route: 10 - 20 mg in one nostril for pain, repeatable after 2 hours.
• Pediatrics: Not generally recommended in children under 18 years of age due to lack of sufficient data on the cardiovascular safety profile.
• Adjustment in Renal Failure: No dose adjustment is required given the null implication of the excretion of unchanged drug.

Security

Contraindications

• Absolute: Established ischemic heart disease, history of acute myocardial infarction, angina pectoris (stable or Prinzmetal); known or suspected coronary spasm; peripheral arterial disease or previous vascular bypass; stroke or transient cerebral ischemia; uncontrolled moderate-severe arterial hypertension; basilar or hemiplegic migraine; concomitant administration of ergotamines or ergot derivatives in the last 24 hours; coadministration with Monoamine Oxidase Inhibitors (MAOIs) or within 14 days after discontinuation; severe liver failure (Child-Pugh C).
• Relative: Presence of multiple cardiovascular coronary risk factors not studied in depth (hypertension, hyperlipidemia, diabetes, menopause, smoking).

Adverse Effects (ADR)

• Common / Mild: Dizziness, transient peripheral paresthesias, drowsiness, mild nausea, waves of facial heat or flushing, feeling of generalized fatigue, local dural pain or tightness.
• Rare / Serious: Acute coronary vasospasm (Prinzmetal's angina induced by the constrictor effect on the basal epicardial coronary arteries); acute myocardial infarction; severe ventricular arrhythmias; ischemic stroke; Peripheral dural ischemic colitis due to mesenteric vasoconstriction.
• "Chest Symptoms due to Triptans": Sensation of chest tightness, dyspnea and constriction in the neck and chest experienced by up to 15% of patients after the subcutaneous dose of sumatriptan. In most cases it lacks an electrocardiographic ischemic correlate and is attributed to diffuse esophageal spasm or non-coronary intercostal muscle contraction. However, it requires an initial ischemic ruling out.

Drug Interactions

• MAOI-A (Moclobemide, Selegiline): Sumatriptan plasma levels drastically increase (increase in AUC greater than 300%) due to the blockade of its main metabolic clearance pathway, inducing severe cardiovascular toxicity and serotonergic hyperactivity.
• Ergotamine, Dihydroergotamine or Methysergide: Pharmacodynamic synergism that causes prolonged arterial vasospasm. A minimum separation interval of 24 hours between taking ergotamines and sumatriptan must be strictly observed.
• SSRIs and SNRIs: Increased risk of inducing Serotonin Syndrome.

Pregnancy and Breastfeeding

Classified in FDA Category C. It moderately crosses the placenta. Its routine prescription should be avoided during pregnancy, reserved exclusively for severe refractory crises and after weighing the risk-benefit relationship. Breastfeeding: Compatible with caution; It is excreted in low quantities in breast milk and it is recommended to stop breastfeeding within 12 hours after breastfeeding to minimize the infant's exposure.