SN3 SHORT NOTE 5M ★ High-yield

Describe the drugs used in the treatment and prophylaxis of migraine.

Pharmacology · 2nd Professional — Para-Clinical

Pathophysiology and Drug Targets

Migraine is a recurrent headache disorder involving trigeminovascular activation, release of CGRP (calcitonin gene-related peptide) and other neuropeptides, neurogenic inflammation and cortical spreading depression.

Serotonin (5-HT) is central — 5-HT1B/1D receptor agonists constrict dilated cranial vessels and inhibit neuropeptide release

Acute Treatment

Step	Drugs	Notes
Simple analgesics	Aspirin, paracetamol, NSAIDs (naproxen, ibuprofen)	Effective for mild to moderate attacks; give early and in adequate dose
With an antiemetic	Metoclopramide or domperidone	Relieves nausea and corrects the gastric stasis of migraine, which otherwise prevents the analgesic from being absorbed — the reason oral drugs so often fail
Triptans	Sumatriptan, rizatriptan, zolmitriptan — 5-HT1B/1D agonists	For moderate to severe attacks; oral, nasal or subcutaneous. Contraindicated in ischaemic heart disease, uncontrolled hypertension and cerebrovascular disease, because they are vasoconstrictors
Ergot alkaloids	Ergotamine, dihydroergotamine	Largely superseded; non-selective vasoconstrictors causing nausea and, with overuse, ergotism with peripheral ischaemia
CGRP antagonists (gepants)	Rimegepant, ubrogepant	No vasoconstriction, so usable in vascular disease

CLINICAL PEARL

Migraine causes gastric stasis, which is why the tablet does not work. The drug sits in the stomach unabsorbed while the headache builds. Adding metoclopramide restores gastric emptying and lets the analgesic in — so the antiemetic is not merely for the nausea, it is what makes the analgesic effective. Taking the drug early, before stasis is established, matters for the same reason.

Prophylaxis

Class	Drugs	Notes
Beta-blockers	Propranolol, metoprolol	First-line; avoid in asthma
Antiepileptics	Sodium valproate, topiramate	Effective; valproate is teratogenic and must not be used in women of childbearing potential; topiramate causes weight loss and paraesthesiae
Tricyclic antidepressants	Amitriptyline	Useful where there is coexisting tension headache, depression or insomnia
Calcium channel blockers	Flunarizine, verapamil	Flunarizine causes weight gain and parkinsonism
CGRP monoclonal antibodies	Erenumab, fremanezumab, galcanezumab	Monthly injection; highly effective but expensive
Botulinum toxin A	—	For chronic migraine

Prophylaxis is indicated when attacks occur more than about four times a month, are disabling, or acute treatment is failing or being overused
Each agent needs an adequate trial of 2 to 3 months at a proper dose before being judged ineffective

Medication Overuse Headache

Frequent use of acute treatment causes a chronic daily headache that is worsened by the very drugs taken to relieve it
Risk thresholds — simple analgesics on more than 15 days a month, or triptans, ergots or opioids on more than 10 days a month
Treatment is withdrawal of the offending drug, with a warning that headache worsens for one to two weeks before improving; prophylaxis is started at the same time
Opioids and combination analgesics carry the highest risk and are best avoided in migraine altogether

Applied Aspects

Treat early and adequately — a full dose at the first sign works far better than repeated small doses once the attack is established
Ask about analgesic frequency in any chronic daily headache; medication overuse is common, easily missed and entirely reversible
Identify and avoid triggers — missed meals, dehydration, irregular sleep, stress, and in some patients specific foods; a headache diary is more useful than any investigation
Triptans are contraindicated in vascular disease; ask about chest pain, claudication and stroke before prescribing
Valproate must not be given to women who could become pregnant; this is now an absolute restriction in most jurisdictions
Warning features requiring investigation — sudden "thunderclap" onset, fever with neck stiffness, papilloedema, focal signs, new headache after 50, or headache worse on lying down or straining

All questions in Autacoids, Nsaids & Antigout

Every Pharmacology chapter →