Migraine Drugs Flashcards
Neurogenic inflammation cascade
Nerve endings release inflammatory substances, some of which activate cyclooxygenase (leading to creation of prostaglandins). These prostaglandins contribute to inflammation and excite nociceptors. Pain transmitted to central nervous system.
Why aren’t opioids used to treat headaches?
Can actually make headache worse:
Increase N/V
Contribute to mast cell degranulation (increased inflammation)
Prevents normal clearance of glutamate, exacerbating CSD.
NSAIDS
Unlikely to cause headache, safe in the presence of vascular disease, non-sedating, no nausea, high doses required.
What is the role of dopamine in migraine?
Dopamine is responsible for the prodromal symptoms of migraine (yawning, cold hands + feet, urination, chocolate craving).
D2 agonist in migraineurs?
Causes migraine
D2 antagonists in migraineurs?
Sedative, antiemetic properties, used to treat migraine
Chlorpromazine, prochlorperazine, droperidol, metoclopramide, domperidone
(Don’t need to know these names)
Advantages of D2 antagonists in migraine treatment?
Disadvantages?
When used IV very effective, reduce nausea/vomiting.
Problems: Prolonged QT, orthostatic hypothension, extrapyramidal effects
Ergot
Potent vasoconstrictor found in rye
Ergotamine
Synthetic ergot, used to treat migraines. Structurally similar to serotonin, NE, and DA. Potent vasoconstrictor – avoid in coronary disease
When to avoid ergotamine?
In patients with coronary disease.
Dihydroergotamine
Injection, intrapulmonary. IV use requires antiemetics.
Long half-life and duration of action.
Useful for medication overuse headaches, but be careful in vascular disease.
Effect of 5-HT IV on migraine
Relieves, but has completely intolerable side-effects
Important serotonin receptors in migraine?
5HT1B (blood vessel constriction), 5HT1D (Nerves), 5HT1F
How do triptans work?
They activate 5HT1B, 5HT1D, 5HT1F (some) autoreceptors, which decrease painful NTs (decrease neurogenic inflammation). Reduce all aspects of migraine disability, no sedation, intrinsic anti-emetics.
Best acting triptan?
Sumatriptan (also has IV form)
Other good triptan?
Eletriptan, metabolized by Cyp3A4, most others by MAO.
Triptan CNS penetration?
Diffuse in passively, pumped out actively by PGP pump. PGP pump inhibitors are chemically similar to CYP3A4 inhibitors, so caution.
What to be careful administering with Sumatriptan?
MAO inhibitors
What to be careful administering with eletriptan?
Ketoconazole, fluconazole (Both antifungals)
Which 5HT receptors in MMA, which 5HT receptors in heart?
5HT1B in MMA, 5HT2 in heart
Contraindications for triptans
Ischemic heart disease, uncontrolled hypertension, SSRI/SNRI
Serotonin syndrome
Life-threatening condition
Classical triad:
Mental status changes
Autonomic hyperactivity (diarrhea, hypertension, fever, shivering)
Neuromuscular abnormalities (myoclonus, rigidity, hyperreflexia)
Do many migraineurs participate in preventive therapy?
No <5 percent
When to consider preventive treatment for migraines?
When frequency is >6x / month. Other things too, but this is most important.
How does prevention therapy work?
Not too sure, but best theory maintains that it works via suppression of CSD.
Glutamate levels with migraine and with prophylaxis
Glu is increased with migraines, and decreased with prophylaxis.
Why are beta blockers effective in migraine prophylaxis?
Penetrate CNS, can stabilize membranes. Bind to 5HT receptors somehow.
Beta blockers used to treat migraine?
Propranolol, nadolol, timolol, atenolol.
TCAs used in migraine prophylaxis
Amitriptyline – but has antimuscarinic (dry mouth, tachycardia, confusion, urinary retention) and antihistaminic (sedation) effects.
SSRIs used in migraines?
Little evidence
Anti-convulsives used for migraine prophylaxis?
Topiramate, valproate (divalproex)
How does divalproex work?
Potentiates post-synaptic effect of gaba
Onabotulinum toxin A and migraine
Approved for chronic migraine, inhibits ACh release at NMJ.
