Headache pharmacology - French Flashcards
What are the first-line agents for migraine termination?
Second line? Third?
Depends on the severity.
NSAIDs are 1st line for mild/moderate migraine.
Triptans (sumatriptan, zolmitriptan) are 1st line for moderate/severe migrain termination.
Ergot Alkaloids (Ergotamine, Dihydroergotamine) are 2nd line.
What are the first-line agents for migraine prophylaxis?
Second line? Third?
Beta-blockers (Propanolol) and anticonvulsants (valproate/topiramate) are the first-line.
Ca channel blockers (verapamil), tricyclic antidepressants (amitryptiline), and Botox are second-line.
ARB/ACEib and gabapentin are third-line (little evidence of benefit).
**Riboflavin (B2) uncategorized, but show benefit after 3 months.
What is the treatment stratification for termination of tension-type headaches?
What is the treatment for prevention of tension-type headaches?
Acetaminophen/NSAID are first-line. Caffeine can be added if unresponsive.
Tricyclic Antidepressants/SSRIs used in prevention.
Describe the role of Serotonin in the pathogenesis of migraine, and note where pharmacologic agents can intervene.
Serotonin binds the 5HT2 receptor causing release of NO. This acts to sensitize nerves and dilate “extracerebral” vessels ( 5HT 1b/d/f receptor). Nerve discharge follows, resulting in neuropeptide release–> pain and some inflammation.
**the diagram is about as clear as goddamn mud
Agonist activity at 5HT1B/1D receptors results in (3)
1) Vasoconstriction in cerebral vessels, reversing vasodilation-induced throbbing headache
2) Inhibition of release of peptides that cause vasodilation, neuroinflammation, and pain
3) Prevention of activation of pain fibers in trigeminal nerves involved in migraine
What drugs are 5HT 1b/1d agonists?
-Triptans (sumatriptan, zolmitriptan)
AND
Ergot Alkaloids (Ergotamine, dihydroergotamine)
Ergot have longer duration, more side effects, and are slightly less effective, hence, second line.
Describe the pharmacokinetics of the -Triptans? How are they administered? What is the half-life? What is the CNS penetration?
Most have a short t1/2 (2-4 hours) except naratriptan, which has a ~24 hour half-life.
sumatriptan is does not achieve good CNS penetration, but newer agents do.
Oral and nasal formulations are available.
What are the side effects of the -Triptans?
What is a notable drug/drug interaction to be aware of in patients with migraine?
Mild: Tingling (paresthesias), flushing, dizziness, drowsiness, fatigue, and a feeling of heaviness, tightness or pressure in the chest
Severe: Triptan drugs can cause coronary vasospasm and angina, myocardial infarction, cardiac arrhythmia; stroke and death have occurred rarely. Avoid in patients with coronary, cerebrovascular or other arterial disease or uncontrolled hypertension.
Should not be used within 24 hrs after an ergot alkaloid because vasoconstriction may be
additive or concurrently with an MAOI (risk of serotonin syndrome up to 50%)
Describe the pharmacokinetics of the Ergot alkaloids. How are they administered? What is the half-life? What is the CNS penetration?
Ergotamine: oral, sublingual, rectal. Poor oral bioavail.
Dihydroergotamine: intranasal, parenteral (must give with metoclopramide - an antiemetic)
What are the side effects (mild/severe) of the ergot alkaloids?
What are notable drug interactions?
Dihydroergotamine is less potent so fewer side effects.
Mild: nausea/vomiting, diarrhea, cramps, parasthesias, vertigo
Severe: vascular occlusion and gangrene due to activation of a1 adrenergic receptors (OD).
DD ix: Don’t use with nonselective BB (alpha-constriction + B2 vasodilation block) = ischemia.
Also don’t use with a triptan (same MOA).
TCAD (tricyclic antidepressants) side effects? Utility?
2nd line.
Additional side effects of TCADs
include dry mouth, constipation, tachycardia, weight gain, urinary retention, weight gain
What are the anticonvulsants? What is their utility in migrain therapy? What are the notable side effects?
1sst line (valproate, topiramate).
Valproate: nausea, tremor, weight gain, hair loss; caution if liver disease, contraindicated in pregnancy
Topiramate: paresthesias, language and cognitive impairment, weight loss (may be advantageous in patients concerned about weight gain from other agents), taste perversion, fatigue
Why is Botox second-line?
When can it be used?
What are the adverse effects?
• Recent evidence from large, multicenter trials supports use in chronic migraine (15 or more headache
days per month, lasting at least 4 hours a day)
• Second-line agent due to high cost and need for experienced clinician to administer (IM at multiple
sites in multiple areas)
• Adverse effects: Headache, neck pain, generalized muscle weakness, drooping eyelids; Category C
