Lecture 9: Migraine Pharmacology Flashcards
Which 2 medication classes are used to treat the prodrome effect of a migraine?
- Triptans
- Ergot alkaloids
Which 4 drug types may be used as preventative agents to limit the frequency and severity of migraine attacks, working in the prodrome stage?
- β blockers
- Tricyclic antidepressants
- Anticonvulsants
- Ca2+ channel blockers
Which is the treatment modality of choice for patients >18 yo who suffer from chronic migraines?
Botox
What are the 2 Ergot Alkaloids used in the treatment/prevention of migraines?
- Dihydroergotamine (DHE)
- Ergotamine + Caffeine
What 2 β-blockers may be used as preventative agents to limit the frequency and severity of migraine attacks?
- Propranolol
- Timolol
What are the 2 Tricyclic Antidepressants used as preventative agents to limit the frequency and severity of migraine attacks?
1) Amitriptyline
2) Imipramine
Which 2 anticonvulsants may be used as preventative agents to limit the frequency and severity of migraine attacks?
- Topirimate
- Valporate
Which Ca2+ channel blocker may be used as a preventative agent to limit the frequency and severity of migraine attacks?
Verapamil
Neural events result in ______ of blood vessels resulting in pain and further nerve activation —–> headaches/migraines
Dilation
The meninges are innervated by which axons?
What occurs when stimulated by vasodilation?
- Trigeminal axons
- When stimulated by vasodilation they generate throbbing unilateral migraine-like pain
Which fibers release Calcitonin-Gene-Related Peptide (CGRP) and Substance P/Neurokinin A?
Has what effect?
- CGRP is released by Ad-fibers –> increases dural vessel vasodilation
- Substance P and neurokinin A from C-fibers –> increases dural vessel permeability
Neuropeptides leading to dilation of cranial blood vessels causing sensitization of nerves to pain which spreads in what direction?
Sensitization spreads from periphery to the brain
What used to treat coronary artery disease can provoke migraine?
Organic nitrates (NO)
What does Cortical Spreading Depression (CSD) lead to?
Accompanied by?
- Leads to cerebral vasoconstriction
- Accompanied by H+, K+, and NO discharge from neurons
Electrolytes (H+ and K+) along with NO discharge from neurons as a result of cortical spreading depression (CSD) lead to what 2 events?
- Dilate cranial arteries
- Depolarize perivascular trigeminal terminals
Release of what promotes neurogenic inflammation?
CGRP and neuropeptides (substance P) act together to produce painful dural inflammation
What elicits the release of CGRP in the pathophysiology of migraines?
Nitric Oxide (NO)
In neurogenic inflammation as a wave of electrical activity and H+/K+ pass through nerve cells they stimulate the release of what?
- Neuropeptides (CGRP and substance P)
- Inflammatory mediators (NO, histamine, and prostaglandins)
What type of serotonin receptors are found on cranial vessels?
Peripheral neurons?
Central neurons?
- Cranial vessels = 5HT-1B
- Peripheral neuron = 5HT-1D
- Central neuron = 5HT-1B/1D
Triptans are selective agonists of which receptors?
5HT-1B/1D
What is the effect of triptans binding to 5HT-1D receptors on presynaptic nerve terminals?
Inhibit presynaptic release of CGRP and other neuropeptides from the peripheral end of the trigeminal nerve
What is the effect of triptans binding to 5HT-1B receptors on vascular smooth muscle?
Stimulates vasoconstriction of dilated meningeal, dural, and pial blood vessels
What are the 2 effects of triptans binding to 5HT-1D receptors on the trigeminal nucleus in the brainstem?
- Modulates incoming painful sensory information from periphery
- Inhibits upward transmission of painful sensory information to the thalamus and higher brain centers where pain is perceived
What 2 triptans can be formulated as nasal spray and when would this be a good option in a clinical setting?
- Sumatriptan and Zolmitriptan
- Effective with nausea/vomiting, simple, works quickly
Which triptan is a pro-drug who’s active metabolite is a 5HT-1D agonist?
Zolmitriptan
Which 2 triptans have some evidence of better tolerance and claims of better efficacy relative to sumatriptan?
- Rizatriptan
- Eletriptan
Which triptan has the longest T1/2 of approximately 24 hours and should be used in a patient who requires long duration of migraine pain relief?
Frovatriptan
Which triptan has approximately 70% bioavailability with a T1/2 of around 6 hours?
Naratriptan
Which triptan is available as an injectable form for quicker action?
Sumatriptan
If a patient is taking MAO inhibitors (MAOIs) which 3 triptans are contraindicated?
- Sumatriptan
- Rizatriptan
- Zolmitriptan
Triptans are contraindicated in patients taking SSRIs, SNRIs, SDRIs, and linezolid (antibiotic - oxazolidinone) as this could lead to?
Serotonin syndrome
Which underlying conditions are contraindications for the use of triptans in a patient with migraines?
- Hx or suspicion of ischemic or vasospastic coronary disease or other significant CVD
- Uncontrolled HTN
What is the effect of all triptans on coronary and renal vessels?
How is this related to these drugs contraindications?
- Modest vasoconstrictors of coronary and renal vessels
- Should be avoided in ischemic/vasospastic coronary disease and those with uncontrolled HTN
Which receptors does the Ergot Alkaloid, Dihydroergotamine, bind to?
- Various serotonin (5HT) receptors, non-selectively
- Adrenergic receptors
- Dopamine receptors
What are the effects of Dihydroergotamine binding to peripheral α1-adrenergic receptors in blood vessels?
Can lead to what harmful effects?
- Causes worse vascular vasoconstriction when compared to triptans
- Can lead to: peripheral ischemia, vascular disease, acute coronary syndrome and/or coronary vasospasm
What effect does high doses of ergot alkaloids have on the heart?
- Bradycardia
- MI
- Angina (pressure/squeezing in chest)
Which drugs can be used during all trimesters of pregnancy for the treatment of migraines?
Acetaminophen ± codeine
Which drugs can be used during the first and second trimester of pregnancy only for treatment of migraines?
- Aspirin
- Ibuprofen
Which drugs used for migraines are contraindicated during pregnancy?
Which is associated with abortion risk?
- Triptans
- DHE and other ergot alkaloids: abortion risk
Which drug combinations are useful for migraine headache treatment?
- Triptan + analgesic –> Sumatriptan + naproxen (NSAID) = Treximet
- Acetaminophen, ibuprofen, naproxen
Preventative agents which limit frequency and severity of migraine attacks, such as β-blockers, tricyclic antidepressants, anticonvulsants, and Ca2+ channel blockers should be taken under what conditions?
Taken daily when patient is ASYMPTOMATIC
What is the significance of Valproate in the treatment of migraines?
Which patients is it used for?
- Effective prophylactic treatment in migraine
- Used in patients who fail triptan therapy
*CONTRAINDICATED in pregnant woman!
Which drug is often the first choice for migraine prevention due to its good side effect profile?
Ca2+ channel blocker –> Verapamil
What are 5 of the possible side effects when using β-blockers (propranolol or timolol) as preventative agents for migraines?
Contraindicated in which patients?
- Fatigue, CNS depression
- Change in sexual function
- Reduced exercise toleranc
- Hypotension and bradycardia
- Bronchoconstriction (contraindicated in asthma patients)
Which routes of administration exist for the Ergot Alkaloid, Dihydroergotamine (DHE)?
Sublingual, intranasal, IV, IM, and SC
Which routes of administration exist for the Ergot Alkaloid, Ergotamine + caffeine?
- Oral tablet
- Rectal suppository
