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#US Neuro 2 Depression COPY ahmed > Lecture 9: Migraine Pharmacology > Flashcards

Lecture 9: Migraine Pharmacology Flashcards

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1
Q

Which 2 medication classes are used to treat the prodrome effect of a migraine?

A
  1. Triptans
  2. Ergot alkaloids
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2
Q

Which 4 drug types may be used as preventative agents to limit the frequency and severity of migraine attacks, working in the prodrome stage?

A
  1. β blockers
  2. Tricyclic antidepressants
  3. Anticonvulsants
  4. Ca2+ channel blockers
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3
Q

Which is the treatment modality of choice for patients >18 yo who suffer from chronic migraines?

A

Botox

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4
Q

What are the 2 Ergot Alkaloids used in the treatment/prevention of migraines?

A
  1. Dihydroergotamine (DHE)
  2. Ergotamine + Caffeine
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5
Q

What 2 β-blockers may be used as preventative agents to limit the frequency and severity of migraine attacks?

A
  1. Propranolol
  2. Timolol
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6
Q

What are the 2 Tricyclic Antidepressants used as preventative agents to limit the frequency and severity of migraine attacks?

A

1) Amitriptyline
2) Imipramine

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7
Q

Which 2 anticonvulsants may be used as preventative agents to limit the frequency and severity of migraine attacks?

A
  1. Topirimate
  2. Valporate
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8
Q

Which Ca2+ channel blocker may be used as a preventative agent to limit the frequency and severity of migraine attacks?

A

Verapamil

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9
Q

Neural events result in ______ of blood vessels resulting in pain and further nerve activation —–> headaches/migraines

A

Dilation

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10
Q

The meninges are innervated by which axons?

What occurs when stimulated by vasodilation?

A
  • Trigeminal axons
  • When stimulated by vasodilation they generate throbbing unilateral migraine-like pain
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11
Q

Which fibers release Calcitonin-Gene-Related Peptide (CGRP) and Substance P/Neurokinin A?

Has what effect?

A
  • CGRP is released by Ad-fibers –> increases dural vessel vasodilation
  • Substance P and neurokinin A from C-fibers –> increases dural vessel permeability
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12
Q

Neuropeptides leading to dilation of cranial blood vessels causing sensitization of nerves to pain which spreads in what direction?

A

Sensitization spreads from periphery to the brain

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13
Q

What used to treat coronary artery disease can provoke migraine?

A

Organic nitrates (NO)

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14
Q

What does Cortical Spreading Depression (CSD) lead to?

Accompanied by?

A
  • Leads to cerebral vasoconstriction
  • Accompanied by H+, K+, and NO discharge from neurons
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15
Q

Electrolytes (H+ and K+) along with NO discharge from neurons as a result of cortical spreading depression (CSD) lead to what 2 events?

A
  1. Dilate cranial arteries
  2. Depolarize perivascular trigeminal terminals
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16
Q

Release of what promotes neurogenic inflammation?

A

CGRP and neuropeptides (substance P) act together to produce painful dural inflammation

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17
Q

What elicits the release of CGRP in the pathophysiology of migraines?

A

Nitric Oxide (NO)

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18
Q

In neurogenic inflammation as a wave of electrical activity and H+/K+ pass through nerve cells they stimulate the release of what?

A
  • Neuropeptides (CGRP and substance P)
  • Inflammatory mediators (NO, histamine, and prostaglandins)
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19
Q

What type of serotonin receptors are found on cranial vessels?

Peripheral neurons?

Central neurons?

A
  • Cranial vessels = 5HT-1B
  • Peripheral neuron = ​5HT-1D
  • Central neuron = 5HT-1B/1D
20
Q

Triptans are selective agonists of which receptors?

A

5HT-1B/1D

21
Q

What is the effect of triptans binding to 5HT-1D receptors on presynaptic nerve terminals?

A

Inhibit presynaptic release of CGRP and other neuropeptides from the peripheral end of the trigeminal nerve

22
Q

What is the effect of triptans binding to 5HT-1B receptors on vascular smooth muscle?

A

Stimulates vasoconstriction of dilated meningeal, dural, and pial blood vessels

23
Q

What are the 2 effects of triptans binding to 5HT-1D receptors on the trigeminal nucleus in the brainstem?

A
  • 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
24
Q

What 2 triptans can be formulated as nasal spray and when would this be a good option in a clinical setting?

A
  • Sumatriptan and Zolmitriptan
  • Effective with nausea/vomiting, simple, works quickly
25
Q

Which triptan is a pro-drug who’s active metabolite is a 5HT-1D agonist?

A

Zolmitriptan

26
Q

Which 2 triptans have some evidence of better tolerance and claims of better efficacy relative to sumatriptan?

A
  • Rizatriptan
  • Eletriptan
27
Q

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?

A

Frovatriptan

28
Q

Which triptan has approximately 70% bioavailability with a T1/2 of around 6 hours?

A

Naratriptan

29
Q

Which triptan is available as an injectable form for quicker action?

A

Sumatriptan

30
Q

If a patient is taking MAO inhibitors (MAOIs) which 3 triptans are contraindicated?

A
  • Sumatriptan
  • Rizatriptan
  • Zolmitriptan
31
Q

Triptans are contraindicated in patients taking SSRIs, SNRIs, SDRIs, and linezolid (antibiotic - oxazolidinone) as this could lead to?

A

Serotonin syndrome

32
Q

Which underlying conditions are contraindications for the use of triptans in a patient with migraines?

A
  • Hx or suspicion of ischemic or vasospastic coronary disease or other significant CVD
  • Uncontrolled HTN
33
Q

What is the effect of all triptans on coronary and renal vessels?

How is this related to these drugs contraindications?

A
  • Modest vasoconstrictors of coronary and renal vessels
  • Should be avoided in ischemic/vasospastic coronary disease and those with uncontrolled HTN
34
Q

Which receptors does the Ergot Alkaloid, Dihydroergotamine, bind to?

A
  • Various serotonin (5HT) receptors, non-selectively
  • Adrenergic receptors
  • Dopamine receptors
35
Q

What are the effects of Dihydroergotamine binding to peripheral α1-adrenergic receptors in blood vessels?

Can lead to what harmful effects?

A
  • Causes worse vascular vasoconstriction when compared to triptans
  • Can lead to: peripheral ischemia, vascular disease, acute coronary syndrome and/or coronary vasospasm
36
Q

What effect does high doses of ergot alkaloids have on the heart?

A
  • Bradycardia
  • MI
  • Angina (pressure/squeezing in chest)
37
Q

Which drugs can be used during all trimesters of pregnancy for the treatment of migraines?

A

Acetaminophen ± codeine

38
Q

Which drugs can be used during the first and second trimester of pregnancy only for treatment of migraines?

A
  • Aspirin
  • Ibuprofen
39
Q

Which drugs used for migraines are contraindicated during pregnancy?

Which is associated with abortion risk?

A
  • Triptans
  • DHE and other ergot alkaloids: abortion risk
40
Q

Which drug combinations are useful for migraine headache treatment?

A
  • Triptan + analgesic –> Sumatriptan + naproxen (NSAID) = Treximet
  • Acetaminophen, ibuprofen, naproxen
41
Q

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?

A

Taken daily when patient is ASYMPTOMATIC

42
Q

What is the significance of Valproate in the treatment of migraines?

Which patients is it used for?

A
  • Effective prophylactic treatment in migraine
  • Used in patients who fail triptan therapy

*CONTRAINDICATED in pregnant woman!

43
Q

Which drug is often the first choice for migraine prevention due to its good side effect profile?

A

Ca2+ channel blocker –> Verapamil

44
Q

What are 5 of the possible side effects when using β-blockers (propranolol or timolol) as preventative agents for migraines?

Contraindicated in which patients?

A
  1. Fatigue, CNS depression
  2. Change in sexual function
  3. Reduced exercise toleranc
  4. Hypotension and bradycardia
  5. Bronchoconstriction (contraindicated in asthma patients)
45
Q

Which routes of administration exist for the Ergot Alkaloid, Dihydroergotamine (DHE)?

A

Sublingual, intranasal, IV, IM, and SC

46
Q

Which routes of administration exist for the Ergot Alkaloid, Ergotamine + caffeine?

A
  • Oral tablet
  • Rectal suppository

#US Neuro 2 Depression COPY ahmed (17 decks)

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