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Ahmed Neuro 2 Depression > Lecture 9: Migraine Pharmacology > Flashcards

Lecture 9: Migraine Pharmacology Flashcards

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?

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
Which triptan is a pro-drug who's active metabolite is a 5HT-1D agonist?
Zolmitriptan
26
Which 2 triptans have some evidence of better tolerance and claims of better efficacy relative to sumatriptan?
- Rizatriptan - Eletriptan
27
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
28
Which triptan has approximately 70% bioavailability with a T1/2 of around 6 hours?
Naratriptan
29
Which triptan is available as an injectable form for quicker action?
Sumatriptan
30
If a patient is taking MAO inhibitors (MAOIs) which 3 triptans are contraindicated?
- Sumatriptan - Rizatriptan - Zolmitriptan
31
Triptans are contraindicated in patients taking SSRIs, SNRIs, SDRIs, and linezolid (antibiotic - oxazolidinone) as this could lead to?
Serotonin syndrome
32
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
33
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
34
Which receptors does the Ergot Alkaloid, Dihydroergotamine, bind to?
- Various serotonin (5HT) receptors, **non-selectively** - Adrenergic receptors - Dopamine receptors
35
What are the effects of Dihydroergotamine binding to **peripheral** α**1-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**
36
What effect does high doses of ergot alkaloids have on the heart?
- Bradycardia - MI - Angina (pressure/squeezing in chest)
37
Which drugs can be used during all trimesters of pregnancy for the treatment of migraines?
Acetaminophen ± codeine
38
Which drugs can be used during the first and second trimester of pregnancy only for treatment of migraines?
- Aspirin - Ibuprofen
39
Which drugs used for migraines are contraindicated during pregnancy? Which is associated with abortion risk?
- Triptans - **DHE** and other **ergot alkaloids**: abortion risk
40
Which drug combinations are useful for migraine headache treatment?
- Triptan + analgesic --\> Sumatriptan + naproxen (NSAID) = Treximet - Acetaminophen, ibuprofen, naproxen
41
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**
42
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!
43
Which drug is often the first choice for migraine **prevention** due to its good side effect profile?
Ca2+ channel blocker --\> **Verapamil**
44
What are 5 of the possible side effects when using β-blockers (propranolol or timolol) as preventative agents for migraines? Contraindicated in which patients?
1. Fatigue, CNS depression 2. Change in sexual function 3. Reduced exercise toleranc 4. Hypotension and bradycardia 5. **Bronchoconstriction** (contraindicated in **asthma patients**)
45
Which routes of administration exist for the Ergot Alkaloid, Dihydroergotamine (DHE)?
Sublingual, intranasal, IV, IM, and SC
46
Which routes of administration exist for the Ergot Alkaloid, Ergotamine + caffeine?
- Oral tablet - Rectal suppository

Ahmed Neuro 2 Depression (16 decks)

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