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Pharmacology Test #6 > Migraine > Flashcards

Migraine Flashcards

1
Q

Migraine

A

severe, recurrent, unilaterial throbbing in temples, eye orbits, front of head, with nausea and vomiting

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2
Q

Required to terminate most migraine attacks

A

sleep

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3
Q

Symptoms of a migraine include

A

aura, photophobia, hyperacusis, polyuria, diarrhea, and disturbances in mood and appetite - may occur up to 24 hours before headache

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4
Q

Most common comorbidities of migraines

A

depression, anxiety disorders, stroke, irritable bowel syndrome, epilepsy, and hypertension

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5
Q

Migraine trigger factors

A
  1. Dietary factors
  2. Food additives
  3. Sleep disturbances
  4. Emotional factors
  5. Environmental factors
  6. Hormones cycles or changes
  7. Medication Use/Overuse/Withdrawal
  8. Excessive exercise
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6
Q

Migraine with Aura definition

A
  1. Minimum of 2 attacks
  2. Exhibits at least 3 of the following characteristics: gradual onset, mild to severe in intensity; reversible aura, lasts 5-60 min; headache follows aura within 60 min; may or may not have nausea and vomiting; photophobia, phonophobia
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7
Q

Migraine without aura definition

A
  1. Minimum 5 attacks lasting 4-72 hours (no aura, stars with headache
  2. Any 2 of: unilateral, pulsating, aggravated by routine physical activity, moderate to severe intensity
  3. Any 1 of: nausea and vomiting, photophobia and phonophobia
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8
Q

Migraine pathophysiology

A

Vasospasm of cerebral arteries - initial vasoconstriction, then vasodilation; sterile neurogenic perivascular edema and inflammation

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9
Q

Drugs that abort migraines are

A

vasoconstrictors

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10
Q

Cortical spreading depression

A

Elevates extracellular: K+, H+, NO, AA;

Activates TG nociceptors (afferents)

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11
Q

TG efferents release:

A

CGRP, substance P, NKA-

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12
Q

5-HT receptors

A

5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors are highly expressed in the trigeminovascular system

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13
Q

5-HT(1B) receptors mediate

A

vasoconstriction

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14
Q

5-HT(1D) receptors likely inhibit

A

neurotransmitter release

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15
Q

5-HT(1F) receptors likely inhibit

A

release of nociceptive signaling molecules

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16
Q

Drugs used to abort migraines

A
  1. Acetominophen
  2. Aspirin/NSAIDs
  3. Serotonin (5-HT(1B/1D/1F)) agonists
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17
Q

Drugs used to prevent migraines

A
  1. beta-adrenergic antagonists
  2. Tricyclic antidepressants
  3. Anticonvulsants
  4. Botulinum Toxin A (Botox)
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18
Q

Nonspecific abortive agents

A
  1. Aspirin
  2. Acetaminophen (APAP)
  3. NSAIDs: ibuprofen, naproxen, ketoprofen, ketolorac
  4. Combination therapy with barbiturates, opiates
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19
Q

Excedrin Migraine

A

APAP 250 mg, ASA 250 mg, Caffeine 40 mg

combination therapy outperformed ibuprofen

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20
Q

Migralam

A

APAP 250 mg, Caffeine 100 mg, Isometheptene 65 mg

caffeine dose may cause insomnia

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21
Q

Midran

A

APAP 325 mg, dichlorophenazone 100 mg, isometheptene 65 mg

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22
Q

Fiorinal

A

butalbital 50 mg, aspirin 325 mg and caffeine 40 mg; with or without codeine 39 mg

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23
Q

FioricetR

A

butalbital 50 mg, APAP 325 mg and caffeine 40 mg; with or without codeine 30 mg

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24
Q

Butorphanol

A

nasal spray

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25
Q

Anti-emetics as adjuncts in migraine

A

Metoclopramide (ReglanR)

26
Q

Metoclopramide (ReglanR)

A

Dopamine (D2) receptor antagonist; decreases nausea, stimulates gastric emptying, gastric emptying decreased in migraines, improves absorption of antimigraine agents

27
Q

Source of ergot alkaloids

A

claviceps purpurea growing on rye

28
Q

Contaminated rye flour caused

A

epidemics of ergot poisoning - gangrenous limbs, psychoses, spontaneous abortions

29
Q

Ergot alkaloids

A

Ergonovine, serotonin, ergotamine

30
Q

Ergot alkaloids used to abort migraines

A

Ergotamine and Dihydroergotamine (DHE)

31
Q

Ergotamine and dihydroergotamine are

A

5-HT (2A/1B/1D/1F) receptor agonists and alpha1-adrenergic receptor agonists

32
Q

Which ergot alkaloid is less prone to cause severe peripheral vasoconstriction with frequent dosing?

A

Dihydroergotamine (DHE)

33
Q

How is DHE administered?

A

IM injection or nasal spray (poorly absorbed from GI tract)

34
Q

How is Ergotamine administered?

A

Sublingual tablets (poorly absorbed from GI tract)

35
Q

Most common toxic effects of ergots

A
  1. GI disturbances including diarrhea, nausea and vomiting
  2. Over-dosage particularly with ergotamine results in prolonged vasospasm
  3. Powerful uterine stimulants; contraindicated in pregnancy
36
Q

Severe toxic effect of ergots

A

May result in gangrene and amputation of arms and legs

37
Q

Drug-drug interactions with ergots

A
  1. HIV protease inhibitors and macrolides increase ergot levels
  2. beta blockers inhibit vasodilation (may cause gangrene)
  3. Dihydroergotamine decreases nitrate efficacy, i.e. decreased antianginal effects
38
Q

5-HT (1B/1D/1F) receptor agonists

A

Serotonin and the “triptans”

39
Q

Sumatriptan (Imitrex)

A

Synthetic 5-HT (1B/1D/1F) agonist; little peripheral effect; faster onset of relief than DHE; oral, nasal or subcutaneous routes of administration

40
Q

Adverse effect of sumatriptan

A

higher incidence of headache recurrence with sumatriptan than with DHE

41
Q

5-HT (1B/1D/1F) agonists slightly more efficacious and better tolerated than sumatriptan:

A

Zolmitriptan (Zomig); Naratriptan (Amerge); Rizatriptan (Maxalt); Almotriptan (Axert); Eletriptan (Relpax)

42
Q

Naratriptan compared to sumatriptan

A

Naratriptan has slow onset, longer duration of action, lower incidence of recurrence than sumitriptan

43
Q

Side effects of “triptans”

A

Mild and transient side effects: warmth and tingling, vertigo, malaise, fatigue, feelings of heaviness, sense of pressure in the chest

44
Q

General contraindication for “triptans”

A

all triptans can precipitate angina; contraindicated in coronary artery disease (ischemic heart disease)

45
Q

Contraindications for Sumatriptan (Imitrex)

A

increases bioavailability of MAO-A inhibitors; combined use is contraindicated

46
Q

Contraindications for Naratriptan (Amerge)

A

Severe hepatic or renal impairment or peripheral vascular disease

47
Q

Contraindications for Zolmitriptan (Zomig)

A

Patients with Wolff-Parkinson-White syndrome

48
Q

Contraindications for Rizatriptan (Maxalt)

A

Contains phenylalanine; PKU patients beware (orally disintegrating tablets only)

49
Q

Criterion for a refractory headache (Status Migrainosus)

A

headahce for >72 hours with or without treatment

50
Q

Treatment for status migrainosus

A

Triptans

51
Q

Treatment for status migrainosus if triptans fail

A

Sub-Q of DHE
+/- IM or IV narcotic
+/- corticosteroid

52
Q

When should preventive meds be used for migraine headache?

A
  1. More than 2 moderate or severe headaches per month
  2. Abortive medications have failed to provide sufficient relief or are contraindicated
  3. Quality of life is significantly decreased due to the migraine severity and/or frequency
  4. You are willing to take daily medications, endure possible side effects, and change medications if necessary
53
Q

1st line agents used to prevent migraines

A
  1. Beta-adrenergic receptor antagonists (propranolol and timolol)
  2. Topiramate
  3. Tricyclic antidepressants
  4. Valproic acid
54
Q

MOA of OnabotulinumtoxinA (Botox)

A

Toxin heavy chains mediate uptake into nerve terminals via endocytosis; toxin light chains cleave SNAP25; NT release is inhibited

55
Q

Cleaved SNAP15 co-localizes with

A

CGRP in the dura

56
Q

Criteria for Botox use in chronic migraines

A
  1. 15 headache days/month for 3 months

2. Migraine medication overuse

57
Q

What is calcitonin gene-related pepetide?

A

a 39 aa peptide and potent vasodilator

58
Q

Where is CGRP released from

A

released from the trigeminal nerve in migraines

59
Q

What does CGRP potentiate

A

potentiates the pain response

60
Q

Potential alternative to triptans for patients sensitive to vasoconstrictors

A

antagonism of the CGRP receptor (effective in aborting migraines)

61
Q

5-HT can inhibit

A

release of inflammatory neuropeptides such as substance P, neurokinin A, and CGRP from perivascular nerve terminals via 5-HT (1F) receptors

62
Q

Lasmiditan

A

selective 5-HT (1F) agonist - in development

Pharmacology Test #6 (12 decks)

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