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Flashcards in Migraines Deck (30):
1

Treatment options for migraines

quick abortive, acute therapy, prophylactic

2

Quick abortative

NSAIDs, combo analgesics

3

Acetaminophen, naproxen, diclofenac, ibuprofen

Class: quick abortive, NSAIDS
-USE: For mild-moderate attacks
-NSAIDS and muscle relaxants for tension headaches
-Acetaminphen works, but remember it’s not anti-inflammatory

4

Combo analgesics

Excedrin (acetaminophen/
aspirin/caffeine)
Midrin (isometheptene/ dichloralphenazone/ acetaminophen)

5

NSAIDS

Acetaminophen, naproxen, diclofenac, ibuprofen

6

Excedrin (acetaminophen/
aspirin/caffeine)

-USE: For mild-moderate attacks

7

Midrin (isometheptene/ dichloralphenazone/ acetaminophen)

-USE: For mild-moderate attacks

8

Acute therapy for Migrane plan of action

first try NSAIDS; if ineffective try triptans or DHE. Some patients may go straight to the triptans – triptans appear to be less toxic and slightly more effective than the ergots, but DHE has a longer duration of action

9

Drugs used in acute therapy

Ergots, Triptans

10

Ergot

Dihydroergotamine (DHE-45), Ergotamine

11

Dihydroergotamine (DHE-45), Ergotamine

Class: Ergot
-structurally similar to D-lysergic acid
-predominantly 5-HT1D agonist but also 5-HT2A/B/C agonist as well as dopamine and noradrenaline alpha receptor agonist → makes it a “dirty” drug
-MOA is similar to triptans
-USE: migraine, also used for acute treatment of cluster headache
-ADMIN: more effective when given early in attack
-available in parental (SC, IM, IV), intranasal preperations and rectal formulations
-injections are usually more rapid acting
-rectal formulations are for patients with nausea but stimulation of dopamine receptors may cause nausea
-when give parenterally it may be used with metoclopramide to prevent vomiting
-some oral and rectal preperations contain caffeine which may enhance absorption
PHARM: Highly non-selective→also stimulates DA, alpha2, 5-HT2 and other receptors
-Tolerance→refractory, rebound h/a (serious!)
-Ergotism—nausea, dizziness, perceptual disturbances, severe vasoconstriction (→possible gangrene b/c + 5HT2/a2 receptors..Tx w/ vasoD, Ca2+ channel blockers)
AE: similar to triptans: nausea, dizziness, parathesias, but also comiting, diarrhea, muscle cramps, cold skin
-vasoconstriction through alpha receptors and 5-HT receptors; contraindicated in coronoary artery disease and PVD
-excessive dosing can cause cerebral vasoconstriction and rebound headache
-because they are alpha agonists they should not be used with beta blockers → could lead to peripheral ischemia
-cytochrome p450 interactions with protease inhibitors and macrolide antibiotics. Combo may cause excessive vasoconstriction

12

Triptans

Sumatriptan
Zolmitriptan
Naratriptan
Rizatriptan

13

Triptan MOA

-block the release of vasoactive peptides from perivascular trigeminal neurons by acting on presynaptic 5-HT1B/D
-they also bind presynaptic receptors in the brain stem that block the release of NT that activate second-order neurons ascending to the thalamus
-most effective when given early in the attach

14

Triptan AE

Common AE: Nausea, dizziness, paresthesias (tingling and burning sensation), somnolence, chest tightness
-blood pressure elevations with triptans are minimal and clinically insignificant in patients w/o cerebro or cardio vascular disease
-chest tightness in 15% of patients
-Contraindications: in patients with angina, history of TIA, family history of coronary arter disease or heart attacks, uncontrolled hypertension, history of stroke, or uncontrolled diabetes
-should not be used with: monoamine oxidase inhibitors (serotonin syndrome); within 24 hours of an ergot or methylsergide (increased vasoconstriction)

15

Sumatriptan

-Class: triptan
-ADMIN: PO (low bioavailability; others below have higher bioavail), SC, nasal → peak plasma levels achieved most rapidly with SC and least rapidly with oral admin
PHARM: Lowest lipophilicity—poor CNS penetration
Plasma t1/2—2 hrs
High first pass metab—MAO-A
Injection onset 10-15 min; high bioavailability; more efficient if given 2 hrs after onset
-relieve 85% of attacks and is slightly superior to DHE
-Recurrence of migraine possible (newer agents listed below have a lower rate of headache recurrence)
-USE: also used for acute treatment of cluster headache

16

Zolmitriptan

-Class: triptan
-Admin/Pharm: PO, nasal
Lipophilic→brain penetrant, centrally active

17

Naratriptan

-Class: triptan
-Admin/Pharm: PO
Effective against menstrual migraine
Most lipophilic

18

Rizatriptan

-Class: triptan
-Admin: PO

19

Classes of prophylactic meds

-cardiac medications (B blockers), antidepressanst, AED, anti-seratonin

20

Methysergide

-Class: Anti-serotonin drug
-MOA: Blocks 5-HT2 receptors
-not widely used
-potentially serious side effects of fibrosis
-withdrawn because of toxicity

21

Anti-serotonin drug

Methysergide

22

B-blockers (only ones FDA approved for migraine)

Propranolol
Timolol

23

Propranolol
Timolol

-Class: B-blockers (only ones FDA approved for migraine)
-MOA in migraine is unknown but may be due to: membrane stabilizing activity; attenuate B-2 vasodilation; somehow interacts with serotonin system; decreased prostaglandin production
-USE: indicated in migraneurs with hypertension and/or angina, with performance anxiety or aggressive behavior
-Contrindications: Do not use in patients with asthma or pulmonary disease or significant depression!!
-AE: fatigue, exercise intolerance, cold extremities, diarrhea, constipation, and dizziness, worsening of depression

24

Tricyclic Antidepressants

Amitryptiline, nortriptyline

25

Amitryptiline, nortriptyline

-Class: Tricyclic Antidepressants
-MOA: block alpha-adrenergic, histamine, and muscarinic receptors (makes them kind of a dirty drug) → likely that their effect is due to central action via inhibition of 5-HT and norepi reuptake and attenuation of central sensitization that occurs via NMDA receptor agonism
-USE: good second line alternative
-used in migraineurs with depression, anxiety, and/or panic
-also may be effective in migraineurs with fibromyalgia
-AE: may unmask manic behavior in bipolar disorder
-antimuscarinic effects: increased heart rate, blurred vision, difficulty urinating, dry mouth, constipation
-weight gain, weight loss, or orthostatic hypertension
-contraindications: MAOI, seizures, enlarged prostate, glaucoma, sedation

26

SSRI’s

-widely used but no data to support their efficacy
-they treat headaches associated with PMS or PMDD

27

Ca2+ Channel Blockers

Verapamil

28

Verapamil

-Class: Ca2+ Channel Blockers
-MOA: block the transmembrane influx of calcium across the cell membranes through slow voltage dependent channels → evidence suggests that their effect on migraine is related to their affect on neurotransmission
-NB: some inhibit vasospasm, including verapamil and nimodipine; nimodopine has little use in migraine prevention so this mech is unclear
-USE in migraineurs with hypertension
-esp affective for hemiplegic migraine (this familial condition is thought to be due to defective calcium channels)
-AE’s: constipation, hypotension, AV block, edema, nausea
-contraindications: bradycardia, heart block, sick sinus syndrome
-cytochrome p450 interactions

29

Antiepileptics

Valproate
Topiramate
Gabapentin

30

Valproate
Topiramate
Gabapentin

-Class: Antiepileptics
Valproate: inhibits low threshold T-type calcium channels, (use dependent block of sodium channels; increased GABA)
Topiramate: mixed action, may antagonize AMPA receptors, may inhibit sodium channel, may potentiate transmission at GABA-A receptors
-Topiramate is esp helpful in overweight migraineurs or with bipolar disorder
-AE’s covered in anti-seizure lecture