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PHAR 255 - Therapeutics (3) > Migraine Headaches > Flashcards

Migraine Headaches Flashcards

1
Q

What is the proposed mechanism of Migraine Development?

A

Potent vasodilators (ie. CGRP, NO) released, inflammatory reactions also take place in the brain & induces pain.

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2
Q

How do Triptans work?

A

Selective Serotonin Agonists; Act as Potent Vasoconstrictors!!!

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3
Q

Auras occur in what percentage of migraine patients?

A

30%

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4
Q

What can trigger a migraine?

A

-Stress
-Skipping Meals
-Cheese / Chocolate
-Alc (espec. Red Wine)
-Dehydration
-Scents
-Barometric Pressure
-Caffeine (can be both withdrawal / overuse)

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5
Q

What is the “POUND” pneumonic?

A

P - Pulsatile Headache
O - One Day Duration
U - Unilateral Headache
N - Nausea & Vomiting
D - Disabling Pain

-0 to 2pts = 17% likelihood of migraine.

-3pts = 64% likelihood of migraine.

-4 to 5pts = 92% likelihood of migraine.

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6
Q

What NSAID demonstrates the best efficacy for acute pain relief in mod - severe migraines?

A

Ibuprofen

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7
Q

Order the following Triptan dosage forms by efficacy:

IN
SC
Oral

A

SC > IN > Oral

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8
Q

Is there a statistical difference in efficacy for migraine pain relief between Ace 1000mg + Metoclopramide vs. Oral Sumatriptan?

A

NOPE

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9
Q

Is it necessary to follow ordered step-up therapy advancements in those with migraines?

A

Nope… Can jump straight to Sc Sumatriptan (ie. Step 4) if attacks are extremely rapid & early vomiting.

KEY IS TO INDIVIDUALIZE

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10
Q

Is Naproxen Base (ie. Apo-Naproxen or other Generics) or Naproxen Sodium (ie. Aleve) better?

A

Naproxen Sodium… Quicker OOA (30mins).

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11
Q

NSAIDs with or without food: Which is preferred for migraines?

A

Without… Usually TWF, but this would delay OOA (faster OOA on an empty stomach means quicker migraine pain relief).

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12
Q

Which Triptans have a slow OOA & long DOA?

A

Naratriptan, Frovatriptan

All others are fast OOA!

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13
Q

What is the benefit of combining Metoclopramide with Triptans / NSAIDs / Acetaminophen?

A

Is an anti-emetic (so helps with nausea via Dopamine Receptor Antagonism), speeds up GI motility (enhances the speed & degree of SI absorption of the other drugs).

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14
Q

If a patient is prone to water-induced vomiting upon taking oral agents for migraine treatment, what can we do?

A

-IN Triptans
-ODTs

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15
Q

What are the primary benefits of migraine prophylactic treatments?

A

-Migraine frequency reduced.

-Decrease in migraine intensity (drugs don’t have to work as hard).

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16
Q

How does Dihydroergotamine (DHE) work?

A

Serotonin Receptor Agonist (similar to Triptans induces vasoconstriction)… However, is dirty (hits many others).

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17
Q

Why do we avoid Opioids in migraine treatment?

A

Doubled risk of Medication Overuse Headaches, increased OD risk.

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18
Q

Why do T3 tablets suck ass for treating migraines?

A

-2x Med Overuse Headaches.

-Subtherapeutic Caffeine (15mg «< 100mg), Ace Doses (300mg «< 1000mg).

-Codeine Metabolism is unpredictable (2D6 polymorphisms).

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19
Q

Even though T3s suck ass, why do Doctors love them so much?

A

Very cheap (9 cents per pill).

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20
Q

When would Triptans be contraindicated?

A

-Uncontrolled HTN
-Previous MI / Stroke
-Generalized CVD
-Ergot use within 24hrs
-MAOIs

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21
Q

Side effects of Triptans?

A

-Chest Tightness
-Palpitations
-Dizziness
-Facial Flushing
-Nausea

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22
Q

How are Triptans dosed?

A

100mg at onset of migraine; Repeat in 2hrs PRN (200mg = Daily Limit).

Note that this is for Sumatriptan… Rizatriptan more commonly 10mg at onset & repeat in 2hrs with daily limit of 20-30mg.

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23
Q

Is nausea completely avoided by using an injectable Triptan?

A

Nope… But definitely reduced.

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24
Q

Which Triptan has the longest t1/2?

A

Frovatriptan (25hrs)

-Naratriptan is 6hrs… Fast Acting ones are 2-3hrs.

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25
Q

What other add-on therapy in migraine treatment works in the same manner as Metoclopramide?

A

Domperidone

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26
Q

What added benefit does Domperidone have over Metoclopramide?

A

Cannot cross BBB… Dopamine Blockade in the brain unachievable, so we avoid Pseudo-Parkinsonism symptoms (ie. Tremor, Movement Disorders).

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27
Q

What is the 3x3 Triptan rule?

A

-Try for three migraines, try three different Triptans before giving up on the class! These drugs are highly individualized, so a particular Triptan may work well for one person & not at all for another.

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28
Q

ODT Triptans take _____ (more or less) time to work than Regular Oral Triptans.

A

More; ODTs are not SL in nature, so lots of drug lingers around in the mouth (thus increasing absorption time).

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29
Q

The rule of thumb (in terms of days per month) for likely diagnosis of Medication Overuse Headaches is what?

A

> 15d / mth

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30
Q

Give the max number of drug days (not doses) per month that you can use these meds without worry of MOH:

Triptans
Opioids
NSAIDs / Ace

A

Triptans: 9d
Opioids: 9d
NSAIDs / Ace: 14d

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31
Q

What options do we have for Menstrual Migraine pre-treatment?

A

-Naproxen 500mg BID x 6d

-Naratriptan 1mg BID x 6d

-Frovatriptan 2.5mg BID x 6d

-Estradiol Gel 1.5mg OD x 7d

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32
Q

Of the four provided Menstrual Migraine pre-treatment strategies, which one demonstrates greatest efficacy?

A

Frovatriptan (but also $$$).

33
Q

Ubrogepant dose?

A

50-100mg

34
Q

Atogepant dose?

A

10-60mg

35
Q

What advantage do CGRP Receptor Antagonists (ie. ‘gepant’ drugs) have over Triptans?

A

CAN BE USED SAFELY IN CVD!!!

36
Q

Who should consider migraine prophylaxis?

A
  • > 6 headache days / mth.
  • > 3 severely disabling attacks / mth.
    -Acute treatments don’t work well or are CI.
37
Q

What four drugs demonstrate best efficacy in migraine prophylaxis?

A

Amitriptyline, Propranolol, Metoprolol, Topiramate

38
Q

If a patient is put onto Amitriptyline for migraine prophylaxis, when would we expect to see tolerance development to nuisance anti-cholinergic side effects?

A

3 - 10d

39
Q

Which prophylactic migraine agents demonstrate the fewest adverse effects?

A

Candesartan, Magnesium, Riboflavin

40
Q

If a patient desires migraine prophylaxis & additionally smokes, what would be a suitable product?

A

Nortriptyline

41
Q

If a patient desires migraine prophylaxis & is an Insomniac, what would be a suitable product?

A

Amitriptyline

42
Q

If a patient is hypertensive and experiences migraines, what would be a suitable ACEi or Ca2+ Channel Blocker to use for prophylaxis?

A

Lisinopril (ACEi) or Verapamil (Ca2+ Channel Blocker)

43
Q

If a patient wants migraine prophylaxis & also has concurrent depression, what would be suitable agents?

A

Venlafaxine, Duloxetine, Amitriptyline (potentially)

44
Q

What is the proposed theory behind using Beta Blockers (ie. Propranolol, Metoprolol) in migraine prophylaxis?

A

Precursor vasodilation relaxes vessels prior to migraine onset… Less capacity for dilation = Less blood rushing suddenly into the brain.

45
Q

Why are Propranolol & Metoprolol considered the best Beta Blocker agents for migraine prophylaxis?

A

Most lipophilic = Better BBB Penetrance.

46
Q

What pneumonic describes the difficult discontinuation process of SNRIs?

A

“FINISH”

F - Flu-Like Symptoms
I - Insomnia
N - Nausea
I - Imbalance
S - Sensory Disturbances
H - Hyperarousal

47
Q

Does it make sense to combine Verapamil with a Beta Blocker for strengthened prophylaxis against migraines?

A

NOOOOO… Can precede Heart Block & Conductance issues!

48
Q

When utilizing herbals (ie. Magnesium Citrate / Oxide, Riboflavin) for migraine prophylaxis, do we need to titrate doses?

A

Nope… Can jump straight to target dose!

49
Q

With long-term use, what is the proposed MOA in migraine prophylaxis for TCAs?

A

Downregulation of Serotonin Receptors = Less likely migraine cascade!

50
Q

If initiating someone on a Biologic for migraine prophylaxis (ie. Fremanezumab, Eptinezumab, Erenumab, Galcanezumab, “Gepant” drugs), how long does it usually take for full effects?

A

24wks

51
Q

What “Gepant” drug is indicated in Canada for Acute Migraines? Migraine Prophylaxis?

A

Ubrogepant - Acute
Atogepant - Prophylaxis

52
Q

Target Beta Blocker doses for migraine prophylaxis?

A

Propranolol: 80mg BID, 160mg (if LA Tablet).

Metoprolol: 100mg BID, 200mg (if SR Tablet).

53
Q

Target Amitriptyline dose for migraine prophylaxis?

A

75mg HS (jump to 100mg if it’s tolerated).

54
Q

Target Nortriptyline dose for migraine prophylaxis?

A

50mg HS (jump to 100mg HS if tolerated)

55
Q

Target Topiramate dose for migraine prophylaxis?

A

50mg BID

56
Q

Target Candesartan dose for migraine prophylaxis?

A

16mg OD

57
Q

Target Magnesium Oxide dose for migraine prophylaxis? Magnesium Citrate dose?

A

Oxide: 500mg OD Elemental (2T OD)

Citrate: 300mg BID (2T BID)

58
Q

Target Fremanezumab dose for migraine prophylaxis?

A

225mg Sc q4wks

OR

675mg Sc q12wks

59
Q

Target Riboflavin dose for migraine prophylaxis?

A

400mg OD

60
Q

Does Botox help with Episodic Migraines (< 15d / mth)?

A

Nope… But, seems to help with Chronic Migraines (> 15d / mth).

61
Q

Propranolol slows Rizatriptan metabolism & thus increases its levels by ____%.

A

70%

62
Q

If a patient is on both Propranolol & Rizatriptan, what Rizatriptan dose should they take?

A

5mg (NOT 10mg too much).

63
Q

What’s one concern with CGRP MABs?

A

Development of resistance to the drug (via AB generation against the drug itself due to long windows between doses).

64
Q

Provincial Drug Plan / NIHB coverage of certain CGRP MABs is limited to who?

A

Those who have failed at least two oral prophylactic agents.

65
Q

What is the average patient response rate to CGRP MABs?

A

40%

66
Q

CGRP Receptor Antagonists are good to use in those with CVD (are not a CI). However, are CGRP MABs good to use in CVD?

A

Probably not… Can invoke HTN & CV patients were excluded from trials!

67
Q

What are some adverse effects of the “gepant” drugs?

A

Nausea & Somnolence

68
Q

Provide some red flag symptoms of Acute Headache that warrant calling an ambulance.

A

-Impaired Speech
-Fever / Neck Stiffness
-Thunderclap Headache
-Ocular Symptoms
-Loss of strength or fading in out of consciousness

69
Q

Provide some red flag symptoms of Acute Headache that warrant physician referral.

A

-1st ever intense headache
-Headache from sex / exercise
-Over 50yrs age
-HIV / Cancer / Lyme Dx / Pregnant
-Papilledema
-Old & Cognitive Disturbances

70
Q

Describe what a migraine headache is.

A

-4 to 72hr duration
-Unilateral (40% bilateral)
-Pulsating, Mod to Sev Pain
-NV / Photo or Phonophobia
-Can be aggravated by routine activities
-Potential Aura presence
-Potential Speech Disturbance

71
Q

Describe a Tension Headache.

A

-30mins to 7d duration
-Typically bilateral
-Pressing / Tightening (BUT NOT PULSATING) Pain; Mild - Mod intensity
-Photo / Phonophobia
-Absence of NV
-Typically not aggravated by routine activity

72
Q

Describe a Cluster Headache.

A

-15mins to 3hrs Duration
-Behind the Eyes Origin
-Stabbing Pains; Sev - Excruciating Intensity
-Frequency of Occurrence Bi-Yearly
-Eyelid Tearing / Swelling, Facial Sweating, Pupillary Constriction, Eyelid Drooping

73
Q

Acute treatments for Tension Headaches? Prophylaxis?

A

-NSAIDs (Acute)
-Acetaminophen (Acute)
-TCAs (Pro)

74
Q

Acute treatments for Cluster Headaches? Prophylaxis?

A

-Sc Suma (Acute)
-Verapamil (Pro)

75
Q

In Medication Overuse Headaches, how long can withdrawal symptoms last?

A

Generally 2-10d, but can last up to 2-4wks in some.

76
Q

When is meaningful headache frequency improvement demonstrated in those who have MOHs?

A

4-8wks after drug discontinuation.

77
Q

Three main strategies for addressing MOHs?

A

1) Stop overused meds abruptly.

2) Stop / taper overused meds & start prophylaxis.

3) Start prophylaxis only & do nothing to overused meds.

78
Q

On average, the three MOH treatment strategies reduce headache frequency by how many days per month?

A

8 - 12d / mth

PHAR 255 - Therapeutics (3) (7 decks)

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