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PHAR 255 Exam 2 > MIgraines > Flashcards

MIgraines Flashcards

1
Q

Migraine Statistics

A

2-3 x more likely in females than males

Tend to hit young adulthood up until 50 – can age out in elderly

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2
Q

Pathophysiology of Migraines

A

Some people have sensitized neurons – unclear why.

A migraine trigger comes along
(e.g. stress, dehydration, lack of sleep … or completely unidentifiable)

The brain releases potent vasodilators (e.g. CGRP, nitric oxide) and inflammation reactions

Vasodilation = big pain; inflammation begets more inflammation. (Positive feedback loop)

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3
Q

Describe where the medications used for migraines work?

A
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4
Q

How do triptans work in the pathophysiology of migraines?

A

Vasodilator – expands blood vessels in the brain

Triptans = selective serotonin agonsists = vasoconstrictors

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5
Q

What is critical in the management of migraines?

A

Early IS CRITICAL for INFLAMMATION MANAGEMENT

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6
Q

What are some common symptoms of a migraine in people?

A

An aura occurs in around 30% of patients
Some possible symptoms:

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7
Q

What are some triggers of a migraine?

A

stress
meal-skipping (consider food insecurity)
foods (e.g. chocolate or soft cheese)
alcohol (especially red wine)
caffeine withdrawal (Has a beneficial effect; at other doses may make it worse)
dehydration (OFTEN UNRECOGNIZED)
menstruation (keep constant levels of hormone, continuous hormonal contraceptive can be benficial)
lights/sunlight
erratic sleep / shift work
perfume/odour
obesity
change in barometric pressure

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8
Q

Diagnosis of a migraine

A
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9
Q

Describe the efficacy of therapy

A

Have so many choices

Some NSAIDS work better than others

Triptans at high dose work bette rthan low dose

Combining an NSAID and triptan is better than a drug alone

Often in trials, go for pain relief at 2 hours – pain relief may not be what we care the most about, one of the goals could be pain resolvement

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10
Q

Caffeine Overall

A

Acet 500 +ASA + caffeine – 84% efficacy – guidelines do not give it credit, do not pull out often – caffeine withdrawal, medication use headache

Caffeine dose (150 mg) – amount of caffeine in coffee – approx. 100 mg – take these two drugs with cup of coffee
Caffeine tablet is also a good way to go

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11
Q

Describe the treatment approach to acute migraines? Is it a step-ladder approach?

A

Algorithm regarding efficacy, but not steps to therapy necessarily

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12
Q

Are NSAID’s useful in migraines?

A

In general, may get response out of 4-5 patients

NSAID’s work relatively well – cheap

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13
Q

Compare triptans to NSAIDS?

A

Triptan – 10x price of NSAID
– may need 2-3 in a month or in a year
– little bit of a boost of an NSAID (response in 5-6 partients; 4-5 with nsaids)

NSAID plus triptan – better than other drug alone

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14
Q

What is Suvex?

A

sumatriptan and naproxen together – way more expensive

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15
Q

At the start of a migraine counsel, a pharamcist should consider?

A
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16
Q

What can be done if an NSAID fails?

A

Naproxen sodium vs naproxen base –> Naproxen sodium is the same formation as ALEVE – 20-30 ish mins faster absorption than base (1/20 to 1/17 will benefit from having something faster than slower)

Diclofenac Potassium – powder formulation – really expensive – probably fastest onset, but so expensive – never going there

Migraines – NSAID with food, delaying its absorption – get it to the small intestine, food makes this process longer

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17
Q

What is an important counselling tip for someone taking an NSAID for an acute migraine?

A

DO NOT TAKE NSAID’s WITH FOOD AS WILL DELAY THE ABSORPTION OF THE NSAID

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18
Q

What are triptans? Do they all have the same onset of action?

A

Triptans are serotonin agonists – vasoconstrictors

Some are fast onset and some are not

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19
Q

What are the slow acting triptans? WHo are they used in?

A

Slow Triptans –> Naratriptan, frovatriptan – long-acting – useful in people who have a couple of hours before it hits

  • Not useful in those who do not have prodromal symptoms
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20
Q

How should triptan failure be managed? What are the fast acting triptans?

A
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21
Q

What is a critical factor in the treatment of migraines?

A

Fast is important in migraines

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22
Q

What is the recommendation for switching triptans?

A

Many serotonin receptors – hit a different ratio of these receptors – rotating triptans is very reasonable thing to do

Try atleast 3 and try it for 3 different migraines before you decide

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23
Q

What is the role of metoclopramide in migraines?

A

Add metoclopramide – Decrease nausea, increase efficacy

Speeds up G.I. motility – pushing things through the small intestine – dopamine blocking, pushes things through the gut – DOPAMINE BLOCKER – increases efficacy by increasing absorption more/faster of other drugs as getting to the small intestine

Metoclopramide – all by itself, still seemed to help migraine response a little

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24
Q

What use does a nasal spray have in migraines? Describe it’s absorption?

A

Nasal Spray – Partially absorbed through the nose, but good chunk is absorbed by the stomach – drips down a little – a lot of people take a pill, need water and little bit of water causes them to throw up

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25
Q

What is the benefit of an ODT?

A

Some triptans are orally disintegrating tablets – do not need to take it with water

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26
Q

What is migraine prophylaxis? WHat is the benefit of prophylaxis?

A

Start migraine prophylaxis – hoping for less migraines, will actually decrease the intensity of migraines – can boost the efficacy of other drugs by decreasing the intensity of migraines

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27
Q

What is DHE?

A

DHE – Dihydro-ergotomy nasal spray - do not use much anymore – hits serotonin receptors causing vasoconstriction but also hits other receptors – lots more side effects – more nausea, feeling weird

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28
Q

Opiods role in migraines?

A

Avoid opioids –

Medication Overuse Headaches – twice as likely any other drugs to cause ,edication overuse headache

Opiod/Barbituate – Do nothing for inflammation (just masking the pain) – opiates are not good choice to shut down the inflammation

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29
Q

What is the issue with using opiods in (Tylenol #3’s) in migraines?

A

Opioids have double the risk of medication overuse headache compared to other agents.

Caffeine dose is subtherapeutic.
~100mg needed for migraine efficacy; ~15mg in one Tylenol #3 tab (migraine perspective not doing anything)

Acetaminophen dose is often subtherapeutic.
Best evidence is for 1000mg of acetaminophen; would need three Tylenol #3 tabs
Codeine metabolism is unpredictable.
~10% of the population do not adequate activate the codeine into morphine

T3 – All 3 drugs are subtherapeutic/not good for migraines, A LOT OF PRESCRIBING – any other drug for migraines

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30
Q

What are the two categories to watch out for regarding triptan D.I., S.e? ?

A

Triptans are potent vasoconstrictors

Triptans are potent serotonin Agonists

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31
Q

What are symptoms and C.I. of triptans regarding there vasoconstriction acitivity?

A

Triptans can cause chest discomfort/tightness; palpitations; dizziness; facial flushing

Contraindicated in cardiovascular disease (e.g. uncontrolled hypertension, previous MI, previous stroke, etc.)

Contraindicated within 24 hours of ergots (e.g. DHE) due to additive coronary vasospasm; also do not combine triptans

Migraines – Vasodilation – rush of blood to the brain

Narrow the blood vessels – vast majority is a feeling more than anything bad

Only so much triptan in one day (do not combine) – too much vasoconstriction (coronary vasospasm)

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32
Q

Sumatriptan (Example) Available Strengths and Max Dosing

A

Sumatriptan – 25, 50, 100 mg tabs – Max a day is 200 mg

Explicit directions on how much you can take a day

Generally, max dose times by 2 – max dose for a day

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33
Q

What are some side effects and c.i. associated with triptans being potent serotonin agonists?

A

Triptans can cause nausea (think of: the opposite of ondansetron)

Triptans are contraindicated with MAOIs (risk of serotonin syndrome) and cautioned with other serotonin drugs (SSRI, SNRI, etc. – often just increase monitoring)

Triptans can cause nausea – nausea can already occur in migraine

Ondansetron – serotonin antagonist (prevents nausea) – mechanism makes sense

SSRI, SNRI – Monitor but not a complete C.I.

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34
Q

Triptan Side Effects with Other Dosage Forms

A

Remember: triptans have unique dosage forms = unique s/e
E.g. injection site reactions with injection; bad taste with the nasal spray

Nausea can still occur with injection

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35
Q

Describe which triptan dosage form has the fastest relief of sx?

A
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36
Q

Which triptan has the best efficacy at 2 hr?Worst?

A

Best efficacy at 2 hours – sub cut

Slow acting have the worst efficacy at 2 hours

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37
Q

Which triptans have the best tolerability?

A
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38
Q

Which triptans have the efficacy for long-lasting attacks?

A
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39
Q

Best triptans for privacy?

A

I

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40
Q

What is the onset of effect for triptan formulations?

A

Onset of 10 mins – subcut

Tabs – 30-60 min

ODT and tabs are the same speed of regular tabs

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41
Q

What should be recommended for attacks that last a long time?

A

If attack lasts long time, aborting an attack completely is better – treating hard, fast and aborting it in an hour – Encourage patients to be more aggressive

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42
Q

What is metoclopramide? Domperidone?

A

Mettoclopramide
USA dos not have Domperidone; so very comfortable using it as metoclopramide

Metoclopramide can get into blood brain barrier, (antipsychotic, parkinsons dx component – Block dopamine)

Parkinsons – lack dopamine
– can cause pseudo-parkinsonisms – EPS symptoms for dopamine blocker

Domperidone does not get into BBB, so less EPS – Big s/e is the cardiac conduction (prolong QTc interval, torsades des pointes)

– adding an anti-emetic can be useful ]

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43
Q

Describe the available triptans and there onset, half life and renal function?

A
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44
Q

What is the highest efficacy triptan?When is it useful?Convienience?

A

The highest efficacy triptan is subcutaneous sumatriptan

Works in up to 80% of patients.
Useful if vomiting / severe nausea with oral agents as can guarantee absorption.
Generic and brand products have an auto-injector

Not affordable for everyone

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45
Q

How long should a triptan be used until switch? What combination can be helpful? What to do if nauseau and vomitting?

A

Try a triptan for 3 migraines before giving up, and try at least 3 triptans before giving up on the class.

Acetaminophen alone or combination can be helpful (but overall is less powerful than an NSAID).

Nausea/vomiting is common with migraines – an orally disintegrating tablet can be useful; an antiemetic can be useful; an intranasal dosage form can be useful; injectable sumatriptan can be useful.

46
Q

Are ODT any faster than regular tabs?What if nauseau with ODT?

A

NO

ODT is slower – Not a buccal tab, needs to absorb in the small intestine – add water, absorption matches

ODT without water – sits in the mouth

Nausea lean towards to nasal spray

ODT triptans are no faster than regular tabs

47
Q

What are medications that can lead to a medication overuse headache? Max days per month?

A

Max days per month of acute medications to help avoid medication overuse headache

48
Q

Define medication overuse headache?

A

Medication overuse headache – taken so many meds that you are causing migraines with the acute drugs

Drugs that use to help are sensitizing them

Hypersensitizing the brain – constantly in withdrawal of the medications

49
Q

What average of migraines per month leans toward overusage of acute drugs?

A

More than 15 migraine in on e month, majority due to acute drugs

50
Q

How can a pharmacist gauge triptan usage and medication overuse headache? What approach should be used?

A

Triptans come in packs of 6 – one per month, they are probably doing fine – more than one pack, red flag to do something

Approach conversation appropriately – approach from perspective, improve things for you and make it better

51
Q

Three strategies for medication overuse headache?

A

Cut them off drug that caused problem (stop triptan, start NSAID)
Add prophylaxis
Both at the same time

52
Q

What is a menstrual migraine?Why does this occur?

A

For some, migraines  during menstruation (perhaps due to changing hormone levels)

53
Q

How can menstrual migraines be treated?

A

Option for pre-treatment (starting ~2 days before mensturation):

Naproxen 500mg BID x ~6 days ($5)
Naratriptan 1mg BID x ~6 days ($100)
Frovatriptan 2.5mg BID x ~6 days ($200)
Estradiol gel 1.5mg daily x ~7 days ($40) – menopause product

Treat menstrual migraines like other migraines – some we have option for pre-treatment

  • Frovratriptan has best evidence
54
Q

What is a preventative option for menstrual migraines?

A

Option for prevention with continuous combined hormonal contraceptives

But: CHCs + migraine with aura –> contraindicated

E.g. CHCs + migraine with aura + smoking = 7x stroke risk

Somewhat controversial – the real risk is when other risk factors like smoking start getting thrown in there.

55
Q

Would the Mireena IUD be effective for menstrual migraines?

A

Continous combined hormonal contraception – give someone mireena IUD and shut down menstrual cycle (does not work, works more locally) – Mireena IUD not changing hormonal levels, more local

Cmbined – progestin and estrogen (not progestin alone)

56
Q

Another class of medications used for an acute migraine is…..

A

Anti-cGRPs

Two types: Monoclonal antibody (prophylaxis) and receptor antagonist oral

CGRP is a vasodilator

Antibody mops everything up – just prophylaxis

57
Q

What are the available CGRP antagonists? Dose?

A

Ubrogepant approved in Canada 2022.
Treatment dose: 50-100mg stat

Rimegepant and Zavegepant approved in USA (not yet in Canada).

Atogepant approved in Canada for prevention of migraines.
Prevention dose: 10-60mg daily;

58
Q

Gepants A/e C.I.

A

Adverse effects: nausea, somnolence.

Not contraindicated in CV disease. (Big potential over the triptans)

59
Q

Gepants Efficacy Compared to Triptans

A

Likely NOT as effective as triptan for acute migraine, although not compared head-to-head.

Appears to have very low risk of medication-overuse headache (more likely no risk – really safe in medication-overuse)

Weaker drugs from acute treatment side of things – a bit too slow to block CGRP receptor
Cost is not good; expensive

60
Q

Who should be offered migraine prophylaxis?

A

Depends on severity, 6 headache days per month (may start earlier – 3 really bad migraines a month) – May still think of prophylaxis based off of career if cannot miss day of work

  • 3 if severe, 6 if less severe – prophylaxis
61
Q

How should an adequate trial of migraine prophylaxis be initiated?

A

Start at low dose, build up tolerability – can cause s/e – ease people into it

  • Target dosage range – want to get people to the target dose – want to be at target for 8-12 weeks – need some time to see efficacy – give it a good try as can be one shot for some
62
Q

What is a reasonable goal for migraine prophylaxis?

A

Reasonable Goal of TX : Reduction in 50% of frequency or intensity

63
Q

How long does it take for a patient to become sensitized to s/e of the prophylatic medication?

A

Make it to 10 days, s/e become more tolerable – at beginning, no benefit and s/e – need to push through – encouragement on our end

64
Q

Is the cost of prophylatic medications particularly limiting in migraine prophylaxis?

A

Cost does not really play a role

Mainly choose around efficacy, s/e and comorbidities

65
Q

What are the available prophylatic migraine options? Effeicacy? S/e?

a)Smoking
b) Insomnia
c) HTN
d) Chronic Pain
e) Depression/Anxiety

A

Best efficacy – 60%ish of the time, propranolol up to 80%
A/e – up to 40%
Cgrp – up to 40%, up to 60%

66
Q

What are the avilable prophylatic medication classes and examples available for migraines?

A

Beta-Blocker - Propranalol, Metoprolol, Timolol

TCA - amitriptylline, Notriptylline

Anti-convulsant - Topiramate, Divalproex

ACEi/ARB - candesartan, Lisinopril

SNRI - Venlafaxine, Duloxetine

CCB - Flunarazine, Verapamil

5HT2- Inhib - Pizotifen

Herbal: Magneisum oxide/citrate, riboflavin, butterbur, co-enzyme Q-10

Anti-CGRP - Fremanezumab, Eptinezumab, ernumab, Galacanezumab, Atogepant, Rimegepant

Other: Memantine, BOTOX

Before tony asks about s can people head away

67
Q

How do beta-blockers work in migraine prophylaxis?

A

Do not really know why beta-blockers work in migraines

High-blood pressure Hypothesis – if we beta-blockade, blood vessels on vasodilated side already – less room for them to dilate them more – may explain why it takes long to see effect

68
Q

Beta-blocker doses

A
69
Q

Which beta-blockers are used in general?

A

Not every beta-blocker – may need drugs to penetrate Brain – drugs in classes and not whole classes

Heart rate, blood pressure

70
Q

What are some a/e of beta-blcoekrs?

A

exercise intolerance is a big deal for younger pt’s (cant go as fast as you want to go) - hold patients back – older pts better tolerate as not working out

Coldness in your fingers (not as much blood in the fingers)

71
Q

What are the TCA doses used in migraine prophylaxis?

A
72
Q

Describe the mechanism by which TCA’s work in migraine prophylaxis?

A

TCA – serotonin, norepinephrine, hit anti-histamines and other recptors as well

  • One theory – may be some downregulation of serotonin receptors if on long enough – migraine cascade is less likely to happen

Other – can be used for chronic pain, numbing some pain areas in the brain so if cascade happens, it happens a little less

73
Q

TCA Side Effects

A

Amitriptylline is more likely to cause drowsiness – Tertiary AMine

Notriptylline has smoking cessation indication – tough to tolerate for migraines
- secondary amine

74
Q

Anti-convulsant Doses in Migraine Prophylaxis

A
75
Q

Anti-convulsant MOA in Migraine Prophylaxis. Tolerability and C.I.?

A

Anti-convulsants – slow down the brain a little bit, less likely to run into big cascade of pain

  • topiramate is best efficacy but very hard to tolerate
  • pregnancy risk (anti-convulsants) – child-bearing age more worried here
76
Q

Acei and ARB Doses in Migraine Prophylaxis

A
77
Q

Acei and ARBs in Migraine Prophylaxis S/e

A

Specific for two drugs – nice cheap, well tolerated drugs

  • S/e – orthostatic hypotension, acei cough, less common with ARB (can happen), renal and elctrolytes  Can cause hyperkalemia
  • Blood pressure – dizziness or fall risk – often normotensive pts. So dizziness may be prevelant
78
Q

What SNRI’s can be used for migraine prophylaxis? Dose?

A
79
Q

MOA of SNRI’s? Most evidence? S/e?

A

Serotonin and norepinephrine
- Just two – venlafaxine has the most evidence
- No SSRI’s – trials do not show that they help
- Dry mouth, increase in anxiety/agitation, insomnia, sexual dysfx – tough to discontinu
- Nauseau when starting

80
Q

When discontinuing an SNRI, what may occur?

A

Discontinuation Syndrome

Flu-like symptoms (lethargy, fatigue, headache, achiness, sweating)

Insomnia (with vivid dreams or nightmares)

Nausea (sometimes vomiting)

Imbalance (dizziness, vertigo, light-headedness)

Sensory disturbances (“burning,” “tingling,” “electric-like” or “shock-like” sensations)

Hyperarousal (anxiety, irritability, agitation)

81
Q

What is unique about venlafaxine?

A

Venlafaxine – short t1/2 – very hard to stop, tough to quit

82
Q

What CCB blockers can be used in migraine prophylaxis? Dose?

A
83
Q

Effeicacy of CCB’s?

A

CCBS – NON-DHP’s – best data with flunarizine – really sedating

Verapamil – constipation is reallyy present

84
Q

Can a BB and non-DHP be combined?

A

NOOOOOOOOOO

85
Q

What is the 5HT2 antagonist? Dose? MOA

A

Pitzoifen – serotonin antagonist
- blocking from serotonin receptors, less serotonin receptors to bind

86
Q

Which herbals can be used in migraine prophylaxis? Dose?

A
87
Q

Efficacy of Herbals? S/e?

A

Herbals just target dose; recommended daily intake of magnesium is 300 mg – main side effect is diarhhea

  • if having constipation, magnesium may be the way to go
    2 tabs of magnesium

Magnesium citrate may be better tolereated but given twice a day

Riboflavin – 1mg per day (RDI)
- Turn urine neon yellow colour

88
Q

What are the biologic anti-CGRP’s? Dose? Use? EDScriteria? Effectiveness?

A

all 4 of the drugs (first) – Biologics – antibodies that bind to cGRP – only migraine prophylaxis – too slow to work for acute (may change)

  • EDS – fail two drugs for prophylaxis – 40%ish response in 3 months, 60%ish in 8 months
89
Q

What are the non-biologic anti-CXGRP’s? Dose?

A
90
Q

Atogepant Role in Therapy? Efficacy?

A

atogepant is indicated for prophylaxis – works about 60%ish a time

91
Q

Memantidine Dose For Migraine Prophylaxis?

A

Memantine – never used; used for alzheimers – NDMA antagonist

92
Q

Botox Dose and Role in Tx?

A

Botox – interesting as helps chronic migraine (more than 15 headache pers month) and less efficacy for someone who has episodic migraines (less than 15 month per month)

93
Q

For all prophylatic methods of migraines, what is the appropriate duration of therapy?

A

Treat at target dose for 8-12 weeks before deciding if prophylaxis is helping.

94
Q

What is a critical drug interaction to consider with migraine prophylaxis?

A

Two high of rizatriptan – extra vasoconstriction – higher risk of coronary vasospasm

95
Q

CGRP Monoclonal Antibodies MOA and Examples

A

Monoclonal antibody targeting calcitonin gene-related peptide
E.g. fremanezumab, erenumab, galcanezumab, eptinezumab

96
Q

CGRP Monoclonal Antibodies Response and Onset

A

Response in about 40% of patients.
Often onset in days (but give 3-6 months for adequate trial).

97
Q

CGRP Monoclonal Antibodies Coverage

A

Some covered in Sask and by NIHB if failed at least two oral prophylactic agents.

98
Q

CGRP monoclonal antibodies Dosing Frequency

A

Some have option to give q3months – but likely monthly preferred.

Allowed to dose some of these cGRPs every 3 months – resistance building up – body could mount an antibody to the antibody (an anti-drug antibody)

99
Q

CGRP monoclonal antibodies A/E

A

Adverse effects: injection site reactions, hypertension. Patients with CV risk were excluded from trials.
Cost: ~$600/month

100
Q

Atogepant Indicated USe in Migraines

A

Atogepant approved in Canada for prevention of migraines.

Prevention dose: 10-60mg daily

101
Q

What are the red-flag symptoms for an acute headache?

A

Fever/Neck Stiffness – Meningitis

102
Q

Compare and contrast the different types of headaches

A

remeber tension type prophylaxis TCA

103
Q

Define medication overuse headache

A
104
Q

Causes of MOH

A
105
Q

Withdrawal Sx MOH

A
106
Q

How can the cycle of MOH be stopped?

A
107
Q

How can MOH be treated? What is resolution defined as?

A
108
Q

Tx options for MOH?

A
109
Q

Tips for MOH

A
110
Q

general Guide for MOH TX

A

PHAR 255 Exam 2 (5 decks)

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