MIgraines Flashcards
Migraine Statistics
2-3 x more likely in females than males
Tend to hit young adulthood up until 50 – can age out in elderly
Pathophysiology of Migraines
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)
Describe where the medications used for migraines work?
How do triptans work in the pathophysiology of migraines?
Vasodilator – expands blood vessels in the brain
Triptans = selective serotonin agonsists = vasoconstrictors
What is critical in the management of migraines?
Early IS CRITICAL for INFLAMMATION MANAGEMENT
What are some common symptoms of a migraine in people?
An aura occurs in around 30% of patients
Some possible symptoms:
What are some triggers of a migraine?
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
Diagnosis of a migraine
Describe the efficacy of therapy
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
Caffeine Overall
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
Describe the treatment approach to acute migraines? Is it a step-ladder approach?
Algorithm regarding efficacy, but not steps to therapy necessarily
Are NSAID’s useful in migraines?
In general, may get response out of 4-5 patients
NSAID’s work relatively well – cheap
Compare triptans to NSAIDS?
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
What is Suvex?
sumatriptan and naproxen together – way more expensive
At the start of a migraine counsel, a pharamcist should consider?
What can be done if an NSAID fails?
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
What is an important counselling tip for someone taking an NSAID for an acute migraine?
DO NOT TAKE NSAID’s WITH FOOD AS WILL DELAY THE ABSORPTION OF THE NSAID
What are triptans? Do they all have the same onset of action?
Triptans are serotonin agonists – vasoconstrictors
Some are fast onset and some are not
What are the slow acting triptans? WHo are they used in?
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
How should triptan failure be managed? What are the fast acting triptans?
What is a critical factor in the treatment of migraines?
Fast is important in migraines
What is the recommendation for switching triptans?
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
What is the role of metoclopramide in migraines?
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
What use does a nasal spray have in migraines? Describe it’s absorption?
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
What is the benefit of an ODT?
Some triptans are orally disintegrating tablets – do not need to take it with water
What is migraine prophylaxis? WHat is the benefit of prophylaxis?
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
What is DHE?
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
Opiods role in migraines?
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
What is the issue with using opiods in (Tylenol #3’s) in migraines?
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
What are the two categories to watch out for regarding triptan D.I., S.e? ?
Triptans are potent vasoconstrictors
Triptans are potent serotonin Agonists
What are symptoms and C.I. of triptans regarding there vasoconstriction acitivity?
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)
Sumatriptan (Example) Available Strengths and Max Dosing
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
What are some side effects and c.i. associated with triptans being potent serotonin agonists?
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.
Triptan Side Effects with Other Dosage Forms
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
Describe which triptan dosage form has the fastest relief of sx?
Which triptan has the best efficacy at 2 hr?Worst?
Best efficacy at 2 hours – sub cut
Slow acting have the worst efficacy at 2 hours
Which triptans have the best tolerability?
Which triptans have the efficacy for long-lasting attacks?
Best triptans for privacy?
I
What is the onset of effect for triptan formulations?
Onset of 10 mins – subcut
Tabs – 30-60 min
ODT and tabs are the same speed of regular tabs
What should be recommended for attacks that last a long time?
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
What is metoclopramide? Domperidone?
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 ]
Describe the available triptans and there onset, half life and renal function?
What is the highest efficacy triptan?When is it useful?Convienience?
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
How long should a triptan be used until switch? What combination can be helpful? What to do if nauseau and vomitting?
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.
Are ODT any faster than regular tabs?What if nauseau with ODT?
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
What are medications that can lead to a medication overuse headache? Max days per month?
Max days per month of acute medications to help avoid medication overuse headache
Define medication overuse headache?
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
What average of migraines per month leans toward overusage of acute drugs?
More than 15 migraine in on e month, majority due to acute drugs
How can a pharmacist gauge triptan usage and medication overuse headache? What approach should be used?
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
Three strategies for medication overuse headache?
Cut them off drug that caused problem (stop triptan, start NSAID)
Add prophylaxis
Both at the same time
What is a menstrual migraine?Why does this occur?
For some, migraines during menstruation (perhaps due to changing hormone levels)
How can menstrual migraines be treated?
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
What is a preventative option for menstrual migraines?
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.
Would the Mireena IUD be effective for menstrual migraines?
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)
Another class of medications used for an acute migraine is…..
Anti-cGRPs
Two types: Monoclonal antibody (prophylaxis) and receptor antagonist oral
CGRP is a vasodilator
Antibody mops everything up – just prophylaxis
What are the available CGRP antagonists? Dose?
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;
Gepants A/e C.I.
Adverse effects: nausea, somnolence.
Not contraindicated in CV disease. (Big potential over the triptans)
Gepants Efficacy Compared to Triptans
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
Who should be offered migraine prophylaxis?
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
How should an adequate trial of migraine prophylaxis be initiated?
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
What is a reasonable goal for migraine prophylaxis?
Reasonable Goal of TX : Reduction in 50% of frequency or intensity
How long does it take for a patient to become sensitized to s/e of the prophylatic medication?
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
Is the cost of prophylatic medications particularly limiting in migraine prophylaxis?
Cost does not really play a role
Mainly choose around efficacy, s/e and comorbidities
What are the available prophylatic migraine options? Effeicacy? S/e?
a)Smoking
b) Insomnia
c) HTN
d) Chronic Pain
e) Depression/Anxiety
Best efficacy – 60%ish of the time, propranolol up to 80%
A/e – up to 40%
Cgrp – up to 40%, up to 60%
What are the avilable prophylatic medication classes and examples available for migraines?
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
How do beta-blockers work in migraine prophylaxis?
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
Beta-blocker doses
Which beta-blockers are used in general?
Not every beta-blocker – may need drugs to penetrate Brain – drugs in classes and not whole classes
Heart rate, blood pressure
What are some a/e of beta-blcoekrs?
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)
What are the TCA doses used in migraine prophylaxis?
Describe the mechanism by which TCA’s work in migraine prophylaxis?
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
TCA Side Effects
Amitriptylline is more likely to cause drowsiness – Tertiary AMine
Notriptylline has smoking cessation indication – tough to tolerate for migraines
- secondary amine
Anti-convulsant Doses in Migraine Prophylaxis
Anti-convulsant MOA in Migraine Prophylaxis. Tolerability and C.I.?
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
Acei and ARB Doses in Migraine Prophylaxis
Acei and ARBs in Migraine Prophylaxis S/e
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
What SNRI’s can be used for migraine prophylaxis? Dose?
MOA of SNRI’s? Most evidence? S/e?
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
When discontinuing an SNRI, what may occur?
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)
What is unique about venlafaxine?
Venlafaxine – short t1/2 – very hard to stop, tough to quit
What CCB blockers can be used in migraine prophylaxis? Dose?
Effeicacy of CCB’s?
CCBS – NON-DHP’s – best data with flunarizine – really sedating
Verapamil – constipation is reallyy present
Can a BB and non-DHP be combined?
NOOOOOOOOOO
What is the 5HT2 antagonist? Dose? MOA
Pitzoifen – serotonin antagonist
- blocking from serotonin receptors, less serotonin receptors to bind
Which herbals can be used in migraine prophylaxis? Dose?
Efficacy of Herbals? S/e?
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
What are the biologic anti-CGRP’s? Dose? Use? EDScriteria? Effectiveness?
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
What are the non-biologic anti-CXGRP’s? Dose?
Atogepant Role in Therapy? Efficacy?
atogepant is indicated for prophylaxis – works about 60%ish a time
Memantidine Dose For Migraine Prophylaxis?
Memantine – never used; used for alzheimers – NDMA antagonist
Botox Dose and Role in Tx?
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)
For all prophylatic methods of migraines, what is the appropriate duration of therapy?
Treat at target dose for 8-12 weeks before deciding if prophylaxis is helping.
What is a critical drug interaction to consider with migraine prophylaxis?
Two high of rizatriptan – extra vasoconstriction – higher risk of coronary vasospasm
CGRP Monoclonal Antibodies MOA and Examples
Monoclonal antibody targeting calcitonin gene-related peptide
E.g. fremanezumab, erenumab, galcanezumab, eptinezumab
CGRP Monoclonal Antibodies Response and Onset
Response in about 40% of patients.
Often onset in days (but give 3-6 months for adequate trial).
CGRP Monoclonal Antibodies Coverage
Some covered in Sask and by NIHB if failed at least two oral prophylactic agents.
CGRP monoclonal antibodies Dosing Frequency
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)
CGRP monoclonal antibodies A/E
Adverse effects: injection site reactions, hypertension. Patients with CV risk were excluded from trials.
Cost: ~$600/month
Atogepant Indicated USe in Migraines
Atogepant approved in Canada for prevention of migraines.
Prevention dose: 10-60mg daily
What are the red-flag symptoms for an acute headache?
Fever/Neck Stiffness – Meningitis
Compare and contrast the different types of headaches
remeber tension type prophylaxis TCA
Define medication overuse headache
Causes of MOH
Withdrawal Sx MOH
How can the cycle of MOH be stopped?
How can MOH be treated? What is resolution defined as?
Tx options for MOH?
Tips for MOH
general Guide for MOH TX
