psych/neuro neuropathic pain+headache and migraine

what is the diagnostic criteria for migraine

any 2 of the following:

⚫️ unilateral pain

⚫️ throbbing pain

⚫️ pain worsened by movement

⚫️ moderate/severe pain

+

any 1 of the following:

⚫️ nausea

⚫️ vomiting

⚫️ photophobia & phonophobia

*diagnostic criteria for migraine rely on these subjective signs only

- no helpful objective info

what is the definition of migraines

chronic disorder of recurrent acute attacks

what are the 4 phases of a migraine attack

1) prodrome

2) aura

3) headache

4) postdrome

how is 5-HT involved in migraines

(1) direct vasoconstrictive action on cranial blood vessels

(2) inhibits release of vasoactive peptides during inflammation

(3) modulation of trigeminovascular and brainstem pain transmission

what is the role of CGRP in migraines

(1) very potent vasodilator that acts upon mast cells to cause histamine release

(2) mediates trigeminovascular pain transmission

abortive treatment of is for (acute/chronic) migraines

acute

preventive treatment is for (acute/chronic) migraines

chronic

what are the classes for acute abortive treatment

1) NSAIDs

2) Triptans

3) CGRP-I

4) Lasmiditan

5) Ergot alkaloids

what are the classes for chronic preventive treatments

1) TCAs

2) AEDs

3) Beta-blockers

4) Ca-channel blockers

5) CGRP-I

what do you want to prevent from occurring in migraines

central sensitization

NSAIDs are the ____ line therapy for ______ headache

first; mild/moderate

what are the advantages for NSAIDs in migraines

safe for heart (compared to triptans)

_____ are first-line acute abortive treatments for moderate-to-severe migraines

triptans

Triptan

(1) MOA:

(2) Indication:

(3) Common ADEs:

(4) Rare ADEs:

(5) DDIs:

(6) Contraindications/Precautions:

(7) PK:

Triptan

(1) MOA:

⚫️ stimulates 5-HT1B/1D receptors on presynaptic membrane to inhibit the release of inflammatory and vasodilating peptides

⚫️ stimulates 5-HT1B/1D to cause vasoconstriction of cerebral vessels

⚫️ stimulates 5HT1B/1D receptors in brainstem to prevent central sensitization

(2) Indication: acute abortive migraine treatment

(3) Common ADEs: nausea...

(4) Rare ADEs:

⚫️ coronary vasospasm

⚫️ angina

⚫️ stroke, heart attack

(5) DDIs: MAO-I ==> serotonin syndrome

⚫️ although safe co-administration = Must Counsel!

(6) Contraindications/Precautions:

⚫️ ischemic cardiac disease

⚫️ cerebrovascular disease

⚫️ uncontrolled HTN

⚫️ history of risk factors for CAD (coronary artery disease)

(7) PK:

⚫️ Differing onset of action

⚫️ Differing t1/2

what is the MOA of triptans

1) stimulates 5-HT1B/1D receptors on presynaptic membrane to inhibit the release of inflammatory and vasodilating peptides

2) stimulates 5-HT1B/1D to cause vasoconstriction of cerebral vessels

3) stimulates 5HT1B/1D receptors in brainstem to prevent central sensitization

what are the common ADEs for triptans

nausea, dizziness/somnolence/malaise, flushing/warm sensations, chest tightness/pressure

what are the serious but rare ADEs of triptans

coronary vasospasm, angina, stroke, heart attack

what are the DDIs for triptans

serotonin syndrome

what are the contraindications/precautions for triptans

ischemic cardiac disease, cerebrovascular disease, uncontrolled hypertension

which triptan is the quickest onset

sumatriptan (injectable or nasal)

⚫️ for severe pain and fast migraines

which triptan has a moderate onset

(1) sumatriptan PO

(2) zolmitriptan (PO, ODT, nasal)

⚫️ moderate - severe pain

which triptan is the slowest onset? what is their half life?

(1) frovatriptan - 26 hours

(2) naratriptan - 6 hours

what is the tmax of sumatriptan PO

*do not need to memorize Tmax, its just relative the relative time you need to be aware of

2.5 hours

what is the dosing for sumatriptan PO

1T (25mg) as soon as possible at onset of migraine

⚫️ may repeat x1 after 2 hours if needed

what might PO dosing for triptans be bad? what can be used instead?

(1) poor absorption

(2) n/v

⚫️ use ODT, nasal spray, or subQ

what is the tmax of sumatriptan injectable?

12 min

what is the tmax of sumatriptan nasal?

1.5 hrs

what is the second line treatment for acute abortive treatment of migraines

CGRP inhibitors - "gepants"

GCRP is potent _____

vasodilator

what are gepants

CGRP receptor antagonists

what is the indication for gepants

acute treatment of migraine in pts who don't respond to triptans or who contraindication

what are the different gepants

(1) ubrogepant

(2) rimegepant

CGRP receptor antagonists ("gepants")

(1) Indication:

(2) ADE:

(3) PK:

(4) Duration of Action:

(5) DDI:

(6) Cost:

CGRP receptor antagonists ("gepants")

(1) Indication: 2nd line acute treatment of migraine (when triptans dont work/contraindication)

(2) ADE: fewer than triptans -- n/v & sedation

(3) PK: Fast (11 mins)

(4) Duration of Action: maintained for 12 hours

(5) DDI: CYP3A4 inhibior

(6) Cost: High ($1000 for 8 T)

what are the ADEs of gepants

fewer than triptans

what are the PK for gepants

fast onset, maintained for 12 hours, CYP3A4 inhibitor

Lasmiditan (Reyvow)

(1) Indication:

(2) MOA:

(3) Class:

(4) Side Effects:

(5) Schedule

(6) Cost

Lasmiditan (Reyvow)

(1) Indication: 2nd line for acute abortive treatment of migraines

(2) MOA: first in class = stimulation of 5HT-1F

(3) Class: new class "ditans" = does NOT vasoconstrict!

(4) Side Effects:

⚫️ dizziness

⚫️ fatigue

⚫️ sedation

(5) Schedule: CV

(6) Cost: High

what is the MOA of lasmiditan

stimulation of 5HT-1F

does lasmiditan vasoconstrict

no

what are the side effects of lasmiditan

dizziness, fatigue, sedation, n/v, muscle weakness

is lasmiditan a CS

yes, C-V

Ergot Alkaloids

(1) Indication:

(2) MOA:

(3) Efficacy:

(4) Side Effects:

Ergot Alkaloids

(1) Indication: last line (due to SE) for acute abortive treatment of moderate/severe migraines

(2) MOA: non selective 5HT1 & 5HT2 receptor agonist

(3) Efficacy: more effective than triptans

(4) Side Effects: more side effects (than triptans) b/c of non-selectivity

⚫️ Risk of severe pulmonary fibrosis

⚫️ Lots of contraindications: heart disease, liver/kidney disease, pregnancy, use with other CYP3A4 drugs

What is the first line treatment for moderate to severe migraine?

A. Ubrogepant

B. Rimegapent

C. Naproxen

D. Zolmitriptan

A. Ubrogepant - gepants = second line for moderate/severe

B. Rimegapent - gepants = second line for moderate/severe

C. Naproxen - nsaids = first line for mild/moderate

D. Zolmitriptan ==> triptans are the first line for MODERATE/SEVERE migraine

What formulations is sumatriptan NOT available in?

A. PO

B. Nasal

C. ODT

D. Injectable

C. ODT -- formulation only available with Zolmitriptan

what is the MOA of ergot alkaloids

non-selective 5HT1 and 5HT2 receptor agonist vs selective 5HT1B/1D

what are the available ergots

ergotamine w/ caffeine (Ercaf, Wygraine) - subQ

dihydroergotamine/DHE 45 (Migranol) - IM, subQ, IV, intranasal

why are ergot alkaloids last line for migraines

more side effects b/c of non-selectively

what are the side effects for ergot alkaloids

extreme n/v, severe pulmonary fibrosis, lots of contraindications: heart disease, liver/kidney disease, pregnancy, use with other CYP3A4 drugs

what are the main classes of drugs used for chronic preventative treatments?

(1) TCAs

(2) AEDs

(3) Beta-blockers

(4) Calcium-channel blockers

(5) CGRP inhibitors

when do you start preventative therapy

frequent or long-lasting migraine headaches

⚫️ >4 episodes/month

⚫️ longer than 12 hours

what are the AEDs for preventative treatment of migraines?

(1) valproate/divalproex

(2) topiramate

what are the main classes of antidepressants used for preventative treatment of migraines?

(1) TCAs

(2) SNRIs

what are the TCAs used for preventative treatment of migraines?

amitriptyline/nortriptyline

what are the beta-blockers for preventative treatment of migraines?

(1) propranolol

(2) timolol

(3) metoprolol

(4) atenolol

(5) nadolol

what Ca-channel blockers are for preventative treatment of migraines?

verapamil

what are the CGRP-I for preventative treatment of migraines

(1) mAB binds receptor

(2) mAB binds CGRP

(3) Gepant.= CGRP receptor antagonist

what are the main CGRP inhibitors (mAB) for preventative migraines?

1) erenumab - SQ qmonth

2) galcanezumab - SQ qmonth

3) fremanezumab - SQ qmonth (225mg) or q3month (675mg)

4) eptinezumab - IV infusion q3month

what are the first line treatments for preventative migraines?

(1) propranolol

(2) topiramate

(3) amitriptyline/nortriptyline

which of the first line treatments for preventative migraines are FDA approved for this use?

(1) propranolol

(2) topiramate

A 32 year old male who have been suffering with migraines for over the past 4 months, is coming to you for advice with preventative treatment options. His PMH includes diabetes and epilepsy. Pt says he has tried sumatriptan but continues to overuse month after month. He also states that his mother has a history of migraines and uses an injection to help but he is unsure of the name and isn't willing to try it as this time.

What medication would the best option for your patient?

A. Propranolol

B. Erenumab

C. Amitriptyline

D. Topiramate

What medication would the best option for your patient?

A. Propranolol

B. Erenumab

C. Amitriptyline

D. Topiramate ==> patient has history of epilepsy