Headache Background

Question 1

Secondary Headache

Answer 1

• Underlying pathological causes

- Head/neck trauma, cranial vascular disorder, psychiatric disorders, lumbar puncture, inflammation, hematoma

Question 2

Tension Headache

Answer 2

• Most common kind of headache
• Sustained contractions ofscalp and neck muscles secondary to anxiety or stress
• Dull, aching pain
• Across forehead or on sides and back of head
• Rarely seek treatment unless is occurs daily
• Treatment: NSAIDs, muscle relaxant, SSRIs, TCA

Question 3

Cluster Headache

Answer 3

• Severe unilateral pain, sudden onset/offset and short duration
• Dilation of blood vessels in the pained area (redness in eye, congestion, sweating)
• Restricted: unilateral areas of nose, temple, and eye socket
• Triggers from alcohol and strong odors
• Associated with trigeminal-sacularactivation and neuroendocrine disturbances
• Acute treatment: sumatriptan and high-flow oxygen
• Multiple prophylaxis drugs

Question 4

Migraine Headache

Answer 4

• Most common headache diagnoses which patients get treatment for
• Diagnose based on recollection of systems and exclusion of secondary causes
• Associated with brain hypersensitivity and lowered threshold for trigeminal-vascular activation
• Can have neck stiffness (like tension HA) and nasal stuffiness/discharge (like sinus HA) as well

Question 5

3 Predictive Migraine Symptoms

Answer 5

1. Moderate to severe disability
2. Photophobia
3. Nausea

Others: unilateral throbbing, vomiting, phonophobia, increased pain with physical exertion

Question 6

Auras

Answer 6

• Migraine with aura: most common visually, 10-15 minutes before CSD
• No auras are more common with migraines

Question 7

Migraine Triggers

Answer 7

• Menses, stress, changes to schedules, loud noises, odors, flickering lights
• Foods: tyramine (wine/cheese), chocolate (phenylethylamines), nitrites
• Drug withdrawal: alcohol, caggeine

Question 8

Sinus Headaches

Answer 8

• Nasal stuffiness or discharge
• Can be treated with nasal costicosteroids or antibiotics if caused by infection
• May need surgery

Question 9

CSD

Answer 9

• Cortical spreading depression
• Possible migraine initiation mechanism
• Depression of neuronal activity spreads across the cortex
• Most likely responsible for aura
• Begins in occipital region and spreads towards the frontal cortex in a propagating wave
• Wave is hyperactivity followed by prolonged suppression in neuronal activity
• Associated with decreased cerebral blood flow (vasoconstriction)

Question 10

Trigeminovascular System

Answer 10

• Trigeminal nerve fibers around basal cerebral and meningeal vessels triggers
• Starts viscous cycle when nerve terminals release CGRP (vasodilation), substance P (extravasation), VIP, and other mediators

Question 11

Mediators create…

Answer 11

• Local neurogenic inflammation
• Trigger vasodilation
• Orthodromic stimulation of the trigeminal nerve terminals back into the brain
• Painful messages then transmitted to thalamus and cortex via trigeminal nucleus which makes pain arise as well as N/V and autonomic activation

Question 12

Abortive Therapies

Answer 12

• Complete pain relief, return to normal function within 2 hours of taking medication
• Decreased pain relief efficacy if central sensitization is developed

Options

• NSAIDs
• Triptans
• Lasmiditan
• Ubrogepant
• Ergot Alkaloids
• Butalbital containing analgesics
• Opioids

Question 13

NSAIDs

Answer 13

• Abortive therapy and intermittent preventative
• First-line treatment for all migraine attacks
• Inhibits prostaglandin synthesis which prevents neurogenic inflammation mechanisms

Question 14

Triptans

Answer 14

• First-line therapy for abortive therapy and acute treatment
• 5HT1B/1D agonists
• Oral, SQ, and nasal spray options available
• SQ good for patients with severe N/V

Question 15

Triptan Options

Answer 15

• Sumatriptan (Imitrex) - SQ, nasal
• Zomitriptan (Zomig) - intranasal
• Almotryptan (Axert)
• Eletriptan (Relpax)
• Rizatriptan (Maxalt)
• Naratriptan (Amerge)
• Frovatriptan (Froval)

half life increases going down list

Question 16

Triptan MoA

Answer 16

• agonists of 5HT1B/1D
• 1B receptors mediate vasoconstriction
• 1D receptors inhibit the release of neuropeptides from trigeminal neurons, preventing neurogenic inflammation
• 1B/1D/1F receptors interrupt pain signals in trigeminal nucleus

Question 17

Lasmiditan

Answer 17

• Rayvow
• Class: Ditan
• Selective 5HT1F agonist
• No vasoconstiction activity
• Ditans penetrate CNS better
• Risk for 5HT syndrome, discourage use with triptans
• CV, may cause euphoria and hallucinations

Question 18

Triptan/Ditan CI

Answer 18

• Don’t combine triptans or use with vasoconstrictor due to risk of CV and hypertensive side efefcts
• 5HT syndrome, especially when combined with SSRIs and SNRIs

Question 19

Triptan Metabolism/Excretion

Answer 19

• Rizatriptan, sumatriptan, zomitriptan, and almotryptin are metabolized MAO (don’t give MAOI for at least 2 weeks)
• Frovatriptan and Naratriptan are partially renally excreted (caution with renal problems)

Question 20

Ubrogepant/Rimegepant

Answer 20

• Ubrelvy/Nurtec
• Latter has longer half life
• CGRP receptor antagonists
• Prevents CGRP vasodilation and pain sensitization
• Rimegepant should be avoided in the renal/hepatic impaired

Question 21

Ergot Alkaloids

Answer 21

• Abortive or acute treatment
• DON’T use prophylactically
• Produce vasoconstiction and decrease neurogenic inflammation
• Interrupts pain signals in trigeminal nucleus
• Black box: peripheral ischemia when given with CYP3A4 inhibitors
• EX: Ergotamine tartrate, Dihydroergotamine mesylate

Question 22

Ergotamine Tartrate

Answer 22

• Oral, SL, IM, IV, suppository
• Also combined with caffeine
• SE: intense vasoconstriction, stimulates CTZ (N/V), Ergotism (vascular, sensorimotor disturbances), thrombotic occlusion of smaller arteries and gangrenous extremities, psychic aberrations/hallucinations

Question 23

Dihydroergotamine Mesylate

Answer 23

• IV, SC, IM favored to intractable migraine

- Intranasal is monotherapy for acute migraine attacks

Question 24

Butalbital-Containing Analgesics

Answer 24

• Fioicet (APAP, caffeine) and Fiorinal (aspirin, caffeine)
• Usually used for tension headcahce
• Potential for overuse which could lead to overuse and rebound headaches

Question 25

Opioids

Answer 25

- Can cause overuse/rebound headaches - No proof to superiority to triptans for migraine treatment - NOT first line therapy - Only use when other standard treatments failed - Butorphanol nasal spray has good evidence for effectiveness

Question 26

Overuse Headache

Answer 26

- Results from frequent use of acute medication - Pattern of increasing headache frequency leading to daily headaches - Limit abortive use to 2-3x a week to avoid - Avoid butalbital and opioids due to increased incidence of overuse HA - Consider preventative migraine therapy instead

Question 27

Prophylaxis/Preventative Therapy

Answer 27

- Daily administration for 3-12 months - Prophylaxis usually takes 4-6 weeks to work - Consider if using abortive meds >2x/week, attacks last >48 hours, or CI/failure to abortive therapy

Question 28

Botox

Answer 28

- Approved for chronic migraines - Chronic migraines: >14 days/month, doesn't work for less frequency (inhibits ACh release) - Given every 12 weeks - Warning: toxin could spread to other areas of body and cause botulism symptoms, difficulty breathing/swallowing could be life threatening

Question 29

Beta Blockers

Answer 29

- Level A Preventative Therapy - MoA: blocking beta adrenergic mediated cerebral vasodilation - Selective and non-selective work but agents with intrinsic activity have less efficacy - SE: well tolerated, sedation, fatigue, dizzy - CI: asthma, heart problems, hypotension, depression - ACE-I, ARBs, and Ca++ channel blockers have also been used (2nd or 3rd line)

Question 30

Antiepileptic Drugs

Answer 30

- Prevents trigeminal nerve activity | - Affects the spreading of cortical depression

Question 31

Topiramate

Answer 31

- Topamax - Level A Preventative Therapy - Prolongs inactivation of Na+ channels - Also a AMPA/kainate antagonist - Good choice for those with epilepsy, bipolar disorder, anxiety, and obesity - Keep doses low to avoid kidney stones, sedation, cognitive changes, and glaucoma

Question 32

Gabapentin

Answer 32

- Neurontin - Third Line Preventative Therapy - SE: sedation

Question 33

Valproic Acid

Answer 33

- Divalproex - Level A Preventative Therapy - Prolongs inactivation of Na+ channels and reduces Ca++ T currents - AE: CNS (sedation, tremor, weight GAIN) - Monitoring: blood dyscrasias, pancreatitis, and liver problems - Black Box: hepatotoxicity, pancreatitis, teratogenicity - Category X for females in child bearing years

Question 34

TCAs

Answer 34

- Second Line Preventative Therapy | - Inhibits central cortical depression and sympathetic activity

Question 35

Amitriptyline

Answer 35

- Elavil - 50-70% reduction in number and intensity of migraine attacks - Lower doses than used for depression - SE: anticholinergic, weight gain, sedation, tachycardia

Question 36

SNRI

Answer 36

- Venlafaxine (Effexor) - 2nd Line Preventative Therapy - Black Box: suicidal thinking and ideation in children, adolescents, and young adults

Question 37

CGRP Monoclonal Antibody Examples

Answer 37

- Erenumab (Aimovig) - Fremanezumab (Ajovy) - Galacanezumab (Emgality) - Eptinezumab (Vyepti)

Question 38

CGRP Monoclonal Antibody MoA

Answer 38

- Aimovig is a CGRP Receptor Ab Target - All others bind to CGRP in synapse to prevent neurotransmitter from activating the receptor - Substance P is coreleased with CGRP which leads to pain signals and leakage of materials to further promote neurogenic inflammation - All have ~1 month half life

Question 39

Midrin

Answer 39

- Additional abortive therapy - Isometheptene mucate, Dichloralphenazone, APAP - Isomethe: sympathomimetic amine, acts by constricting dilated cranial/cerebral arterioles - Dichoral: mild sedative - APAP: analgesic