Pharmacologic Management of Headaches

Question 1

Abortive tx for migraine headaches

Answer 1

• Aspirin, acetaminophen, NSAID, Combination thereof including caffeine
• *Triptans: 5-HT 1b/1D agonists
  
  • (like alpha 2 for NE) (sumitriptan or Imitrex) (60-85% effective)
• *Ergotamine derivative
  
  • not often used b/c cause nausea. Super effective (90% abort)
• * Migraine specific analgesic
  
  • e.g. combo drug: ibuprofen/caffeine/aspirin

Question 2

Prophylactic tx for migraine headaches

Answer 2

• daily dosing, limit side effects (about 50% effective at limiting migraines in terms of frequency, duration, or severity)
• ​Beta blockers
• Calcium channel blockers
• Tricyclic antidepressants
• Anti-epileptics

Question 3

Cluster headache tx

Answer 3

• Oxygen, triptans, ergots, lidocaine locally
• Transitional (use during cluster): corticosteroids to get over hump
• Prophylaptic: Ca channel blocker, lithium (not effective in other HA types), anti-epileptics

Question 4

Tension headache tx

Answer 4

• Abortive - aspirin, NSAID, tylenol, muscle relaxants
• Prophylactic: trycyclic antidepressant (amitriptyline), SSRI (e.g prozac)

Question 5

Serotonin involvement in first phase of migraine headache

Answer 5

• First phase is characterized by cerebral vasoconstriction and ischemia.
  
  • Serotonin release (5HT) from neurons and platelets (PERIPHERAL MECHANISMS) that acts on 5-HT2 receptors contributes to this phase.
  • Target: decrease release of seratonin with a _triptan _
    
    • triptans MOA ~ alpha-2 agonist effect on NE release

Question 6

Serotonin involvement in second phase of migraine headache

Answer 6

• Second phase is characterized by cerebral vasodilation and pain.
  
  • Neurons in the trigeminal complex release the vasoactive peptides substance P and calcitonin gene-related peptide [CGRP] ==> vasodilation and neuroinflammation of pial and dural vessels (SENSORY NERVE DISCHARGE).
  • This in turn stimulates nociceptive fibers of the trigeminal nerve that causes pain.
  • Target: decrease vasodialtion - triptans
    
    • MOA: agonist @ serotonin receptors ==> vasoconstriction
    • • decreases sub P/CGRP release

Question 7

Triptans examples & general use

Answer 7

• sumatriptan
• zolmitriptan
• abortive tx for migraine headache
• 1st line for severe headache (if no CV issues)

Question 8

Triptans (sumatriptan, zolmitriptan) MOA

Answer 8

• Vasoconstriction,
• Inhibition of inflammatory mediators presynaptically
• Inhibit activation of trigeminal neuron

Question 9

Triptans (sumatriptan, zolmitriptan) Route of administratration

Answer 9

• Oral
• Nasal
• subcutaneous possible for sumatriptan

Question 10

Triptans (sumatriptan, zolmitriptan) Route of onset/duration

Answer 10

• onset: ~30-60 min
• duration: short
  
  • t_1/2 = 2-4 hr

Question 11

Triptans (sumatriptan, zolmitriptan) side effects

Answer 11

• Paresthesias, flushing, dizziness, drowsiness, chest tightness
• Rarely: coronary vasospasm, angina, MI, arrythimia, stroke, death

Question 12

NSAIDs examples and general use

Answer 12

• Ibuprofin
• Naproxin
• abortive therapy for tension or migraine headaches

Question 13

NSAIDs MOA & route of administration

Answer 13

• Inhibition of COX-2
• Decrease inflammation
• oral administration

Question 14

NSAIDs onset/duration

Answer 14

• 4-6 hours duration (ibuprofen)
• 8-12 hours duration (Naproxen)

Question 15

NSAIDs side effects

Answer 15

• Increased risk of bleeding if taking anticoagulants/antiplatelets
• take caution in pts w/peptic ulcer, acute gastritis, renal insufficiency, or bleeding disorder

Question 16

Ergot Alkyloids examples and general use

Answer 16

• dihydroergotamine
• 2nd line in severe HA

Question 17

Ergot Alkyloids (duhyrdoergotamine) MOA

Answer 17

• Seratonin (5HT) 1b/1d agonist = ~similar MOA to triptans
  
  • inhibits serotonin release (similar to alpha-2 receptor effect on NE)
• ==> vasoconstriction
• ==> inhibition of inflammatory mediators presynaptically
• ==> inhibiton of activation of trigeminal neuron

Question 18

Ergot Alkyloids (duhyrdoergotamine) route of administration

Answer 18

• dihydroergotamine: intranasal or paranasal
• ergotamine: oral

Question 19

Ergot Alkyloids (duhyrdoergotamine) onset & duration

Answer 19

• rapid onset
• long duration

Question 20

Ergot Alkyloids (duhyrdoergotamine) side effects

Answer 20

• Less effective + more toxic than triptans, 2nd line
• Cause N/V, diarrhea, cramps, parathesis.
  
  • Give w/ anti-emetic.
• SERIOUS: vascular occlusion and gangrene (strict dosage limits) → alpha 1 adrengergic vasoconstriciton
• Severe peripheral ischemia with beta blockers due to vasoconstriction

Question 21

NSAIDs in migraine prophylaxis: efficacy vs. safety/side effects

Answer 21

• used as short term prevention
• SE: gastric problems, increased risk of bleeding if taken w/anticoag or antiplatelets

Question 22

Beta-Blockers (propanolol) in migraine prophylaxis: efficacy vs. safety/side effects

Answer 22

• First line drug of choice:
  
  • reduces migraine frequency by 50% in 50% of patients.
  • dose must be titrated to each patient
• SE: Fatigue, exercise intolerance, depression, orthostatic hypertension

Question 23

Calcium-channel blockers (verapamil) in migraine prophylaxis: efficacy vs. safety/side effects

Answer 23

• less effective than BB
• limited evidence of effectiveness
• contraindicated with concurrent BB use b/c of heart block

Question 24

Tricyclic antidepressants (amitriptyline) in migraine prophylaxis: efficacy vs. safety/side effects

Answer 24

• occassionaly efficacy in migraine prevention
• SE:
  
  • sedation
  • dry mouth
  • constipation
  • tachycardia
  • urinary retention
  • weight gain

Question 25

Anticonvulsant agents (topiramate) in migraine prophylaxis: efficacy vs. safety/side effects

Answer 25

* Reduces frequency of migraines by 50% in 50% of patients * SE: * sedation * nausea * weight gain * tremor * hair loss * contraindicated in pregnancy