Pharmacologic Management of Headaches Flashcards
Abortive tx for migraine headaches
- 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
Prophylactic tx for migraine headaches
- 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
Cluster headache tx
- 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
Tension headache tx
- Abortive - aspirin, NSAID, tylenol, muscle relaxants
- Prophylactic: trycyclic antidepressant (amitriptyline), SSRI (e.g prozac)
Serotonin involvement in first phase of migraine headache
- 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
Serotonin involvement in second phase of migraine headache
- 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
Triptans examples & general use
- sumatriptan
- zolmitriptan
- abortive tx for migraine headache
- 1st line for severe headache (if no CV issues)
Triptans (sumatriptan, zolmitriptan) MOA
- Vasoconstriction,
- Inhibition of inflammatory mediators presynaptically
- Inhibit activation of trigeminal neuron
Triptans (sumatriptan, zolmitriptan) Route of administratration
- Oral
- Nasal
- subcutaneous possible for sumatriptan
Triptans (sumatriptan, zolmitriptan) Route of onset/duration
- onset: ~30-60 min
- duration: short
- t1/2 = 2-4 hr
Triptans (sumatriptan, zolmitriptan) side effects
- Paresthesias, flushing, dizziness, drowsiness, chest tightness
- Rarely: coronary vasospasm, angina, MI, arrythimia, stroke, death
NSAIDs examples and general use
- Ibuprofin
- Naproxin
- abortive therapy for tension or migraine headaches
NSAIDs MOA & route of administration
- Inhibition of COX-2
- Decrease inflammation
- oral administration
NSAIDs onset/duration
- 4-6 hours duration (ibuprofen)
- 8-12 hours duration (Naproxen)
NSAIDs side effects
- Increased risk of bleeding if taking anticoagulants/antiplatelets
- take caution in pts w/peptic ulcer, acute gastritis, renal insufficiency, or bleeding disorder
Ergot Alkyloids examples and general use
- dihydroergotamine
- 2nd line in severe HA
Ergot Alkyloids (duhyrdoergotamine) MOA
- 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
Ergot Alkyloids (duhyrdoergotamine) route of administration
- dihydroergotamine: intranasal or paranasal
- ergotamine: oral
Ergot Alkyloids (duhyrdoergotamine) onset & duration
- rapid onset
- long duration
Ergot Alkyloids (duhyrdoergotamine) side effects
- 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
NSAIDs in migraine prophylaxis: efficacy vs. safety/side effects
- used as short term prevention
- SE: gastric problems, increased risk of bleeding if taken w/anticoag or antiplatelets
Beta-Blockers (propanolol) in migraine prophylaxis: efficacy vs. safety/side effects
- 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
Calcium-channel blockers (verapamil) in migraine prophylaxis: efficacy vs. safety/side effects
- less effective than BB
- limited evidence of effectiveness
- contraindicated with concurrent BB use b/c of heart block
Tricyclic antidepressants (amitriptyline) in migraine prophylaxis: efficacy vs. safety/side effects
- occassionaly efficacy in migraine prevention
- SE:
- sedation
- dry mouth
- constipation
- tachycardia
- urinary retention
- weight gain
Anticonvulsant agents (topiramate) in migraine prophylaxis: efficacy vs. safety/side effects
- Reduces frequency of migraines by 50% in 50% of patients
- SE:
- sedation
- nausea
- weight gain
- tremor
- hair loss
- contraindicated in pregnancy
