Managementof Headaches Flashcards
In general…
AVOID TRIGGERS
Serotonin & NSAIDS can
Prevent and Treat HA
Role of Spreading Cortical Depression:
self-propagating wave of neuronal and glial depolarization hypothesized to:
Cause the aura of migraine
Activate trigeminal afferents
Alter BBB permeability via changes in metalloproteinases
Role of Trigeminovascular System
sensory neurons that project to cerebral and pial vessels and to dura mater
activation–> Release peptides–> neuroinflammation–> vasodilate–> Pain
Inflammation has role in prolongation and intensification of migraine pain (sensitization)
Role of Sensitization
likely responsible for many migraine clinical symptoms
Throbbing quality of pain
Worsening of pain with coughing-bending-sudden head movements
Hyperalgesia
Allodynia
Role of Serotonin (5-HT)
Agonists of 5HT receptors important component in acute treatment - BUT role in generation of migraine unclear
Medication Overuse Headache
Can lead to tension HA by using too much analgesics
activation–> Release peptides–> neuroinflammation–> vasodilate–> Pain
Trigeminovascular System
PathoPhys Migraine
Trigeminal Neurovascular Dysfunction–>
** Trigeminal Neurovascular Activation–>
** Release of Vasoactive Peptides–>
- Neuroinflammation (including PG release)
- Vasodilation of Pial and Dural Vessels–>
Moderate to Severe Pain
- TARGET of NSAID analgesics
- TARGET of triptans-ergot alkaloids [5HT 1B-1D agonists]
Triptans
are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches.
Trigeminal Neurovascular Dysfunction–>
** Trigeminal Neurovascular Activation–>
** Release of Vasoactive Peptides–>
- Neuroinflammation (including PG release)
- Vasodilation of Pial and Dural Vessels–>
Pain
- TARGET?
- TARGET of NSAID analgesics
Sumatriptan
Triptans
MOA in Migraine: 5HT1B/D Agonist
Cerebral vasoconstriction–> reverse dilation-induced HA
Inhibit neuropeptide release–> dec. vasodilation, pain, neuroinflammation
Prevent activation of pain fibers in trigeminal nerves
Aborts attack
Triptans- ADRs
Rarely: coronary vasospasm, angina, MI, arrhythmia, stroke, death
Trigeminal Neurovascular Dysfunction–>
** Trigeminal Neurovascular Activation–>
** Release of Vasoactive Peptides–>
- Neuroinflammation (including PG release)
- Vasodilation of Pial and Dural Vessels–>
Pain
** TARGET?
triptans-ergot alkaloids [5HT 1B-1D agonists]
Triptans- DDIs
Additive vasoconstriction with ergot alkaloids
Increased risk of serotonin syndrome** with MAOIs - risk very much less with SNRIs-SSRIs
Triptan vs Ergot
Triptan fairly well tolerated
Ergot More toxic - NOT first-line
used clinically for the purpose of vasoconstriction (5-HT1 receptor agonists) and in the treatment and alleviation of migraines (w/ caffeine) and Parkinson’s
Ergot Alkaloids
Aborts attack
Ergot Alkaloids ADRs
Serious effects: vascular occlusion and gangrene* (strict dosage limits)
Mediated via α1 adrenergic vasoconstriction
Ergot Alkaloid DDIs
Severe peripheral ischemia if used with non-selective (β1-β2) beta-blockers
Non-Opioid Analgesics[tNSAIDs-Acetaminophen-Celecoxib-Aspirin]
MOA in Migraine
Inhibition of COX-2
Interrupts neuroinflammatory pathway initiated by release of CGRP (Calcitonin Gene-Related Peptide)
May be sufficient for migraines of mild-moderate intensity
Calcium channel blockers ex
verapamil
ACEIs ex
lisinopril
Dihydroergotamine
Intranasal-parenteral; rapid and reliable onset
Aborts attack
Non-Opioid Analgesics (NSAIDs) ADRs**
Generally well tolerated
Should be avoided in patients with acute gastritis, peptic ulcer disease, renal insufficiency, or bleeding disorders
Non-Opioid Analgesics (NSAIDs) DDIs**
Increased bleeding risk in patients receiving antiplatelet agents (clopidogrel-prasugrel) or anticoagulants (warfarin)
Chronic Migraine (>15/mo)
Botox
Abort HA Attack
NSAIDs Acetaminophen Triptans Ergots 5HT
Prevent HA Attack
AVOID TRIGGER NSAIDs anti-htn anticonvulsant anti-dep 5HT- Antag
Anti-HTN in HA
**B-Blocker
ccb
acei
Antidepressants in HA
TCAD
SSRIs
