Migraine Headaches--Treatment and Prevention Flashcards
Migraine–neural events provoke
-dilation of cranial blood vessels
Goal of therapeutic agents
-rescue patient from start of a migraine
Medication taken in prodrome phase
- Triptans–5HT1B/1D Receptor agonists
- Ergot alkaloids
Medications taken in headache phase
- NSAIDS
- Acetaminophen
Preventative agents
-B blockers
-Tricyclic antidepressants
-anticonvulsants
-Ca channels
(given in asymptomatic phase)
neurogenic inflammation theory of migraine
-wave of electrical cavity
-stimulates release of neuropeptides (CGRP, substance P) and inflammatory mediators
(NO, histamine, prostaglandins)
-dilate cranial blood vessels and sensitive nerves to pain
step 1
- brainstem dysfunction sparks a wave of excitation/depression in Cortex–H, K, NO discharge from neurons
- cerebral vasoconstriction
step 2
- electrolytes and NO diffuse and dilate cranial arteries and depolarize perivascular trigeminal terminals
- CGRP and neuropeptides promote neurogenic inflammation
step 3
neurogenic inflammation irritates TG n and transmits migraine pain
2 key mediators–interact throughout trigeminal neuromuscular system
-CGRP and NO
used to treat coronary a disease
- Organic nitrates (NO)
- Can provoke migraine
cranial vessels–R
5HT-1B
peripheral neuron R
5HT-1 D
central neuron R
-5HT 1B/iD
serotonin receptor-vascular and synaptic
- vascular-5HT1B R
- synaptic-5HT 1 D R
Triptans mechanism
- selective 5HT1D/1B receptor agonist
- 5HT-1B Receptor stimulates vasoconstriction
- 5HT-1D Receptor inhibits pre-synaptic release of CGRP
Triptan prototype
Sumatriptan
Sumatriptan–p.o.
- Cmax=1-2 hours
- 15% bioavailability–unreliable in some patients
- clearance-t/12=1-2 hours
Sumatriptan-other delivery options
- SC-Cmax=15 minutes
- nasal spray=30 minutes
Sumatriptan-metabolized by
MAO-A
Other triptans
- Almotriptan
- Naratriptan-70% bioavailability; t/12 is 6 hours
- Zolmitriptan–active metabolite
- Rizatriptan
- Eletriptan
- Frovatriptan–t1/2=24 hours
choice of delivery route
- oral-easy to take, ineffective if patient vomits
- nasal spray–effective with vomiting, simple, works quickly; few triptans formulated as nasal sprays
- injection–works quickly; inconvenient
Sumatriptan–delivery options
- injectable subcutaneous
- nasal spray
- tablets
Zolmmitriptan-delivery options
- tablets
- orally disintegrating tablets
- nasal spray
Quick onset–what delivery options
- nasal spray–fast
- subcutaneous–sumatriptan fastest
is patient taking other medications? consider?
- serotonin syndrome
- MAO interactions
Triptans–contraindications
- ischemic/vasospastic coronary disease
- cardiovascular disorder
- uncontrolled hypertension
contraindicated in patients taking MAO inhibitors
-Sumatriptran
-rizatriptan
-zolmitriptan
(metabolized by MAO)
used for severe or refractory migraine
-ergot alkaloids
Ergot alkaloids
- Dihydroergotamine
- Ergotamine and caffeine
- less specific!!
NEVER use what together??
triptan and DHE
Ergot alkaloids–side effects
- strong emetic action
- vasoconstriction–St. Anthony’s fire
migraine treatment in pregnancy
- acetaminophen and codeine
- aspirin-1 and 2nd trimester only
- ibuprofen–1st and 2nd trimester only
- triptans-cautiously
migraine treatment in pregnancy–contraindicated
- DIhydroergotamine
- Other ergot alkaloids
Botox and migraines?
- inhibits ACh release at motor endplates–reduce m activity
- not approved for migraines unless migraine isn’t received from other meds
preventive agents–taken daily, asymptomatic
- B blockers
- Tricyclic antidepressants
- Anticonvulsants
- Ca channel blockers
B blockers mechanism
- propranolol, timolol
- anxiolytic action
- decrease sympathetic activity
- blunts cortical spreading depression
- effective in 60-80%
B blockers–cautions
- Normal well tolerated
- bronchoconstriction–contraindicated in asthma patients
Tricyclic antidepressants
-amitriptylene, imipramine
anticonvulsants
-topiramine, valproate
Ca channel blockers
verapramil
considerations for preventative therapy
- > 2 migraines per month with disability
- disability lasting >3 days per month
- adverse effects from acute treatments
- rescue medication used >2x per week
- uncommon migraine conditions
Ca channel blockers for migraine prevention–mechanism
- Verapamil
- Lessens Ca dependent vesicle fusion
- normalizes vessel tone
