Pharmacologic Management of Headaches Flashcards
Recommended pharmacotherapeutic classes or agents for prophylaxis and abortive therapy of migraine
Preventing: B-blockers, anticonvulsants, antidepressants, calcium channel blockers, NSAIDs, 5-HT2 receptor antagonists
Aborting: DHE, erotamine, isometheptene, NSAIDs, tramadol, triptans
Recommended pharmacotherapeutic classes or agents for prophylaxis and abortive therapy of cluster headaches
Preventing: Lithium, mehysergide, verapamil
Aborting: DHE, erotamine, glucocorticoids, lidocaine, oxygen, sumtriptan
Recommended pharmacotherapeutic classes or agents for tension headaches
Preventing: TCADs- SSRIs
Aborting: NSAIDs-Acetaminophen
Describe the role of serotonin neuronal systems and prostaglandin inflammatory mediators in the pathogenesis of migraine headache
First Phase of migraine: Cerebral vasocontriction and ischemia. Serotonin release (5HT) from neurons and platelets act on 5-HT2 receptors
Second Phase of migraine: Cerebral vasodilation and pain. Neurons in the trigeminal complex release Substance P and calcitonin gene-related peptide that trigger vasodilation and neuroinflammation of pial and dural vessels»_space; causes pain
Describe the general treatment approach to termination of migraine headaches.
Use migraine-specific agents (triptans and ergot alkaloids) for more severe headaches or headaches that have not responded to NSAID analgesics (stratified care vs stepped care).
•Importance of route: Effect of oral meds can be delayed by migraine-related decrease in GI motility and / or nausea-vomiting (consider use of anti-emetics [metoclopramide]). Onset is fastest via parenteral route (SC > NASAL > PO
Ergot alkaloids (dihydroergotamine): Discuss mechanism of action, route of administration, rate of onset and duration of action, and most common and use-limiting
Mechanism: Agonist activity at 5HT receptors result in Vasocontriction in cerebral vessels, Inhibition of release of peptides that cause vasodilation/inflammation/pain, Prevent activation of activation of pain fibers in trigeminal nerves
Administration: Oral, sublingual, rectal, intranasal and parenteral
Rate of onset/duration:
Common uses: Mod-Severe migraines. NOT first line because is less effective and more toxic than triptans, although may help pts that do not respond to triptans
Side-effects: Mild- nausea/vomiting, diarrhea, muscle cramps, paresthesias and vertigo. SERIOUS effects include vascular occlusion and gangrene due to stimulation of a-adrenergic receptors. Should not be used within 24 hours of a triptan. Avoid use with non-selective beta-blockers
NSAIDS (ibuprofen / naproxen):
Discuss mechanism of action, route of administration, rate of onset and duration of action, and most common and use-limiting
Mechanism: Interrupts inflammatory mediator synthesis/release initiated by CGRP
Administration: Oral, OTC. Indomethacin can be suppository.
Rate of onset/duration: Duration 4-6 hours or 8-12 hours
Common uses: Mild-to-Mod migraine without nausea or disability
Side-effects: Avoid in pts with gastritis, peptic ulcer disease, renal insufficiency and bleeding disorders. NOT recommended for chronic daily. Acetaminophen associated with risk of liver toxicity
Triptans (sumatriptan / zolmitriptan):
Discuss mechanism of action, route of administration, rate of onset and duration of action, and most common and use-limiting
Mechanism: Agonist activity at 5HT receptors result in Vasocontriction in cerebral vessels, Inhibition of release of peptides that cause vasodilation/inflammation/pain, Prevent activation of activation of pain fibers in trigeminal nerves
Administration: Oral (onset 30-60 min), Nasal (onset 10-15min) SC (onset 10 min)
duration: 2-4 hours
Common uses: First line for mod-severe migraines
Side-effects: Tingling, flushing, dizziness, drowsiness, fatigue, feeling of heavyness/tightness/pressure on chest. Can cause coronary vasospasm and angina. Avoid in pts with coronary or other arterial disease or uncontrolled hypertension
Describe the general treatment approach to prophylaxis of migraine headaches
- Prophylactic treatment is indicated when the headaches are severe, frequent (more than four headaches per month), long lasting (> 12 hours), or disabling. Drug factors: failure or overuse of acute therapies, contraindication to acute vasoconstrictor therapy, or occurrence of adverse reactions.
- Each drug requires 3-4 weeks before the benefit can be assessed and a trial of 4-6 weeks is recommended before switching to another drug
Beta-blockers (propranolol)
x
Calcium channel blockers (verapamil)
x
Antidepressants (amitriptyline)
x
Anticonvulsant agents (topiramate, valproic acid)
x
Steps in the pathophysiology of a migraine, and identify the primary targets for therapeutic intervention
- Trigeminal Neurovascular Dysfunction
- Trigeminal Neurovascular Activation (target of triptans and ergot alkaloids [5HT receptor agonists])
- Release of Vasoactive Peptides (target of triptans and ergot alkaloids [5HT receptor agonists])
4a. Neuroinflammation, including PG release. (Target of NSAID analgesics [COX-2 inhibitors])
4b. Vasodialiation of Pial and Dural Vessesls (target of triptans and ergot alkaloids [5HT receptor agonists])
- Moderate to severe pain of migraine
