Headache & HA Pharmacology Flashcards
Trigeminal Neuralgia
Intense pain of short duration occurring in the distribution of the trigeminal nerve
Causes: Idiopathic (primary), vascular compression (secondary), demyelination (secondary)
Treatment: anti-epileptics, baclofen, surgery
Headache Red Flag Acronym
S - Systemic Symptoms N - Neurologic Symptoms/Signs O - Onset that is sudden, abrupt O - Older (>50 years) P - Previous HA history (first headache or pattern change)
Which intracranial structures receive pain innervation?
Meninges
Blood vessels - dural sinuses, meningeal vessels, intracranial cerebral arteries
Dermis
Innervated by the trigeminal system (C2-4)
Migraine - Diagnostic Criteria
At least 5 recurring headaches, lasting 4-7 hours, characterized by at least 2 of the following:
Unilateral
Pulsating
Moderate to severe intensity
Pain increases with physical activity
+ Nausa/vomiting, photophobia, and/or phonophobia
Phases of Migraine
Premonitory - alterations in mood, alertness, appetite up to 24 hours before headache
Aura - experienced by 30%; most often visual, unilateral, gradually developing, lasting 5 minutes - 1 hour
Headache
Resolution
Tension Headache - Diagnostic Criteria
At least 10 episodes of headache that last 30 minutes to 7 days; each episode accompanied by at least 2 of the following:
Pressing/tightening sensation Mild to moderative severity Bilateral Not aggravated by physical activity Lack of nausea/vomiting Only photophobia OR phonophobia; not both
Tension Headache - Treatment
Prophylactic: tricyclic antidepressants, SSRIs
Abortive: Aspirin, acetaminophen, NSAIDs
Cluster Headache - Diagnostic Criteria
At least 5 episodes of severe, unilateral, periorbital/temporal pain recurring at least every other day up to 8x/day; one of the following ANS signs must be present ipsilaterally:
Lacrimation Nasal congestion Rhinorrhea Eyelid edema Ptosis Miosis Facial swelling Ear fullness
Cluster Headache - Prophylactic Treatment
Calcium channel blockers
Lithium
Anti-epileptics
Cluster Headaches - Abortive Treatment
Oxygen
Lidocaine
Corticosteroids
Nerve Blocks
Idiopathic intracranial hypertension - Definition
Idiopathic elevated ICP with normal CSF, normal neuroimaging, normal neurological exam except for 6th nerve palsy and papilledema
Idiopathic intracranial hypertension - Clinical features
Elevated ICP with:
HA that worsens with exertion HA that is worse upon wakening, or awakens patients from sleep Nausea/Vomiting Transient visual obscurations Photopsias Diplopia Vision loss 6th Nerve Palsy Papilledema
Giant Cell Arteritis
Mainly a disease of the elderly; 95% of cases occur with headache and associated features: jaw claudication, temporal scalp tenderness, blindness, joint pain, fever, malaise, weight loss
Diagnosed by temporal artery biopsy; ESR and CRP are often elevated
Treatment - Steroids
Phases of migraine pathophysiology
- Cerebral vasoconstriction and ischemia; serotonin release from neurons and platelets
- Cerebral vasodilation and pain; neurons in the trigeminal complex release substance P and CGRP that trigger vasodilation and neuroinflammation of pial and dural vessels, which stimulates nociceptive fibers of the trigeminal nerve
Culminates in cortical spreading depression, a self-propagating wave of neuronal depolarization associated with decreased cortical blood flow which triggers aura and activates trigeminal nerve afferents in the meninges
Triptans - Mechanism in migraine treatment
5HT1B/1D receptor agonists; causes vasoconstriction of cerebral vessels, reversing vasodilation-induced throbbing headache; inhibition of vasodilatory and inflammatory peptide release; prevention of activation of pain fibers in trigeminal nerves
Triptans - Pharmacokinetics
Oral ROA; intranasal/SC preparations available
Sumatriptan has poor CNS penetration; newer triptans are more lipophilic and achieve higher brain concentrations
Short duration (2-4 hours); can see recurrence rate of 20-40%
Triptans - Adverse Effects
Paresthesias Flushing Dizziness Drowsiness Fatigue Heaviness, tightness, pressure in chest
Rarely: Coronary vasospasm, angina, MI, cardiac arrhythmia
Triptans - DDIs
Should not be used within 24 hours after an ergot alkaloid because vasoconstriction may be additive
Should not be used concurrently with an MAOI (risk of serotonin syndrome)
Increased risk of serotonin syndrome with SSRIs or SNRIs
Ergot Alkaloids - Mechanism in migraine
5HT1B/1D agonists
Similar to triptans but somewhat less effective/more toxic; third line agent
Ergot Alkaloids - Pharmacokinetics
ROA: Oral, sublingual, intranasal, parenteral, rectal
Ergot Alkaloids vs. Triptans - Benefits/Risks
Ergot Alkaloids are less effective/more toxic than Triptans but provide longer duration of effect and relatively milder side effects
Ergot Alkaloids - Adverse Effects
Nausea/vomiting Diarrhea Muscle Cramps Paresthesias Vertigo
Rarely, vascular occlusion/gangrene due to a1-adrenergic mediated vasoconstriction
Ergot Alkaloids - DDIs
Non-selective B-blockers - causes severe peripheral ischemia due to combination of alpha-vasoconstriction + blockade of Beta-2 vasodilation
Should not be used within 24 hours of Triptans - vasoconstriction may be additive
Contraindicated with strong inhibitors of CYP3A4 (itraconazole, macrolides, protease inhibitors) - increased risk of vasospasm
Use of B-Blockers in migraine prophylaxis
I.e. Propanolol and Timolol - first line
Reduces frequency and severity of migraine in 60-80% of patients
Adverse Effects: Fatigue, exercise intolerance, orthostatic hypotension; CI ina sthma, cardiac conduction disturbances, heart failure
Use of hypertensives in migraine prophylaxis
First line - Beta Blockers (Propanolol, Timolol)
Also some evidence that ACEIs/ARBs and Calcium Channel Blockers may be useful
Use of anti-depressants in migraine prophylaxis
I.e. TCADs (Amitriptyline)
Second line prophylactic agent; useful in patients with insomnia or depression
Side effects: Sedation, dry mouth, constipation, tachycardia, weight gain, urinary retention
Use of anticonvulsants in migraine prophylaxis
I.e. Valproate, Topiramate (FDA approved) - first line
Reduce migraine frequency by 50% in 50% of patients; efficacy similar to Propanolol
Use of Botox in migraine prophylaxis
Use indicated in chronic migraine (15+ headache days per month, lasting at least 4 hours/day)
Adverse effects: Headache, neck pain, generalized muscle weakness, ptosis
Use of dietary supplements in migraine prophylaxis
Riboflavin (vitamin B2)
Feverfew
Role of 5-HT1B/1D agonists in migraine treatment
Prevents initial vasodilatory effect of 5HT
Vasoconstriction of extracerebral vessels
Decreased neuropeptide (CGRP, SP) release
Inhibition of trigeminal neuron activation
Serotonin Syndrome - Signs & Symptoms
Neuromulscular effects (clonus) ANS changes Mental status changes (agitation, delirium, hypervigilance)
Methysergide - use in migraine prophylaxis
5HT2 blocker - blocks serotonin-mediated vasodilation that initiates the migraine attack
Role in refractory migraine with high attack frequency
