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45 Cards in this Set
- Front
- Back
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Serotonin role in migraine
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5-HT drops during HA onset.
Reserpine (serotonin depletion) induces HA Familial hemilpegic migraine gene |
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Familial hemiplegic migraine gene
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Controls serotonin release in the CNS
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Vascular changes - role in migraine
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Irritation of meningial BVs induce head pain. (nociceptors on the wall)
Vasodilators cause head pain During migraine, there is spread oligemia (deficiency in blood) followed by hyperemia (excess of blood). NOTE - even in non-aura migraines, there is a strange change in blood flow. |
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Cortical elec excitation - role in migraine
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Spreading oligemia observed progresses at same rate of spreading depression.
This spreading dep corresponds to spread of migraine auras. |
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Trigeminal nerve - role in migraine
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Innervates meningeal vessels - stimulation of these releases neuropeptides to promote protein extravasation and sterile inflammation.
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NO and migraine
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NO donors like nitroglyc can induce headache.
Histamine also induces HA by activating NO synthase so NO might be the final common mediator of vascular headaches. (in both migraine and cluster HA) |
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Pathway of migraine
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Trigger --> spreading depression --> activation of CNV endings and antidromic peptide release --> vascular inflamm --> head pain.
During a migraine, there is dramatic metabolic activity particularly in the brainstem and trigeminal systems. |
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Metoclopramide in acute migraine tx
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Restores GI motility and enhances absorption in pts with gastric dysfunction.
and in general, don't use oral rt with vomiting episodes (duh). |
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Acute Migraine tx
Simple analgesics |
ASA, acetaminophen, caffeine
Non-specific SE - GI effects |
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Acute Migraine tx
NSAIDs |
Non-specific
Indomethacin Ketorolac Ibuprofen Naproxen SE: GI effects and renal toxicity. |
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Acute Migraine tx
Combo meds |
Non-specific
Butalbital, isometheptine SE: addiction, sedation |
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Acute Migraine tx
Opioids |
Non-specific
Oxycodone, hydrocodone SE: addiction |
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Acute Migraine tx
Neuroleptics, antiemetics |
Non-specific
Prochlorperazine (Compazine) Chlorpromazine (Thorazine) SE: Dystonia, akathisia (wanting to jump out of skin) |
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Ergotamine tartrate and Dihydroergotamine (DHE)
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For acute migraine tx
Activates 5HT1B and 1D receptors to suppress inflammation SEs: vasoconstriction, chest tightness, sedation, nausea Contraind - Coronary artery disease DHE is more effective and less SE but only IV and nasal spray. Long half life these have a history of causing LSD-like symptoms |
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Triptans
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For acute migraine tx
Mechanism: 5HT1B and 1D agonists. (at the trigeminal nerve endings) tp cause vasoconstriction 70% improvement in two hours. SEs - chest tightness, sedation, nausea Contraind - Coronary art disease and stroke This was consciously invented by pharmacologists. Specifically interact with SSRIs and MAOIs Zolmitriptan is the gold standard. |
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Triptan interactions
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SSRIs and SNRIs.
MAOIs Rizatriptan levels inc by propanolol Eletriptan (and zolmitriptan a little bit) metab by P450 Also note that flovatriptan is weak but has a long half life compared to the others. |
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Escalation of expectations
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When a pt is having less HA but doesn't even realize.
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First tier prophylactic migraine meds
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Beta-blockers
Cyclic antidep Valproate GABApentin Topiramate Calcium channel blockers Methysergide |
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Second tier proph migraine meds
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ARBs
SNRIs MAO inh Clonazepam NSAIDs, COXII antag Neuroleptics Herbals and supplements. |
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Beta blockers
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1st tier proph prev of migraines
Reduces adrenergic output to reduce vessel reactivity. SEs: fatigue, bradycardia (leading to wooziness), bronchospasm, increased lipid levels, lowered BP, DEPRESSION Contraind - Asthma, insulin-dependent diabetes (type 1 - because the beta 2 block reduces recovery from hypoglycemia) Good effects - reduce intraocular pressure, stage fright, anxiety, tremor |
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Beta 1 and 2 blockers
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Propanolol, nadolol
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Beta 1 blockers
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Metoprolol, atenolol
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Cyclic antidepressant
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Proph tx of migraines
Amitriptyline, nortriptyline are very good Not so good - Doxepin, protriptyline, desiprimine, bupropion (does't even work) Also SSRIs and SNRIs Mech of action - Promotes NE and serotonin. AEs - weight gain, sedation, anticholinergic, sexual dysfunc, tachycardia, QT prolongation. Side effects are often a deal breaker |
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SSRIs
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Fluoxetine, sertraline
Both ineffectrive and may actually cause HA |
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SNRIs
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Venlafaxine and duloxetine
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Calcium channel blockers
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Good for cluster HA, not so much for migraines
Verapimil, amlodipine (diltizem, flunarizine) Nifedipine often worsens migrain. Mech - Prev SM contraction, prev neurovasc inflamm, prev 5-HT release, inhibits spreading depression. AEs: edema, decreased BP, constipation Beneficial - antiHTN |
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Antiepileptic drugs
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Migraine proph
Suppress cortical excitation Valproate (depakote) - weight gain, alopecia (hair loss), hepatotoxicity. V. effective GABApentin (Neurontin) - cognitive decline Topiramate (topamax) - v. effective. cognitive decline, weight loss, nephrolith formation (kidney stones) Felbamate (felbatol) - aplastic anemia Lamotrigine (lamictal) - rash and possible Stevens-Johnson syndrome (epidermis separates from dermis) |
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Divalproex sodium
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AKA depakote
V. effective Mech - reduces CNS toxicity SEs are very dramatic and long: hepatotoxicity, bleeding diathesis, nausea, diarrhea, mestrual irreg, tremor, somnolence, weight gain, hair loss Many medicine interactions (kicks lots of proteins off their bidning sites) |
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Topiramate
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Good evidence of efficacy
Reduces CNS excitability via GABA rec AEs: cog dysfunc, somnolence, nephrolithiasis, paresthesis (numbness), weight loss, glaucoma |
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Herbal/vitamin tx for migraine
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Magnesium, B2/riboflavin, feverfew, butterbur, caffeine
Valerian root and ginger root doesn't work!!! |
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FDA pregnancy risk
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A - no risk
B - no human risk C - risk to humans not ruled out D - risk to humans based on human/animal studies X - Contraindicated in pregnancy. |
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Drugs we learned - FDA preg risk
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B: acetaminophen, caffeine, ibuprofen, naproxen, prednisone, metaclopramide, meperidine, oxycodone, morphine, butorphanol, fluoxetine, sertraline, paroxetine
C: ASA, codeine, hydrocodone, butalbital, sumatriptan, prochlorperazine, promethazine, isometheptene, propranolol, metopralol, nadolol, verapimil, doxepin, trazodone, hydroxyzine D: Divalproex, amitriptyline, nortriptyline, benzodiazepines X: ergotamine, DHE ----- Opioids are category D if used in high doses at term Aspirin and NSAIDS are category D if used near term Beta blockers are category D in 2nd and 3rd trimester |
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Migraine - what to use in pregnant woman?
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Acetaminophen, oxycodone, NSAIDS (not in third trim), metoclopramide, lifestyle adjustments.
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Common causes of analgesic rebound
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Acetaminophen, combo meds, butalbital, opioids, ergots.
Less likely - NSAIDs, triptans. |
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Tension HA tx (generally)
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OTCs help but analgesic rebound is a risk.
Lifestyle: sleep, exercise, lifestyle changes are even more important than in migraines |
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Proph tx of tension HA
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Tricyclic anti-dep
beta blockers sodium divalproex physical measures behav medicine measures |
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Cluster HA proph tx
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Corticosteroids, calcium channel blockers, lithium, depakote (AKA valproate AKA divalproex sodium)
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Cluster HA acute tx
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Oxygen, sumatriptan (subcutaneous), DHE (IV, IM), antiemetics, opioids, intranasal lidocaine
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Lithium
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Proph tx of cluster HA
AEs: tremor, nausea, fatigue, QT prolongation (causing torsade de pointes) |
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Lithium interactions
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Indomethacin/NSAIDs and diuretics can raise lithium levels.
Neuroleptics and antidepressants - unpredictable what they will do. |
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Drugs prolonging QT
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Can cause torsade de pointes
Methadone, droperidol, chlorpromazine, erthryomycin, lithium, ondansetron (zofran), venlafaxine (effexor), tizandine (zanaflex), quetiapine (zyprexa), cyclic antidepressants. In this disorder, QT overcorrects at high heart rates and undercorrects at low heart rates |
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Tx of intractable persistent HA
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IV DHE
IV Chlorpromazine or prochlorperazine Sedative tx (benzos, barbs, propofol) |
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New ideas for HA prophylaxis
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Novel AEDs, ARBs, NO inh, botulinum toxin, cGRP antagonists, NMDA antag, serotonin antag, herbal supp, transcranial magnetic stimulation.
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5HT-1B receptor
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On meningeal BVs
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5HT-1D receptor
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On Trigeminal nerve.
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