Term
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Definition
| An early treatment for migraine, drilling a hole to free evil spirits |
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Term
| What drug classes are used to TREAT migraines? |
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Definition
- ergot alkaloids - alpha 1 receptor agonists
- Triptans - 5-HT receptor agonists, specifically 5-HT1D/B. Serotonin is too low in migraines
Both produce vasoconstriction
- Trying to develop: CGRP inhibitors, NO synthase inhibitors, TRPV1 inhibitors, prostanoid receptor inhibitors, glutamate receptor inhibitors. |
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Term
| What drugs are used to prevent migraine attacks? |
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Definition
Beta adrenergic receptor blocking agents
Antidepressants - TCAs, SSRIs
Anticonvulsants - Topamax, Depakote, Neurontin
Angiotensin modulators - usually ARBs
Calcium channel blocking agents - Verapamil
Botulinum toxin Type A |
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Term
| What drugs can treat the prodromal phase? |
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Definition
Reglan - GI stimulant and anti-emetic. An increase in GI activity increases Ach - serotonin agonism and DA antagonism. Blocks DA2 in the CTZ, TNC = antiemetic
Dihydroergotamine (DHE) |
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Term
| What drugs can be used to treat an aura? |
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Definition
- Phenergan
- Lasix - removes K from CNS?
- Ketalar/ketamine - NMDA antagonist, decreases glutamate levels
- Diamox/acetazolamide
- Depakote
- MGSO4 - reduces stimulation of NMDA |
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Term
| What are nonspecific treatments for migraine pain? |
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Definition
Not directed at migraine mechanisms:
- analgesics
- NSAIDs
- Rx analgesics - Midrin, fiorinal, esgic, tramadol |
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Term
| How are serotonin receptors affected in migraine? |
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Definition
5-HT1D - presynaptic, 5-HT1B - postsynaptic
Released by GI, taken up by platelets. NOT MADE BY PLATELETS. Also found in raphe nuclei in the brain.
Triptans: 1D stimulation inhibits release of neurotransmitter. 1B on neuron decreases activation. 1B on BVs = constriction! major MoA |
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Term
| How do triptans affect 5-HT1D? |
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Definition
Presynaptically, inhibits adenylyl cyclase = no cAMP --> decrease of calcium and hyperpolarization
Act PRE-synaptically at trigeminal nerve junction to inhibit signal --> inhibit mediators such as CGRP, or at TNV to inhibit neurotransmitter |
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Term
| How do triptans affect 5-HT1B? |
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Definition
Post-synaptically in a BLOOD VESSEL: cAMP is not formed, calcium can move in and smooth muscle contracts. Normal adenylyl cyclase/cAMP in smooth muscle = dilation
--> Prevention of afferent impulse or contraction of a blood vessel intracranially |
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Term
| What are adverse effects of triptans? |
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Definition
- usually minor: N/V, drowsy, parasthesia, flushing
- Vasoconstriction - caution in CAD, other CV problems
- Triptophobia - fear of a coronary event from triptans
- Remember: lower pKi = more potent |
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Term
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Definition
Sumatriptan/Imitrex
Rizatriptan/Maxalt
Frovatriptan/Frova
Zolmitriptan/Zomig
Almotriptan/Axert
Eletriptan/Relpax
Naratriptan/Amerge |
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Term
Which drugs are ergot alkaloids?
How do they work? |
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Definition
Ertogamine/Ergomar
Ergonavine/Ergotrate
Bromocriptine/Parlodel
Methylsergide
LSD
DHE/Migranal
- 5-HT1B/1D agonists as well as alpha 1 agonists. Stimulates 5-HT2 on uterus |
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Term
How do ergots work?
What are their side effects? |
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Definition
- stimulation of alpha receptors and 5-HT1B constricts cerebral as well as peripheral BVs.
- Inhibition of CGRP.
- DHE used more than ergotamine - less N/V, less effect on the uterus
- N/V through direct emetic stimulation, pregnancy category X, gangrene from constriction |
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Term
| How does caffeine cause vasoconstriction? |
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Definition
| Blocks adenosine receptors --> prevents vasodilation and enhances release of NE --> constriction. Enhances absorption of ergots |
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Term
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Definition
-Isometheptene - sympathomimetic that constricts arterioles
-Dichloralphenazone - sedative
- APAP - analgesia, raises threshold to pain. |
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Term
| What 2 causes of migraines are prevented with prophylactic treatment? |
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Definition
- Central neuronal hyperexcitability - increases in glutamate, calcium, NO, CGRP lead to hyperexcitability
- Nociceptive dysmodulation - greater perception of pain |
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Term
| How do beta blockers work for migraine prevention? |
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Definition
| - Inhibits action on neurons of the thalamus - B1 blockade decreases response to glutamate in a 3rd order neuron. |
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Term
| How do Alpha 2 receptor agonists work for the prevention of migraines? |
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Definition
- Inhibit release of glutamate from 1st order neurons
- Augment endogenous analgesic pathway
- Inhibits release of NO
- Catapres/clonidine
-Tenex/Guanfacine |
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Term
| How do ARBs work for the prevention of migraines? |
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Definition
| Blocks AT1 pre-synaptically --> INCREASE in GABA --> inhibition of glutamate |
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Term
| Do SSRI's work for the treatment of migraine? |
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Definition
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Term
| How would anti-seizure drugs work for the prevention of migraines? |
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Definition
Either block sodium or calcium channels
potentiate GABA
Inhibit glutamate - Block NMDA |
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Term
| What is the only agent approved for prevention of chronic migraines? |
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Definition
Botox!
Blocks release of excitatory mediators. Can cause muscle paralysis by stopping release of Ach
- Proteins found on the membrane are required for vesicle fusion. Botox inhibits these (SNAPS) - prevents release of CGRP and Ach and Glutamate
Can have major side effects having to do with muscle paralysis. |
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