Explains what happens at each of the various migraine stages.
1. Prodrome: 12-36 hours before the headache (yawning, depression, craving, distaste in their mouth)
2. Aura: Period of no pain that normally lasts for 15-20 minutes (aka classic migraine)
3. Headache: Where most of the pain occurs!
4. Postdrome: Exhaustion and Fatigue
Which drugs can stop a migraine and on which phase of the migraine will these drugs act on?
Which drugs can be used to prevent a migraine from occuring? Which phase of the migraine do they work on?
Thobbing pain that is sensed during a headache occurs through which system?
Trigeminal Nervous System
Migraines are not caused by a primary vascular event. If this is the case, what does the current research believe is the cause?
Scientists think it's due to a dysfunctional ion channel (within the aminergic brain-stem nuclei)
Put the following events in order as they relate to the Trigeminal Neurovascular System:
1. Vasodilation causes release of presynaptic vesicles that contain Substance P and CGRP
2. Cortical Spreading Depression
3. Dysfunction of Ion Channel
4. NO is going to be released from blood vessels in order to reverse the cerebral vasoconstriction
5. Cerebral vasoconstriction
6. CGRP and Substance P work together to produce painful dural inflammation
3 - 2 - 5 - 4 - 1 - 6
Who is responsible for sensing the pain during a migraine?
How will that pain present?
Meninges! (They are innervated by the Trigeminal Nerve)
Presents as throbbing unilateral migraine-like pain
Explain why you need to be careful when prescribing nitrates to patients that develop migraines.
Nitrates are composed of synthetic NO that is used for pts that experience chest pain. If you prescribe nitrates to a pt with migraines, you could potentiate the effect of the migraine due to the NO effects!
Serotonin has a shorthand marking of 5HT. Which subset of serotonin receptors are located in:
1. Peripheral Neurons
2. Cranial Vessels
3. Central Neurons
1. Peripheral Neurons: 5HT-1D
2. Cranial Vessels (meninges): 5HT-1B
3. Central Neurons: 5HT-1B/1D
When serotonin binds to its receptor, it is going to ____________ the release of CGRP into the synaptic cleft and that will _________ the pain stimulus.
Triptans are drugs that act like _______ . Their function is to _________ the release of CGRP which will ________ the pain that is felt during a migraine.
True or False: Triptans are antagonists on Serotonin Receptors.
They are AGONISTS
Triptans can bind to _________ receptors on vascular smooth muscle and that will stimulate __________ of dilated meningeal, dural and pial blood vessels.
Triptans bind to ________ receptors on presynaptic nerve terminals and that will ________ presynaptic release of CGRP and other neuropeptides from the peripheral end of the trigeminal nerve.
Triptans can bind to _________ receptors on the trigeminal nucleus in the brainstem and that will ________ upward transmission of painful sensory information to the thalamus and higher brain centers where pain is perceived.
Which triptan has a Cmax PO (1-2 hours), Nasal Spray (30 mins), SC (15 mins); 1/2 life of 1-2 hours, metabolized by monoamine oxidase A; And has a similar structure to serotonin and melatonin?
Which Triptan has the highest bioavailability?
Naratriptan (70%, 1/2 life of 6 hours)
Which two triptans are said to have better tolerance and bettern efficacy relative to sumatriptan?
Which tryptan is used for PROLONGED migraine relief?
Frovatriptan (has a 1/2 of 24 hours)
Which triptan is going to have an active metabolite of a 5HT-1D agonist?
List the Pros and the Cons of taking triptans via the various routes (Oral, Nasal Spray, and Injection)
Which triptans have the most diverse delivery options?
Which triptan and route of administration is going to have the fastest pain relief?
Which triptan is going to be used for long duration of migraine pain relief?
Sumatriptan, Rizatriptan, and zolmitriptan are contraindicated when a patient is taking ___________ .
Which syndrome can you elecit in your patient while prescribing them triptans?
Why do you have to watch out when prescribing Triptans to patients with uncontrolled hypertension or vasospastic coronary disease?
Triptans can act as vasoconstrictors on renal and coronary vessels!
*** This is the location of the 5HT-1B/1D receptors
________ arise from a fungus and were termed "St. Anthony's Fire" in midevil times. Now they are used in treatment of severe or refractory migraines.
Ergot Alkaloids (Dihydroergotamine and Ergotamine + Caffeine)
True or False: Ergot Alkaloids are less specific than Triptans.
True or False. Injectable Triptans work faster than injectable DHE and Triptans work longer than DHE.
DHE works longer in the body than Triptans!!!
Explain why you should never combine a Triptan with DHE.
If you combine these two drugs, you will advance the effect of DHE in which the vasoconstriction will be so severe that you will have a Gangrene effect.
Also, if you have a patient who will vomit, you might not want to give them an ergot alkaloid because that is going to potentiate the effect!
_______ + ______ are acceptable agents when treating migraines during ALL trimesters of pregnancy.
Acetaminophen + Codeine
_______ and _______ are acceptable agents to use during the 1st and 2nd trimesters only!
Explain why DHE and other ergot alkaloids are contraindicated during pregnancy.
They are going to cause constriction of the uterine muscles and can lead to an abortion!
Sumatriptan + naproxen (analgesic) = ________ .
__________ is considered when a pt has:
- more than 2 migraines per month with disability
- Disability lasting more than 3 days per month
- Rescue medication used more than 2 times per week
- Uncommon migraine conditions
- Failure of, contraindication for, or adverse events from acute treatments
________ is a Ca2+ channel blocker and acts to treat migraines by lessening Ca2+-dependent vesicle fushion (which will decrease the release of ______ into the synapse).
_______ are used due to their anxiolytic action, decreases in sympathetic activity, and blunting of cortical spreading depression.
Beta-Blockers (Propranolol or Timolol)
_______ is a major contraindiaction for Beta-Blockers.
Asthma Patients (causes Bronchoconstriction)
________ cleaves SNAP-25 in motor neurons which inhibits Acetylcholine release at the motor endplate. With migraines, you are going to inhibit the fusion of vesicles and the release of _______ with this drug.
What is a side effect of Verapamil?
Beta blockers (Propranolol or timolol), TCAs (Amitriptylene or Imipramine), Anticonvulsants (Topirimate or valproate) and Ca2+ channel blockers (Verapamil) are drugs that are taken daily when a patient is _________. They are used in ________ therapy.