Migraine medications

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Introduction0:00–1:18

Migraine medications include a wide variety of drugs used to treat a specific type of headache called migraine. Migraines are the second most common primary headache.
They’re often preceded by symptoms like irritability, depression, and fatigue that can begin hours to days before the headache itself.
Sometimes there can be an aura where people experience strange smells, lights, visual disturbances, or even hallucinations before the onset of the migraine.
The migraine itself usually feels like a pounding or pulsating, typically localized to one side of the head and can last from hours to days.
As if this was not bad enough, these headaches tend to come with nausea and vomiting, irritability, and pain or discomfort with lights, sounds, and smells called photophobia, phonophobia, and osmophobia, respectively.
During childhood, individuals can have nausea and vomiting without the headaches; and that’s called an abdominal migraine.
After a migraine is over, it can leave people feeling sore at the location of the pain and generally fatigued. To remember the main features of migraines, you can use the mnemonic POUND, where P stands for pulsatile headache, O stands for one-day duration, U stands for unilateral, N for nausea, and D for disabling.

Pathology1:18–2:05

Although the underlying mechanism causing migraines isn’t well understood, there are some clues. Concentrations of the neurotransmitter, serotonin, increase during the aura, triggering vasoconstriction, and then decrease to lower-than-normal levels during the migraine attack, triggering vasodilation.
This change in the blood vessel size may be a trigger for pain receptors, causing the headache. The initial vasoconstriction may also trigger cortical spreading depression, which is a phenomenon when the brain becomes hypersensitive to certain stimuli like lights, sounds, and smells.
Migraines are often associated with specific triggers like the smell of cigarette smoke, foods like chocolate or cheese, and drinking wine.
Even sleeping too much or too little can sometimes trigger a migraine. There are two treatment approaches for migraine: acute treatment to help manage the pain; and preventive treatment to keep headaches from happening in the first place, in individuals that have severe, debilitating headaches.

Mechanism of Action2:05–2:17

Acute Treatment2:17–2:48

The acute treatment includes common analgesic drugs, triptans, and ergot alkaloids. For people with mild or moderate symptoms, initial treatment may involve only analgesics, such as NSAIDs or the opioid agonist butorphanol.
Acutely, pain medications work best if they’re used at the first sign of an attack, during the early symptoms, and aura.
If the pain is very severe, triptans or ergotamine, which are serotonin agonists, can be useful because they mimic serotonin to cause vasoconstriction.
So, triptans should be prescribed when people with mild symptoms don’t respond to analgesics, or when symptoms are moderate to severe.

Triptans2:48–4:43

The common suffix for these medications is -triptan, like sumatriptan, zolmitriptan, naratriptan, or rizatriptan. All of them can be given by mouth, but this may be impractical for people who have nausea or vomiting during the attack.
For these situations, subcutaneous injections or a nasal spray of sumatriptan are available. Triptans are agonists at 5-HT1B and 5HT1D serotonin receptors, therefore preventing vasoactive peptide release, reducing trigeminal nerve activation, and causing vasoconstriction.
Side effects are generally mild, and include mild pain or burning sensations at the site of injection, paresthesia, fatigue, or dizziness, when given per orally.
In addition, not only they cause vasoconstriction on the blood vessels in the brain, but also in other blood vessels, which can raise blood pressure.
Also, as it causes coronary vasospasm, it can bring about a type of chest pain called angina. Although it’s an uncommon side effect, that’s why triptans are contraindicated in people with hypertension, coronary artery disease, prinzmetal angina, and peripheral vascular disease.
It can also rarely cause myocardial ischemia or infarction, and arrhythmias as well. Now, when used together with other serotonin receptor agonists, triptans can induce a serotonin syndrome, that comprises of cognitive symptoms, like headache, hallucinations, or coma; somatic symptoms, like tremors or hyperreflexia; and autonomic symptoms like tachycardia, nausea, diarrhoea, shivering, and sweating.
So, people who have recently been given ergot alkaloids or other serotonin agonists mustn’t use triptans, at least for 24 hours.
Okay so, sometimes, NSAIDs or triptans aren’t effective to relieve the symptoms. So we can move on to the ergot alkaloids, or simply ‘ergots’, which include ergotamine and dihydroergotamine.

Ergot Alkaloids4:43–6:32

Ergotamine can be administered in sublingual tablets, and dihydroergotamine can be injected or used as a nasal spray. Ergots are also agonist at 5-HT serotonin receptors.
However, they're not specific for 5-HT1 receptors, and that means they have more side effects than triptans. For example, when they stimulate 5HT3 receptors in the vomiting center of the brain, they can trigger nausea or vomiting.
Also, just like triptans, ergot alkaloids causes vasoconstriction and are contraindicated in people with coronary artery disease or hypertension.
In a similar aspect, as ergot stimulate contraction of the smooth muscle in the wall of blood vessels, they also stimulate contraction of the uterine smooth muscle, an oxytocic effect that can lead to premature labor in pregnant women, causing fetal distress and miscarriage.
So, they’re contraindicated during pregnancy. Ergot alkaloids are widely metabolized in the liver, that’s why they’re contraindicated in patients with liver impairment.
Leg weakness and muscle pain in arms and legs are also common side effects. Finally, a situation called ergotism happens when people intoxicate with ergot alkaloids, manifesting mainly with spasms, seizures, psychiatric and gastrointestinal symptoms, and gangrene in the hands and feet due to vasoconstriction.
Anticoagulants, vasodilators and low molecular weight dextran come in handy to treat these symptoms. It’s important to point out that all the medications for acute treatment should be used sparingly.
Otherwise, they can cause medication overuse headache, or rebound headaches if used chronically. People who have multiple episodes of migraines each year can benefit from a prophylactic treatment.

Prophylactic Treatment6:32–7:20

There are many options, including specific beta-blockers, like propranolol, nadolol, timolol or metoprolol; calcium channel blockers, like verapamil; tricyclic antidepressants, like amitriptyline; and some anti-seizure medications, like topiramate.
Although the exact mechanisms to prevent migraine attacks aren’t completely elucidated, these medications have proven to be effective.
OnabotulinumtoxinA, more commonly known as Botox, is another medication that could be useful for prophylactic treatment.
It’s injected into the head and neck muscles, and it blocks neurotransmitter release from trigeminal sensory nerve, therefore blocking pain sensation.
Finally, there’s a new class of medications developed specifically for prophylactic treatment. These are the anti-CGRP antibodies that includes erenumab, fremanezumab, and galcanezumab; all of them administered by subcutaneous injection.

Anti-CGRP7:20–8:29

These medications are monoclonal antibodies that target and block either the calcitonin gene-related peptide, or its receptor.
The peptide is involved in the transmission of sensory nerve impulses throughout the trigeminal nerve, which is the key to migraine’ headache.
So, basically, no nerve impulse, no pain. As if it weren’t enough, these medications have the plus side of being relatively safe with mild side effects like pain at the site of injection.
And they aren’t metabolized by the liver, so drug interactions are less likely to be an issue. In addition, lifestyle changes are also useful to prevent migraine attacks.
For example, it’s important to have good eating and exercise habits, have a regular sleeping time, and try to avoid getting stressed or things that could trigger migraine attacks, for example: some medications, like nitroglycerin; air pollution; or extreme heat or cold.
Now, let’s make a simple and fun mnemonic that’ll help you efficiently memorize these pharmacology facts. So let’s go to an ice cream parlor where a lot of people are getting ice cream headaches.

Memory Palace8:29–10:47

Right by the counter we have the medications used for acute treatment and by the door, we have the prophylaxis medications.
For acute treatment, we have a lady holding a large spring for Aspirin and the other NSAIDS. Next to her, is a vacationer who’s on a trip to get a great tan, and he represents the “triptans.” Behind him, is the ergot alkaloids.
Now ergots are a type of fungus that infest grains, so let’s use a mushroom eating a bowl of rotting cereal to represent these drugs.
Let’s put in a red velvet rope to separate the triptans from the ergots, since these drugs can cause serotonin syndrome if used together.
For side effects, since both kinds of medication can cause hypertension, angina, or even MIs, let’s wrap a blood pressure cuff around the red velvet rope.
Then, we can put a little heart on top of it with a knife in its chest. Okay, there’s also a few side effects specific to each drug class.
The ergots cause ergotism, so let’s have the mushroom vomit from the bad cereal, he’s waving one arm around wildly to represent spasms.
Finally, the arm is also gangrenous and looks rotten. On the ground, there’s a crying baby mushroom in a little puddle to help you remember this drug could cause premature labor.
Triptans can cause pain or burning sensations at the injection site, so let’s give the tanned person a sunburn and stick a syringe there.
These medications can also cause paraesthesia so let’s cover the man’s arms in bandages. Okay moving on to the prophylactic medications by the door.
So there are 2 shields hanging by the entrance. One has a bottle of milk on it for the calcium channel blockers, and the other has a bee for beta blockers.
Next, we have a boy on a tricycle wearing a smiley face mask for the tricyclic antidepressants. Welcoming him is a cartoon bear holding a giant pot of honey.
He represents OnabotulinumtoxinA since botulinum toxin is often found in honey. Finally, we have the anti-CGRP antibodies that all end in “mab” so let’s throw 4 large marbles on the ground with the letters C,G,R, and P on them.
For the side effects, there’s a discarded syringe on the ground to represent pain at the injection site, so hopefully no one trips on those marbles.
All right, as a quick recap… Migraine medications include a variety of drugs used to treat a specific type of headache called migraine.

Review10:47–11:30

The acute treatment for a migraine headache includes analgesic drugs, like NSAIDs, triptans, and ergot alkaloids. For people with mild or moderate symptoms, analgesics could be enough.
When people don’t respond to analgesics, or symptoms are more severe, triptans are the best choice. If these don’t work, the last option are ergot alkaloids.
Prophylactic treatment includes beta-blockers, calcium channel blockers, tricyclic antidepressants, some anti-seizure medications, OnabotulinumtoxinA, and anti-CGRP monoclonal antibodies.
But wait, there’s more: Here’s a mind map with all of the mnemonics. Go ahead and pause the video so you can test yourself to see what you remember.

Mind Map11:30–11:40

Stay tuned for the answers after the credits.