USMLE® Step 1 style questions USMLE
A 50 year old woman with a history of headaches presents with complaints of chest pain. She described the pain as pressure, and tightness in her chest. She said that the pain occurred after taking a drug, the name of which she forgot. The most likely mechanism of this drug is?
Content Reviewers:Yifan Xiao, MD
Contributors:Tanner Marshall, MS, Evan Debevec-McKenney, Victoria Recalde, Elizabeth Nixon-Shapiro, MSMI, CMI
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.
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.
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.
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 do 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.
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.
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