RX411 Serotonin Receptors and Migraines

What drug classes are used for acute migraine treatment?

- Triptans

- Lasmiditan

- Ergots

- NSAIDs

- Gepants

- Antiemetics

What drug classes are used for migraine prevention?

- Beta blockers

- Anticonvulsants

- TCA antidepressants

- Onabotulinum toxin

- Monoclonal antibodies against CGRP

What is serotonin derived from?

Tryptophan

What does serotonin do in the periphery?

- Induces blood platelet aggregation

- Stimulates GI smooth muscle movement

- Stimulates pain and itch sensory nerve endings

- Induces contraction of vascular smooth muscle

- Causes vasodilation in skeletal and heart muscle

Where are cell bodies of serotonin neurons located?

Midbrain raphe nucleus

What does serotonin do in the brain?

- Sleep/arousal

- Mood/emotion

- Appetite

- Body temperature

What serotonin receptors are Gi/o-coupled (decrease cAMP)?

- 5HT1A

- 5HT1B

- 5HT1D

- 5HT1F

What serotonin receptors are Gq-coupled (increase calcium)?

- 5HT2A

- 5HT2B

- 5HT2C

What serotonin receptor is a ligand-gated cation channel?

5HT3

What serotonin receptors are Gs-coupled (increase cAMP)?

- 5HT4

- 5HT5

- 5HT6

- 5HT7

How does buspirone work?

- Partial agonist

- Targets 5HT1A

- Treats anxiety

- Decreases cAMP

How do triptans work?

- Targets 5HT1B

- Targets 5HT1D

- Decreases cAMP

- Treats migraines

- Agonist

How does lasmiditan work?

- Targets 5HT1F

- Decreases cAMP

- Agonist

- Treats migraines

How do risperidone and olanzapine work?

- Targets 5HT2A

- Targets 5HT2C

- Increases calcium

- Antagonist

- Treats schizophrenia

How does LSD work?

- Targets 5HT2A

- Targets 5HT2C

- Increases calcium

- Agonist

How does ondansetron work?

- Targets 5HT3

- Antagonist

- Treats chemotherapy-induced emesis

What is the first-line treatment to treat acute migraines?

Triptans

Activation of which type of serotonin receptors leads to decreased cyclic AMP in cells?

5-HT 1D

3 multiple choice options

What is SERT?

- Serotonin transporter

- Located on the presynaptic terminals of serotonin neurons

- Target of antidepressants and psychostimulants

What causes the migraine aura?

Cortical spreading depression

What causes migraine pain?

- Activation of trigeminal system

- Vasoactive neuropeptides (CGRP)

What drugs are used as adjuvants for acute treatment of mild to moderate migraines?

- Naproxen

- Caffeine

- Metoclopramide

How does caffeine work as an adjuvant for acute treatment of mild to moderate migraines?

- Cerebral vasoconstriction

- Can potentiate analgesics

How does metoclopramide work as an adjuvant for acute treatment of mild to moderate migraines?

- Agonist at D2 receptor

- Anti-emetic

- Enhances gastric emptying

What are the treatment options for acute treatment of severe migraines?

- Triptams

- Ergots

- Lasmiditan

- CGRP receptor blockers

How do ergots work for migraines?

Non-selective 5HT receptor agonists

What are the ergots used for acute treatment of severe migraines?

- Ergotamine

- DHE (dihydroergotamine)

What are the CGRP receptor blockers used for acute treatment of severe migraines?

- Ubrogepant

- Rimegepant

What drugs are in Treximent?

- Sumatriptan

- Naproxen

Which triptans are available as nasal sprays?

- Sumatriptan

- Zolmitriptan

Which triptan is available as a powder?

Sumatriptan

What are the main side effects of triptans?

- Coronary artery vasoconstriction

- Serotonin syndrome

What should not be used while on a triptan?

- MAOIs

- Serotonin reuptake inhibitors

- Certain herbal supplements (St. John's wort)

What are the symptoms of serotonin syndrome?

- Autonomic instability (tachycardia, hyperthermia)

- N/V/D

- Muscle hyper-reflexia

- Incoordination

- Agitation

- Hallucinations

What are the side effects of lasmiditan?

- Dizziness

- Fatigue

- Paresthesia

- Serotonin syndrome

- Sedation

What are the key points of lasmiditan?

- Not for migraine prevention

- Treats acute migraines, not first-line

What ergot comes as a nasal spray for acute migraines?

DHE (dihydroergotamine)

What are the side effects of ergots?

- Nausea/vomiting

- Dizziness

- Cramps

- Vertigo

- Prolonged vasospasm causing angina/gangrene

After how long does ergotamine dependence occur?

> 3 weeks

In what patients are ergots contraindicated?

- Pregnancy

- Sepsis

- Vascular diseases

With what drug classes do ergots interact?

- Triptans

- Beta blockers

- Nicotine

What is the main reason that ergots are contraindicated in pregnancy?

Ergots cause vasoconstruction and decrease blood supply to the placenta

3 multiple choice options

What are the CRGPs that treat migraines in adults?

- Ubrogepant

- Rimegepant

- Zavegepant

What CRGPs are used for preventative treatment of episodic migraines in adults?

- Atogepant

- Erenumab

- Galcanezumab

- Fremanezumab

- Eptinezumab

In what dosage form is ubrogepant available?

Oral tablet

3 multiple choice options

In what dosage form is rimegepant available?

Oral dissolving tablet

3 multiple choice options

In what dosage form is zavegepant available?

Nasal spray

3 multiple choice options

In what dosage form is atogepant available?

Oral tablet

3 multiple choice options

In what dosage form is erenumab available?

Subcutaneous injection

3 multiple choice options

In what dosage form is galcanezumab available?

Subcutaneous injection

3 multiple choice options

In what dosage form is fremanezumab available?

Subcutaneous injection

3 multiple choice options

In what dosage form is eptinezumab available?

IV injection

3 multiple choice options

What are the beta blockers used to prevent migraines?

- Propranolol

- Timolol

What are the anticonvulsants used to prevent migraines?

- Valproate

- Topiramate

What is the antidepressant used to prevent migraines?

Amitriptyline