NEURO 19: Pharmacology for Headaches

NSAIDs

1) How does preventing prostaglandin synthesis help with migraines

1) Prevents neurogenic inflammation in the trigeminovascular system

Activation of the trigeminal nerve occurs through which receptors

5HT1B/D

Migraine drugs that work on 5-HT receptors are 1) ______ and stimulation can result in what 3 things

AGONISTS

1. VasoCONSTRICTION of intracranial arteries

2. INHIBITION of vasoactive peptide release

3. INHIBITION of pain transmission

ERGOTS

1) Drug name (1)

2) MOA (3)

3) ADR (

4) CI (3)

5) DDI

1) Dihydroergotamine

2)

• 5-HT1B/D receptor AGONIST

• Dopamine AGONIST

• Alpha1/2 adrenergic receptor AGONIST

3) Nausea, tingling, paresthesia, drowsiness, dizziness, chest discomfort, diarrhea, muscle cramps, serotonin syndrome

4)

• CV disease

• Hemiplegic / basilar migraine

• Pregnancy

5) DO NOT USE WITHIN 12 hours of TRIPTANS

GEPANTS

1) Drug names (4)

2) MOA

3) Useful in patients with ____ who cannot tolerate triptans

4) ADR (3)

5) What’s one GOOD THING about this class

1) Urbogepant, Rimegepant, Atogepant, Zavegapent

2) CGRP Receptor ANTAGONIST

• Binds DIRECTLY to CGRP receptor and prevents it from activating which leads to less inflammation / vasodilation

3) CV disease

4) Nausea, somnolence, dry mouth

5) NOT commonly implicated with medication over-use headaches!

TRIPTANS

1) MOA

2) Fastest acting generic name

3) Dosage forms from fastest → slowest

4) Long-acting generics (2)

5) Long-acting benefits

6) Longest half life

1. 5-HT1b/d AGONIST (selective)

   1. Normalization of dilated intracranial arteries

   2. Inhibition of vasoactive peptide release

   3. Inhibition of pain transmission to thalamus

2. Sumatriptan

2. SC, nasal, oral

4. Naratriptan, Frovatriptan

5. Best tolerability

6. Frovatriptan

OPIOIDS

1) What does it target (MOA)

2) Does it have vasopressor or anti-inflammatory effects?

3) Can cause ___ which increases risk of ____

4) Used as a last resort; can actually increase risk of ___

1) Mu receptor AGONIST

2) NO

3) Central sensitization, increases risk of MOH

4) Headache

What are the drug classes used for ABORTIVE treatment of migraines

1) Simple analgesics

2) Triptans

3) Ergots / Gepants (NOT ALWAYS)

4) Opioids — last resort

What drug classes are used for prophylaxis therapy of migraines

1. Beta Blockers

2. TCAs (Tricyclic Antidepressants)

3. Anticonvulsants

4. CGRP Inhibitors

TRICYCLIC ANTIDEPRESSANTS

1) Names of drugs (2)

2) MOA (what does it target)

3) How does this MOA improve migraines (2)

4) ADR (3)

1) Amitriptyline, nortriptyline

2) 5HT2a ANTAGONIST

3)

• Inhibiting serotonin an norepinephrine reuptake (as increased levels of this can lead to increase pain perception)

• Activates opioid receptors (reducing pain perception)

4) WEIGHT GAIN, CV effects, anticholinergic effects

BETA BLOCKERS

1) Names of the ones we use for migraines

2) MOA (basic)

3) CONTRAINDICATIONS

1) Propranolol, Metoprolol

2) Stabilizes blood vessels + reduces sympathetic NS activity

3) ASTHMA

ANTICONVULSANTS

Topiramate

1) MOA

2) ADR (3)

Valproic Acid (Divalproex)

3) MOA

4) ADR (3)

5) CI (1)

6) DDI (2)

1) Blocks Na / Ca channels; reduces neuronal activity

2) Weight LOSS, cognitive issues, kidney stones

________________________________

3) Increases GABA; decrease glutamate (calms brain activity)

4) Weight GAIN, liver toxicity, tremors

5) Pregnancy — Teratogenic

6) ASA, Warfarin

CGRP MONOCLONAL ANTIBODIES

1) Names

2) MOA

3) Which one has a different MOA + what is it

4) CI

1) Erenumab, Fremanezumab, Galcanezumab, Eptinezumab

2) Binds to CGRP and neutralizes it before it reaches receptor

3) Erenumab binds to the CGRP receptor itself and prevents CGRP from activating it

4) STOP 6 months BEFORE pregnancy

1) Which CCBs are used (2)

2) Which ARB is used

1) Verapamil, Flunarazine

2) Candesartasn