Migraine HA: Treatment And Prevention

Question 1

What is a migraine?

Answer 1

Special form of neurovascular headache. Neural events provoke dilation of cranial blood vessels, which result in pain, further sensory and central nerve activation.

Question 2

What is the feature of a classic migraine headache?

Answer 2

Aura-> visual disturbance.

Question 3

What are the three main phase of a migraine time course?

Answer 3

1) prodrome-yawning, depression, lethargy, excitability
2) headache-mostly unilateral photophobia, photophobia, N/V
3) postdrome- exhaustion fatigue

Question 4

What are the class of drugs that are used for therapy (not prevention) of migraines and when should they be taken?

Answer 4

• Tripatans- 5HT1B/1D receptor agonists
• Taken at the start of the prodrome phase

-Ergot alkaloids are the older drug of choice to be given during this phase.

Question 5

What are the drugs of choice that can be used during the headache phase of a migraine?

Answer 5

• NSAIDS

- Acetaminophen

Question 6

What are the agents that can be used for prevention of migraines?

Answer 6

• Beta blockers
• Tricyclic antidepressants
• AEDs
• Ca2+ channel blockers

Question 7

What is the etiology of a migraine?

Answer 7

-A wave of electrical activity and H+, K+ passing through nerve cells stimulates the release of neuropeptides ( CGRP, substance P) and inflammatory mediators (NO, histamine, prostaglandins) that dilate cranial blood vessels and sensitize nerves to pain.

Question 8

What is the generalized accepted events that lead to migraine formation?

Answer 8

1) Brainstem dysfunction sparks a wave of excitation/depression in cortex. This is accompanied by H+, K+, NO discharge—> cerebral vasoconstriction pushes blood into the cranial vasculature!
2) Electrolytes and NO diffuse and dilate cranial arteries and depolarize peri vascular Trigeminal terminals. This leads to CGRP and neuropeptides release–> promote neurogenic inflammation.
3) The neurogenic inflammation irritates TG nerve and transmits migraine pain.

Question 9

What commonly used CV medication can provoke migraines?

Answer 9

NO used in angina

Question 10

What subtype of 5HT receptors are located on cranial vessels, peripheral neurons, and central neurons?

Answer 10

• Cranial vessels-> 5HT-1B
• Peripheral vessels-> 5HT-1D
• Central Neuron-> 5HT-1B/1D

Question 11

What is the MOA of Triptans?

Answer 11

• Binding to 5HT1B receptor (on blood vessels) lowers cAMP and oppose the dilation.
• Binding to 5HT-1D receptor (on nerves) lowers cAMP thus inhibiting pre-synaptic release of CGRP.

Question 12

What is the prototypical Triptan?

Answer 12

• Sumatriptan.
• Can be administered via nasal spray and oral tablet (poor bioavability)
• meatabolized by MAO

Question 13

What two Triptans have longer t1/2?

Answer 13

• Almotriptan
• Naratriptan

T1/2 about 6 hrs

Question 14

What Triptan has an active metabolite?

Answer 14

Zolmitriptan

Question 15

What are the forms of administration of Sumatriptan?

Answer 15

-injection, nasal spray, tablets

Question 16

What are the forms of administration of Zolmitriptan?

Answer 16

-Tablets, orally disintegrating tablets, nasal spray

Question 17

When are Triptans contraindicated?

Answer 17

-Patients with ischemic heart disease, uncontrolled HTN, other CV disorders.

Question 18

What is the next mediations that can be used if Triptans do not provide relief for the patient?

Answer 18

• Egot alkaloids.
• Dihydroergotamine
• Ergotamine and caffeine

These are less specific, they interact with alpha receptors, dopamine receptors, and various 5HT receptors. Act as agonists, partial agonists, and antagonists.

Question 19

What is a potential serious side effect of ergot alkaloids?

Answer 19

• Strong emetic action

- Most severe is vasoconstriction! Can lead to dry gangrene( St. Anthony’s Fire)

Question 20

What is the Ca2+ blocker that can be used in prophylactic treatment of migraines?

Answer 20

Verapamil-> very safe and do not desentisize overtime.