Agents for Migraines and Headaches

Question 1

What are the types of primary headaches?

Answer 1

Migraine, Tension-type, and cluster headaches

Question 2

What are secondary headaches?

Answer 2

Symptoms of an underlying medical condition

Question 3

Describe migraine headaches with respect to location, characteristics, duration, and associated symptoms.

Answer 3

Location - typically U/L; possibly bifrontal or global

Characteristics - may be preceded by an aura, crescendo pattern, and aggravated by activity

Duration - 2 hours to 3 days

Associated Sx - photo-/phonophobia, N/V

Question 4

Describe tension headaches with respect to location, characteristics, duration, and associated symptoms.

Answer 4

Location - B/L; headband distribution

Characteristics - waxing and waning tension/tightness

Duration - variable

Associated Sx - none

Question 5

Describe cluster headaches with respect to location, characteristics, duration, and associated symptoms.

Answer 5

Location - U/L always; near temple or eye

Characteristics - sudden in onset with deep, excruciating pain

Associated Sx - I/L lacrimation, orbital hyperemia, and rhinorrhea

Question 6

Describe the pathophysiology of migraines and how serotonin may play a role.

Answer 6

The distribution of the trigeminal nerve involves intracranial arteries. These nerves release neuropeptides such as CGRP, which are potent vasodilators. These neuropeptides also induce dural perivascular edema –> mechanical stretching of dura. Serotonin binding to the trigeminal neurons –> inhibition of neuropeptide release.

Question 7

What is the 5HT-1B/1D agonist prototype?

Answer 7

sumatriptan

Question 8

Describe the MOA, uses, ADRs, and CIs for sumatriptan?

Answer 8

MOA - binds 5HT-1B/1D receptors on the trigeminal nerve inhibiting the release of vasodilating peptides

Uses - 1st line Tx for acute mild to severe attacks

ADRs - Think carcinoid neoplasm Mx.s; Specifically: altered sensations, dizziness, muscle weakness, fatigue, and coronary vasospasm

CIs - Any ischemic heart disease, uncontrolled HTN, or recent ergotamine and MAOI therapy

Question 9

What are the prototype ergot alkaloids used for migraine treatment?

Answer 9

Dihydroergotamine (DHE) and ergotamine (sometimes with caffeine)

Question 10

Describe the ergot alkaloids with respect to MOA, uses, ADRs, and CIs.

Answer 10

MOA - vasoconstriction of peripheral and cranial blood vessels; partial agonist at 5HT-1B/1D receptors

Uses - Migraines; DHE for intractable attacks and ergotamine for severely prolonged attacks

ADRs - N/V/D

CIs - Uncontrolled HTN, ischemic heart disease, collagen diseases, renal/hepatic dysfunction, and gangrene

Question 11

What analgesic is most commonly used for the treatment of migraines?

Answer 11

Combination aspirin, acetaminophen, and caffeine (AKA excedrin)

Question 12

Describe the MOA, uses, ADRs, and CIs of analgesics in migraine therapy.

Answer 12

MOA - prevention of neurogenic inflammation by prostaglandin synthesis inhibition

Uses - Common headache, mild-to-moderate migraines, and migraines previously responsive to analgesics

ADRs - N/V/D, overuse headaches

CIs - peptic ulcer disease and renal dysfunction

Question 13

What types of drugs are used for prophylactic management of migraines?

Answer 13

Beta-blockers, calcium channel blockers, anti-depressants, and anti-convulsants

Question 14

Describe the MOA, uses, ADRs, and CIs of beta-blockers with respect to migraines.

Answer 14

MOA - modulates adrenergic and serotonergic pathways in the cortex and subcortex

Uses - 1st line prophylaxis of migraines

ADRs - Drowsiness, fatigue, vivid dreams, memory disturbance, and depression

CIs - Diabetes, heart failure, PVD, dysrrhythmias, and depression

Question 15

Name two beta-blockers used for migraine prophylaxis

Answer 15

metoprolol and propanolol

Question 16

Describe the use of calcium channel blockers for the prophylaxis of migraines.

Answer 16

Verapamil has been used “off-label” to reduce vasodilation in patients who suffer from migraines and cluster headaches. There has been some success in the prevention of cluster headaches, but evidence in the prevention of migraines is still WEAK.

Question 17

Describe the name, MOA, and ADR of tricyclic anti-depressants with respect to migraine prophylaxis.

Answer 17

Drug - amitiyptyline

MOA - downregultes central 5HT-2 receptor and increases synaptic NE

ADR - sedation (give near bed time)

Question 18

Describe the name, MOA, and ADRs of anti-convulsants with respect to migraine prophylaxis

Answer 18

Drug - topiramate

MOA - increases GABA and modulates glutamate, while inhibiting sodium and calcium channels

ADRs - weight loss, anorexia, taste perversion, parasthesia, and fatigue

Question 19

What is the Tx approach for mild-to-moderate migraines?

Answer 19

Begin treatment with a simple analgesic

If nausea is concurrent, use an anti-emetic (metoclopramide; D2-like antagonist)

If migraine is refractory to simple analgesic, use a combination analgesic (aspirin + acetaminophen + caffeine)

If migraine continues to be refractory, use sumatriptan. If the migraine continues to be refractory, use higher dosesn, a different triptan, or another class.

Question 20

What is the Tx approach for moderate-to-severe migraines?

Answer 20

Begin with the use of a triptan.

If the migraine is refractory, use an anti-emetic and ergot alkaloid.

Question 21

When should preventive therapies for migraines be initiated (4 situations)?

Answer 21

1. If significant disability recurs with acute therapy
2. Attacks occur >2/week
3. CIs or ADRs prevent symptomatic treatment
4. Patient prefers prophylaxis

Question 22

Describe how the choice of prophylactic therapy for migraines is made. (4 situations)

Answer 22

1. If migraines occur at a predictable and regular interval, give triptans or NSAIDs
2. Healthy or patient with co-morbid HTN or angina, give beta-blockers (CCBs when beta-blockers contraindicated)
3. If diagnosed with depression or insomnia, give tricyclic anti-depressants
4. Seizure disorder, give anti-convulsants

Question 23

Describe the acute and prophylactic therapy of tension headaches.

Answer 23

Acute - simple analgesics or NSAIDS

Prophylactic - tricyclic anti-depressants

Question 24

Describe the acute and prophylactic therapy of cluster headaches.

Answer 24

Acute - oxygen, triptan, or ergot alkaloids

Prophylactic - verapamil, lithium, prednisone, or topiramate