10-21 Headache PHARM

Question 1

Theory of Migraine Pathophysiology

Answer 1

1. CSD - cortical spreading depression spreading wave (excitation followed shortly by depression; Leão) leads to:
   2a. aura
   2b. winding up trigeminal (CN V) system —> neuropeptide release —> innervates meningeal BVs
2. vacsular inflammation + vasodilation —> head pain
   * *∆s in blood flow follow CSD immediately in rabbit studies

Question 2

Migraine Triggers

Answer 2

1. weather
2. sensory stim
3. hormonal state
4. sleep depriv.
5. foods + additives
6. EtOH
7. meds

Question 3

principles of migraine tx

Answer 3

1. re-assure pt they’re not going to die
2. control acute sx (w/ NON-oral meds)
3. education and rx for prevention

stratified care&raquo_space; step care (start at an appropriately high dose)

behavioral/lifestyle ∆s help but this is NOT a psychiatric illness

Question 4

classes of drugs with examples for ACUTE migraine mgmt

Answer 4

1. analgesics/analgesic combos:
—ASA, acetaminophen, caffeine
2. NSAIDs:
—indocin, ketorolac, ibu, napro
3. Combo meds:
—butalibital (in Firocet), sedatives
4. Opioids
—oxy, hydro
5. Neuroleptics (DA antagonists), antiemetics
—prochlorperazine, chlorpromazine (Thorazine)
7. Specific Migraine Rxs
—ergotamine, dihydroergotamine (DHE), triptans

Question 5

Ergotamine and DHE
—MOA
—Efficacy
—Duration
—ADRs
—Contraindications

Answer 5

MOA - broad receptor agonist incl. 5-HT 1B&D, also anti-inflamm and vasoconstrictor
Efficacy good esp IV
DHE t1/2 = 10hrs
ADRs = vasoconstriction, chest pain, sedation, nausea
Contraindicted = heart dz
**note similarity to triptans

Question 6

Triptans
—MOA
—Efficacy
—Duration
—ADRs
—Contraindications
—Interactions

Answer 6

MOA = 5-HT 1B&D (5-HT look alike; yet migraine not serotoninopathy)
Efficacy = 70% improvement in 2 hrs
ADRs = vasoconstriction, chest tightness, sedation, nausea
Contraindicated = heart dz, CVA
Interactions =
—SSRIs/SNRIs—>serotonin syn
—MAOIs
**note similarity to DHE

Question 7

Where do the serotenergic drugs (DHE, Triptans) work?

Answer 7

trigeminal afferents and meningeal blood vessels

Question 8

Indications for Migraine Prophylaxis

Answer 8

— > 2x/wk
—overusing acute meds
—disabling/poor QOL b/c of HAs
—unresponsive or unable to tolerate acute meds
—hemiplegic migraine, prolonged aura, migrainous —stroke (rare!)
—cepalgiaphobia (fear of HAs)

Question 9

Migraine Proph drug classes
—avg efficacy
—most common side effects

Answer 9

Beta Blockers
Cyclic antidepressants
Antiepiletics
CEBs
Botulinum toxin

avg eff = freq decr by 50%
ADRs = wt gain, sedation, mental status ∆s

(2nd line: other anti-sz, ARBs, SNRIs, MAOIs, clonazepam, NSAIDs, methysergide, neuroleptics, herbals)

Question 10

Beta blockers for migraine
—classes w/ examples
—MOA
—ADRs
—Contras

Answer 10

B1&2: PROPRANOLOL, nadolol
B1: metoprolol, atenolol
MOA: ? reduce adrenergic outflow in CNS and PNS
ADRs: fatigue, brady, brochospasm, hi lipids, low BP
Contraindicated: asthma, IDDM (b/c B2 block reduced recov from hypoglycemia)

Question 11

Cyclic antidepressants for migraines
—classes w/ examples
—MOA

Answer 11

Examples:
—TCAs:AMI- and NOR-TRIPTYLINE, doxepin
—Bupropion (fewer sexual & wt. ADRs)
—SNRIs: venlafexine, duloxetine (NOT SSRIs!)
—MOA: central NE, 5-HT

Question 12

AED (Anti-epileptic drugs)
—best two?
—MOA

Answer 12

MOA: messes w/ protein binding (so lots of interactions); ? stops spreading depression

1. valproate (a.k.a. divaproex sodium)
2. topiramate

Question 13

valproate

Answer 13

efficacy good evidence
MOA = reduces CNS excitability
ADRs = hepato, bleeding, n, diarrhea, menstr irreg, tremor, somnolence, wt gain, alopecia,
Interactions = numerous

Question 14

topiramate

Answer 14

efficacy good evidence
MOA = reduces CNS excitability
ADRs = cognitive dysf, somn, nephrolith, paresthesias, wt loss, glaucoma

Question 15

botulinum toxin

Answer 15

Efficacy unclear; *studies not blinded b/c of youthful look =)
MOA = inhib ACh release at NMJ but effect on migraine unknown; ? ∆s scalp trigeminal firing?
ADRs = weakness, rare ANS

Question 16

non-pharm HA tx

Answer 16

—lifestyle: avoid triggers! sleep, diet, exercise
—reverse analgesic rebound
—behav med: decr stress w/ biofeedback, relaxation techn
—manual therapies e.g. massage
—botanical (esp. Mg and Butterbur)

Question 17

options during pregnancy

Answer 17

APAP, oxy (B), NSAIDs in first 2 tri’s, metoclopramide, SSRIs, ?CEBs
—rest, avoid triggers, relax, biofeedback

Question 18

def of analgesia rebound HA

Answer 18

HA 2° to anaglesics use >2d/wk
—MOA = withdrawl receptor ∆s
—common causes = APA, combos, butalbital, opioids, ergots, triptans

Question 19

tx of analgesia rebound HA

Answer 19

d/c meds safe to stop
—taper others
—consider replacement w/ less likely (NSAIDs and some triptans)
—behav/lifestyle/prophylax RX
—hospitalize PRN

Question 20

Case on slide 46

Answer 20

?answer

Question 21

Acute Tension-Type HA (TTH) Tx

Answer 21

—NSAIDs, APAP
—OTC preps like excedrin, midrin
—RX fioricet/fiorinal
—limit use to prevent rebound

Question 22

Prophylactic TTH Tx

Answer 22

TCAs, Beta block, valproate
—physical measures
—behavioral

Question 23

Cluster HA info

Answer 23

—MOST SEVERE —> suicide HAs
—usu. in men, periorbital
—1-2X/d qD for cluster of wks =(

Question 24

Acute Cluster HA cycle

Answer 24

—O2 8L/min
—sumatriptan SC
—DHE IV
—antiemetics IV
—opioids IV
—intranasal lido

Question 25

Prophylaxis/Break Cluster HA cycle

Answer 25

10 day course prednisone

—for few weeks: CEBs, LiCO3, valproate

Question 26

CEBs
—examples
—MOA
—ADRs

Answer 26

—verapamil, amlodipine, diltiazem, flunarizine
—MOA: prevent SMM contract, inflamm and ? 5HT release
—ADRs: edema, low BP, constip

Question 27

Lithium
—MOA
—ADRs
—Follow-up
—Interactions

Answer 27

—MOA: unknown
—ADRs: tremor!!!, nausea, fatigue, QT prolong **Narrow therapeutic window
—Follow blood levels
—Interactions: NSAIDs, diuretics, ACE inhib (incr Li levels), neuroleptics, antidepressants

Question 28

Tx for status migrainosis and intractable HA

Answer 28

—IV DHE x3d
—IV chlorpromazine or prochlorperazine
—sedation: benzos, barbs, propofol