Pharm: Headache (not done yet)

Question 1

What are the 4 phases of migraine?

Answer 1

Prodrome
Aura
Headache
Resolution

Question 2

Gender differences in migraines

Answer 2

Before puberty, slightly more common in boys

After puberty 3:1 ratio of women:men.

Question 3

What is the prodrome of a migraine?

Answer 3

• occurs in 20% of migraineurs
• hours to days before onset of migraine
• psychological, neurologic, constitutional, or autonomic features

Question 4

What is the aura of a migraine?

Answer 4

• a complex of focal neurological symptoms that precedes, accompanies, or follows the headache
• most are 5-20 min and usually less than 60
• may occur w/o headache
• MC is visual, followed by parasthesias

Question 5

What is the headache part of a migraine?

Answer 5

• unilateral, throbbing, moderate-severe
• aggravated by physical activity and relieved by rest
• most often starts between 5 AM- noon
• 4-72 hours
• a/w anorexia, nausea, vomiting, osmo/photo/phonophobia

Question 6

What is the resolution of a migraine?

Answer 6

• headache wanes, person is tired, washed out and irritable

- may have impaired concentration, scalp tenderness, or mood changes

Question 7

Pathophys of migraine baseline

Answer 7

migraine has a strong familial association

Question 8

Pathyophys of migraine prodrome

Answer 8

sx suggest hypothalamic role, but we don’t rly know

Question 9

Pathophys of aura

Answer 9

• a/w reduction of cerebral blood flow that moves across that cortex at a rate of 2-3 mm/min
• not a primary vascular event b/c it’s not due to vasoconstriction and it doesn’t respect cerebral vascular territories
• actually the result of neuronal dysfunction called CORTICAL SPREADING DEPRESSION

Question 10

Pathophys of migraine headache

Answer 10

• activation of trigeminovascular system (trigem nucleus and sensory nerve fibers from opthalmic division of trigem nerve)
• these fibers release vasodilating and permeability-promoting peptides (substance P, calcitonin gene-related peptide) from perivascular nerve endings
• peptides promote sterile inflammation –> pain
• cascade mediated by presynaptic 5HT1B-D receptors

Question 11

Pathophys of migraine treatment

Answer 11

• 5HT1 is a family of inhibitory G protein linked receptors
• Triptans are 5HT1-B agonists which cause vasoconstriction of intracranial extracerebral blood vessels and block inflammation

Question 12

Acute/abortive pharmacologic tx for migraine

Answer 12

• Used after attack has already begun

- Can be specific for migraine or nonspecific (effective for migraine as well as other nonheadache pain)

Question 13

Analgesics for migraine

Answer 13

• some NSAIDS and analgesic better than placebo for mild-moderate migraine: aspirin, acetaminophen, naproxen, indomethacin, piroxicam, diclofenac, ibuprofen
• combo of acetaminophen, aspirin, + caffeine effective for moderate migraine

Question 14

Barbiturates for migraine

Answer 14

• sometimes prescribed, but never been shown to be effective in RPC studies
• side effects: drowziness, dizziness, risk of overuse and withdrawal

Question 15

Opioids for migraine

Answer 15

• several available for migraine: codeine, meperidine, oxycodone, hydromorphone, morphine, methadone, butorphanol
• oral, parenteral, or nasal form
• widely prescribed but high risk for overuse and development of chronic daily headaches
• should not be used more than 2 days a week
• good for situations when other meds are contraindicated

Question 16

Steroids for migraine

Answer 16

• various forms available
• not known how they work
• used for brief periods of time in prolonged headache state

Question 17

Ergotamine and DHE for migraine

Answer 17

• ergot: a-adrenergic and serotenergic agonist
• DHE: weaker arterial vasoconstrictor, less emetic and less effect on uterus
• both act by reducing cell activity in the trigeminovascular system (5HT1b-d agonist)
• DHE IV used for status migrainosus, a severe and intractable headache-state lasting over 72h

Question 18

Triptans

Answer 18

• premier migraine abortive meds
• 5HT1b-d agonists that penetrate CNS, causing vasoconstriction of extracerebral intracranial vessels + inactivation of the trigeminovascular system
• also reduce photo/phonophobia, nausea + vom

Question 19

Preventive migraine tx

Answer 19

• Recommended for people with more than 3 severe headaches/month, more than 2 mild-moderate headaches/week, inability to use effective symptomatic therapy, overuse of acute meds, pt preference

Question 20

Antidepressants for migraine

Answer 20

• TCAS: amitriptyline, nortriptyline, protriptyline

- SSRIS: fluoxetine, paroxetine, sertraline for coexistent depression and chronic daily headache

Question 21

Antihypertensives

Answer 21

• Beta blockers and calcium channel blockers
• Propanalol MC, nadolol + atenolol longer half lives, timolol
• side effects: drowsy, depression, low libido, hypotension, memory probs. contraindicated in asthma, DM, CHF, Reynauds
• Verapamil best for pts with prolonged aura or complicated migraines

Question 22

Anti-epileptic drugs for migraine

Answer 22

• divalproex sodium ER: side effects - sedation, hair loss, weight gain, tremor, change in cognition, hepatotoxicity, blood dyscrasias, pancreatitis
• Topiramate: side effects - changes in cognition, paresthesias, weight loss, kidney stones, acute closed angle glaucoma, decreased serum bicarb

Question 23

Botox for migraine

Answer 23

• FDA approved for chronic migraine (migraine >15 days/month for more than 3 months in the absence of medication overuse)
• 155 units of botox given q12weeks in 31 fixed-site fixed-dose (up to 40 more units at doc’s discretion)
• Adverse effects: distant spread of toxin, dysphagia, dysarthria, dyspnea
• Side effects: injection site pain, headache post injection, neck weakness, ptosis

Question 24

Tension type headache

Answer 24

• MC primary headache syndrome
• Episodic vs. chronic
• No prodrome or aura, pain is dull, achey, non-pulsatile, pressure-like, bilateral, usually mild-moderate in severity, may have neck discomfort
• photo/phonophobia and nausa may be present but mild
• poor sleep is a trigger

Question 25

Pathophys of TTH

Answer 25

- initial belief was that sustained muscle contraction of pericranial muscles as a consequence of stress caused TTH --> this is not true - no association w/ depression/anxiety - some NTs are diff than controls, but we don't know the significance

Question 26

Acute tx of TTH

Answer 26

- Analgesics alone or in combo w/ caffeine, codeine, or anxiolytics --> can cause overuse headache - Naproxen, ketorolac, indomethacin most effective NSAIDS - Combos w/ caffeine, butalbital sometimes effective - Muscle relaxants NOT effective

Question 27

Chronic tx of TTH

Answer 27

- used if more than 2 headaches/week for 4+ hours and severity might lead to disability or med overuse - TCAs followed by SSRIS - maybe muscle relaxants, Botox

Question 28

Cluster headache

Answer 28

- annual rhythm, occur at same time of day, usually after falling asleep - male:female ratio is 4:1, age of onset 27-31 - familial complonent - leonine facies - many are smokers, alcohol and altitude are triggers - SEVERE unilateral pain, pt is restless, a/w ipsilateral lacrimation, nasal congestion, rhinorrhea, facial sweating, miosis, ptosis, eyelid edema, conjunctival injection

Question 29

Episodic cluster headache vs chronic cluster headache

Answer 29

Episodic: periods lasting 7 days-1 year separated by pain free periods lasting 1 month Chronic: more than 1 year without remission or remission less than 1 month

Question 30

Pathophys of cluster headache

Answer 30

- who knows - location implies involvement of opthalmic division of trigem - sympathetic dysfunction and parasympathetic overaction - annual rhythm and daily occurrence suggest hypothalamic source

Question 31

Acute tx for cluster headache

Answer 31

- Oxygen (tx of choice) - triptans - DHE - anesthetics

Question 32

Chronic tx for cluster headache

Answer 32

- short term preventatives: corticosteroids, daily ergotamine - long term: verapamil, topiramate, divalproex sodium, lithium