Unit 3 - Pharmacotherapy of Primary Headache Syndromes Flashcards Preview

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Flashcards in Unit 3 - Pharmacotherapy of Primary Headache Syndromes Deck (57):
1

what are primary headaches?

headache itself is the disease
1. migraine (w/ or w/o aura, or other types)
2. tension-type (episodic, chronic, other)
3. cluster (episodic, chronic, paroxysmal hemicrania, other)
4. miscellaneous (idiopathic, external compression, cold stimulus, benign exertion or cough (associated with sex)

2

what are secondary headaches?

headaches are caused by or associated with something else
-head trauma
-vascular disorder (or non-vascular disorder)
-substances
-non-cephalagic infection
-metabolic disorder
-disorder of facial or cranial structures
--cranial neuralgias: trigeminal, occipital, glossopharyngeal
-not classifiable

3

what must one look for in history of headaches? what happens if there are red flags?

-attack onset, duration, timing, and frequency
-pain location, severity, and quality
-associated features
-aggravating, ameliorating, and precipitating factors
-impact, PMH, SH, FH
-caveats: patient may have more than one headache disorder (each receives own diagnosis), but not necessary to Dx each individual headache attack

if there are red flags, it's probably a secondary headache disorder --> run diagnostic tests

4

what is the prevalence of episodic tension-type, migraines, and chronic daily headaches?

ETT: most common (>40% prevalence in men and women)
migraines: 17% prevalent in females, 6% in men
chronic daily: 5% prevalent in females, 3% in men

5

what age group is prevalence of migraines highest?

25-55 age group

6

what are the phases of migraines?

1. prodrome
2. aura
3. headache
4. resolution

7

what is migraine prodrome?

first phase of migraines, in 20% of patients
-occurs hours to days before onset
-change in mental status: drowsy, depressed, irritable, hyperactive, euphoric, talkative
-neurological changes: phono/photophobia, yawning, difficulty concentrating, dysphasia
-general changes: anorexia, food craving, thirst, urination, fluid retention, diarrhea/constipation, stiff neck

8

what is migraine aura?

second phase of migraines (15%) that is defining factor (w/ or w/o aura)
-complex of focal neurologic symptoms (positive or negative) that precedes, accompanies, or follows headache
-duration is anywhere from 4 to 60 minutes
-aura may occur alone, and patients may have more than one type of aura
--visual area is most common, then paresthesias (Jacksonian march typical)

9

what is the headache phase of migraine?

third phase of migraine
-usually unilateral, throbbing, moderate-severe, and aggravated by activity but relieved at rest
--may evolve from unilateral to bilateral and vice versa
-most often starts between 5 AM to noon, and lasts 4-72 hours
--gradual onset (peak 2-12 hours) and resolution
-pain associated with anorexia, nausea, vomiting, osmo/photo/phonophobia (seeks dark quiet room)
--other: blurry vision, nasal stuffiness, diarrhea, pallor, abdominal cramps, diaphoresis, scalp/neck tenderness, lightheadedness, fatigue, irritability

10

what is the resolution phase of migraines?

fourth and last phase
-headache wanes and person may feel tired, washed out, or irritable
-scalp tenderness, impaired concentration, depression
-rarely feel refreshed or euphoric

11

baseline pathophysiology of migraine?

1. strong familial association and early onset of disorder --> genetic component
-familial hemiplegic migraine is the only type of migraine with identified genetic locus (Xm 19p13; Ca channel mutations)
2. "sensitive brain" hyperexcitability leads to susceptibility to migraine
-migraine patients have exaggerated responses to normal stimuli

12

prodrome pathophysiology of migraine

symptoms suggest hypothalamic role, but little else known
-potentially suprachiasmatic nucleus

13

aura phase pathophysiology of migraine?

associated with reduction in cerebral blood flow that moves across cortex at 3 mm/min
-usually begins in occipital lobe
-oligemia not due to vasoconstriction and doesn't respect cerebral vascular territories
--likely result of neuronal dysfunction (cortical spreading depression)
--rates of progression of spreading oligemia, migrainous scotoma, and spreading depression are equal (but unknown how common these changes are)

14

what is cortical spreading depression?

neuronal dysfunction during aura
-precedes vascular changes

15

pathophysiology of headache phase

activation of trigeminovascular system
-dura and meningeal blood vessels are innervated by V1
-during attack, nerve fibers release vasodilating and permeability-promoting peptides from perivascular nerve endings
--promotes "sterile" inflammation that causes increased intracranial mechanosensitivity and hyperalgesia to previously innocuous stimuli (coughing, head movement)

16

what is released by trigeminal nucleus and sensory nerve fibers during migraines? what blocks release?

vasodilating and permeability-promoting peptides
-substance P
-calcitonin gene-related peptide
-neurokine A

release blocked by Triptans (mediate prejunctional 5-HT1b/d receptors)

17

what are the steps to activating the trigeminovascular system?

1. vasodilation
2. neuropeptide release
-causes vasodilation and neurogenic inflammation
3. pain signal transmission
4. central pain transmission

but what exactly activates the system is unknown

18

what are the three types of headache treatment?

1. preventive (prophylactic)
2. behavioral (begin with this)
3. acute (abortive or symptomatic)

can combine all 3

19

what are nonpharmacologic treatments of headache?

-healthy habits: adequate sleep, regular balanced meals, regular exercise, stop smoking, etc.
-psychological factors should be addressed
-psychophysiological Rx: reassurance, stress management, relaxation Rx, biofeedback
-trigger identification and avoidance (but cannot avoid weather-related migraines)

20

what are acute/abortive/symptomatic pharmacological therapies?

used after attack has begun to reverse or stop progression
-treatment is tailored to be specific to patient and characteristics of migraine syndrome (headache severity)
--be aware of PMH, allergies, Rx (current and previous)
--mode of administration depends on headache characteristics and associated N/V (can't give oral)
--statified care preferred over step care

21

what should one give if headaches are mild to moderate?

NSAIDs --> triptans, DHE

22

what should one give if headaches are severe?

oral triptans/DHE --> parenteral triptan/DHE, steroids, Depakote, neuroleptics/opiods

23

what is the difference between nonspecific and specific migraine medications? examples?

nonspecific: effective for migraine and non-headache pain disorders
-NSAIDs, COX2 inhibitors, combo analgesics, neuroleptics, antiemetics, corticosteroids, opioids
-mild/moderate headache intensities, pregnant, children, CV risk, etc.
-overuse of barbiturate-containing can cause drug-induced headaches

specific: effective for migraine, but not non-headache pain disorders
-ergotamines/DHE
-triptans

24

explain "rebound headaches" from medication overdose?

most symptomatic medications, when taken daily, cause "rebound" phenomenon
-caffeine and barbiturate-containing medications and narcotics are leading culprits
-specific migraine medications may also cause regound
-medication overuse is most common cause of chronic daily headaches

25

describe analgesics for migraine

acute, non-specific treatment
-inhibit COX (esp. COX2i)
-aspirin, acetaminophen, naproxen, indomethacin, piroxicam, diclofenac, ibuprofen
--combo of acetaminophen, aspirin, and caffeine (Excedrin) effective in moderate migraine
--acetaminophen preferred in kids b/c danger of Reye's with other NSAIDs

26

describe barbiturates for migraine

acute, non-specific treatment
-never been shown to be effective in RCT
--used only when specific migraine Rx not available or contraindicated
-frequent side-effects are drowsiness and dizziness
--risk of overuse and withdrawal
--limit use to 2-3 treatment days per week

27

describe opiods for migraine

acute, non-specific treatment
-various forms (codeine, merperidine, oxycodone, hydromorphone, morphine, methadone, butorphanol) in oral, parenteral, or transnasal formulations
-high risk for overuse and development of chonic daily headaches (limit to 2 days a week)
-used if pregnant women, or if other treatments not tolerated

28

describe steroids for migraine

acute, non-specific
-various oral and parenteral forms available
-unknown mechanisms
-usually only for brief periods of time in prolonged headache states (only for a couple days)

29

describe ergotamine and dihydroergotamine (DHE) for migraine
-mechanism
-forms
-side effects
-contra-indications

acute, specific treatment
-alpha adrenergic and serotonergic agonist
--DHE is weaker arterial vasoconstrictor, less emetic, and has less effect on uterus
-reduce cell activity in trigeminal pathway (second order neurons in caudal brainstem)
-ergotamine can be combo with caffeine, oral tablet, or suppository
-DHE can be nasal spray, IM, or IV formulation
-maximum 2 days/week usage
-side effects: N/V, chest pain, abdominal pain, dizziness
-avoided in pregnant women, uncontrolled HTN, sepsis, renal/hepatic failure, cerebral/coronary/peripheral vascular disease

30

what is DHE IV mainly used for?

status migrainosus (severe and intractable constant headache state that lasts >72 hours)

31

describe triptans for migraines
-types and mechanism
-what else are they effective for?
-side effects?

acute, specific treatment
-premier migraine abortive medications
-7 possible triptans, differing in onset and duration of action, side effect profile, and formulation
--all penetrate CNS to some extent, thus constricting extracerebral intracranial vessels and inhibiting trigeminovascular system
--5-HT1B/D agonists
-can take more than once without worry of overdose
-reduce photo/phonophobia, N/V, but no evidence that supports use during aura
-avoid in vascular disease, uncontrolled HTN, complicated migraine
-side effects: flushing, tingling, dizziness, chest discomfort (non-cardiac; from esophageal blood vessel spasm; in 4% of patients)

32

how good is the pain relief with triptans in different forms?

80% patients have relief with subcutaneous doses
60% efficacy if oral
-headache recurs in 1/3 of patients

33

what is the only triptan that can be injected?

Sumatriptan

34

what are the triptans that can be a nasal spray?

Sumatriptan, zolmitriptan

35

what are the triptans that are orally disintegrating?

Rizatriptan, zolmitriptan

36

what are the triptans that are oral tablets?

all 7 of them

37

adjunctive treatment for migraines

acute treatment that involves antiemetics and neuroleptics

38

describe preventive treatment of migraines?
-types?
-dosage?

to reduce frequency, duration, and severity of migraine
-long-term, preemptive, and short-term
-most are used at relatively low doses
--increased slowly until therapeutic effects develop, side effects occur, or therapeutic ceiling is reached
-improve response to acute therapies

39

what are requirements for drugs for chronic prevention of migraines?

-recurrent severe migraines > 3/mo
-recurrent mild-moderate migraines >2/wk
-inability to use effective symptomatic Rx
-overuse of acute medications
-patient preference
-special migraine syndromes (hemiplegic, etc.)

40

can preventive treatment for migraines be used during pregnancy?

should be avoided unless severe pain or disability create benefits from medication that overshadow risk

41

what are the major preventive migraine medications?

-antidepressants
-antihypertensives
-antiepileptics
-vitamins/minerals
-NSAIDs and COX2i also included

42

describe antidepressant treatment for migraines?
-types
-names?
-ASE?

preventive treatment (tricyclic antidepressants and SSRIs)

TCA:
-amitriptyline, nortriptyline, protriptyline
--ami: fairly consistent supportive data for efficacy
-ASE: dry mouth, constipation, weight gain, cardiac toxicity, orthostatic hypotension

SSRI:
-fluoxetine, paroxetine, sertraline
-sometimes used to treat coexistent depression and chronic daily headache
-ASE: weight gain, sexual dysfunction

43

antihypertensives for migraine treatment?
-types
-names
-ASE
-contraindications

preventive (beta-blockers and Ca-channel blockers)

BB:
-propranolol (most used), timolol, nadolol, atenolol
--N/A have longer half-life and tolerability, but P/T are FDA-approved
-ASE: drowsiness, depression, decreased libido, hypotension, memory disturbance
-CI: asthma, diabetes, CHF, Raynaud's

CCB:
-Verapamil
-most useful if prolonged or disabling aura (hemiplegic migraine)
-ASE: constipation, dizziness

44

antiepileptics for migraine treatment?
-names?
-ASE

valproic acid: ER divalproex Na is more common and approved
-ASE: sedation, hair loss, weight gain, tremor, cognitive changes
--serious: hepatotoxicity, blood dyscrasias, pancreatitis
--must obtain CBC and LFT (liver function test) at baseline

topiramate: most frequently used AED, FDA approved
-ASE: cognitive changes, paresthesias (commonly fingertips, lips), weight loss
--3% of patients in clinical trials got kidney stones (as metabolized through kidneys)
--acute angle-closure glaucoma rare but potential adverse reaction
--decreases serum bicarbonate levels

45

onabotulinum toxin A (Botox) for migraine treatment?
-administration?
-mech?
-ASE?

FDA approved for chronic migraine (>15x/m for >3mo)
-155 units every 12 weeks in 31 fixed-site, fixed-dose injections with additional max 40 units at physician's discretion
-unknown mechanism (possibly decreases afferent stimulation of trigeminovascular system, downregulation of sensory and parasympathetic receptors, etc.
-ASE: injection site pain, headache post-injection, neck weakness, ptosis (like Horner's) possible
--serious distant spread of toxin effect, dysphagia, dysarthria, or dyspnea not expected

46

what are tension-type headaches?
-definition?
-type of pain?

most common primary headache syndrome
-divided into episodic and chronic (but can evolve from E to C)
-TTH varies widely in frequency, duration, severity
-no prodrome or aura
-dull, achy, non-pulsatile, pressure-like pain (band-like)
--bilateral, mild-moderate in severity (if severe, must be migraine)
--may have neck discomfort or tenderness
--photo/phonophobia and nausea are mild if present at all
--poor sleep is known trigger

47

pathophysiology of TTH?

poorly understood
-initially believed to be (but disproven) due to sustained muscle contraction of pericranial muscles as consequence of stress
-no clear association with depression or anxiety

48

treatment types for TTH?

behavioral, acute, and preventive
-acute: simple analgesics (naproxen, ketorolac, indomethacin) that may be in combo (with opioids, barbiturates, caffeine)
--no role for muscle relaxants for ETTH
-preventive: considered if frequency (>2/wk), duration (>4hr), and severity of ETTH may lead to significant disability or medication overuse
--mainstay for CTTH treatment
--includes TCA (amitriptyline), SSRIs, muscle relaxants (tizanidine), and Botox (into pericranial muscles)

49

what are cluster headaches?

episodic and chronic
-clockwork daily and annual rhythm
-more often in men (4:1), onset 27-31 yo
--14-39-fold increase in risk of cluster in 1st-degree relative
-some patients have heavy facial features (leonine men, masculine women) which may be due to smoking

50

difference between episodic and chronic cluster headaches?

episodic: occurs in periods lasting 7d to 1yr, separated by pain-free periods lasting 1 mo
chronic: attacks occur for >1yr w/o remission or with remissions lasting <1mo

51

what are cluster headache symptoms?

1. severe unilateral orbital, supraorbital, temporal pain lasting 15 min to 3 hr
2. frequency: one every second day to 8 per day
3. associated with: lacrimation, nasal congestion, rhinorrhea, forehead/facial swelling, Horner's, eyelid edema, conjunctivial injection, sense of restlessness or agitation during headache

52

how do cluster headaches differ from migraines?

CH patients are restless when they experience a headache, to the point that they may kill themselves
-peaks very quickly (from when it starts to when it gets worse)

53

cluster headache pathophysiology?

overlaps with migraines
-location of pain implies involvement of opthalmic division of trigeminal nerve
-sympathetic dysfunction and parasympathetic overreaction
-annual rhythm and daily occurence suggest hypothalamic source

54

what are treatments for cluster headaches?

can be acute/abortive or preventive
-patients should not nap during the day, or drink alcohol if experiencing a cluster

55

what are acute therapies for cluster headaches?

since attacks peak quickly, acute treatments must be fast-acting
-O2: high-flow delivered via non-breathing mask effective in 15 minutes
--safe, cost-effective, and portable --> top choice
-triptans: sumatriptan SC also 70% effective in 15 minutes (first-line)
--nasal spray not as effective, as is zolmitriptan nasal spray
-DHE: IM and nasal spray are effective
-anesthetics: local intranasal agents (lidocaine) are limited in effectiveness

56

what are preventive treatments for cluster headaches?

indicated when attacks are too frequent, severe, rapid onset/short-lived, or symptomatic Rx not effective
-for short-term and long-term prevention
--short (21-28-day courses when already experiencing cluster): oral corticosteroids (prednisone, methylprednisone), daily DHE
--long: verapamil, topiramate, divalproex sodium, lithium

57

information on lithium as headache treatment?
-mech
-ASE
-toxicities
-drug reactions

preventive treatment for cluster headaches
-alters circadian rhythms, but its mode of action is unknown
-78% of CCH, 63% of ECH respond
-blood levels necessary to monitor efficacy
-ASE: weakness, nausea, thirst, tremor, lethargy, blurred vision, slurred speech
-toxicity: vomiting, anorexia, diarrhea, confusion, nystagmus, extrapyramidal signs, seizures
-don't use indomethacin or Na-depleting diuretics (increase lithium levels)