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Neurology 2 > Pharm - Headaches > Flashcards

Pharm - Headaches Flashcards

1
Q

What is the most important mediator of headaches?

A

Serotonin

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2
Q

State the goals of long-term migraine treatment

A
  • reduce attack frequency, severity, and disability
  • reduce reliance on poorly tolerated, ineffective, or unwanted acute pharmacotherapies
  • avoid acute headache med escalation
  • reduce headache-related distress and psychological symptoms
  • educate and enable pts to manage their disease to enhance personal control of migraines
  • improve quality of life
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3
Q

State the goals of acute migraine treatment

A
  • treat attacks rapidly and consistently without recurrence
  • restore the patient’s ability to function
  • minimize the use of back-up and rescue medications
  • have minimal or no ADR
  • be cost-effective for overall management
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4
Q

What are the nonpharmacologic measures for migraine?

A
  1. hydration
  2. ice to head; periods of sleep in dark, quiet room; avoidance of triggers
  3. behavioral tx: relaxation training, biofeedback, cognitive-behavioral training (stress-management)
  4. physical tx: acupuncture, cervical manipulation, mobilization therapy
  5. headache diary to facilitate ID of triggers
  6. avoid factors that consistently provoke migraine attack
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5
Q

Name the migraine specific drugs

A

ergotamine’s and triptans

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6
Q

Name the migraine nonspecific drugs

A
  • analgesics
  • antiemetics
  • NSAIDs
  • corticosteroids
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7
Q

Which patients need prophylaxis?

A
  • when a pt begins to experience recurring migraines with significant disability despite acute therapy
  • frequent attacks occurring more than 2x/week with risk of developing medication-overuse headache
  • symptomatic therapies that are ineffective or contraindicated, or produce serious ADR
  • uncommon migraine variants that cause significant disruption and/or risk of permanent neurologic injury
  • patient preference to limit the # of attacks
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8
Q

What are the first-line agents for mild-moderate migraines?

A

Analgesics and NSAIDs

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9
Q

MOA of NSAIDs

A

Prevent neurogenically mediated inflammation in the trigeminovascular system by inhibiting prostaglandin production

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10
Q

List the analgesics

A
  • Acetaminophen (Tylenol)

- Acetaminophen 250mg/ aspiring 250mg/ caffeine 65 mg (Excedrin migraine)

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11
Q

What is the dose of acetaminophen (Tylenol)?

A

1gm at onset; repeat every 4-6 hrs as needed

MAX daily dose 4gm

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12
Q

List the NSAIDs

A
  • aspiring
  • ibuprofen (Motrin)
  • naproxen sodium (Aleve)
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13
Q

What is the dose of naproxen sodium (Aleve)?

A

550-825mg at onset; repeat 220mg in 3-4 hrs; avoid doses > 1.375/day

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14
Q

List the ergot alkaloids and derivatives (migraine specific products)

A

ergotamine tartrate:

  • Cafergot tabs (with caffeine)
  • Ergomar sublingual tab
  • Cafergot rectal supp.

dihydroergotamine:

  • D.H.E. 45 (injectable)
  • Migranal (nasal spray)
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15
Q

What is the dose of ergotamine tartrate (Cafergot) rectal suppository?

A

1/2 to 1 supp. initially, then repeat after 1 hr PRN.
MAX dose 4mg/day or 10mg/week.
-may need to pretreat with anti-emetic

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16
Q

What is the dose of dihydroergotamine (D.H.E 45 injectable)?

A

0.25mg to 1mg at onset IM, IV, of SC.
Repeat every hr PRN.
MAX: 3mg/day or 6mg/week

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17
Q

Ergot alkaloids MOA

A

these drugs are non-selective serotonin (5-HT1) receptor antagonists that constrict intracranial blood vessels and inhibit the development of neurogenic inflammation in the trigeminovascular system.

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18
Q

ADRs of ergot alkaloids

A
  • N/V is the MC
  • abdominal pain, diarrhea, chest pain
  • serious ADR: severe peripheral ischemia (ergotism) with symptoms of cold, numb, painful extremities, continuous paresthesias, diminished peripheral pulses, and claudication.
  • this is a result of vasoconstrictor action of the drug
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19
Q

Ergot alkaloids contraindications

A

DO NOT use triptans and ergot derivatives within 24 hrs of each other!!!!

  • renal of hepatic failure
  • coronary, cerebral, or peripheral vascular disease
  • uncontrolled HTN
  • sepsis
  • pregnancy or breastfeeding
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20
Q

Triptans MOA

A

these drugs are selective agonists of the 5-HT1B and 5-HT1D receptors (varying affinity for 5-HT1A, 5-HT1E, and 5-HT1F). They have 3 actions:

  1. normalization of dilated intracranial AA through enhanced vasoconstriction
  2. inhibition of vasoactive peptide release from perivascular trigeminal neurons
  3. inhibition of transmission through 2nd order neurons ascending to the thalamus
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21
Q

Triptans are considered first-line agents for…

A

mild to severe migraine. Also used as rescue therapy when nonspecific meds are ineffective.

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22
Q

List the triptans

A
  • almotriptan
  • eletriptan
  • frovatriptan
  • naratriptan
  • rizatriptan
  • sumatriptan
  • zolmitriptan
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23
Q

Which triptans have the fastest onset?

A
  1. sumatriptan injection and autoinjector (12-15 min)***
  2. zolimtriptan nasal spray (15 min)
  3. sumatriptan tab (20-30 min)
  4. rizatriptan (1-1.2 hrs)
  5. eletriptan (1-2 hrs)
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24
Q

Which triptans have the slowest onset?

A
  1. frovatriptan***

2. naratriptan

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25
Q

What are the combination triptans?

A
  • Treximat: sumatriptan 85mg and naproxen 500mg

- sumatriptan + metoclopramide

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26
Q

ADR of triptans

A
  • paresthesias, fatigue, dizziness, flushing, warm sensations, and somnolence
  • SC: injection site rxn
  • intranasal: taste perversion, nasal discomfort
  • “triptan sensations”: tightness, pressure, heaviness, or pain in the chest, neck, or throat
  • cardiac: isolated cases of MI and coronary vasospasm with ischemia
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27
Q

Triptan contraindications

A
  • h/o ischemic heart disease
  • uncontrolled HTN
  • cerebrovascular disease
  • avoid in pts who are at high risk for CVD
  • hemiplegic and basilar migraine
  • routine use in pregnancy
  • DO NOT use within 24 hrs of ergotamine derivative
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28
Q

Which triptans are metabolized by MAO?

A
  • almotriptan
  • rizatriptan
  • sumatriptan
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29
Q

Within 72 hrs of using a potent CYP3A4 inhibitor, you should avoid…

A

eletriptan

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30
Q

What is the only opiate analgesic indicated for use in migraines?

A

Butorphanol nasal spray (Stadol)

*only indicated for use in severe migraines

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31
Q

List the antiemetics that can be combined with migraine drugs.

A
  • metoclopramide (reglan)
  • chlorpromazine or prochlorperazine (Compazine)

*administered (orally, rectally, IV or IM) 15-30 min before the pt is given an oral agent to abort an attack

32
Q

List the flow of drugs for mild-moderate migraine

A
  1. analgesics, NSAIDs
  2. combination analgesics (i.e. Excedrin migraine)
  3. triptans
  4. medication combo, rescue therapy
33
Q

LIst the flow of drugs for severe migraine

A
  1. dihydroergotamine or ergotamine tartrate

2. medication combo, rescue therapy

34
Q

Migraine prophylaxis: predictable pattern of headache recurrence

A

NSAID or triptan when symptoms most likely to occur

35
Q

Migraine prophylaxis: healthy or comorbid HTN or angina OR NSAID/triptan was ineffective

A

beta blocker or verapamil if BB is contraindicated or ineffective

36
Q

Migraine prophylaxis: comorbid depression or insomnia

A

tricyclic antidepressant or venlafaxine

37
Q

Migraine prophylaxis: comorbid seizure disorder or bipolar illness

A

anticonvulsant OR BB or verapamil

38
Q

Migraine prophylaxis: other agents ineffective

A

Consider combo therapy or refer to specialist

39
Q

State the goal of prophylactic therapy

A

to reduce or minimize the frequency and severity of migraine attacks (NOT curative).
2/3 will have 50% reduction in frequency of HA

40
Q

Prophylactic agents

-beta-adrenergic antagonists: MOA

A

unknown, but may raise threshold by modulating serotonergic neurotransmission in cortical or subcortical pathways, inhibit NE release, or delay reduction in tyrosine hydroxylase activity (rate limited step in NE release)

41
Q

List the beta-adrenergic antagonists

A
  • propranolol
  • metoprolol
  • timolol
42
Q

What is the dose for propanolol (Inderal)

A

40-160mg/day in two divided doses

43
Q

Beta blocker ADRs

A
  • fatigue
  • depression
  • nausea
  • dizziness
  • insomnia
  • vidid dreams (propranolol)
  • bradycardia
  • impotence
44
Q

Beta blocker contraindications

A

asthma, COPD, CHF (unstable heart failure), peripheral vascular disease, AV conduction disturbances, depression, diabetes.

45
Q

Prophylactic agents

-antidepressants: MOA

A

beneficial effects independent of antidepressant effects
-mechanism related to down-regulation of central 5-HT2 receptors on cerebral vessels, increased levels of synaptic norepinephrine, and enhanced endogenous opioid receptor actions

46
Q

List the antidepressants used for migraine prophylaxis

A
  • amitriptyline (Elavil)

- venlafaxine XR (Effexor XR)

47
Q

What is the dose of amitriptyline (Elavil)?

A

20-50mg at bedtime, start at 10mg d/t sedating effects

48
Q

ADRs of antidepressants

A

Amitriptyline:

  • drowsiness
  • anticholinergic
  • weight gain
  • orthostatic hypotension
  • cardiac toxicity (slows AV conduction)

Venlafaxine XR:

  • N/V
  • drowsiness
49
Q

Migraine prophylaxis

-anticonvulsants: MOA

A

enhance GABA-mediated inhibition, modulation of excitatory neurotransmitter glutamate, and inhibit sodium and calcium ion channel activity.

50
Q

List the anticonvulsants

A
  • valproate (Depakene)
  • divalproex sodium ER (Depakote ER)
  • topiramate (Topamax)
51
Q

Topiramate (Topamax) ADRs

A
  • paresthesias
  • fatigue
  • N/V
  • anorexia
  • abnormal taste
  • word finding difficulties
52
Q

Anticonvulsants contraindications

A
  • avoid in pts with h/o kidney stones
  • pregnancy (valproate) d/t potential teratogenicity
  • h/o pancreatitis
  • chronic liver disease
53
Q

What is the dose for topiramate (Topamax)?

A

25mg daily; titrating up

54
Q

How should you take NSAIDs for prophylaxis?

A

initiate 1-2 days prior to expected onset of HA and continue through usual period of vulnerability

  • evidence is strongest for naproxin
  • used to prevent HA recurring in a predictable pattern, such as menstrual migraine
55
Q

How should you take triptans for prophylaxis?

A
  • frovatriptan has established efficacy

- start triptan 1-2 days before expected onset and continue through period of vulnerability

56
Q

Botulinum toxin for prophylaxis

A

statistically insignificant for episodic migraine, may be some evidence for chronic migraine (onabotulinumtoxin A)

57
Q

Define menstrual related migraines

A

Menstrual related migraine (MRM) or pure menstrual migraine (PMM)

PMM without aura occurring exclusively on days -2 to +3 (first day of menses labeled +1) at least 2 of 3 menstrual cycles without migraine at other times in cycle.
^MRM as above but can occur at other times during cycle

58
Q

Prophylaxis for PMM

A
  • frovatriptan***
  • naratriptan
  • zolmitriptan
  • naproxen
  • estradiol
59
Q

What is the dose for frovatriptan?

A

2.5mg daily or BID (-2 days to +4 days)

60
Q

Why is caffeine added to ergotamine?

A

To enhance absorption and potentiates analgesia

61
Q

Why should you not take triptans and ergot derivatives within 24 hrs of each other?

A

Due to potent vasoconstrictor properties of both drugs.

62
Q

Why should you avoid use of butalbital and opioids in tx of headaches?

A
  • opiates have no vasopressor effect and no anti-inflammatory effect
  • increases risk of med overuse headache and can interfere with efficacy of other treatments
63
Q

What is the goal of prophylaxis for MRM?

A

to eliminate or sufficiently minimize the premenstrual decline in estrogen that precipitates these migraines

64
Q

Products for MRM

A
  • extended cycle estrogen progestin products (LoSeasonique)
  • cyclic estrogen-progestin contraception with supplemental estrogen
  • combined hormonal contraceptives that limit the decline in estrogen
  • menstrually targeted estrogen supplements
65
Q

What is the mainstay of tension-type headache (TTH) treatment?

A

Analgesics and NSAIDs

66
Q

Nonpharmacologic therapy for TTH

A
  • cognitive behavior therapy: stress management, relaxation therapy, biofeedback
  • hot or cold packs, stretching, exercise, acupuncture, manipulations, massage, etc.
67
Q

Goals of therapy for TTH

A
  • pt is pain-free and functioning normally in 2-4 hrs (at most) after tx
  • tx works consistently without routine HA recurrence
  • pt is able to plan their day
  • pt is comfortable with med side effects
68
Q

Meds for TTH

A
  • NSAIDs

- Acetaminophen (1000mg) and aspirin

69
Q

Agents for acute TTH include:

A
  • single dose of ibuprofen 200 or 400mg
  • naproxen sodium 220 or 550mg
  • aspirin 650 to 1000mg
  • single dose of acetaminophen 1000mg if cannot tolerate NSAIDs
70
Q

How do pts avoid medication-overuse headaches?

A

the use of triptans or OTC combo analgesics should be limited to 9 or fewer days a month on average, butalbital-containing analgesics to 3 or fewer days a month, and NSAIDs to 15 or fewer days a month.

71
Q

Therapies for prevention of TTH

A
  • tricyclic antidepressants: amitriptyline 10-12.5mg nightly and increased to 10-12.5mg every 2-3 weeks as tolerated and as needed for sleep until there is improvement in headache or until MAX dose of 100-125mg nightly is reached.
  • botox: uncertain benefit
72
Q

Etiology of cluster headaches

A
  • not common
  • Males 3:1 females
  • > 65% are smokers or have h/o smoking
73
Q

Tx for cluster headaches

A

oxygen

  • triptans (SC sumatriptam 6mg)
  • ergotamine derivatives (IV dihydroergotamine)
74
Q

What is the dose of oxygen for cluster headaches?

A

rate of 12 L/minute for 15-30 min, repeat administration may be necessary

75
Q

Prophylactic therapy for cluster headaches

A
  • verapamil (first-line**)
  • lithium (high ADR)
  • corticosteroids (not used long-term but to induce remission)

Neurology 2 (21 decks)

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