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Flashcards in Pharm - Headaches Deck (75)
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1
Q

What is the most important mediator of headaches?

A

Serotonin

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
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
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
5
Q

Name the migraine specific drugs

A

ergotamine’s and triptans

6
Q

Name the migraine nonspecific drugs

A
  • analgesics
  • antiemetics
  • NSAIDs
  • corticosteroids
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
8
Q

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

A

Analgesics and NSAIDs

9
Q

MOA of NSAIDs

A

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

10
Q

List the analgesics

A
  • Acetaminophen (Tylenol)

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

11
Q

What is the dose of acetaminophen (Tylenol)?

A

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

MAX daily dose 4gm

12
Q

List the NSAIDs

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

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)
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

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

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.

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
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
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
21
Q

Triptans are considered first-line agents for…

A

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

22
Q

List the triptans

A
  • almotriptan
  • eletriptan
  • frovatriptan
  • naratriptan
  • rizatriptan
  • sumatriptan
  • zolmitriptan
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)
24
Q

Which triptans have the slowest onset?

A
  1. frovatriptan***

2. naratriptan

25
Q

What are the combination triptans?

A
  • Treximat: sumatriptan 85mg and naproxen 500mg

- sumatriptan + metoclopramide

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
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
28
Q

Which triptans are metabolized by MAO?

A
  • almotriptan
  • rizatriptan
  • sumatriptan
29
Q

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

A

eletriptan

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

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)