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Pharm Block 2 > Pharmacology of Headache > Flashcards

Pharmacology of Headache Flashcards

1
Q

For an acute migraine with nausea or vomiting, how should treatment be given?

A

Non-oral routes should be used

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2
Q

What are examples of nonspecific drugs fro acute headaches?

A
  • Analgesics
  • NSAIDS
  • Opioids
  • Neuroleptics
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3
Q

What are examples of simple and combination analgesics?

A
  • Aspirin
  • Acetaminophen
  • Caffeine.
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4
Q

What are examples of NSAIDS used for acute headache?

A
  • Naproxen sodium
  • Ibuprofen
  • Ketorolac
  • Indomethacin
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5
Q

What are examples of opioids used for acute headache?

A

hydrocodone, oxycodone

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6
Q

What are examples of neuroleptics for acute headache?

A
  • Anitidopaminergic
  • Prochlorperazine iv
  • Chlorpromazine iv
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7
Q

What are specific acute migraine treatments?

A
  • Ergotamine (with caffeine, mostly of historical interest)
  • Dihydroergotamine
  • “Triptans”
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8
Q

How does ergotamine work?

A

1) Activates receptors: serotonin, adrenergic, dopaminergic.
2) Suppress neurogenic inflammation ( agonists at
5-HT1B and 5HT 1D receptors)
3) Vasoconstrictors (avoid in CAD)

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9
Q

In what population should ergotamine be avoided?

A

Pregnant women

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10
Q

Describe the kinetics of ergotamine.

A
  • Narrow therapeutic window (nausea, vomiting)
  • DHE with 10 hour half-life.
  • Used mainly iv, im, intranasal.
  • Very effective
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11
Q

How do triptans work?

A
  • Sumatriptan (Imitrex®) the prototype
    • Similar to serotonin but with an amino-ethyl group and a sulfonamide group
  • 5-HT1B (blood vessels) and 5-HT 1D (neurons) agonists.
  • Vasoconstrictors
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12
Q

Describe the efficacy of triptans.

A
  • Efficacy 60-80% at 2 hours

- 40% recurrence in 24 hours.

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13
Q

What are the adverse effects of triptans?

A
  • Chest/neck tightness, flushing, sedation
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14
Q

What contraindications are associated with triptans?

A
  • CAD, stroke
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15
Q

Which triptans have the shortest and longest half lives?

A

Sumatriptan and Rizatriptan => 2 hours

Frovatriptan => 25 hours

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16
Q

Which triptans have the lowest and highest bioavailability?

A

Sumatriptan => 15%

Naratriptan and Almotriptan => 70%

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17
Q

What are the major drug interactions of triptans?

A
  • SSRIs/ SNRIs
  • MAOIs
  • Rizatriptan levels are increased by propranolol
  • Eletriptan/zolmitriptan are metabolized by the cytochrome P450 system
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18
Q

When should preventative management be implemented with migraines?

A

1) Migraine significantly interferes with the patient’s daily routine
2) Acute medications are contraindicated, ineffective, or intolerable adverse effects
3) Frequent headache
4) Uncommon migraine conditions
5) Cost consideration
6) Patient preference (fear of migraine)

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19
Q

What are major pharmacologic prevention of migraines? (don’t memorize this list)

A

1) Beta-blockers
2) Antidepressants
3) Anticonvulsants
4) Calcium channel drugs
5) Botulinum toxin
6) ARBs
7) ACE inhibitors
8) NSAIDs
9 ) Methysergide (currently unavailable, methylergonovine is major metabolite)
10 )Vitamin B2, magnesium, coenzyme Q10, butterburr

20
Q

What are level A preventive drugs (A= good evidence of prevention)?

A
  • Divalproex sodium
  • Topiramate
  • Metoprolol
  • Propranolol
  • Timolol
  • Frovatriptan
    • For short-term prophylaxis of MRM(menstrually-related migraine)
21
Q

What are level B preventative drugs (B = some evidence of prevention)?

A
  • Amitriptyline
  • Venlafaxine
  • Atenolol
  • Nadolol
  • Naratriptan and zolmitriptan
    • For short-term prophylaxis of MRM
22
Q

What beta blockers have FDA indication for migraine?

A

Propranolol and timolol have FDA indication.

- Some use atenolol, metoprolol, nadolol.

23
Q

Beta blockers for migraine are also good/bad in which conditions?

A

Good for:
- MVP, HTN, anxiety, tremor

Bad for:
- Bad if depression, Raynaud’s, fibromyalgia, asthma

24
Q

Which antidepressant has the best evidence as an anti-migraine treatment?

A

Amitriptyline

25
Q

What are the adverse drug effects of amitriptyline?

A
  • Weight gain, sedation, dry mouth, orthostatic hypotension, cardiac arrhythmias
    • Watch long QT on EKG
26
Q

What is amitryptyline particularly good for?

A
  • Good choice for sleep disturbance, neck pain, TTH
27
Q

What are the adverse effects of topiramate?

A
  • Weight loss, cognitive difficulty, acute glaucoma, nephrolithiasis, paresthesia
28
Q

How does topiramate work?

A

Reduces firing of neurons in the TNC

29
Q

Topiramate is best used in what type of migraine?

A

Best evidence of efficacy in chronic migraine

30
Q

How does valproate work?

A
  • Enhances GABA activity
  • Reduces excitatory neurotransmission
  • ## Reduces the firing rate of midbrain 5-HT neurons
31
Q

What is the major precaution in valproic acid usage?

A
  • Watch out in pregnant women

- Approximately 1% risk of spina bifid a (not used in women of reproductive age)

32
Q

What calcium channel antagonist is used in migraine treatment?

A

Flunarizine most effective (not available in the US)

33
Q

What are the adverse effects of calcium channel antagonists?

A
  • Constipation (verapamil), heart block

- Depression, weight gain, extrapyramidal side effects (flunarizine)

34
Q

What are the (broad) mechanisms of action of preventative migraine treatments?

A
  • Inhibit peripheral and central sensitization
  • Block neurogenic inflammation
  • Inhibit cortical spreading depression
  • Enhance antinociception
35
Q

Which drugs raise the threshold for initiation of CSD (cortical spreading depression)?

A

Amitriptyline, propranolol, valproate, topiramate, methysergide

36
Q

What is the indication for Botox?

A

Botox injection is indicated for the prophylaxis of headaches in adult patients with chronic migraine (15 or more days/month)
- Doesn’t work in episodic migraine

37
Q

Describe the action of the heavy chain of botulinum toxin.

A

Heavy chain binds to cholinergic nerve terminals

  • Allows internalization at the nerve terminal
  • L light chain cleaves SNAP-25,
  • Prevents exocytosis of ACh
38
Q

What is the mechanism of action of botulinum toxin?

A
  • Prevents release of ACh (also affects neurons that release pain transmitters)
  • Prevents glutamate release (and CGRP and substance P co-localize with glutamate)
  • Prevents CGRP release
39
Q

What side effects are associated with Onabotulinumtoxin A (Botox-used for migraine prophylaxis)?

A
  • Neck pain/weakness, ptosis, diplopia, a “Spock” eyebrow, flu-like illness
  • All side effects are transient
40
Q

What are effective (grade A) non-pharmacologic treatments?

A
  • Relaxation training
  • Thermal biofeedback with relaxation training
  • EMG biofeedback
  • Cognitive behavioral therapy
    • all complementary with pharmacologic treatments
41
Q

What drugs are used in pediatric migraine?

A
  • Acute-acetaminophen, ibuprofen, sumatriptan nasal spray (>12yo).
  • Utility of antiemetics (remember children may be more prone to dystonic reactions)

*Avoid aspirin (Reye syndrome).

42
Q

What drugs should be avoided in pregnant women?

A

Avoid drugs to the extent possible.

  • Many patients (50-80%) improve
  • Usually migraine without aura/MAM by the end of the first trimester
43
Q

What are secondary causes of headache in pregnant women?

A
  • Venous sinus thrombosis
  • Stroke
  • Pituitary tumors
  • Eclampsia
44
Q

Which drugs are useful in pregnant women?

A
  • Acetaminophen (po and pr)
  • NSAIDS until week 32 (effect on ductus arterioles)
  • Antiemetics (prochlorperazine, promethazine)
  • IV hydration
  • Metoclopramide
  • Magesium
  • Steroids
  • Occipital nerve blocks
45
Q

Generally how should headaches be treated in pregnant women?

A
  • Avoid drugs and prophylactic drugs if possible
  • Don’t forget anti-pharmacologic therapies
    • pay special attention to drug infiltration of breast milk

Pharm Block 2 (15 decks)

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