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Pharmacotherapeutics - Fall 21 > Pharmacotherapy of HAs-french > Flashcards

Pharmacotherapy of HAs-french Flashcards

1
Q

Medication overuse HA can result from _______

A

overuse of analgesics in tx of migraine or tension headache

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2
Q

Medication overuse HA is defined as a dull or migraine-like HA that occurs at least ____ days/month

A

15 days/month

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3
Q

Ex’s of Risks for developing medication overuse HA:
-highest risk associated with which medication clas?

-lowest risk assoc. with ?

A

1 in 25 over use pain meds–> 1 in 4 of these –>MOH

High risk: butalbital combos, ASA-acetaminophen-caffeine, opioids

Moderate: -triptans, ergot alkaloids

Low: NSAIDs

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4
Q

Preventative measures for medication overuse HA

A
  • Restrict drug use (per attack - per week - per month)

- Initiate prophylactic therapy as necessary

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5
Q

Describe the Simplified Pathophysiology of Migraine(with or without aura)

A

Trigeminal Neurovascular Dysfunction–>

    • Trigeminal Neurovascular Activation–>
    • Release of Vasoactive Peptides (CGRP)–>
  • Neuroinflammation (including PG release)
    • Vasodilation of Pial and Dural Vessels–> Mod to severe pain***
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6
Q

Target of NSAID analgesics–>

A

COX-2 inhibitors

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7
Q

Target of triptans-ergot alkaloids=

A

5HT 1B-1D agonists

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8
Q

Role of Spreading Cortical Depression= (describe)

A

=self-propagating wave of neuronal and glial depolarization hypothesized to:

–Cause the aura of migraine

–Activate trigeminal afferents

–Alter BBB permeability via changes in metalloproteinases

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9
Q

Role of Trigeminovascular System=

A

sensory neurons that project to cerebral and pial vessels and to dura mater

–Activation releases vasoactive peptides (SP-CGRP)–> Neurogenic inflammation–> Vasodilation and plasma protein extravasation

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10
Q

________ has role in prolongation and intensification of migraine pain (sensitization)

A

Inflammation

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11
Q

Role of Sensitization: likely responsible for many migraine clinical symptoms
–list ex’s of some of these clinical sx

A

Throbbing quality of pain

Worsening of pain with coughing-bending-sudden head movements

Hyperalgesia

Allodynia

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12
Q

Role of Serotonin (5-HT):

agonists of 5HT receptors are an important component in ____ treatment

A

**Acute–BUT role in generation of migraine unclear

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13
Q

slide 8

A

?

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14
Q

Neurotransmitter in diffuse CNS systems that has a role in migraine pathophysiology and is a primary target for pharmacotherapy:

?

A

serotonin

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15
Q

Pt with severe HA symptoms presents to the ED–> with N/V:

-treatment?

A

-SC sumatriptan
IV metaclopramide (or prochlorperazine)
+diphenhydramine for **dystonia ADRs

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16
Q

Which of the following would be a reasonable choice for initial treatment of a mild migraine attack without nausea or vomiting in a 28-year-old nonpregnant woman?

  • Acetaminophen
  • Butalbital/acetaminophen/caffeine
  • Oxycodone/acetaminophen
  • Ergotamine
A

A. acetaminophen or an NSAID

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17
Q

The drug of choice for treatment of moderate to severe migraine is:

  • Aspirin
  • A triptan
  • An ergot
  • Onabotulinum toxin A
A

triptan

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18
Q

“Triptans” (5HT1B/D Agonists) - Sumatriptan:

-MOA in migraine? (3 things)

A
  • Cerebral vasoconstriction –> reverse dilation-induced HA
  • Inhibit neuropeptide release–> DECREASES vasodilation, pain, neuroinflammation

Prevent activation of pain fibers in trigeminal nerves

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19
Q

T/F: do triptans differ in onset and duration?

A

YES.

-sumatriptan: onset=30-60 min, and 3-4 hr duration

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20
Q

Orally administered short-acting triptans have an onset of action of about:

  • 5-10 minutes
  • 15-30 minutes
  • 30-60 minutes
  • 60-90 minutes
A

30-60 min

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21
Q

Which of the following triptan formulations has the fastest onset of action?

  • Almotriptan tablets
  • Naratriptan tablets
  • Zolmitriptan nasal spray
  • Frovatriptan tablets
A

Zolmitriptan nasal spray (10-15 min)

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22
Q

Compared to oral sumatriptan, the subcutaneous formulations:

A

?

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23
Q

Triptans: ADRs?

(are they well tolerated?

A
  • Generally well tolerated if no CVS conditions and 24 hr limits observed - **pregnancy category C
  • Paresthesias, flushing, dizziness, drowsiness, chest tightness (increased with sumatriptan)
  • **Rarely: coronary vasospasm, angina, MI, arrhythmia, stroke, death
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24
Q

Triptans: DDIs

-Additive vasoconstriction with ________

A

-ergot alkaloids

-

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25
Q

Triptans: DDIs

-Increased risk of serotonin syndrome** with ______ - risk very much less with SNRIs-SSRIs

A

MAOIs

-**Neuromuscular effects (clonus), ANS changes, mental status changes (agitation, delirium, hypervigilance

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26
Q

“Ditans” (5HT1F Agonists): Lasmiditan

-MOA in migraines?

A

-5HT1F Agonist

–>Similar to triptans, but selective agonist activity on 5HT1F receptors

Unlike triptans, use is NOT contraindicated in patients with vascular disease

No direct comparisons with triptans or “gepants”

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27
Q

“Ditans” (5HT1F Agonists) - Lasmiditan

  • Absorption?
  • metabolism?
A

Absorption: given orally reaches a Tmax at 1.8 hrs

Metabolism: Via hepatic and extra-hepatic enzymes primarily by non-CYP enzymes - half-life ~ 6 hours

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28
Q

Lasmiditan ADRs are _______ related

-list ex’s of ADRs?

A

**incidence is dose-related

CNS-related S/E MC: dizziness, sedation and paresthesias

  • Label warning against driving or operating machinery for at least 8 hours after taking drug
  • Decreases in heart rate have occurred – use with caution with other HR-lowering drugs
29
Q

Lasmiditan: DDIs ?

-caution in concomitant used of _______

A
  • alcohol or other CNS depressants

- Use with other serotonergic drugs may increase risk for serotonin syndrome

30
Q

“Gepants” (CGRP Receptor Antagonists)

Urbegepant - Rimegepant: MOA in migraines?

A
  • ->Small molecule antagonists that bind to calcitonin gene-related peptide (CGRP) receptor
  • -CGRP is a neuropeptide widely distributed but especially common in trigeminal ganglia
  • -Potent vasodilator and pain-signaling transmitter
31
Q

Are geptants more effective than triptans?

A

NO, they are less effective than triptans, BUT they can be used in Pts with vascular disease

–Rimegepant is also approved for migraine prevention given every other day

32
Q

“Gepants” (CGRP Receptor Antagonists)–>Urbegepant/ Rimegepant

  • Given orally–> they begin reducing migraine pain within _____ min
  • half-life?
A

-60 min

Half-life: rimegepant ~ 11 hours – urbogepant ~ 6 hours

Metabolized by CYP3A4 – avoid use with inhibitors or inducers; also P-glycoprotein substrate

33
Q

“Gepants” (CGRP Receptor Antagonists)–>Urbegepant/ Rimegepant

-ADRs?

A

generally well-tolerated

Nausea and somnolence in less than 5% of patients

-NOT associated with medication overuse headache

34
Q

Ergot Alkaloids - Ergotamine-DHE

MOA in Migraine?

A

=5HT1B/D Agonist

  • Similar to triptans, somewhat less effective, affect multiple receptors
  • **More toxic - NOT first-line
  • Try if no response to triptans, prolonged attacks, or frequent recurrence
35
Q

Pharmacokinetics: Ergotamine

oral absorption?

A

Ergotamine: Oral (INCREASED absorption w/caffeine) - SL - PR; long duration

Dihydroergotamine: Intranasal-parenteral; rapid and reliable onset

36
Q

Ergot Alkaloids: ADRs?

A
  • Nausea / vomiting (give w/antiemetic), diarrhea, cramps, paresthesias
  • Serious effects: vascular occlusion and gangrene (strict dosage limits)
  • **Mediated via α1 adrenergic vasoconstriction
37
Q

Ergot Alkaloids: DDIs ?

-SEVERE peripheral ischemia can occur if used with _______

A

non-selective (β1-β2) beta-blockers

38
Q

Which of the following statements is true?

  • The combination of ergotamine and caffeine is safer and more effective than a triptan for acute treatment of migraine
  • Patients who do not respond to a triptan alone should take both a triptan and an ergot
  • Dihydroergotamine may be effective in some patients who do not respond to a triptan
  • All of the above
A

-Dihydroergotamine may be effective in some patients who do not respond to a triptan

39
Q

A 35-year-old woman with severe episodic migraine attacks with nausea and vomiting asks about switching from sumatriptan oral tablets to the nasal spray formulation. You should tell her that:

  • Intranasal sumatriptan generally starts relieving pain in about 10-15 minutes
  • Intranasal sumatriptan can have an unpleasant taste
  • Sumatriptan nasal spray is partially absorbed in the GI tract, and absorption of the drug could be reduced in patients with vomiting
  • All of the above
A

ALL the above

40
Q

Which of the following drugs should not be used for treatment of migraine in patients with vascular disease?

Lasmiditan
Zolmitriptan
Ubrogepant
Ibuprofen
All of the above
A

Zolmitriptan??

41
Q

Non-Opioid Analgesics[tNSAIDs)

-list Ex’s

A

-Acetaminophen-Celecoxib-Aspirin]

42
Q

NSAIDs MOA in migraines?

A

**Inhibition of COX-2

Interrupts neuroinflammatory pathway initiated by release of CGRP (Calcitonin Gene-Related Peptide)

May be sufficient for migraines of mild-moderate intensity

43
Q

Therapy for migraine prevention would be considered if:

Headaches are severe
Headaches don’t respond to opioid therapy
Patient cannot tolerate NSAIDs
Patient has a contraindication to acute vasoconstrictor therapy
Headaches last longer than 2 hours
Headaches are disabling

A

??

44
Q

NSAIDs:

-which form is used most often>

A

Oral route used most commonly – indomethacin available as suppository

Durations of action range from 4-6 to 8-12 hours

45
Q

Non-Opioid Analgesics (tNSAIDs): ADRs?

which Pts should avoid them?

A

Generally well tolerated

–Should be avoided in patients with acute gastritis, peptic ulcer disease, renal insufficiency, or bleeding disorders

46
Q

Non-Opioid Analgesics (tNSAIDs): DDIs?

-increased bleeding risk in Pts receiving _______

A

antiplatelet agents (clopidogrel-prasugrel) or anticoagulants (warfarin)

47
Q

Isometheptene MOA: ?

A

Elicits sympathomimetic effect; constricts dilated cerebral/cranial arterioles

48
Q

Dichloralphenazone MOA?

A

Elicits mild sedative effect; reduces emotional response to painful stimulus

49
Q

Acetaminophen MOA?

A

Inhibits prostaglandin synthesis in CNS - decreases sensitization

50
Q

When are prophylactic meds indicated for Pts suffering from migraines?

A

-If migraines are severe, frequent (> 4/month), long lasting (> 12 h), or disabling**

51
Q

Drug factors that may indicated the need for a Pt to be started on Prophylactic meds for migraines

A

Failure or overuse of acute therapies

Contraindications to vasoconstrictor therapies

Occurrence of adverse drug events

52
Q

Prophylactic Management of Migraines: MOA

  • which meds are TOC?
  • how much time is needed before effects are seen?
A

no single medication as treatment of choice

**Generally requires 3-4 weeks for benefit

Trial of 4-6 weeks recommended before switching

Migraines may improve independent of treatment - consider slow taper off if good control

53
Q

Therapy for migraine prevention would be considered if:

Headaches are severe
Headaches don’t respond to opioid therapy
Patient cannot tolerate NSAIDs
Patient has a contraindication to acute vasoconstrictor therapy
Headaches last longer than 2 hours
Headaches are disabling

A

?

54
Q

For migraine prevention, beta blockers should be used with caution or not be used at all in patients who have:

Asthma
Depression (comorbidity - may be aggravated)
Decompensated heart failure
All of the above

A

All of the above

55
Q

What role does BP have in migraine tx?

A

BP treatment appears to reduce the overall prevalence of headaches –> likely to be effective for migraines also

56
Q

which BBs are approved for prophylactic tx of migraines?

A

Beta blockers - **propranolol-timolol FDA-approved for prophylaxis (metoprolol-atenolol-nadolol also used)

  • BBs are commonly used for continuous prophylaxis
  • **Propranolol reduces frequency and severity of migraine in 60-80% of patients
  • Less enthusiasm for use in patients >60 yo or smokers
57
Q

Which CCB can be used for migraine prophylaxis tx?

A

verapamil, diltiazem, nifedipine

**Verapamil MC used, evidence for effectiveness is limited

ACEIs [lisinopril] / ARBs [candesartan]–> Small studies show decrease in migraine frequency

58
Q

which TCAs are approved for tx of migraines?

A
  • **Amitriptyline, venlafaxine (SNRI), nortriptyline
  • Postulated mechanism in migraine is uncertain
  • [?] Enhancement of monoamine neurotransmission in brain pain pathways
  • Can prevent migraine in some Pts and may be given concurrently with other prophylactic meds
59
Q

About what percentage of patients achieve a ≥ 50% reduction in migraine headache frequency when taking topiramate or valproate for migraine prevention?

20%
50%
75%
90%

A

50%

60
Q

which anticonvulsants are FDA approved for migraine proph?

A

**Valproate and topiramate – FDA approved for migraine prophylaxis (gabapentin also effective)

  • Postulated mechanism in migraine is uncertain - [?] alteration of neuronal transmission in CNS
  • Reduce migraine frequency by > 50% in 50% of patients - similar to propranolol
61
Q

Erenumab (Aimovig®) - new in 2018

-MOA?

A

=Human monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) receptor

-CGRP is a neuropeptide widely distributed but especially common in trigeminal ganglia

–Potent vasodilator and pain-signaling transmitter

-*Once-monthly SC injection reduces migraine frequency - may be effective when other therapies failed

62
Q

Erenumab (Aimovig®):

-Adverse effects?

A

similar to placebo

Injection site reactions (5-6%) - constipation (1-3%)

Long-term efficacy and safety unknown, esp. in patients with cardiac risk factors

63
Q

A 31-year-old woman with a history of frequent severe migraine attacks has been taking valproate for 3 years for migraine prevention. She tells you that she is planning to become pregnant in the near future. You should:

  • Increase her dose of valproate because serum levels of the drug decrease significantly during pregnancy
  • Switch her to topiramate because it is safer for use during pregnancy
  • Switch her to dihydroergotamine nasal spray taken once weekly during pregnancy
  • Discontinue valproate because it can cause congenital malformations
A

Discontinue valproate because it can cause congenital malformations

64
Q

Botulinum Toxin Type A (Botox®):

-can this be used for migraine tx?

A

**Recent evidence trials supports use in chronic migraine if ≥ 15 HA days per month, lasting at least 4 hours

-2nd line agent, high cost

65
Q

Botulinum Toxin Type A (Botox®): Adverse effects?

A

Headache, neck pain

Generalized muscle weakness, drooping eyelids

Category C in pregnancy

66
Q

Nonsteroidal Anti-inflammatory Drugs (NSAIDs):

  • Ex’s for migraine tx?
  • used for _______
A

Naproxen and flurbiprofen

-**Short-term prevention of migraine (e.g., menstrual migraine), as well as for aborting acute attacks

67
Q

Methysergide (limited availability in U.S.): what is the MOA?

A

Serotonin receptor antagonist - 5HT2 blocker

Blocks serotonin-mediated vasoconstriction that initiates the migraine attack

Role in refractory migraine with high attack frequency

Effective, but side effects and insidious toxicity limit use (reserved for severe cases if other drugs not effective)

68
Q

Agents that can be used for migraine headache prophylaxis include:

Amitriptyline
Botulinum toxin type A
Sumatriptan
Lisinopril
Verapamil
Dihydroergotamine
Ibuprofen
Diphenhydramine
Valproic acid
A

Amitriptyline?

Pharmacotherapeutics - Fall 21 (7 decks)

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