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PMCOL 200 > Lecture 22 - Migraine > Flashcards

Lecture 22 - Migraine Flashcards

1
Q

a primary headache disorder characterized by recurring headaches that are moderate to sever, pulsating in nature, last from 2-72 hours, sensitivity to normal sensory input (makes pain worse), and sometimes nausea/vomiting

A

migraines

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2
Q

~20% of migraines are preceded by:

A

aura (visual disturbances consisting of flashing lights or zigzag lines moving across the field of vision)

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3
Q

migraines are thought to be driven by:

A

cortical spreading depression

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4
Q

a wave of neuronal depolarization followed by desensitization/depression that propogates across the cortex

A

cortical spreading depression

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5
Q

migraine risk is likely due to:

A

genetic and environmental factors

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6
Q

do migraines affect women or men more?

A

women

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7
Q

the increased incidence in women after puberty indicates that _____ may play a role in migraines

A

sex hormones

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8
Q

migraines that involve weakness of half the body, and follow an autosomal dominant inheritance pattern

A

familial hemiplegic migraines

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9
Q

what are the three major genetic mutations associated with familial hemiplegic migraine?

A
  • P/Q type Ca++ channel
  • Na+/K+ ATPase
  • Na+ channel subunit
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10
Q

how do genetic mutations to Ca++ channels, Na+ channels, and ATPases impact migraine prevelance?

A

mutations lower the threshold for cortical spreading depression

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11
Q

the largest cranial nerve

A

the trigeminal nerve (CN V)

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12
Q

what are the three branches of the trigeminal nerve?

A
  • ophthalamic
  • maxillary
  • mandibular
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13
Q
  • senses pain and temperature in the head region
  • innervates the dura mater
  • controls cerebral blood vessels
    these are all functions of the:
A

trigeminal nerve

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14
Q

pain in the head is detected by the _____ of the trigeminal nerve innervating the _____ and associated _____

A

opthalamic branch, dura mater, blood vessels

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15
Q

the cause of migraine is still unkown, but they are thought to be a:

A

neurovascular disease

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16
Q

what three factors provide evidence to the idea that migraines are a neurovascular disease?

A
  • extracerebral vessels dilate during migraine attack
  • cranial blood vessel stimulation provokes headache
  • vasoconstrictor drugs alleviate pain
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17
Q

the release of 5HT leads to:

A

vasoconstriction

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18
Q

migraineurs have low levels of _____ between attacks

A

5HT

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19
Q

true or false: 5HT is released during migraine attacks

A

true

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20
Q

a molecule located in trigeminal peripheral afferents which are released in response to pain and lead to vasodilation

A

calcitonin gene-related peptide (CGRP)

21
Q

true or false: CGRP levels are elevated in those with migraine

22
Q

migraine treatments that are taken daily to prevent attacks

A

prophylactic treatments

23
Q

migraine treatments that are taken once an attack occurs

A

abortive treatments

24
Q

what are the major non-pharmacological prophylactic treatments to migraines?

A

identifying and avoiding triggers (diet, exercise, consistent sleep, avoiding excessive caffeine and alcohol, minimizing stress)

25
what are the major pharmacological prophylactic treatments to migraines?
- beta blockers (propanolol) - anticonvulsants (gabapentin) - antidepressants (amitriptyline)
26
in what cases are pharmacological prophylactic treatments best used?
best for people with very frequent migraines (5+ a month)
27
why might pharmacological prophylactic treatments not be best for people with infrequent migraines?
lots of side effects associated with medications
28
what are the major abortive treatments to migraines?
non-specific analgesics (aspirin, acetominophen, NSAIDs, opioids)
29
what is the risk of using abortive migraine treatments (particularly opioids)?
risk of medication overuse headache
30
are aspirin, acetominophen, and NSAIDs effective at treating migraine pain?
not really (severity of pain is too much for them to handle)
31
caffeine is an:
adenosine receptor antagonist
32
adenosine receptor antagonists lead to:
vasoconstriction and increased absorption of some analgesics (like acetominophen and ergotamines)
33
caffeine can improve migraine treatment during an attack, but may also trigger:
headaches or result in rebound headache (withdrawl)
34
the first specific anti-migraine agents (no longer first line therapy due to risks)
ergot alkaloid
35
ergot alkaloids are agonists for ______ receptors that inhibit ______
5HT-1b/d, neurogenic inflammation
36
what are the major risks of using ergotamines as a migraine treatment?
off-target effects, coronary vasoconstriction (ischaemic changes and anginal pain)
37
the use of ergotamines to treat migraine pain is not recommended in patients with:
peripheral vascular disease, coronary heart disease, uncontrolled hypertension, stroke, etc
38
first line migraine therapy that acts as a selective agonist at the 5HT-1b/d agonist
triptans (sumatriptan)
39
what are the two mechanisms of sumatriptan?
vasoconstriction and inhibition of trigeminal nerve
40
what are the two major types of CGRP inhibitors?
- small molecule CGRP antagonists - monoclonal antibodies to CGRP or CGRP receptor
41
why are CGRP inhibitors being developed as a migraine treatment?
people with migraines have higher levels of CGRP in their brains
42
monoclonal antibodies inhibit CGRP signalling leading to:
vasoconstriction
43
there are several small molecule antagonists to the CGRP receptor that have been approved in the last five years known as the:
gepants
44
why are small molecule drugs normally preferred over antibodies?
- faster and easier to manufacture - less immunogenic risk - better tissue permeability (antibodies are too big) - can be given orally (antibodies must be given via IV)
45
what are the major advantages of developing antibody treatments?
- more selective for targets (less off target effects) - quicker to develop a new antibody than a new small molecule drug
46
a CGRP inhibitor which was efficient at treating migraine, but had poor bioavailability and was abandoned at the Phase II clinical trial
olcegepant (BIBN4096)
47
a CGRP inhibitor which had several Phase III clinical trials supporting anti-migraine efficacy and safety, but issues associated with liver toxicity and was abandoned
telcagepant (MK-0974)
48
CGRP inhibitor which has been approved for market distribution that is effective at treating migraine and has little effect on liver aminotransferase levels
rimegepant (Nurtek)

PMCOL 200 (35 decks)

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