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Pharmacology > !Neuropharm Migranes > Flashcards

!Neuropharm Migranes Flashcards

1
Q

LO

A

Classify pharmacological agents used in the treatment of migraine as therapeutic or preventative and select the best drug for clinical scenario

  • select an appropriate triptans for use in the treatment
  • infer side effects or ergot alkaloids from their mechanisms of action
  • recognize appropriate drug combinations useful for te treatment of migraine
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2
Q

What triggers migraines

A

Glare, bright lights, sounds, hunger, let down forms tress, physical exertion, stormy weather or barometric pressure changes, hormonal fluctuations during menses, lack of or excess sleep, alcohol or other chemical stimulation

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3
Q

Classic migraine vs common

A

Classic has mini headache before?

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4
Q

What is the course of a migraine attack

A

Prodrome, headache, postdrome

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5
Q

What can be used to treat prodrome

A

Triptans, ergot alkaloids

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6
Q

What is used to treat the headache

A

NSAIDS

Acetaminophen

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7
Q

What are preventative agents used for

A

Limit frequency and severity of attack

Treat asymptomatic phase, before the prodrome

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8
Q

What are preventative agents

A

B blockers
Tricyclic antidepressants
Anticonvulsants
Ca channel blockers

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9
Q

Name ergot alkaloids

A

Dihydroergotamine (DHE)

Ergotamine+caffeine

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10
Q

Name triptans

A 
Sumatriptan
Almotriptan 
Naratriptan
Zolmitriptan
Riatriptan
Electric tan
Frovatriptan
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11
Q

Name B blockers

A

Propranolol

Timolol

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12
Q

Name tricyclic antidepressants

A

Amitriptyline

Imipramine

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13
Q

Name anticonvulsants

A

Topiramate

Valporate

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14
Q

Name Ca channel blocker

A

Verapamil

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15
Q

Botros for migraines MOA

A

Acts on motor neurons to reduce muscle activity by cleaving SNAP-25 in motor neurons, which inhibits acetylcholine release at the motor end plate

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16
Q

What is Botox prescribed for

A

Chronic migraine

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17
Q

What is a chronic migraine

A

Fifteen or more days each month with headache lasting 4 or more hours each day in people 18 or older

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18
Q

Neurovascular headache

A

Neural events result in the dilation of blood vessels

Results in pain and further nerve activation

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19
Q

Meninge sense pain?

A

They are innervated by trigeminal axons

When stimulated by vasodilation they generate throbbing unilateral migraine like pain

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20
Q

Calcitonin gene related peptide migraine CGRP

A

Released from trigeminal ad-fibers which increases dural vessel vasodilation

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21
Q

Substance P and neurokinin A migraine

A

Released from trigeminal C fibers and increase dural vessel permeability

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22
Q

Neurogenic inflammation theory of migraine

A
  • a wave of electrical activity and H/K pass through nerve cells
  • stimulates the release of neuropeptides (CGRP and Substance P) and inflammation (NO, histamine, and prostsagladins)
  • leads to dilation of cranial blood vessels and sensitized nerve to pain
  • sensitization spreads from periphery to the brain
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23
Q

CGRP and NO interact throughout the __ __ __

A

Trigeminal neurovascular system

At the cranial dura mater, trigeminal ganglion, and spinal trigeminal nucleus

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24
Q

___ ____ used to treat coronary artery disease can provoke migraine. How

A

Organic nitrates

At cranial dura mater, trigeminal ganglion, and spinal trigeminal nucleus

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25
Q

Brainstem dysfunction sparks a wave of excitation and depression in cortex-___ ___ ___

A

Cortical spreading depression

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26
Q

What does cortical spreading depression lead to

A

Cerebral vasoconstriction

Accompanied by H, K, and NO discharge from neurons

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27
Q

Dilation of cranial arteries-depolarization of perivascular trigeminal terminals

A

Electrolytes and NO dilate cranial arteries and depolarize perivascular trigeminal terminals

CGRP and neuropeptides release promotes neurogenic inflammation

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28
Q

Neurogenic inflammation irritates trigeminal nerve and transmits migraine pain

A

Pain is associated with inflammation and dilation of the meninges
CGRP and substance P act together to produce painful dural infalmmation

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29
Q

Cranial vessels and presynaptic trigeminal nerve terminals express a subset a serotonin receptors

A

5HT-1B on cranial vessels

5HT-1D peripheral neuron

5HT-1B/1D central neuron

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30
Q

Serotonin and its receptors modulate CGRP actions

A

5HT-1B receptor vasculature

5HT-1D receptor synaptic

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31
Q

Vascular 5HT-1B receptor for CGRP

A

Dilation bv

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32
Q

Synaptic 5HT-1D receptor forCGR????????????

A

Pain

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33
Q

What are triptans

A

Selective serotonin 5HT1B/1D receptor agonists

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34
Q

What do tripatans stop

A

Pain and dilation

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35
Q

What happens when triptans bind 5HT1B receptors on vascular smooth muscle

A

Vasoconstriction of dilated meningeal, dural and pail blood vessels

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36
Q

What happens when triptans bind to 5HT1D receptors on presynaptic nerve terminals

A

Inhibits presynaptic release of CGRP and other neuropeptides from the peripheral end of the trigeminal nerve

37
Q

Triptans binding to 5HT1D receptors on the trigeminal nucleus in the brainstem does what

A

Modulates incoming painful sensory information from the periphery

Inhibits upward transmission of painful sensory information to the thalamus and higher brain centers where pain is perceived

38
Q

Sumatriptan Cmax

A

PO-1-2 hours
Nasal spray-30 min
SC-15 min

39
Q

Sumatriptan clearance

A

T1/2-1-2 hours

Metabolized by monoamine oxidase A

40
Q

Sumatriptan is an ____

A

Indoleamine

Similar structure to serotonin and melatonin

41
Q

What does sumatriptan help

A

Persistent pain, nausea, and photophobia

42
Q

What triptans have better tolerance and claims of between efficacy relative to sumatriptan

A

Rizatriptan

Eletritpan

43
Q

Name other triptans

A 
Almotriptan
Naratriptan
Zolmitriptan
Rizatriptan
Eletriptan
Frovatriptan
44
Q

Naratriptan bioavailability

A

70%

T1/2 is 6 hours

45
Q

Zolmitriptan

A

Active metabolite is a 5HT1D agonist

46
Q

Frovatriptan half life

A

24 hours

47
Q

Oral oral triptans

A

Easy to take

Ineffective if patient vomits

48
Q

Nasal spray triptans

A

Effective with nausea/vomiting, simple works quickly

-few triptans formulated as nasal sprays

49
Q

Injection of triptans

A

Works quickly

Inconvenient

50
Q

Delivery sumatriptan

A

Injectable, nasal spray, tablets

51
Q

Zolmitriptan routes

A

Orally disintegrating tablets, nasal spray, tablets

52
Q

Does clinical failure with one triptans forecast clinical failure with all triptans in a particular patient

A

No

53
Q

Shoul a doctor prescribe a different triptans if the first one he/she tried did not relieve pain in a particular patient

A

Yes

54
Q

Subcutaneous injection with fastest onset-for immediate relief

A

SQ Sumatriptan injection is fastest

Second fastest is nasal spray of sumatriptan, zolmitriptan

55
Q

What triptans has longest HL is patient needs long duration of migraine

A

Frovatriptan has a 24 hours HL

56
Q

What triptans can not be used with MAO inhibitors

A

Sumatriptan, rizatriptan, zolmitriptan

57
Q

What medications may make a patient at risk for serotonin syndrome if taken with triptans

A

Selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, serotonin dopamine reuptake inhibitors, linezolid

58
Q

Who are triptans contraindicated in

A

History or suspicion of ischemic or vasospastic coronary disease, or other significant cardiovascular disorder

Uncontrolled HTN

59
Q

Why cant triptans be used with heart vascular issues

A

They are all vasoconstrictors of coronary and renal vessels

60
Q

What are all triptans vasoconstrictors

A

5HT1B/D

61
Q

33 yo male presents with substernal chest pain. He had headaches for 2 weeks he took 20 tablets in 5 days of cafergot (ergotamine tartate 1 mg an caffeine 100mg) which helped then he took more to make a total of 34. Within two minutes he noted tingling in his forehead and the onset of substernal pressure. He vomited, substernal pressure, increased breathing and pulse. Pupils and eye movements are ok. No increase in ICP. Inversion of T wave, ST segment elevations, biphasic T waves . Start nitroglycerin was started and the pain resolved. Had anteroseptal and inferior MI

A

Yikes

62
Q

Central effects of ergotism

A

Agitation, cerebrovascular ischemia, hallucinations, headaches, miosis, nausea, seizures, twitching , vomiting

63
Q

Peripheral calinical manifestations of ergotism

A

Bradycardia

64
Q

Clinical manifestation of ergotism ischemic effects

A 
Angina
Gangrene
Hemorrhagic vesiculations and bullae
Mesenteric infarction 
Myocardial infarction 
Renal infarction
65
Q

Duhydroergotamine MOA

A

Binds 5HT 1B, 1D, and 1F and adrenergic receptors, dopamine receptors

66
Q

What happens when dihydroergotamine binds to peripheral a1-adrenergic receptors

A

Causes worse vascular vasoconstriction when compared with triptans can lead to peripheral ischemia, vascular disease, acute coronary syndrome and/or coronary vasospasm

67
Q

Treating migraine during all trimesters of pregnancy

A

Acetaminophen with or without codeine

68
Q

Treating migraine during first and second trimester of pregnancy

A

Aspirin and ibuprofen

69
Q

__, ___, __ are contraindicated during pregnancy

A

Triptans

DHE and ergot alkaloids

70
Q

Why are DHE and other ergot alkaloids contraindicated in pregnancy

A

Abortion risk

71
Q

What is a useful combination useful for migraine headache treatment

A

Triptans+analgesic

(Sumatriptan+naproxen= treximet

Acetaminophen, ibuprofen, naproxen)

72
Q

What are some drugs that are taken daily when a patient is asymptomatic in order to limit frequency and severity of migraine attacks

A

B blockers -propranolol, timolol

Tricyclic antidepressants-amitriptyline, imipramine

Anticonvulsants-topiramate, valproate

Ca channel blockers -verapamil

73
Q

Chronic migraine ;considerations for preventative therapy

A
  • more than 2 migraines per month with disability
  • disability lasting more than 3 days per month
  • rescue medication used more than 2 times per week
  • uncommon migraine conditions (with aura)
  • failure of , contraindication for, or adverse events from acute treatments
74
Q

Valproate

A

Used in patients who fail triptans therapy

Effective prophylactic treatment in migrine

75
Q

MOA valproate

A

Increases brain GABA levels

May suppress migraine related events in cortex, perivascular parasympathetic, trigeminal nucleus caudalis

76
Q

Who is valproate contraindicated in

A

Pregnant women.. FDA warning

77
Q

Why is valproate contraindicated in pregnant women

A

Decrease IQ scores in children born from women using the drug

78
Q

Verapamil

A

Ca channel blocker used for migraine prevention

79
Q

What is verapamil used for

A

1st choice for migraine prevention -not many side effects

Proposed mechanisms of action -normalizes vessel tone, lessens Ca dependent vesicle fusion

80
Q

Propranolol / timolol

A

B blockers used for migraine prevention

Lowers frequency of migraine attacks by 50%

81
Q

MOA propranolol and timolol

A
  1. Anxiolytics action
  2. Decreases sympathetic activity
  3. Blunts cortical spreading depression
82
Q

Side effects propranolol

A

Limited

Fatigue, CNS depression 
Change in sexual function 
Reduced exercise tolerance
Hypotension and bradycardia 
BRONCHOCONSTRICTION (contraindicated in asthma patients)
83
Q

Who is propranolol and timolol contraindicated in

A

Asthma bc of bronchoconstriction

84
Q

What are the ergot alkaloids used to treat migraines

A

DHE (dihydroergotamine)

Ergotamine+caffeine

85
Q

How is DHE given

A

Sublingual, intranasal, IV, IM, SC

86
Q

How is ergotamine+caffeine given

A

Oral tablet, rectal suppository

87
Q

Ergot alkaloids are __ specific than the triptans

A

Less

88
Q

What do triptans interact with

A

A-adrenergic, dopamine, and 5HT receptors

89
Q

Are ergot alkaloids agonists or antagonists

A

Agonist, partial agonist, or antagonist

Pharmacology (52 decks)

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