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

!Neuropharm Migranes Flashcards by Hadley C

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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What triggers migraines

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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Classic migraine vs common

Classic has mini headache before?

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What is the course of a migraine attack

Prodrome, headache, postdrome

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What can be used to treat prodrome

Triptans, ergot alkaloids

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What is used to treat the headache

NSAIDS

Acetaminophen

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What are preventative agents used for

Limit frequency and severity of attack

Treat asymptomatic phase, before the prodrome

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What are preventative agents

B blockers
Tricyclic antidepressants
Anticonvulsants
Ca channel blockers

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Name ergot alkaloids

Dihydroergotamine (DHE)

Ergotamine+caffeine

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Name triptans

Sumatriptan
Almotriptan 
Naratriptan
Zolmitriptan
Riatriptan
Electric tan
Frovatriptan

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Name B blockers

Propranolol

Timolol

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Name tricyclic antidepressants

Amitriptyline

Imipramine

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Name anticonvulsants

Topiramate

Valporate

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Name Ca channel blocker

Verapamil

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Botros for migraines MOA

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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What is Botox prescribed for

Chronic migraine

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What is a chronic migraine

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

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Neurovascular headache

Neural events result in the dilation of blood vessels

Results in pain and further nerve activation

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Meninge sense pain?

They are innervated by trigeminal axons

When stimulated by vasodilation they generate throbbing unilateral migraine like pain

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Calcitonin gene related peptide migraine CGRP

Released from trigeminal ad-fibers which increases dural vessel vasodilation

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Substance P and neurokinin A migraine

Released from trigeminal C fibers and increase dural vessel permeability

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Neurogenic inflammation theory of migraine

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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CGRP and NO interact throughout the __ __ __

Trigeminal neurovascular system

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

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

Organic nitrates

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

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

Cortical spreading depression

What does cortical spreading depression lead to

Cerebral vasoconstriction Accompanied by H, K, and NO discharge from neurons

Dilation of cranial arteries-depolarization of perivascular trigeminal terminals

Electrolytes and NO dilate cranial arteries and depolarize perivascular trigeminal terminals CGRP and neuropeptides release promotes neurogenic inflammation

Neurogenic inflammation irritates trigeminal nerve and transmits migraine pain

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

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

5HT-1B on cranial vessels 5HT-1D peripheral neuron 5HT-1B/1D central neuron

Serotonin and its receptors modulate CGRP actions

5HT-1B receptor vasculature 5HT-1D receptor synaptic

Vascular 5HT-1B receptor for CGRP

Dilation bv

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

Pain

What are triptans

Selective serotonin 5HT1B/1D receptor agonists

What do tripatans stop

Pain and dilation

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

Vasoconstriction of dilated meningeal, dural and pail blood vessels

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

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

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

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

Sumatriptan Cmax

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

Sumatriptan clearance

T1/2-1-2 hours | Metabolized by monoamine oxidase A

Sumatriptan is an ____

Indoleamine Similar structure to serotonin and melatonin

What does sumatriptan help

Persistent pain, nausea, and photophobia

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

Rizatriptan | Eletritpan

Name other triptans

``` Almotriptan Naratriptan Zolmitriptan Rizatriptan Eletriptan Frovatriptan ```

Naratriptan bioavailability

70% | T1/2 is 6 hours

Zolmitriptan

Active metabolite is a 5HT1D agonist

Frovatriptan half life

24 hours

Oral oral triptans

Easy to take | Ineffective if patient vomits

Nasal spray triptans

Effective with nausea/vomiting, simple works quickly | -few triptans formulated as nasal sprays

Injection of triptans

Works quickly | Inconvenient

Delivery sumatriptan

Injectable, nasal spray, tablets

Zolmitriptan routes

Orally disintegrating tablets, nasal spray, tablets

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

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

Yes

Subcutaneous injection with fastest onset-for immediate relief

SQ Sumatriptan injection is fastest Second fastest is nasal spray of sumatriptan, zolmitriptan

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

Frovatriptan has a 24 hours HL

What triptans can not be used with MAO inhibitors

Sumatriptan, rizatriptan, zolmitriptan

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

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

Who are triptans contraindicated in

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

Why cant triptans be used with heart vascular issues

They are all vasoconstrictors of coronary and renal vessels

What are all triptans vasoconstrictors

5HT1B/D

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

Yikes

Central effects of ergotism

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

Peripheral calinical manifestations of ergotism

Bradycardia

Clinical manifestation of ergotism ischemic effects

``` Angina Gangrene Hemorrhagic vesiculations and bullae Mesenteric infarction Myocardial infarction Renal infarction ```

Duhydroergotamine MOA

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

What happens when dihydroergotamine binds to peripheral a1-adrenergic receptors

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

Treating migraine during all trimesters of pregnancy

Acetaminophen with or without codeine

Treating migraine during first and second trimester of pregnancy

Aspirin and ibuprofen

__, ___, __ are contraindicated during pregnancy

Triptans DHE and ergot alkaloids

Why are DHE and other ergot alkaloids contraindicated in pregnancy

Abortion risk

What is a useful combination useful for migraine headache treatment

Triptans+analgesic (Sumatriptan+naproxen= treximet Acetaminophen, ibuprofen, naproxen)

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

B blockers -propranolol, timolol Tricyclic antidepressants-amitriptyline, imipramine Anticonvulsants-topiramate, valproate Ca channel blockers -verapamil

Chronic migraine ;considerations for preventative therapy

- 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

Valproate

Used in patients who fail triptans therapy | Effective prophylactic treatment in migrine

MOA valproate

Increases brain GABA levels May suppress migraine related events in cortex, perivascular parasympathetic, trigeminal nucleus caudalis

Who is valproate contraindicated in

Pregnant women.. FDA warning

Why is valproate contraindicated in pregnant women

Decrease IQ scores in children born from women using the drug

Verapamil

Ca channel blocker used for migraine prevention

What is verapamil used for

1st choice for migraine prevention -not many side effects Proposed mechanisms of action -normalizes vessel tone, lessens Ca dependent vesicle fusion

Propranolol / timolol

B blockers used for migraine prevention Lowers frequency of migraine attacks by 50%

MOA propranolol and timolol

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

Side effects propranolol

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

Who is propranolol and timolol contraindicated in

Asthma bc of bronchoconstriction

What are the ergot alkaloids used to treat migraines

DHE (dihydroergotamine) Ergotamine+caffeine

How is DHE given

Sublingual, intranasal, IV, IM, SC

How is ergotamine+caffeine given

Oral tablet, rectal suppository

Ergot alkaloids are __ specific than the triptans

Less

What do triptans interact with

A-adrenergic, dopamine, and 5HT receptors

Are ergot alkaloids agonists or antagonists

Agonist, partial agonist, or antagonist

!Neuropharm Migranes Flashcards

(89 cards)