migraine for pharm

8/19/2019 Migraine for Pharm

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NNC CMU

The Northern Neuroscience CentreChiang Mai University

Migraine and Headache:

the management in drugstore

Surat Tanprawate, MD, MSc(Lond.), FRCPT

CMU Headache Clinic, The Northern Neuroscience Centre1 Division of Neurology2, Chiang Mai University


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the Global Burden ofDisease Survey

2010


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Scalp, galea (epicranial aponeurosis), fascia,

muscles:

--150 observations, 30 subjects--thermal,chemical, mechanical, electrical stimulation

Dural artery (middle meningeal artery):

--96 observations, 11 subjects

--stimuli: faradizing, distending, stroking,

stretching, crushing

Ventricles, aqueduct of Sylvius,

Choroid plexuses--24 observations, 4 subjects

--a balloon placed through a small

opening into anterior horn and body

of lateral ventricle

Harold G Wolff and BronsonRay (1940)


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!"#$%&!'#()*+,#-./"!0International Classification of

Headache Disorder-2004

International Classification ofHeadache Disorder 2004

http://ihs-classification.org

Part 1. The primary headaches (!"#$%&'"()*+&$,-./ 012 !"#$%&'"()3

4567890:)

- Migraine, TTH, CH and other TACs,and other primary headache disorder

Part II. The secondary headaches (!"#$%&'"()*+&;


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!"#$%&'"()$,-./3FG

4HI2=!"#$%&'"()*+&J?9#K=&

!"#4-9A"D !"#$%&'"()

*+&LD M


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!"#$%&


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A. '(")"*+,-.//012(3"&4(# 5 56&

B. (")"*+,-7"7 4-72 8,92& ($"):;:*?@'A)?B@C&D(:+E 1. +,->*?@F"&0G#,

2. +,-H/ I

3. '5,"2J7.*& +"7)K"&L&2")

4. MB@+,- ("NO(&P)

D. '(")"*C&D(:+EQ,2F(R-F($S&

1. 5T7:U $V( ("0W#7

2. )A,.X& $V( 0Y#&

E. :;'(")"*Z[&\L&9*5]7 I

“0)B^)"*_`Na#9*5:20)*7”

:20)*7/"&!`-N@'(")"* b (((Q", aura)


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$%&'"()NG M O8?9P=%

Q8$%&-8A@)6#RD4CH%=

*2G9SDB2D

TAU72G

45*2GV7?W89%X8$%&


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123!#&(0"/4! , 123!#&567"!"#8 (Migraine with aura) 123!#&59:;7


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28A8"]E8?A8"-2?9^D (visual aura)


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28A8"]V$XA M

-2?9^D_8F`&9a=%

b&cG8Ad2DV"?9e=D'"()


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Brain hyperexcitability in Migraine

f%DY2?7-2?36#%8-g&$A


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From papyrus, 2500 BC


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0\AY2?A8"iA(84-9A"D

1. 9O8T@!"#

2. 0jA9k=?l?A")mDVX)$iG9$k=DFn


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“The most important thing is to understanding their pain”


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l?A")mD4-9A"D (trigger factors)

28A8u

A8"D2D

2808"


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l?A")mD4-9A"D (trigger factors)

9#K=&

V7?W8 9v=? AwD

"2G9x2D


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#".c+,->*?@:20)*7


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Site of pharmacologic action for acute migraine therapy• Opioid receptor

• opioid

• DA antagonists

• anti-emetics

• Inhibit neurogenic inflammation

• NSAIDs, corticosteroid

• 5-HT agonist

• ergotamine, DHE, Triptan


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#"d)?"(")"*+,->*?@0e#/fA7

(Ideal)

• '+*@g=hi"fR7)"**@j/(")"*+,->*?@:


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#".c+,-

>*?@:20)*7


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Ergotamine


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Ergot

yz8 “ergot” -8@8A"8A{F|z8 “argot” }?9SD_8(8

~•?9u(!G"8h “cock spur” 012 “9x2=Y2?4€”

The ergot of RyeCock spur

400 BC 9Z&_8%) ergotism }?T‚9Z&- vasospasm (9CD9ƒ2&0&„%2…8?†DV"?)- VYDY8Y8&9ƒ2&- V‡?ˆB"

9SD9‰2"8Š2 “Claviceps purpurea ”

‹ #.u.1862: ergot Œ]-89SD=8V$%& 4-9A"D


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Ergotamine and the

headache response

“the most acceptable explanation of theheadache- ending effect:--cranial arterial walls which are painfully

stretched

and dilated--Narrow through the vasoconstrictoraction of ergot”


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O2‚8-Tr ergot

• !"#0X2&9ƒ2& Ž%T@ 7-2? VX) Y8 6A8"G„D

• #D‡2?

• 4B 012 „G ?8Dg&$A<

• !"##%8-D!X‘B’?3#%G“-4H45P

• 9#=V”=8• 45#%"Tr9Z& 10 D–29x2D9F"8)28@T‚6

_8%)$%&'"()@8AA8"Tr=89ZDYD8&4H


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“The Beggars” by Pieter Bruegel the Elder, a painting believed to show

victims of ergotism.


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—˜%=0™?4E= 28pFF=8G8X E8D Ergotamine 10 9š& 9SD

9%X8 10 ‹“rebound vasodilatation”


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XJ+.K@F(.7@bR7)"*Rp

Ergotamine tartrate• Ergotamine 0q7#"Z'+*@g=hi"fGR7)"**@j/(")"*+,-

>*?@:20)*70e#/fA7.K@*"5":;.f&

• nKF"&0o#&Zf/:


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Triptan


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Triptans

• 5-HT 1B/1D receptor agonists• seven different formulations• options for route of delivery

• oral tablets or melts

Less side effect than

ergotamine

Sumatriptan Eletriptan Zolmitriptan


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Ever S, Afra J. Eur J Neurol 2009, 16:968-981

Migraine- specific

medication (Imigran)

(Zomig)

(Relpax)

Ergotamine/ Caffeine

1 mg/100 mgCaffeine

B


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Evers, S et al. European Journal of Neurology 2009, 16: 968–981

Triptans

(Imigran)

(Zomig)

(Relpax)

Sumatriptan 2.5

Zolmitriptan

Eletriptan3.31.0-2.0

Time to peak plasma(h)


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XJ+.K@F(.7@bR7)"*Rp Triptan

• Triptan 0q7#"Z'+*@g=hi"fG2")R7)"**@j/(")"*+,->*?@:20)*70e#/[email protected]'*"5"•&

• nKF"&0o#&Zf/:


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NSAIDs


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Evers, S et al. European Journal

of Neurology 2009, 16: 968–981

Non-specific

migraine

medication:

Analgesics withevidence of efficacyEFNS migrainetreatment guideline

2009

Eliminatio NNT: 2NNT 2 D I t l (If


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DrugTmax

(Hours)n Half-

Life

(Hours)

hourheadache

relief

NNT: 2hour pain

freeDose (mg)

Dosage Interval (Ifrepeated) and

Maximum daily dose

Acetaminoph

en 0.5-1 2 5 12 1000

q 4 hrs; max 4000

mg

ASA (tablet) 1-2 5-6 4.9 8.1 975-1000q 4-6 hrs; max

5.4g/d

Ibuprofen

(tablet)1-2 2 400

q 4 hrs; max 2400

mg

Naproxen

sodium

2 14 6 11 500-550Twice a day; max

1375 mg

Diclofenac

potassium(tablet)

1 2 6.2 8.9 503-4 time/day; max

150 mg

Becker WJ. Headache 2015;55:778-793


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XJ+.K@F(.7@bR7)"*Rp NSAIDs

• NSAIDs 0q7#"Z'+*@g=hi"fGR7)"**@j/(")"*+,->*?@ :20)*70e#/fA7.K@'*"5":;•&

• nKF"&0o#&Zf/:


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Faster is Better


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Drug on the pipeline- CGRP antagonist

New route for drug delivery- Intranasal delivery (OptiNose TM )

- Transdermal delivery (Zelrix TM )- Oral inhalers (Levadex TM )

OptiNose TM

Zelrix TM

Levadex TM


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Diclofenac potassium (powder for oral solution)


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Enrolled N = 328

Received all 3 treatments N = 274Evaluated 3 migraine attack with

- DCF sachet + P + P

- P sachet + DCF tab + P

- P sachet + P + P

Variable- pain free at 2 h- Headache response at 2 h- Sustained headache

response- Sustained pain free

Cephalalgia 2006; 26:537–547

“Diclofenac-K sachet vs Diclofenac tab vs Placebo”


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DCF?7@

DCF 3A+

%B@ (placebo)

sachet > tab = placebo

sachet > tab > placebo

sachet = tab > placebo

Mean VAS headache intensity at different

time points (intention-to-treat population)


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2 sides of the same coin


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M(/‡B5d/

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