The Northern Neuroscience Centre Chiang Mai University
NNC CMU Migraine and Headache: the management in drug store Surat Tanprawate, MD, MSc(Lond.), FRCPT CMU Headache Clinic, The Northern Neuroscience Centre1 Division of Neurology2, Chiang Mai University
2010 the Global Burden of Disease Survey
Ventricles, 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
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,
Harold G Wolff and Bronson Ray (1940)
!"#$%&!'#()*+,#-./"!0 International Classification of Headache Disorder-2004 Part 1. 1. The primary headaches (!"#
$%&'"()*+&$,-./ 012 !"#$%&'"()3 4567890:) - Migraine, TTH, CH and other TACs, and other primary headache disorder Part II. II. The secondary headaches (!"#
$%&'"()*+&;<=./ 012!"#$%&'"()3 67890:)
International Classification of Headache Disorder 2004
-$%&'"()9>2?@8A .... (B8-7890:) Part III. III. Cranial neuralgias ($%&9CD $")78E)
http://ihs-classification.org
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1. +,->*?@F"&0G#, 2. +,-H/ I 3. '5,"2J7.*& +"7)K"&L&2") 4. MB@+,- ("NO(&P)
:20)*7/"&!`-N@'(")"* b (((Q", aura)
D. '(")"*C&D(:+EQ,2F(R-F($S& 1. 5T7:U $V( 5T7:U $V( ("0W#7 2. )A,.X& $V( 0Y#& E. :;'(")"*Z[&\L&9*5]7
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123!#&(0"/4! , 123!#&567"!"#8 (Migraine with aura) 123!#&59:;7< (Common migraine)
")=)Y2?A8"9Z&28A8"$%&'"()4-9A"D9[=GF\D
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“The most important thing is to understanding their pain”
l?A")mD4-9A"D (trigger factors)
2808"
28A8u
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l?A")mD4-9A"D (trigger factors)
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• Opioid Site of pharmacologic action for acute migraine therapy receptor • •
DA antagonists •
•
anti-emetics
Inhibit neurogenic inflammation •
•
opioid
NSAIDs, corticosteroid
5-HT agonist •
ergotamine, DHE, Triptan Triptan
#"d)?"(")"*+,->*?@0e#/fA7 (Ideal) •
'+*@g=hi"fR7)"**@j/(")"*+,->*?@:
•
(()k=l0m,
•
:;'nKF"&0o#& $V( nKF"&0o#&4(#
•
*"5":;.f&
#".c+,>*?@:20)*7 <"%=)*+51>$39". •
•
analgesics (NSAIDs, combination analgesics)
<"%=)*+5$39". •
ergotamine
•
DHE
•
selective 5-HT1 agonist (triptan)
anti-emetics
•
opioids
•
corticosteroids
•
DA antagonists
Ergotamine
Ergot Cock spur
The ergot of Rye
yz8 “ergot” -8@8A"8A{F|z8 “argot” }?9SD_8(8 ~•?9u(!G"8h “cock spur” 012 “9x2=Y2?4€” 9SD9‰2"8Š2 “Claviceps purpurea ” 400 BC 9Z&_8%) ergotism }?T‚9Z& - vasospasm (9CD9ƒ2&0&„%2…8? †DV"?) - VYDY8Y8&9ƒ2&
V‡?ˆB"
‹ #.u.1862: ergot Œ ]-89SD=8V$%& 4-9A"D
Ergotamine and the headache response “the most acceptable explanation of the headache- ending effect: --cranial arterial walls which are painfully stretched and dilated --Narrow through the vasoconstrictor action of ergot”
ergot 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
“The Beggars” by Pieter Bruegel the Elder, a painting believed to show victims of ergotism.
—˜%=0™?4E= 28pFF=8G8X E8D Ergotamine 10 9š& 9SD 9%X8 10 ‹ “rebound vasodilatation”
XJ+.K@F(.7@bR7)"*Rp Ergotamine tartrate •
•
•
•
0q7#"Z'+*@g=hi"fGR7)"**@j/(")"*+,>*?@:20)*70e#/fA7.K@*"5":;.f&
Ergotamine
nKF"&0o#&Zf/:<[(#:<.r 5T7:U 0s#7>*?@ 5T7:U 0s#7>*?@ RNt7 u"2RpR757:F/"&)v2 9-#0wf"@9*5="&$K(-0x(-.K@57 y(& :;5,*Rp2"))z" 8 {7D(0|(7 0f*"@("N}Ru0~-i",@+,>*?@N"))"*Rp#"0~7:<
Triptan
Triptans
Less side effect than ergotamine
• 5-HT 1B/1D receptor agonists • seven different formulations • options for route of delivery • oral tablets or melts
Zolmitriptan
Sumatriptan
Eletriptan
Ergotamine/ Caffeine
Migraine- specific medication (Imigran) Ever S, Afra J. Eur J Neurol 2009, 2009, 16:968-981
(Zomig)
(Relpax)
1 mg/100 mg Caffeine
B
Triptans
(Imigran)
Time to peak plasma(h)
(Zomig)
Sumatriptan Zolmitriptan Eletriptan
2.5 3.3 1.0-2.0
(Relpax)
Evers, S et al. European Journal of Neurology 2009, 16: 968–981
XJ+.K@F(.7@bR7)"*Rp Triptan •
Triptan 0q7#"Z'+*@g=hi"fG2")R7)"**@j/(")"*+,-
>*?@:20)*70e#/[email protected]'*"5"•&
•
•
•
nKF"&0o#&Zf/:<[(#:<.r 5T7:U 0s#7>*?@ 5T7:U 0s#7>*?@ RNt7 (0$€(7 cafergot .Df/nKF"&0o#&4(#)z" ) u"2RpR757:F/"&)v2 9-#0wf"@9*5="&$K(-0x(-.K@57 y(& :;5,*Rp2"))z" 8 {7D(0|(7 0f*"@("N}Ru0~-i",@+,>*?@N"))"*Rp#"0~7:<070G#,‚/ Ergotamine
NSAIDs
Non-specific migraine medication: Analgesics with evidence of efficacy EFNS migraine treatment guideline 2009 Evers, S et al. European Journal of Neurology 2009, 16: 968–981
Drug
Eliminatio NNT: 2 NNT: 2 Dosage Interval (If Tmax n Halfhour repeated) and hour pain Dose (mg) (Hours) Life headache Maximum daily dose free (Hours) relief
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
975-1000
q 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
500-550
Twice a day; max 1375 mg
Diclofenac potassium (tablet)
1
2
6.2
8.9
50
3-4 time/day; max 150 mg
XJ+.K@F(.7@bR7)"*Rp NSAIDs •
NSAIDs 0q7#"Z'+*@g=hi"fGR7)"**@j/(")"*+,->*?@
:20)*70e#/fA7.K@'*"5":;•& •
•
nKF"&0o#&Zf/:<4(#)z"#"R7)v2 ergotamine .K@ triptan u"2RpR757:F/"&)v2 :<.r u"2RpR757:F/"&)v2 :<.r ƒ„,#9*5)*@0f"@ 9*5:…}&"7:; +)†
•
9()"XR7)"*0~-)"*†-#".K@+,->*?@N"))"*Rp#"0~7M7"-4(#
•
RpQ,2‚/ Ergotamine .K@ Triptan :<
Faster is Better
Drug on the pipeline - CGRP antagonist
New route for drug delivery - Intranasal delivery (OptiNose TM ) - Transdermal delivery (Zelrix TM ) - Oral inhalers (Levadex TM )
Zelrix TM
OptiNose TM
Diclofenac potassium (powder for oral solution)
“Diclofenac-K sachet vs Diclofenac tab vs Placebo” Cephalalgia 2006; 26:537–547
Enrolled N = 328 Received all 3 treatments N = 274 Evaluated 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
sachet > tab = placebo sachet > tab > placebo
sachet = tab > placebo %B@ (placebo)
DCF 3A+
DCF ?7@
Mean VAS headache intensity at different
2 sides of the same coin
M(/‡B5d/
