DIENOAN Y H O C Chuyen de trong thang
THUOC KHANG LEUKOTRIENE TRONG DIEU TRI HEN PHE QUAN
Tran Thiiy Hanh*, Nguyen Hu'u Trirffng*
Nhieu nghien cim dd khdng dinh vai trd quan trgng cua Leukotriene Irong ca che benh sinh cua hen phe quan vd cdc benh di img. Khdng Leukotriene Id mdi nhdm thudc mdi dugc dira vdo .sir dung di dieu tri hen phe quan trong thai gian gdn ddy. ldc dgng ire che cua nhdm thudc ndv tren cdc receptor hoge qud trinh long hgp Leukotriene dem lgi ca hieu qua gidn phi quan vd chdng viem. Cdc thudc khdng Leukotriene dd chirng minh dugc hieu qua trong diiu tri cdc trudng hgp hen mirc dp nhe vd Irung binh. Sir ra ddi cua cdc thudc khdng Leukotriene dirge coi Id mpt tiin bp quan trgng trong diiu tri hen phi quan, mac dit hieu qud cua nhdm thudc ndy vdn cdn nhieu franh cdi.
Trong nhung nam gan day, nhieu diem mbi trong CO che benh sinh ciia hen phe quan da dugc lam sang tb, trong do, vai trb eiia yeu tb viem man tinh niem mac dubng hb hap vbi su tham gia eiia nhieu loai te bao va eae hoat chat trung gian dugc dae biet nhan manh.
Leukotriene (thubng dugc biet vbi ten ggi SRS-A) la mbt nhbm cac hoat chat trung gian hoa hgc cb ban ehat la eae axit beo, duge Samuelsson va cbng sy phat hien vao nam 1979 [7]. Day la san pham eiia qua trinh chuyen hoa axit arachidonie theo con duang enzyme 5-Lipoxygenase gan tren mang ciia cac bach cau ai toan, te bao Mast va
lympho bao. Qua nhieu nghien ciiu, ngubi ta nhan thay vai trb het sire quan trgng eiia nhbm boat chat trung gian nay trong ca che benh sinh eiia hen phe quan. Theo cac nghien euu db, Leukotriene dugc san xuat rat nhieu b eac benh nhan hen phe quan so vbi nguoi binh thubng va khi tac dgng tren eae receptor a phbi, chimg cb the gay co that phe quan va mbt loat cac phan irng tien viem. Tren eo' sb nay, trong thai gian gan day, cac thube vbi tac dung iic ehe qua trinh san xuat hoac canh tranh receptor eiia Leukotriene (ggi tat la thube khang Leukotriene) da dugc nghien ciru thir nghiem va dua vao sii' dung trong dieu trj hen phe quan.
Bdngl. Tdc dung sinh hgc cua leukotrienet Gay co thit phi quan (manh hon histamine 100-10000 lan).
Tang tinh phan irng ciia ea tron phe quan, vi du dbi vbi dj nguyen
• Lbi keo te bao viem, dae biet la bach eau ai toan.
' Tang tinh thim thanh mach (gay phii ne va tac nghen dubng tho) ' Tao ra cac mit nhay (gay tic nghen dubng tha nang ne hon)
*Benh vien Bgch Mai
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D I E N O A N Y HOC Chuyen d§ trong thang
CAC THUOC KHANG LEUKOTRIENE
Co 2 each tiep can nham giam bbt cac hoat tinh cua cac Leukotriene la ire che sy tong hgp Leukotriene hoac canh tranh vj tri ciia chimg tren cac receptor te bao. Cac thuoc ire che tong hgp leukotriene cb the dugc chia la 2 nhbm dua vao vj tri tac dgng: nhbm ire che enzyme 5-Lipoxygenase gan vao vj tri hoat dgng ciia enzyme nay va nhbm phong be protein hoat hoa enzyme 5-Lipoxygenase, ca 2 nhom thuoc na\ deu ire che dugc su tong hgp ciia 4 loai Leukotriene B^. C^, Dj va E^. Trong nhbm nay, hien moi chi co Zileuton do trai qua cac nghien
ciiu va dugc dua ra thj truang [3].
Cac thuoc ire chi canh tranh receptor vbi Leukotriene chu yeu tac dgng tren receptor Cys-Ll 1 ciia Leukotriene D^, mgt receptor quan trgng gay co that phe quan. Do ca leukotriene C^ va E^ cung gin vao receptor nay nen cac thuoc ire che canh tranh vbi Leukotriene D^ eung ngan chan dugc tac dung ciia ca Leukotriene C^ va E^. Mbt sb thube trong nhbm nay da qua nghien ciru va dugc chap nhan sir dung trong dieu trj hen nhu Zafirlukast, Pranlukast va Montelukast [3,4].
Bdng 2. Cdc thudc khdng Leukotriene'
Canh tranh receptor leukotriene D4
Tomelukast Verlukast Motelukast Zafirlukast Pobilukast Pranlukast
Phong be Protein hoat hoa enzyme 5-Lipoxygenase MK-886
MK-0591 BAY XI005
Ue che enzyme 5 - Lipoxygenase Zileuton (A 64077) ZD2138
A-79175
VAI TOO CUA THUOC KHANG LEUKOTRIENE TRONG DIEU TRI HEN PHE QUAN
Rat nhieu nghien eiiu tren lam sang da khang djnh tac dung cua cac thube khang Leukotriene dbi vbi tinh trang co that phe quan. phan img viem va trieu chiing ho a ngubi benh hen, Ngoai ra, khi danh gia vai tro ciia cac thube nay trong dieu trj kiem soat hen, nhieu cau hoi da dugc dat ra va di tim lbi giai nhu: Thube eb ngan ehan dugc sy tien trien eiia benh hay khbng? Tac dung ehu yeu eiia thube trong dieu trj kiem soat hen la gi, gian phe quan hay chong viem hay ca hai, hieu qua ciia nhom thube nay nhu the nao khi so sanh vbi cac thube dieu trj hen khac... ?
Doi vai kha nang ngan ngira su tien trien ciia
benh, mgt so nghien eiiu mil doi eb dbi ehung cho thay, zileuton dimg trong dy phong hen giiip giam sb dgt cap ciia hen khoang 50% trong 13 tuan sir dung khi so voi gia dugc, ben canh db, ca Zafirlukast va Zileuton deu giam dugc sb lan thirc giac ve dem, nhu cau sir dung thuoc cat con va cac trieu chirng hen khi so vbi gia dugc [1,6]. Ngoai ra, nhieu nghien ciiu cung chi ra rang, cac thube khang Leukotriene su dung keo dai dem lai sy eai thien ro ret va ben vung ve ehi so FEVI. Nhung ket qua nay eho thay thuoc khang Leukotriene cb the gbp phan giam mirc do benh va lam chain su tien trien cua hen phe quan [3] .
v l CO chi tac dung cua thuoc khang Leukotriene trong dilu trj hen, vbi kha nang ire chi hoat tinh
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I Y HOC LAM SANG
So 51 (Thang 04/2010)DIENOAN Y HOC Chuyen de trong thang ^ M l
ciia Leukotriene, cac thu6c khang Leukotriene cb tac dung tren ca truong luc duong tha va qua trinh viem man tinh a day. Hieu qua gian phe quan cua nhom thuoc nay mac dii khbng nhanh va manh nhu cac thuoc cuang beta 2 giao cam, nhung cac nghien ciiu cho thay, su phoi hgp 2 thuoc tren dem lai hieu qua gian phe quan tot hon tiing thube don le. Ben canh db, nhieu truang hgp co that phe quan khong dap irng vbi cac thuoc cubng beta 2 van dap iing tot vbi thube khang Leukotriene. NhCrng ket qua nay cho thay, thuoc khang Leukotriene eb the tac dgng den phan tae nghen phe quan dgc lap voi phan tac dgng cua cac thube cuong beta 2 [6].
So sanh hieu qua ciia thuoe khang Leukotriene voi cac thuoc dieu trj hen khac. ket qua ciia mgt so nghien ciiu da chi ra rang, Pranlukast 300 -450 mg diing 2 lan mbi ngay dem lai hieu qua kiem soat hen tuong duong vbi Beclomethasone 84 fig 4 lan moi ngay. Ngoai ra, Zileuton hoac Montelukast khi phbi hgp vbi lieu thap glucocorticoid duong hit dem lai hieu qua tuong duong voi lieu cao ciia glucocorticoid duong hit nhung it tac dung phu hon [2, 3].
TINH AN TOAN CUA THUOC KHANG LEUKOTRIENE
Mac dii cac nghien ciru ve mirc do an toan ciia thuoc khang Leukotriene van dang dugc tien hanh nhung hau het eae tac dung phu dugc ghi nhan deu a miic do nhe va thoang qua nhu dau dau, roi loan tieu hoa, dau hgng (Zafirlukast), nbi ban do, tang men gan thoang qua (Zileuton). Khi dugc diing a lieu dieu trj, cac tac dung phu nay chi gap trong khoang 2- 4 % sb ngubi sir dung. Ngoai ra, eac nghien ciru sii' dung Pranlukast va Montelukast keo dai trong it nhat 1 nam eung khong nhan thay CO hien tugng nhan thuoc [2. 3, 5].
c i n day, mbt sb bao cao ghi nhan sy x u i t hien ciia Hgi chirng Churg - Strauss (mbt benh
ly viem mach he thbng hiem gap) sau diing Zafirlukast phbi hgp vbi glucocorticoid dubng ubng giam dan lieu, nhirng ca che cbn chua dugc hieu ro. De ngan ngiia kjp thai tai bien nay. cac benh nhan dang sir dung Zafirlukast can dugc theo doi chat che de phat hien cac trieu chiing som ciia Hgi chirng Churg - Strauss nhu: sbt, dau co'. dau dau, giam can [ 1 , 7].
CHI DINH DIEU TR| CUA THUOC KHANG LEUKOTRIENE TRONG HEN PHE QUAN
Theo hubng dan ciia G I N A (cap nhat nam 2009) dua tren ket qua ciia nhung nghien ciru gan day ve hieu qua ciia cac thuoc khang Leu- kotriene dbi vbi hen phe quan, nhbm thuoc nay dugc chi djnh trong dieu trj du phbng b nhung benh nhan hen nhe dai dang (bae 2) khbng dap ung vbi glueoeortieoid duang hit hoac gap khb khan khi su' dung binh xjt glucocorticoid nhu: tre nho, ngubi cb eac van de ve tam than.... Thube cung CO the dugc dimg phbi hgp de giam lieu glucocorticoid dubng hit a eae benh nhan hen trung binh hoac nang khbng dung nap dugc hoac eb ehbng chi djnh vbi glucocorticoid duong hit lieu cao. Ngoai ra, nhCrng benh nhan hen nang khong dap img vbi glucocorticoid dubng hit don thuan nhung khong dung nap duge vbi eac thuoc phbi hgp khac nhu Theophyllin phbng thich eham hoac cuang beta 2 keo dai cung cb the dimg thuoc khang leukotriene de phoi hgp vbi glucocorticoid duong hit. Cb nhCrng nhbm benh nhan dap iing kha nhanh vbi dieu trj khang leukotriene (trong vbng 2 tuan dau), trong khi do cb nhung benh nhan phai mat 6-8 tuan mbi thay dugc hieu qua eiia thuoc. Theo doi luu lugng dinh va ghi nhat ky trieu ehirng tai nha la phuang phap tot n h i t d l danh gia hieu qua eiia thube. Cach dung mgt sb thuoc khang Leukotriene trong dieu trj hen duge trinh bay trong bang 3.
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D I E N O A N Y HOC
Chuyen 6h trong thang
Biing 3.
Thuoc
Montelukast (Singulair)
Zafirlukast (Accolate)
Zileuton (Zyflo)
Cdch ddng mpt .sd thudc khdng leukotriene trong diiu tri hen
Lieu diing theo tuoi
• NL: 10 mg truoc khi di ngii
• TE 6-14 tuoi: 5 mg trube khi di ngii
• TE 2-5 tuoi: 4 mg truac khi di ngii
• 11 tuoi: 20 mg x 2 lan mbi ngay
• 7-11 tubi: 10 mg x 2 lan moi ngay
>12 tubi:
600 mg X 4 lan moi ngay
Lu'u y
• Khbng can chinh lieu trong suy than
• Giam lieu trong suy gan
• Khbng can chinh lieu trong suy than
• TD men gan 2-3 thang mbt lan
• Ubng 1 trube hoac 2 gia sau bua an
• Uc che chuyen hba warfarin (Coumadin'
• Uc che chuyen hba warfarin, theophyl- line, propranolol.
• TD men gan 2-3 thang mbt lan Ngoai nhCrng tinh huong uu tien lya chgn
a tren, mbt so nhbm dae biet ciia hen phe quan cung thu dugc nhieu lgi ich tir dieu trj khang Leukotriene nhu: hen nhay cam vai aspirin, hen do gang sire, hen vbi bieu hien ho don thuan... Cac nghien ciru cho thay, nhieu benh nhan hen khbng dung nap aspirin va eae thuoc chong viem giam dau khong phai steroid khi dugc dieu trj vbi cac thube khang Leukotriene da co the sii' dung mgt each an
toan iihCrng thuoc nay [4]. Tuong ty, dieu trj khang Leukotriene co the dy phong dirge eae can hen do gang sire, ke ca nhung truang hgp khong dy phong dugc bang cromonyl hoac thube cuong beta 2, hieu qua bao ve nay cb the keo dai 20 - 24 gib sau dimg thuoc [5]. Mgt so nghien cii'u gan day cho thay, cac truong hgp hen lien quan den chu ky kinh nguyet eung thuang dap irng tot vbi dieu trj nay [4].
TAI LIEU THAM KHAO
1. TS. Hallstranda. WR. Henderson. "An update on the role of leukotrienes in asthma". Ciirr Opin Allergy Clin Immunol 2010. 10. pp.60-'66.
2. W. Busse. M. Kraft. "Cysteinyl Leukotrienes in Allergic Inflammation". Chest 2005, 127. pp. 1312-1326.
3. PM. O'Byrne, GM. Gauvreau. DM. Murphy. "Efficacy of leukolriene receptor antagonists and synthesis inhibitors in asthma". J Allergy Clin Immunol 2009. 124. pp.397-403.
4. DT. Scow, GK. Lutlermoser, KS. Dickerson. "Leukolriene Inhibitors in the Treatment of Allergy and Asthma". Am Fam Physician 2007. 75. pp. 65-70.
5. M.E. Krawiec, N. J. Jarjoiir 'Leukotriene Receptor Antagonists". Seminars in respiratory and crilcal care medicine 2002. 23. 4. pp. 399-410.
6. H. Ohnishi. N. Miyahara. EW. Gelfand. "The Role of Leukolriene B4 in Allergic Diseases ". Allergology Inlernalioiial 2008. 57. pp. 291-298.
7. R. Polosa. "Critical appraisal of aniileukotriene use in asthma management". Ciirr Opin Piilm Med 2007. 13. pp. 24-30.
8. Global Inilialive for Asthma (GINA). Workshop Report: "Global Strategy for Asthma Management and Prevcniion ". (Update 2009j.
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