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THUOC DIEU T R I U MAU
QUANH HOC MAT 6" TRE EM
Nguoi djch: Bd Quang Ngpc*
A Review of the Literature. (Seminars in Ophthalmology, 24, 178-184, 2009)
Nguyen J., Fay A.**
TOMTAT
U mdu (hemangioma) la cdc khoi u mach mdu thudng gap d tre em dgc biit Id d viing ddu vd co.
O vimg quanh hoc mdt, cdc u mdu nay khong chi dnh hudng den thdm my md con co thi dnh hudng din chiec ndng ciia mdt. Sie phdt triin ciing nhu thodi triin cua cdc u mdu dugc kiem sodt bdiphiec hgp tuang ho giiea cdc chdt dieu hda vi hoc-mon, vi ti bao vdphdn tie. Cho tdi nay, vdn chua co phuang phdp diiu tri ndo tuyet doi an todn vd hiiu qud cho viec diiu tri u mdu d tre em. Rdt nhiiu phucmg phdp dieu tri da dugc dp dung nhdm di ngimg phdt triin hoac thodi triin khoi u nhu: dimg thuoc todn thdn vd tgi cho, sir dung laser, phdu thudt vd bit mgch... Bdi bdo ndy, se tong hgp lgi cdc thuoc dugc dp dung trong diiu tri u mdu d tre em.
M d D A U
U mau la khoi u mach mau thudng gap d tre em nhat la d tre gai va tre sinh non. Ty le benh d tre dil thang la 1,1 -2,6%) va ty le nay la 10-12%o d tre da trang I tudi. Cac khdi u mau nay thudng ehua xuat hien hoac neu ed thi rat nhd khi sinh ra, phat trien nhanh chdng trong nhirng thang dau, sau do dn djnh va cd the ton tai ca thang den hang nam. Cac u mau khu trii quanh hdc mat cd the gay hau qua nghiem trpng tren ca phuong dien tham my va chuc nang vdi 43-60% benh nhan cd the bj nhugc thj. Su phat trien thj luc bj anh hudng khi ma cac khoi u mau vung mi mat chen ep len cung mac va giae mac gay ra loan thj va dan den nhugc thj. Cac u mau phat trien viing mi mat cdn ed the chen ep gay ra sup mi
Iam che lap true thj giac can trd qua trinh nhin va gay ra nhugc thj do bj che lap. Cac u mau viing hdc mat edn cd the chen ep gay ra loi mat, gay hd mi, chen ep thj than kinh, gay di lech true nhan eau va nhugc thj do lac.
can nguyen cua u mau van cdn chua hoan toan sang td va ngudi ta cho rang cd lien quan den qua trinh hinh thanh mach mau (angiogenesis) va tao mach mau (vasculogenesis). Trong qua trinh hinh thanh, cac mach mau mdi phat trien, lan rpng va cd su phan bo lai eua cac mach mau cd san tir trudc. Cac u mau dien hinh bao gdm: cac te bao ngi mo cd mang day gdm nhieu ldp gidng nhu cae sgi colagen typ IV va di kem theo la cac t l bao thanh, cae nguyen bao xa va cd su ket tu eiia cac duong
*Khoa Nhdn nhi, Binh viin Mdt Trung uang
^'^Pharmacologic Therapy for Periocular Infantile Hemagiomas
bao ciing cac dai thuc bao. Cd rat nhieu yeu to te bao nhu: cac cam thu lien quan den su hinh thanh mach mau Eselectin, integrins avP3 and a5y91 va yeu td phat trien nguyen bao xo co ban bFGF (la yeu td tim thay trong qua trinh hinh thanh mach mau binh thuong) deu thay d nhiing te bao bieu mo mach mau binh thudng hay d trong cac u mach mau. 0 cac u mach tang sinh, cac yeu to tang trudng mach mau bao gdm ca yeu td tang trudng npi md (VEGF), yeu to tang trudng giong insulin 2 (IGF-2) deu tang cao va dugc cho la yeu td thiic day su phat trien u mach tir nhung mach mau ed san. Gia thuyet tao mach mau thi cho rang u mach cd the xuat phat tir nhirng cau triic npi mo sd'm la nhirng npi md phat trien thanh npi tam mac va npi md cac mach mau ldn. Cac te bao cua cac cau triic nay xuat phat tu cac nguyen bao mach mau cd nguon goc tu trung bi va la yeu td dugc cho la cd chuc nang hoat dpng nhu ngudi khdi xudng (progenitor) cho ea qua trinh tao mau va te bao npi md. Rat nhieu nghien ciiu da thay rang te bao npi md tu u mau viia cd bieu hien la te bao npi md vira la te bao tao mau. Do do, nd iing hp gia thuyet tao mach mau.
Sir tang sinh va thoai trien ciia u mau dugc kiem soat bdi rat nhieu yeu td dieu hda d cac miic dp khac nhau bao gdm ca nhiing thay ddi hoc mdn, thay doi te bao va phan tu. Ca che dan den sir thoai trien cua u mau cdn chua hoan toan sang td. Su thoai trien ciia u mau ket hpp vdi su tang len ve sd lupng cua duong bao, su tang len eua sd lupng t l bao chit theo chuong trinh (apoptosis) ma 1 phan ba trong sd chiing la te bao npi md. Mac dii, nhiing hilu bilt vl sinh hpe tuong ddi phiic tap nay ciing vdi cac phuong phap dieu trj khac nhau da dugc ap dung nhu dimg thudc, laser, phau thuat, diing chit gay xa... thi cho tdi nay vin chua cd phuong phap nao tuyet ddi an toan va hieu qua de kiem soat duge su phat triln cua khdi u. Bai bao nay, se tdng hpp lai cac thuoc khac nhau dugc sir dung de dieu trj u mau.
1. Corticosteroid
1.1. Corticosteroid todn tlidn
Tir nam 1967, hieu qua cua corticosteroid toan than de dieu trj u maeh duge phat hien tinh cd khi Zarem va Edgerton nhan thiy sir thoai trien ciia u mau kh i diing Prednisolone dl dilu trj cho benh nhan bj benh giam tieu cau. Sau dd, 7 benh nhan khac bj u mau tien trien dugc dieu trj bang corticosteroid toan than thay u mau ngimg hoac thoai trien sau 2 tuan diing thudc. Nhieu nghien eiiu sau do da iing hp dieu nay va corticosteroid toan than da trd thanh phuong phap chii yeu de dieu trj u mau.
Tinh hieu qua cua corticosteroid dieu trj u mau dan den rat nhieu nghien cuu ve co che tac dung ciia thudc. Tir nam 1953, Zweifach va cong sir da chiing minh rang: corticosteroid lam tang sir nhay cam cua mach mau vdi cac yeu to luu thong trong mach mau va lam tac cac mach mau ciia khoi u.
Folkman va cong su khi nghien ciiu hoat dpng tao mach mau bang viec su dung mang nieu nang ciia phdi ga cd cho them cortisone nham lam giam qua trinh viem, tac gia rat ngac nhien khi thay rang qua trinh tao mach mau khdi u bj uc che khi Heparin (diing de tang tdc dp phat trien cua phan ung tao mach mau) va cortisone them vao. Su phdi hgp heparin-steroid lam thoai trien cac mach mau dang phat trien bang nhirng te bao npi md hinh trdn, su ngiing tang sinh te bao npi md, su trde ra cua te bao npi md va su eo keo cac mam mao mach. Nhirng hien tupng nay xay ra sau 24-48 gid va kem theo la hien tugng phan tach mang day ciia cac mach mau mao mach mdi.
Do u mau cd ai tfnh vdi gidi nir nen anh hudng ciia npi tilt cung dugc cho la ylu td phat triln u mau. Sasaki va cdng su thiy cd su tang cao ndng dp estradiol-17p va cam thu estrogen trong huyet thanh d benh nhan u mach va tac gia suy luan ring corticosteroid dieu trj cd the lam mat tac dung ciia estradiol. Hasan va cdng su quan tam nghien cuu
nhiing thay ddi phan tu d benh nhan u maeh dugc dieu trj bang corticosteroid va tac gia thay rang cd su chuyen doi cua sic td bao ty lap the b d nhung md u mau thoai triln tu phat hoac dugc dieu trj bang triamcinolone. Gen ty lap thi kit hop vdi su lao hda te bao va cd the ddng vai trd quan trpng trong hien tugng chet te bao theo chuong trinh. Nhirng thay ddi ve hieu qua cua cac corticosteroid khac nhau ddi vdi te bao u mau nudi cay ciing dugc nghien ciiu trong ong nghiem. Hasan thay rang triamcinolone va dexamethasone cd tac dung uc che sir phat trien mao mach sau khi dung thude 11-13 ngay trong khi methylprednisolone chi can 7 ngay la cd tac dung.
Su tang chuyen ddi cua sac to bao ty lap the b ciing dugc thay d u mau dugc dieu trj bang triamcinolone, dexamethasone va methylprednisolone. Su ure che phat trien mao maeh dupe dieu trj bang tat ca cac corticosteroid (ngoai trii' triamcinolone) phdi hpp vdi tang chuyen ddi cua clusterin/apolipoprotein J, la gen chet te bao. Su chuyen ddi cua interleukin-6 (lL-6), mpt cytokine tien sinh mach mau giam di ro ret bdi tat ca cac glucocorticosteroid. Cac dac diem nay nhan manh tac dpng phan tu phuc tap cua corticosteroid ddi vdi su thoai trien cua u mau va cd the phan anh cac dap iing lam sang khac nhau.
Ke tu bao eao dau tien eua Zarem va Edgerton, corticosteroid toan than dugc sii dung thudng xuyen de dieu trj cac u mau hdc mat hay cac u mau ldn tien trien d cac vj tri khac tren ca the gay de dpa chirc nang hoae anh hudng den hinh thai eac CO quan. Phan tich ciia Bennett va cong su cho thay sir dap ling cua u mau vdi corticosteroid dudng udng. Lieu tuong duang prednisone trung binh hang ngay la 2,9mg/kg vdi thdi gian trung binh 1,8 thang trudc khi giam lieu cd ty le dap iing dieu trj la 84%. Lieu cao hon 3mg/kg/ngay thi 94%o dap iing vai dieu trj, tuy nhien tac dung phu cung nhieu hon.
Sadan va Wolach bao cao ket qua dieu trj 22 benh nhan u mau vdi prednisone udng lieu cao (3 hoac
5mg/kg/ngay) trong 6-12 tuan. Khoi u mau xep di trong 24 gid dau sau khi dieu trj va cai thien thj lire sau 1-2 tuan. Delesalle va cong su thay rang truyen tTnh maeh methylprednisolone (2mg/kg x 2 lan/ngay trong 2 ngay) sau do, udng prednisolone 2mg/kg/ngay trong thdi gian trung binh 5,65 thang Iam thoai trien u mau ma it gay tac dung phu (chu yeu la cham Idn). Su khac nhau ve lieu lupng va each diing thudc thudng la do kinh nghiem sir dung cua cac nha nghien cuu khac nhau va dieu do cung phan anh mong muon cai thien ket qua dieu trj u mau bang each giam thieu toi da viec su dung corticosteroid toan than ciing nhu giam thieu cae tac dung phu ciia thuoc gay ra.
Hieu qua dieu trj ciia steroid toan than bao gdm ea viec sir dung dudng udng hay dudng truyen tTnh mach va gdi bang dudng udng, sau do deu bj han che bdi nhiing tac dung phu da duge neu ra trong y van. Phan Idn nhirng tac dung phu hay gap la thay ddi hanh vi va kich thich, gia Gushing va cham Idn (vdi ty Ie cd the tdi 35%)). Boon va cdng su bao cao tac dung phu lam giam chieu cao va can nang 35%) va 42%) vdi 91 Vo benh nhan phuc hdi dudng cong phat trien chieu eao trude dieu trj trong 24 thang.
Nghien ciru hoi eiiu tren 22 benh nhan duge dieu tri bang prednisone lieu 2,23mg/kg/ngay trong thdi gian trung binh 6,5 thang, George thay 36%) benh nhan phai diing hydroehlothiazide de dieu trj tang huyet ap. Cac tac dung phu khac ciia thudc bao gdm kich irng da day-rupt, suy thugng than va tang nguy CO nhiem triing. Do thdi han ngan dang ke eiia viee su dung corticosteroid toan than ma sinh ra khai niem sir dung corticosteroid tai chd.
1.2. Corticosteroid tiem dudi bao Tenon
Vai nhung benh nhan khdng sii dung dugc corticosteroid dudng udng thi tiem thudc dudi bao Tenon la phuong phap dilu trj cd hieu qua, tuy nhien phuang phap nay cung ed tac dung phu cua nd. Coats va cong sir [3] dilu tri cho 7
benh nhan u mach quanh hdc mat gay Idi mat, lac mit va nhugc thj bing each tiem hdn hgp 50:50 dung djch Triamcinolone acetonite (40mg/ml) va Betamethasone phosphate (6mg/ml) cho 6 benh nhan va Betamethasone phosphate eho 1 benh nhan vao bao Tenon bang kim dau tii. Cac benh nhan nay deu da hoac dang diing corticosteroid dudng udng va su thoai trien ciia u mach dupe ghi nhan d nhdm nghien cuu nay. Dua tren nghien cuu cua Coats, Friling phoi hgp ca tiem vao khoi u mach va tiem corticosteroid vao khoang dudi bao Tenon de dieu trj u mach phuc tap (ca u mach mi va hoc mat) khong dap ung vdi corticosteroid toan than. Tac gia thay rang cac benh nhan u mach hoc mat hoac quanh hdc mat khong dap ung vai tiem vao khdi u triamcinolone/betamethasone va udng betamethasone (0,5mg/kg/ngay) thi phuang phap dieu trj tiem corticosteroid vao khoang dudi bao Tenon giiip giam loi mat va che lap true thj giac. Tuy nhien, phuong phap dieu trj nay ciing khdng mang lai su thay ddi ve tinh hinh khiic xa ciia benh nhan.
1.3. Corticosteroid tiiin vdo ll mach
Sir dung corticosteroid tai chd de dieu trj (bao gom ca tiem, truyen hoac boi tai cho) giiip han che tac dung toan than cua corticosteroid. Vao nam 1982, Kushner, mot bac sT mat nhi ndi tieng la ngudi dau tien tien hanh tiem corticosteroid vao khdi u mach de dieu trj u mach quanh hdc mat. Ca sd eiia phuang phap dieu trj nay la dua thudc ndng dp cao true tilp vao khoi u ma lai giam su hap thu toan than va do dd lam giam tac dung phu ciia thudc. Tac gia thiy rang dp loan thj lech khiic xa tren 2,5 di op giam tdi 64% d 3 tre tu 2-10 thang tuoi sau khi tiem hon hgp triamcinolone acetonite (40mg) va betamethasone phosphate (6mg/ml). Morrell va Willshaw nhan thay dp loan thj tren 1,50 di dp giam 56%) d 6/6 benh nhan duai 1 tudi nhung giam it hoac khdng giam d 3/4 benh nhan Idn tudi hon khi tiem triamcinolone
va betamethasone. Weiss va Kelly thiy ring tiem 0,3-1ml hdn hpp 50:50 triamcinolone acetonite (40mg/ml) va dexamethasone phosphate (4mg/ml) giiip giam 63%) dp loan thj. Nghien cuu tren 13 tre cd dp loan thj tren 1,5 di dp, dp loan thj trudc dieu trj trung binh 3,75 di dp giam xudng cdn 1,25 di dp trong thdi gian tir 1-14 thang sau khi tiem. Tuy van chua cd nhirng thii nghiem hoi ciiu nhung tiem corticosteroid vao khoi u td ra la phuong phap phd bien nhat de dieu trj cae u mau quanh hdc mat.
Mac dil, tiem corticosteroid tai chd cd hieu qua de dieu trj u mach nhung phuang phap nay khdng phai la khdng cd nguy ca bien chirng. Viec tiem thuoc corticosteroid vao khdi u vdi ap lire cao hon ca ap lire dpng mach va gay ra nguy ca cac phan tli thuoc cd the lam tac nghen sir luu thdng su tuan hoan dpng mach trong mat. Cac bien chung mat nang khac bao gdm tac dpng mach mat, tac dpng mach hay tTnh mach trung tam vong mac. Cac bien chiing khac nhu mat sac to mi, teo mo dudi da, hoai tu mi mat va su vdi hda quanh hdc mat cQng da dugc bao cao. Cac bien chiing toan than hiem han cd the la gia Gushing, cham Idn, suy tuyen thugng than. Viec tiem tai chd bang kim sac true tiep vao hdc mat cdn cd the gay ra nguy eo xuat huyet hau nhan cau hoac tiem vao nhan eau. Do do, viee chi djnh tiem thude can dugc can nhac ky cang va khdng the coi nhe dugc.
1.4. Corticosteroid boi tin chd
Corticosteroid bdi tai chd nhac lai cd the lam ngimg phat trien cac u mach ndng, mac du thudc khdng giiip lam giam bdt tat khiic xa eua benh nhan.
Nghien ciiu danh gia hieu qua cua corticosteroid bdi tai cho dl dilu trj u mach, Garzon [8] thay ring: 4/10 benh nhan cd u mach ndng quanh hdc mit cd dap irng tdt (u mach ngung phat triln, xep xuong roi phing hoac trang ra) khi su dung ma Clobetasol propionate 0,05%. 30% benh nhan bj ca u mach nong va sau dap img 1 phan vdi thudc boi
tai cho betamethasone dipropionate 0,05%) hoac vdi Clobetasol propionate. Tac dung phu tai cho khi sii' dung keo dai cd thi la teo hoac mit sac to da. Nguy CO tang nhan ap va due bao sau thi thiiy tinh cung cd the xay ra. Chua cd trudng hpp nao bj suy tuyen thugng than. Nhin chung day la phuong phap dieu trj it nguy co va ciing it hieu qua.
2. Interferon a
Interferon a-2a va -2b (INF a) ban dau dugc nghien cuu nhu la mpt thuoc chong virus. Tuy nhien, do thudc cd ca tac dung chong tao mach va ehdng tao u nen thudc cung cd hieu qua de dieu trj cac u mach khang steroid khi sir dung steroid toan than that bai. Thir nghiem lam sang d benh nhan suy giam mien djch mac phai, interferon a-2a giiip cai thien u sarcoma Kaposi. Vao nam 1989, cd 2 bao cao su thoai trien cua u mach khang steroid sau khi dieu trj bang interferon a-2a. Sau nay nhieu nghien ciiu vdi sd lupng benh nhan Idn hon khang djnh hieu qua cua INF dieu trj don thuan. Ezekowitz va cong su bao cao ket qua eua 18/20 benh nhan u mach thoai trien sau khi tiem INF a-2a tiem dudi da hang ngay (vdi lieu tdi 3 trieu don vj/m2 dien tich da CO the) vdi thdi gian dieu trj trung binh 7,8 thang. Mpt sd bao cao khac cdng bo ket qua thoai trien hoan toan hoac gan hoan toan d 45%) trudng hgp va thoai trien vua phai trong 35%) benh nhan.
Tac dung phu thudng gap cua fNF a bao gom sot, khd chju, giani bach cau trung tinh thoang qua va thieu mau. Mgt sd tac dung phu khae cung dupe ghi nhan nhu: tang men gan, chan an, sut can, Ian Ion, mat ngii... Chung liet eo cung (spastic displegia) mpt hinh thai eua bai nao vdi tang truong Iuc va co ciing CO chi dudi ciing dugc thay d 5/26 benh nhan (20%)) dugc dieu trj u mach bang interferon a-2a.
Liet vTnh vien xay ra 3/5 benh nhan. Co che cua cac tac dung phu nay edn chua dugc biet. Michaud cho ring 2,5%o (11/441 benh nhan) dugc dilu trj bing
INF vdi thdi gian dieu tri trung binh 11,2 thang cd chung liet co cung. Rdi loan phat trien van dpng nhu tang phan xa gan, rdi loan dang di hoae mat kiem soat van dpng ehinh xae dupe thay d 4,1%) tre duoi 30 thang tuoi (18/441) trong thdi gian dieu trj trung binh 12,7 thang, tuy nhien cac rdi loan nay mat di trong 90%) trudng hgp. Phat hien sdm cac rdi loan than kinh va ngiing thudc ngay se giiip phuc hdi eac trieu chung nay. Tuy nhien, cac trieu chung nay ciing cd the xuat hien rat muon tham chi la tdi 16 thang sau khi da ngung thudc dieu tri. Do do, neu sii' dung fNF de dieu trj thi can kham than kinh thudng xuyen nham phat hien sam cac trieu chimg ngd dpc than kinh do diing thuoc gay ra. Tuy vay, cho den thdi diem hien nay ban than tac gia bai bao nay ciing khuyen cao khong nen sir dung INF a-2a de dieu trj u mach.
3. Vincristine
Nguy CO ngd dpc than kinh cua INF a Iam cho cac tac gia quan tam den Vincristine la thudc chong phan bao tac dung tren cac vi quan (microtubule).
Vao nam 1988, Ghadially la ngudi dau tien xac djnh nong dp cao tubulin trong te bao npi mo. Ndng dp cao tubulin trong te bao ngi md Iam cho qua trinh tao mach mau rat nhay cam vdi Vincristine. Thuc te la Vincristine cd hieu qua dieu trj cac u mach npi md hinh thai kaposi phdi hop vdi hien tugng Kasabach-Meritt khang steroid. Lieu lupng thdng thudng dimg cho ehi djnh dieu trj nay la 0,05mg/
kg d tre em dudi 10kg hoac l,5ing/m2 d tre em nang hon 10kg va tiem tTnh maeh tuan/lan. Cac tac dung phu ciia thuoc cd the la: rdi loan tieu hda da day-rupt, tao bdn, sdt, nhuc dau, benh li than kinh ngoai vi va than kinh tu dpng. Cae nghien cuu vl SU' dung Vincristine de dieu trj u mach quanh mit van cdn han chi. Trong nghien cuu cua Delesalle, chi cd 1/15 benh nhan dugc dilu trj bd sung bing Vincristine vi u mach Idn khdng dap iing va tai phat
vdi corticosteroid dudng udng. Vincristine ciing da ddng vai trd thay the INF a nhu la su lira chpn so 2 trong viec dieu tri cac u mach khang steroid nhung de dpa thj luc hoac tinh mang benh nhan.
vai thdi gian theo doi trung binh 10 thang. Nhu vay, Cyclophosphamide cd thi phii hgp de dilu trj bd sung nham tranh dpc tinh cua viec sii dung interferon keo dai.
4. Cyclophosphamide
Su dung tac nhan alky I de dieu trj u mach lan dau tien bdi Rush vao nam 1966 [20], khi tac gia diing truyen dpng mach nitrogen mustard de dieu trj u mach da ldn khdng dap iing vdi tiem sodium morhuate la chat tiem xa. Nhieu bao cao sau nay cong bo hieu qua ciia sir dung cyclophosphamide truyen tTnh mach lieu lOmg/
kg trong 3-4 ngay hoac dudng udng trong 2-3 dgt de dieu trj cac u mach khang steroid va de dpa tinh mang benh nhan. Cyclophosphamide cd tac dung ngan chan hay lam giam su tang sinh ciia cac mao mach mdi. Qua trinh tao mach ciia cac te bao npi mo rat nhay cam vdi Cyclophosphamide va ket qua la lam cho cac u mach nhan lai thoai trien va xo hda. Suy tiiy thoang qua va tang men gan la nhung tac dung phu ciia thudc da dupe neu ra. Cae tac dung phu khac do nhiem dpc Cyclophosphamide nhu: ton thuong tuyen sinh due, viem tui mat xuat huyet, hay u ac tinh thu phat thudng it khi xay ra vdi lieu lugng thuoc thap va thdi gian dieu trj ngan nhu vay.
Cyclophosphamide thudng khong sir dung don thuan de dieu trj u mach. Wilson dieu trj cho 5 benh nhan u mach khdng dap ii'iig vdi steroid bang Cyclophosphamide lieu thap (lOmg/kg/ngay trong 3 ngay va cii' 2 tuan nhac lai) phoi hop vdi INF a-2a (3 trieu don vj/in2/ngay 1 lan/ngay) vdi thai gian dieu trj toi da 4-6 thang. 4 benh nhan thoai trien u mach dang ke tu 40-60% va giam 16i mit, hd giac mac va che lap true thi giac. Khdng benh nhan nao bj nhugc thj. Tac dung phu bao gom:
giam bach cau trung tinh nhe va nhiem khuin thdng thu'dng. Khong cd trieu chung nhiem dpc than kinh
5. Imiquimod
Imiquimod (Aldara, Graceway Pharmaceuticals, LLC, Bristol) la chat dieu hda dap ung mien dich cd tac dung loai trii' san xuat tai chd ciia cac cytokine tu te bao sung (keratinocyte), bach cau don nhan thong qua mien djch bam sinh va mac phai, nhd do giiip Iam thoai trien rat nhieu benh Ii ve da lieu. Thudc da dugc sir dung cd hieu qua de dieu trj mun com sinh due (wart), carcinoma te bao day nong, carcinoma te bao vay tai chd, sung hda quang hda (actinic) va mgt so tdn thuong khac. Mpt sd bao eao lam sang mo ta viec su dung thude de dieu trj carcinoma te bao day mi mat va dieu tri u sac td tai chd. Tren dpng vat thuc nghiem, Imiquimod giiip san xuat ra tai ehd mpt so cytokine duge eho la lam thoai trien u maeh. Thdng qua su hoat hda qua trinh mien dich bam sinh, INF a, IL-6 va yeu td hoai tir u a (TNF- a), cytokine dugc biet nhd tac dung chet te bao theo chuong trinh, thay tang len khi su dung imiquimod. INF- a cd the la yeu td kich hoat giup thoai trien u mach khi su' dung toan than INF- a.
Tren chugt va meo, su' dung kem bdi imiquimod 1%) va 5%) tai chd giup tang len INF- a va TNF- a vdi su tang len rd ret cua su chet te bao theo chuong trinh. Qua trinh mien djeh mac phai dugc tang len thong qua viec san xuat eac interleukin nhu IL-1, IL-5, lL-8, IL-10 va lL-12 cimg vdi cae yeu td kich thich bach cau hat va dai thuc bao.
Viec san xuit lL-12 lam tang te bao lympho dpc t l bao va giai phdng interferon y (INF- y). INF-y cd till din din sir thoai trien u mach thong qua viec hoat hda cac te bao giet tu nhien bdi INF-y cd kha nang pha huy te bao u mach.
Martinez thiy ring: Imiquimod dac biet cd hieu qua dilu trj cac u mach nim d viing tran. Tac gia nghien cuu 16 benh nhan bj u mach ndng thay rang 3/4 benh nhan bj u mach hdc mat (nam d long may va vimg tran) dap ung tdt vai Imiquimod boi 3 lan/tuan trong thdi gian tu 7-33 tuan. Tac dung phu chu yeu ciia thudc la ban do va cung ngoai da.
Trong khi Imiquimod la thudc hiia hen cd hieu qua de dieu tri u mach ndng, tuy nhien nghien eiiu ve thuoc nay con han che. Do do, can them cd nhiing nghien cuu de xac dinh vai trd va dp an toan cua thuoc d viing xung quanh hoc mat.
6. Propranolol
Propranolol la mpt thuoc chen beta khong chpn Ipc chii yeu su dung de dieu trj benh tang huyet ap. Thuoc ciing dupe su dung trong tim mach nhi de dieu trj mpt sd dj tat tim bam sinh va chirng loan nhjp tim. Nam 2008, Leaute-Labreze va cong su con thay rang: Propranolol cd the uc che su phat trien cua cae u mau nang. Trudng hgp u mau d mui khong dap ung vdi cocticoid dieu trj, dupe su dung propranolol de dieu trj benh co' tim phi dai tac nghen thi thay u mau mem ra va sam lai ngay ngay thu 2 sau khi diing propranolol. Khdi u mach khong phat trien them va mat di khi tre 14 thang tuoi. Tac gia cdn bao cao 10 trudng hgp u mau nang khac thoai trien sau khi dugc dieu tri bang propranolol 2mg/kg/ngay vdi thdi gian 9 thang. Khdng cd tac dung phu nao dugc ghi nhan. Co mach dugc cho la CO che tac dung cua thude. Su giam che tiet cua gen VEGF va beta FGF la 2 yeu to tien sinh mach trong giai doan phat trien thong qua su dilu hda xudng cua men proteinase hoat hda RAF-mitogen va kieh hoat su chet theo chuong trinh cua t l bao
npi mo mao mach la nhung giai thich cho tac dung cua dieu trj. Gan day, Haider va cong sir bao cao ket qua 17 benh nhan tuoi tu 3 tuan den 12 thang tuoi bj u mau mi ehe lap gay nhugc thi dugc dieu trj bang propranolol dudng uong vdi lieu tang dan tdi 2mg/kg/ngay trong vong 1-2 tuan. Ket qua 10 benh nhan rat tdt (kieh thude khoi u giam > 50%), 6 benh nhan dat ket qua tdt (giam kich thudc khoi u < 50%) va 1 benh nhan khoi u mau khong tien trien them. Tac dung phu xay ra tren 6 benh nhan nhu: kich thich tieu hda, met mdi khi diing thuoc...
Tuy nhien, khong xay ra tac dung phii nghiem trpng nao can phai ngung dieu trj. Tat ca cac gia dinh benh nhan deu hai Idng vdi ket qua dieu trj. Nhung bai bao co tinh giai thoai chung thuc cho hieu qua ky dieu ciia propranolol trong dieu trj u mau. Tuy nhien, can phai cd nhung nghien cuu de hieu ro hon hieu qua, nhiing han che cung nhu cac tac dung phu cua propranolol trong dieu tri u mau.
KET LUAN
Sii' dung thuoc dieu trj van la mpt trong nhung phuong phap dieu trj u mau hiia hen nhat cho den hien nay. Khac vdi cac phuong phap dieu trj bang laser, bang phau thuat hoac eae can thiep npi md mach mau, dimg thudc dieu trj cd the tac dpng den tat ca cac cau triic giai phau va cd the sir dung d tat ca cae giai doan tien trien cua benh. Tuy nhien, cac thudc de dieu trj u mau hien nay cung deu cd tac dung phu cua nd. Do do, can bang giua Igi ich dilu tri va tac dung phu cua thude la rat quan trpng trong viec lira chpn thudc su' dung dl dilu trj. Ngoai ra, su phoi hgp cua cac thuoc dieu trj ed thi mang lai ket qua tot hon trong qua trinh dieu trj eae u mau quanh hoc mat d tre em.