B Y TTRNG I HC Dc H NI****CQ|****NGUYN TH HNGKHO ST TC DNG KHNG
MONG MUN CA GLUCOCORTICOID TRN BNH NHN MC BNH H THNG IU TR TI KHOA
D NG -MIN DCH LM SNG -BNH VIN BCH MAI (KHO LUN TT NGHIP Dc s KHO
2001- 2006)Ngi hng dn:Th.s Bi c LpBSCKII Trng Thanh Lan Ni thc
hin:B mn Dc lm sng -Trng i hc Dc H Ni Bnh vin Bch Mai Thi gian thc
hin:01/2006-05/2006IH NI, 05/ 2006V-X-.-, i U . - j&eAMm&i
in. eht thjnh iy, i Ltig, evi LiAiL ac. ti:^Ite. i l (Bi
^e.MqLfL(Be. i lduMMt idtUt. I I ^n i n g ,^uL Multn tinh htiq, dti
ti hjiut tkt Uh. Lutl n-.Q eng. ht ehti thnh em. t t :th, e qi^l
mtt ne. lm. ijcuijg.,ee. Im tnmt kh,ea phn. l%ut ^Mn. it hi^n)uje.
'. Qli , du dt ti iu^ 5nttt h&e, fi ti. eA e./,- tcLUhiHLn)i
nj. - Jtn. dleh. lm iMtt. -^nh ltL^aeh JHai IMLei fnhiL itt fifi*i.
3( Ujeh ttt. hfft. -it (Baeh JHai t &u Uitt eht- ti hsn. thnh.
Uh UitL ll nhip, rt,.i eng, itt (%. t lt, tt ti nhi. ntii htt ^t.
ia invluuLIxLu*lehtnAj.,tiiitltjC^ijg,^&tt.lrtOgip,it^t i
tprig, thnh lm*Lq. eu&. sn l nhip,.'J Qlif n. 13 thM. 5 nnt
2006. Sinh ain (MJijit^ t t 'Taatjq.MC LCT VN
..................................................................................................
1PHN 1:TNG
QUAN.................................................................................
21.1. Tng quan v bnh h
thng...................................................................
21.1.1. Khi nim, c im, phn
loi.......................................................21.1.2.
Nguyn nhn v c ch bnh
sinh................................................... 31.1.3.iu
tr.............................................................................................
31.2. Tng quan v
glucocorticoid...................................................................
51.2.1. Ngun
gc.......................................................................................
51.2.2. Dc ng
hc.................................................................................51.2.3.
Phn
loi..........................................................................................
51.2.4.C ch tc
dng...............................................................................
61.2.5. Tc
dng..........................................................................................
81.2.6.Ch
nh..........................................................................................111.2.7.Chng
ch
nh...............................................................................111.2.8.
Tc dng khng mong
mun.........................................................121.2.9.
Tng tc
thuc.............................................................................
161.2.10.Mt s iu cn lu khi dng
glucocorticoid...........................17PHN 2: I TNG V PHNG PHP
NGHN cu................ 182.1. i tng nghin
cu.............................................................................182.1.1.
Tiu chun la
chn.....................................................................
182.1.2. Tiu chun loi
tr.........................................................................182.2.
Phng php nghin
cu.......................................................................182.3.
X l kt
qu..........................................................................................
182.4. Ni dung nghin
cu..............................................................................18PHN
3:KT QU NGHIN cu V BN LUN..............................203.1. Kho
st chung v bnh h
thng........................................................
203.1.1. M hnh cc bnh h thng gp ti khoa c s dng GC.............
203.1.2. Phn loi bnh nhn theo la
tui................................................. 213.1.3. Thi
gian mc
bnh.....................................................................
223.2. Thuc iu tr bnh h
thng...............................................................
233.2.1. Tnh hnh s dng GC trongiu tr cc bnh h
thng..............233.2.2.Cc nhm thuc c dng phi hp vi
GC............................. 273.2.3. Tng tc gia GC vi cc thuc
dng phi hp..........................293.3. Tc dng khng mong mun ca
GC v bin php khc phc........ 303.3.1.So snh t l gp TDKMM trong tng
bnh v gia cc bnh... 303.3.2.Cc tc dng khng mong mun
gp.......................................323.3.3. Cc bin php khc
phc TDKMM ca GC................................. 373.3.4. Cc nhm
thuc dng iu tr TDKMM ca GC.....................39PHN 4:KT LUN V
XUT.........................................................464.1.
Kt
lun..................................................................................................
464.2.
xut....................................................................................................
47TI LIU THAM KHOPH LCCH GII CH VIT TTD- MDLS: GC KSKSRTH MC nNSAID
SLE STTTDKMM VDC VNQM XCB CMDD ng -Min dch lm sngGlucocorticoidKhng
sinhKhng st rt tng hpMineralcorticoidS lng bnh nThuc chng vim khng
steroidLupus ban h thngS th tTc dng khng mong mun Vim da cVim nt
quanh ng mch X cng b c ch min dichT VN
Bnhhthng-bnhcnhhngrtlnncucsngcacon ngi k t khi mc, n c lin quan n
ri lon h thng min dch trong c th.C n 50 nghn ngi M ch yu l ph n mc
bnh h thng, c bit nhng ngitrong tui lm vicv nuicon[31].Mctiuiu
trnhm bnh nychlluibnh bngcchs dngnhiunhmthuc khc nhau.
Trong,glucocorticoidlnhmthucclachnutin.Tnhng nm1940,GC c dng trong
iu tr bnh lin quan n min dch[27] v n khng nh c vai tr to ln ca mnh,
khng nh Steroids - Keys to life (steroid - cha kho ca cuc
sng)[32].Hin nay,GC khng chcdngtrongccbnh linquann min dch m n cn c
s dng ph bin vd nhiu mc ch khc nhau ko theo
slmdngcorticoidngycngtng.Chnhvth,nhngtcdngkhng mongmuncaGC
xuthinngycng nhiuvngycngtrmtrnghn trn mi i tng, mi la tui v trn mi
ng dng khc nhau.iu ny lmchobnhtnhthmphctp,nhhcmgludins phttrinv
sckhovtrtuconngi.Lmsao hnch nhngtcdngkhng mongmuncaGC?
cnlmtcuhilfn.ccinhncthvthy cmcnghimtrngdonhngTDKMMcaGCgyra,chngti
tinhnhnghincuti;Khosttcdngkhngmongmunca
glucocorticoidtrnccbnhnhnmcbnhhthngtikhoaDng- Min dch lm sng - Bnh
vin Bch MaiVi mc tiu:1.KhostmhnhbnhhthngkhoaDng-Mindchlm sng - Bnh
vin Bch Mai.2.KhosttnhhnhsdngGCtrongiutrbnhhthng,tc dng khng mong
mun ca GC v bin php khc phc.T , gp phn s dng GC an ton, hp l, kinh
t v hiu qu hn.PHNl TNG QUAN1.1. TNG QUAN V BNH H THNG1.1.1.Khi nim,
c im, phn loi1.1.1.1. Khi nim [9]Bnh h thng l mt nhm bnh c biu hin
vim mn tnh lan to hay ri rc tchc lin kt v tn thng l kt qu ca s gii
trng hp nhng mucopolysaccharidtrongchtcbncathnhphntokeotrongtchc
lin kt.1.1.1.2. c im ca cc bnh h thng [2], [9],
[13]Vimkodinhiuni,nhiubphn,nhhngnhiunth chung.^
Tnthnggiiphubnh:thoihodngt huyt,tchcbnhc nhiu lympho xm nhp.Tng
Yglobulinmu,gim bth,cmt hay nhiuloit khngth, hoc c dng t bo T t phn
ng chng li nhiu t chc,Rilonhthngmindchnnchunhhngcacoiticoidvcc thuc
c ch min dch.Yutkhiphtthngxyrasaunhimtrng,nhimc,chn thng.Bnh c
khuynh hng duy tr v t pht trin qua nhiu t tin trin.1.1.1.3. Phn loi
[9]Theo G.Klempeper (c) nhm bnh ny gm c 4 bnh:Lupus ban h thng X
cng b h thng Vim da c hay vim da v c Vim nt quanh ng
mchNgoira,mtsnginghxpthmvonhmnyccbnhnh: vim khp dng thp, cc bnh khp
ca ct sng, hi chng Sjogren.. .[8].1.1.2.Nguyn nhn v c ch bnh sinh
[9]Cnhiugithuytnhngchonnayhunhthngnhtxpnhm bnh ny vo cc bnh t min
dch trn mt c a c bit.1.1.2.1. Nhng bng chng v t min dch ca
bnhCcbnhnyctrngbisxuthinnhngt khngthtrong
huytthanh:khngthkhngnhn,khngthkhngccacidnhn(ADN,
ARN...),khnghiston,khngcchuytcu(hngcu,tiucu,bchcu).
ngthilngbthgimrrttrongmu.Phthinccphchp min dch trong mu v t chc.T l
cc t bo lympho T v B thay i trong
mu.Cthgybnhthcnghimtrnscvtbngphngphpmin dch.iu tr bng cc thuc c ch
min dch c kt qu.1.1.2.2.Yu t c aHu ht cc bnh h thnggp ph n, tr tui
hoc trung nin. Mt s trng hp c tnh cht gia nh.1.1.2.3. Nguyn nhn trc
tip gy bnhHin nay, ngi ta vn cha bit chnh xc nguyn nhn gy bnh nhng
tathycvaitrcaccyuttmin,yutnghnghip,yutdi truyn, mi trng sng...c nh
hng n cc bnh .1.1.3.iu tr[9]1.13.1. Mc tiu iu trBnh hthngl
nhmbnhmntnh,xenkgiacct tintrin l thi k lui bnh.Mc ch iu tr ch nhm
kim sot cc t cp ca bnh v duy tr trng thi lui bnh vi s lng thuc t gy
tc dng ph nht.1.1.3.2. Phc iu tr^ Thuc chng vim v c ch min dch,Thuc
iu tr triu chng,Trnh cc yu t nguy c.1.1.43. Cc thuc s
dngCorticoid:da trn tcdng chngvim v tcdng cch min dch ca GC lm gim
cc phn ng vim,gim cc triu chng ca bnh.Liu dng tu thuc mc nng nh ca
bnh, nn chn loi GC vi liu ph hp ci thin tin lng ca
bnh.Thucchngvimkhngsteroid:mithuctrongnhmnyucthsdngcdatrntcdngchngvimcandocchenzym
cyclooxygenase,gimtng hp prostaglandin-cht trunggiangyphn ng vim v
do n lm bn vngmng lyzosom, ngn gii phng cc enzym phn gii, c ch qu
trnh vim.Thuc khng st rt tng hp:Chloroquin (Nivaquin),
Delagyl...Hinnay,vnchabitcthc ch tcdngca nhmthucny.Mts
tcgichorng,ccthucnyctcdnglmnnhmnglyzosom,c ch qu trnh phn bo,cch
gii phng cc enzym v cytokin thc y qu trnh vim;thayicn
bngacid-baseca t bo,do hn ch kh nng hnh thnh khng th.Thuccch
mindch:Dobnh hthngclinquan n t mindchnnvics dng cc thuc CMD c hiu
qu.Cc thucnyc nhiu tcdngphnnchcdngkhibnhnhnkhngpngviGC.Cc
thuchaydngnh:azathiopiin,cyclophosphamid,cyclosporin,chlorambucid...Cc
thuc khc:Danazol, globulin min dch...Cc thuc iu tr triu chng: hi
chng Raynaud, nhim trng, tnghuyt p...Ngoira,iutrccbnhtrncns
dngccphngphp iu tr c bit
nh:Boluscortison:truynliucaomethylprednisolon1000-1500 mg/ngy trong
3 ngy lin tip.Lc huyt tng.Ringvibnhxcngbtacthsdngccthucginmch,
vitamin E, iod, D-penicillamin kt hp steroid...1.2. TNG QUAN V
GLUCOCORTICOID1.2.1.Ngun gc [3],[6]CcGC t nhindovngb thngthnsnxut
ragmc2chtl hydrocortison (cortisol) v cortison.Cc GC tng hp nh
methylprednisolon, dexamethason...1.2.2.Dc ng hc[3],[24]Cc GC t
nhin v dn xut ca n thng c dng qua ng ung. Ngoi ra, n cn cs dng qua
ng tim bp, tim tnh mch, tim di
da,phunmvbitrnda.Nichung,nhpthuttquangtiuho.
Phnbvottcccmtrongcth,quacnhauthaivsammt lng nh.Thuc lin kt vi
protein huyt tng trn 90%qua hai protein l
CBG(globulingnvicorticosteroid)valbumin.Trong,chyul globulin.Cc GC
c chuyn ho gan v thi tr qua thn l ch yu.1.2.3.Phn
loiCnhiucchphnloiGCdatheongungc,theocimtc dng hoc theo thi gian tc
dng...1.23.1.Theo ngun gc [3]GC t nhin do c th sn xut ra nh
hydrocotison...GC tng hp nhmethylprednisolon...1.2.3.2. Theo thc
hnh [22]Loi gi nc mnh l cc cht khng c delta Ci_2-V d:cortison,
hydrocortison, Auocortison...^ Loi gi nc t l cc cht c delta Ci_2 .V
d:prednisolon, dexametheson, triamcinolon... 1.233.Theo ng dng thuc
ng ungng tim: tim tnh mch, tim bp, tim ni khp...Dng ti ch:kh dung,
bi ngoi da, tht hay np hu mn...1.23.4. Theo tc dng dc lLoi n thun
ch c tc dng GC nh:betamethason...Loi km theo tc dng MC rt t nh :
methylprednisolon... Loi km tc dng MC va nh :prednison,
prednisolon... Loi km tc dng MC nhiu nh :cortison, hydrocoitison...
/.2.5.5.Theo thi gian tc dng [3], [24]Bng 1.1:Phn loi GC theo thi
gian tc dngPhn loi Tc dng ngn Tc dung trung bnhTc dng diThi gian tc
dng 8 h - 12h 1 2 h - 3 6 h 36h-72hV d
CortisonCortisolPrednisolonMethylprednisolonTriamcinolonFludrocortisonBetamethasonDexamethason1.2.4.C
ch tc dng [4],[5], [14], [28]Transcotin1.GC t dovo t boBo tngNhnGR-
GC c phosphoryl ho v di chuyn6.GR c phc hiCc GR chc nng nh monome
hay dimeHnh 1.1:C ch phn t tc dng ca GC[28](GR:Receptor ca
GC;Hps:Cc protein lin kt)GC tn ti trongmu as dnglin kt
viproteingnGC(CBG) vmt phn nh dngt do.GC a lipidd khuychtnqua mng t
bo, gnvoreceptortrongbotng.Ccreceptorlchiu,chcilcvi
GC,khngtophccviandrogen,estrogen,Cortison,prednison(ring
cortisonvprednisonchlinktcvireceptorkhichuynhosang cortisol hay
prednisolon hot tnh).Saukhinhnphnphiliintch,phchpGC-receptortinvo
nhn,kthpviChromatinti.TinhntbophchpGC-Re- Chromatinkchthchsaom
mcRNAquatrunggianRNA-polymerase tng hp RNA thng tin.T to iu kin tng
hp nhng protein c hiu c tc dng dc l, quy nh nhng tc dng ca
GC.15n20phtsaukhiphchpGC-receptorvonhnthybin ivnchuyn glucosequa
mng,cch hp thu,cch st nhp acetat volipid nhn.Sau khi phc hp GC -
receptor vo nhn1 - 2gi, nhiu tc dng c ch chuyn ho xut hin.Thi gian
tip xc gia cortisol v receptor ngn (Mhnh bnh h thnggp khoa D ng-Min
dch lmsng-Bnh vin Bch Mai,>Tui ca bnh nhn,>Gii tnh,>Thi
gian mc bnh.18Kho st v thuc iu tr bnh h thng:>Cc loi GC c dng ti
khoa (tnbit dc, hot cht, hmlng v ng dng),>Liu dng GC,>Thi
gian dng GC ti bnh vin,>Cc nhm thuc phi hp,>Tng tc gia GC v
cc thuc phi hp.Cc tc dng khng mong mun ca GC v bin php khc
phc.19PHN 3KT QU NGHIN ctru V BN LUN3.1. KHO ST CHUNG V BNH H
THNG3.1.1. M hnh cc bnh h thng gp ti khoa c s dng GCtngthigian khc
nhau,tl bnh nhn mcccbnh h thngs khc nhau. Trong nm 2005, qua hi cu
trn 436 bnh n, chng ti thu c kt qu trong bng 3.2:Bng 3.2:M hnh cc
bnh h thng gp ti khoa c s dng GCBnhChtiuSLE XCBVNC>M TngNam N
Nam N Nam N Nam Nam Nn 21 335 16 37 4 12 2 9 43 393T l% 5,90 94,10
30,19 69,81 25,00 75,00 18,18 81,82 9,86 90,14Tng 356 53 16 11 436T
l% gia cc bnh81,65 12,16 3,67 2,52 100,00x' = 35,904; p < 0,05Vi
s liu t bng, ta c biu : 81,65%2,52%-3,67%16% SLE XCB 0VDC
nVNQMHnh3.5:Biu th hin m hnhbnh h thng khoa c s dngGC20Trong 4 bnh
h thng theo phn loi ca G.Kempeper th bnh SLE gp
nhiunhttrongnm2005,chimn81,65%nhiuhnsoviktqu
nghincucangNgcTrcvTrnNgcntrong10nm(1979- 1988) l 59,00%[4].iu ny c
th biu hin c phn no rng t l mc
bnhSLEtngln.Ktquchngtithucvmiquanhgiagii tnh v t lmc bnh cng tng t
nghin cu ,ccbnh nhn mcbnh h thng ch yu l n, trong t l n gp trong
bnhSLE l rt cao chim 94,10%.Hinnay vncha gii thch c r rng tisao cc
bnh h thng li gp n nhiu hn, c gi thuyt cho rng l do yu t
hormon.Trong nghincuny,chngtithytlmcbnhphthucgiitnh vitin cy 95%(x^
= 35,904; p < 0,05).3.1.2.Phn loi bnh nhn theo la tuiCcbnh
hthngclinquan n ccyu t t mindch,yu t c a v tui ca bnh nhn cng c nh
hng n t l mc bnh.Kt qu thu c khi kho st v la tui ca bnh nhn c th
hin trong bng 3.3:Bng 3.3:Phn loi bnh nhn theo la tui^ nhL \tul\^
SLE XCB VDC VNQM Tngn T l%n T l% n T l%n T l%n T l%60 8 2,34 2 3,78
2 12,50 3 27,28 15 3,44Tng 356 100,00 53 100,00 16 100,00 11 100,00
436 100,00=104,241; p< 0,0521Tl%80604020063,53 0.09 60TuiHnh
3.6:Biu biu hin phn loi bnh nhn theo la
tuiTheobngtrn,slngbnhnhnmcccbnhhthngcaonht
tronglatui18-40,chim63,53%.Ktqunyphhpviccnghin cu trc y v dch t bnh
h thng,cc bnh nhn ch yu l n trong
tuilmvicvnuidycon[8],[31].Cthtrongtuinyltui
sinh,hmlngEstrogentngcaohnsovicclatuikhcnntl mc bnhcao hn[11].T l
mc tng la tui trong 4 bnh cs khc bitv khc nhauc ngha thng k vi
tincy95%=104,241;p 150mg prednisolon/ngy iu tr.Khi bnh nhn khng p
ng tt vi thuc,bc s chuynsangdngliu bolus(truyn
tnhmchSolumedrol500/l/ngy
trong3ngylintip,sauchuynsangungprednisolon5mg/vinX8
vin/ngy).ThngthngsaumttdngGC liucaotrong2tunu, bc s s gim liu mt
cch t tvi mc ch gim TDKMM v c th
theo25dipngcabnhnhnkhigimliuGC.Ktquchngtithuc
cngphhpviiu,liudngcabnhnhnlcravinliutrung bnh15-50 mg
prednisolon/ngy chim80,30%s bnhn hicu v dng qua ng ung.3.1.13.Thi
gian bnh nhn dng GC ti bnhvinThigiandngGCquytnhtnsutxuthinccTDKMMvn
cng gn nh bng thi gian bnh nhn iu tr ti bnh vin.Trong thi gian
ny,bnh nhnthngdngliuGC cao theongtim tnh mch v tl gp tai bins nhiu
hn so vi khi ngoi tr.Chng ti khost thi gian bnh nhn dng GC ti bnh
vin, kt qu thu c th hin trong bng 3.7: Bng 3.7:Thi gian bnh nhn dng
GC ti bnh vinrhi gian dng GC (ngy)SLE VDC VNQMn T l % : n n T l % n
T l %20 106 29,77 27 50,94 8 50,00 2 18,18Tng 356 100,00 53 100,00
16 100,00 11 100,00= 93,555; p < 0,05 >20ngy 11-20ngy Nhm chn
knh calci: niedipin, amlodipin, diltiazem...6,4mmolA),chim
5,96%.KhikhostccbinphpkhcphcTDKMMny,chngtithu c kt qu trong bng
3.16.Bng 3.16:TDKMM tng ng huyt v bin php khc phcTDKMM tng ng
huytBnh n khng c can thipBnh n c can thipThuc iu
trInsulinGliclazid(Diamicron)n 5 21 13 10T l % 19,23 80,77 61,90
38,4643Quabngtrntathy,khigpTDKMMtngnghuyt,80,77%
bnhnhnccanthipbngcchsdngccthucgyhnghuyt.
Trongkhostny,chngtithybcschobnhnhndng1 trong2
thuchnghuytlinsulinvgliclazid hockthpc2loi,trong insulin cs dng
nhiu hn, chim 61,90%.ng ch l t l bnh nhn
khngccanthipchimti19,23%.Khitraoiviccbcs iutr
khoaD-MDLS,ccbcschorngnubnhnhnctngnghuyt
nh,chacnthitdngccthuciutrngayvkhibnhnhnngng thuc, nng glucose trong
mu s v mc bnh thng.33.4.8. Lot d dy t trngyl mt TDKMM gp kh
nhiu,trn83bnh nhn,chim19,04% viccbiuhinbnhnhnthy nngrtvngthngv hi,
chua,au vngthngv...Trongchc32bnhnhn(chim34,41%)clmxt
nghimcnlmsngnisoid dyvcchnonvimddy,cnli
chltheocmgiccabnhnhn.khcphccctcdngtrn,cc bc s dng cc nhm thuc trong
bng 3.17.Bng 3.17:Cc nhm thuc iu tr TDKMM lot d dy t trngSTT Nhm
thuc Thuc s dng n T l%1 AntacidGastropulgitePepsan70 84,342c ch bm
protonOmeprazol (Losec, Helizol) Esomeprazol (Nexium)56 67,473 Khng
th th H2CimetidinRanitidin (Dudine, Zan tac)23 27,7144Qua bngta
thy,khibnh nhnccmgicnngrtddy, chua.
Antacidlnhmthuccbnhnhnsdngnhiunhtchim84,34%, tip theol nhm c ch bm
proton,chim 67,47%.c bit,c 47bnh n c s dng phi hp hai nhm antacid v
nhm c ch bm proton hoc nhm khngththH2.Trong khi khost,chngti
thyc7bnh nhncbin chngxuthuyttiuhovciutrbngCimetidin400mg/ng/ngy
quangtim tnh mch.Vi cc bnh nhn ny,sau mt thigianiu tr ti bnh vin, h
ht cm gic nng rt vng thng v v khi iu tr ngoi tr vn c dng cc thuc d
phng lot d dy t trng.45PHN 4 KT LUN V XUT4.1. KT LUNSau khi hon
thnh ti, chng ti rt ra mt s kt lun sau:V bnh h thng90,14% bnh nhn
mc bnh h thng l n.M hnh bnh h thng:SLE (81,65%);XCB(12,16%);VDC
(3,67%) v VNQM (2,52%).63,53% bnh nhn trong tui t 18 n 40.