NGUYN TC S DNG GLUCOCORTICOID

Nguyn Th Mai Hong MC TIU: Sau khi hc xong bi ny, sinh vin c th: 1. Trnh by c c ch iu ha tit cortisol trong c th. 2. Phn tch c mi lin quan gia tc dng v tc dng khng mong mun ca cc thuc nhm glucocorticoid. 3. Trnh by c cc bin php khc phc tc dng khng mong mun ca glucocrticoid. 4. Phn tch c cc nguyn tc s dng glucocorticoid trong iu tr. 5. Vn dng nguyn tc s dng glucocorticoid vo cc tnh hung lm sng c th.

M U
Corticosteroid l hormone ca v thng thn c phn loi thnh 2 nhm da trn hot tnh: glucocorticoid (GC) c tc ng ln chuyn ha v mineralocorticoid c tc ng iu ha in gii. Trong , GC l hormone c vai tr quan trng v n nh hng n nhiu hot ng c tnh cht sinh mng ca c th (chuyn ha nng lng, chuyn ha nc in gii, tc ng trn h thn kinh trung ng, h to mu). Hormone thin nhin do c th sn xut ra l cortisol (hydrocortisone) c dng u tin trong liu php hormone thay th cho bnh nhn suy v thng thn (bnh Addison). Ngoi tc ng trn chuyn ha, GC v cc dn cht tng hp cn c nhiu tc dng khc nh khng vim, c ch min dch Chnh tc dng ca corticosteroid trong iu tr nhiu bnh l vim v t min khin GC tr thnh 1 trong nhng nhm thuc c ch nh rng ri nht. iu ng lu l c tc dng chng vim hay c ch min dch cn phi dng liu cao hn sinh l rt nhiu v nguy c xut hin tc dng ph do cng tng ln ng k, thm ch c th gy nguy him n tnh mng ca bnh nhn. V vy, trc khi quyt nh iu tr bng corticoid, lun phi cn nhc gia ch li trong iu tr v nguy c ca vic dng thuc i vi bnh nhn. Trn cng v l ngi dc s lm sng, cn phi hiu r nhng nguyn tc s dng GC. Nhng ni dung trong bi ny nhm cung cp kin thc c bn s dng GC an ton v hiu qu.

1 NHP SINH L CA S TIT CORTISOL

Cortisol (hydrocortison) l GC thin nhin c hot tnh do v thng thn tit ra. Nng glucocorticoid thch hp trong c th c iu ha bi trc di i tuyn yn tuyn thng thn (trc HPA) (hnh 1). C 3 cch iu ha hot ng ca trc HPA: nhp ngy m, iu ha ngc bi GC v tng tng hp steroid p ng vi stress.

Nhp ngy m

Stress

Vng di i

Tin yn

iu ha ngc

V thng thn

Cortisol (gn protein)

Cortisol (T do)

Tc ng ln cc qu trnh sinh l v chuyn ha

Thn (tuyn thng thn trn)

Cortisol t do trong nc tiu

Hnh 1: C ch iu ha s bi tit cortisol trong c th.

1.1 iu ha ngc bi GC
Bnh thng, v thng thn bi tit cortisol di s kch thch ca ACTH (adrenocorticotropic hormone) ca thy trc tuyn yn. S phng thch ACTH li chu kch thch ca CRH (Corticotropin-releasing hormone) ca vng di i. Ngc li, khi nng cortisol trong mu cao s c ch ngc li vng di i v tuyn yn lm gim sn xut CRH v ACTH. Tng t, khi iu tr bng GC tng hp liu cao trong thi gian di, cc thuc ny s c ch vng di i v tuyn yn gim sn xut cc hormone iu ha bi tit cortisol, dn n suy gim chc nng ca tuyn thng thn. V vy, i vi nhng trng hp ny, lun phi gim liu GC t t trc khi ngng iu tr.

1.2 Nhp ngy m

Nhp bi tit hng ngy ca cortisol c to thnh do trung tm iu ha no theo chu k ng - thc. Theo , nh nng ACTH t c vo sng sm dn n nng cortisol lu thng trong mu tng cao v t nh vo khong 8h sng. Mc hormone s gim dn cho n 24h m v bt u tng tr li t khong 3-4h sng (hnh 2

2). Nh vy, tuyn thng thn ngh v m. Nu nh ta dng thuc GC vo bui chiu th tuyn thng thn s b c ch lin tc v suy gim chc nng mnh khi ngng thuc. V l do ny, nn ch nh dng GC vo bui sng hoc ch dng thuc cch ngy i vi nhng trng hp bt buc phi dng thuc ko di.

Cortisol huyt thanh (g/dl)

Gi (h) Hnh 2: S dao ng ca mc cortisol c bi tit trong ngy

1.3 nh hng ca stress

Bnh thng, mi ngy v thng thn tit khong 15 25 mg cortisol nhng khi c stress (chn thng, phu thut, st, nhim trng, tn thng tm l), lng hormone ny tng ln 2-3 ln hay thm ch n 10 ln. Trong nhng trng hp ny, nu chc nng tuyn thng thn bnh thng th c kh nng tng hot ng p ng nhu cu. Ngc li, nu chc nng thng thn suy gim s khng kh nng p ng v c th dn n suy thng thn cp. S thiu ht hormone t ngt c th dn n t vong do cc c quan phc v chc nng sng nh tim, no, thn b thiu nng lng. Suy thng thn cp cng thng xy ra khi ngng t ngt GC sau 1 t iu tr vi liu cao v ko di. Khi , chc nng thng thn ch tr li bnh thng sau khong 3-4 thng, thm ch l 1 nm sau khi ngng GC. V l do ny, nn theo di bnh nhn cho ti 1 nm k t khi ngng iu tr. Trong thi gian ny, nu gp cc stress th nht thit phi cho bnh nhn dng li GC vi liu dng trc khi ngng thuc.

2 TC DNG
2.1 Tc dng sinh l 2.1.1 Tc dng trn chuyn ha
2.1.1.1Trn chuyn ha glucide GC kch thch d tr glycogen ti gan v tng tng hp glucose t cc acid amin v glycerol. Ti m ngoi bin, GC ngn cn vn chuyn glucose vo trong t bo, do lm gim s dng glucose m ngoi bin, tng glucose huyt. iu ny gip c th tit 3

kim nng lng dnh cho cc c quan sinh mng (no, tim). Trong iu tr, GC c th gy ra hoc lm nng thm tnh trng i tho ng sn c. 2.1.1.2Trn chuyn ha protein GC lm tng thoi ha protein cung cp cho qu trnh tn to glucose, dn n teo c, thng bng N m tnh v nh hng n nhiu m trong c th: m lin kt km bn vng do gim tng hp collagen gy rn da, chm lin so; m lympho b teo, xp xng do teo cc thm m lin kt ni lng ng cc cht v c to nn khung xng dn n d gy xng, ln t sng, hoi t v khun c xng i. 2.1.1.3Trn chuyn ha lipide GC c tc dng hy lipid trong cc t bo m m, gii phng glycerol v acid bo t do. Ngoi ra, GC cn c tc dng phn b li m trong c th, lm m tp trung nhiu mt (khun mt trng rm moon face), c v na thn trn (g tru buffalo hump), nhng li gim phn b m cc chi v na thn di. C ch gy ri lon phn b m nh trong bnh Cushing n nay vn cha c hiu r. C gi thit cho rng t bo m na thn trn p ng ch yu vi tng insulin do GC lm tng ng huyt, trong khi cc t bo m cc chi v thn di li km nhy cm vi insulin v p ng vi tc dng hy lipid. 2.1.1.4Trn chuyn ha nc v in gii GC cng c tc dng mineralocorticoid gy gi Na+ v nc, tng bi xut K+ nhng yu hn nhiu so vi aldosterone. GC lm tng o thi Ca2+ qua thn, lm gim hp thu Ca2+ rut do i khng vitamin D. Ca2+ huyt gim kch thch tuyn cn gip tng huy ng Ca2+ t xng gy long xng, tr em chm ln.

2.1.2 Tc dng trn cc c quan, m

Trn h thn kinh trung ng: lm thay i tnh tnh, gy thm n. Trn h to mu: GC t nh hng n s to hng cu liu sinh l nhng li lm tng hng cu khi dng liu cao hoc khi b Cushing v ngc li, gim hng cu trong hi chng Addison. Vi bch cu, GC lm tng bch cu a nhn nhng li lm gim s lng lympho bo do hy cc c quan lympho, lm gim chc nng ca bch cu (thot mch, di chuyn n t chc vim). Cc tc dng ca GC trn s to mu c ng dng trong iu tr ung th bch cu hoc lm tng nhanh lng hng cu sau x tr hay ha tr liu ung th. Trn h tim mch: Ngoi tc dng mineralocorticoid gy gi mui v nc, GC cn gp phn iu ha huyt p do lm tng hot tnh ca cc cht gy co mch nh norepineprine v angiotensin II. Trn h tiu ha: tng tit acid dch v v pepsin, gim tit cht nhy, gim tng hp prostaglandin E1, E2 bo v nim mc d dy.

2.2 Tc dng c dng trong iu tr 2.2.1 Tc dng khng vim

GC l thuc khng vim mnh nht v thng c dng nht trong cc bnh vim cp v mn tnh do bt k nguyn nhn g nh hen, vim mi d ng, thp khp, 4

lupus ban . Khc vi cc thuc khng vim non-steroid (NSAIDs) ch tc ng trn giai on cui ca qu trnh sinh tng hp prostaglandin, GC tc ng giai on sm hn - c ch phospholipase A2, ngn tng hp acid arachidonic, do lm gim phng thch leucotrien v prostaglandin. Tc dng ny cn c tng cng nh GC lm gim tit cc cht trung gian ha hc nh serotonin, histamin t t bo mast, gim tnh thm thnh mch v c ch s di chuyn ca bch cu n t chc vim. Cc GC tng hp, c bit l loi c nhm th F nh dexamethasone, betamethasone c hot tnh khng vim cao hn cortisol t nhin (bng 1).

Hnh 3: V tr tc ng ca GC v NSAIDs

2.2.2 Tc dng khng d ng

Cc phn ng d ng xy ra do s gn IgE hot ha trn cc receptor c hiu ca t bo mast v basophil di tc dng ca d nguyn lm phng thch cc cht trung gian ha hc. GC ngn chn phn ng d ng bng cch c ch phospholipase C dn n phong ta s phng thch cc cht trung gian ha hc ca phn ng d ng. Nh vy, d IgE gn trn t bo mast nhng khng th hot ha c nhng t bo . V vy, GC l nhng cht chng d ng mnh.

Hnh 4: C ch tc dng chng d ng ca GC

2.2.3 Tc dng c ch min dch

GC tc dng ch yu trn min dch t bo (lympho T), t nh hng n min dch th dch (lympho B). C ch tc dng bao gm: c ch tng sinh cc t bo lympho T do lm gim sn xut interleukin-1 t i thc bo v interleukin-2 t T4. Gim hot tnh gy c t bo ca cc lympho T (T8) v cc kt bo git t nhin (natural killer NK) do c ch sn xut interleukin-2 v interferon gamma. c ch sn xut yu t hoi t u (tumor necrosis factor TNF) v interferon dn n lm suy gim hot tnh dit khun, kh nng nhn din khng nguyn ca i thc bo v gy c t bo. Nh tc dng c ch min dch, GC c s dng chng thi ghp trong ghp c quan hay iu tr cc bnh t min nh lupus ban , hen, hoc phi hp trong x tr shock phn v. Ngoi ra, do c ch tng sinh, GC c tc dng tt trong iu tr bnh bch cu lympho cp, bnh Hodgkin. Tuy nhin, cng do c ch min dch, GC lm gim sc khng ca c th v lm tng nguy c nhim trng, nhim nm.

Bng 1: So snh hot lc ca mt s corticoid thng dng

Hot cht Cortisol Cortison Prednison Prednisolon methyl-prednisolon Triamcinolon Dexamethason Betamethason t1/2 (h) 1,5 0,5 1,0 2,5 2,5 3,5 3,5 5,0 Thi gian tc ng (h) (*) 8 - 12 8 - 12 12 - 36 12 - 36 12 - 36 12 - 36 36 - 72 36 - 72 Hiu lc khng vim 1 0,8 4 4 5 5 25 25 Hiu lc gi Na+ 1 0,8 0,8 0,8 0,5 0 0 0 Liu sinh Liu khng l (mg) vim (mg) 20 25 5 5 4 4 0,75 0,75 80 100 20 20 15 15 3 3

(*):Na i sinh hc ca thuc, c chia thnh 3 loi: ngn (8 12h); trung bnh (12 36h) v di (36 72h)

3 NG DNG TRONG IU TR
3.1 iu tr thay th khi thiu hormone
GC c ch nh iu tr thay th cho bnh nhn suy thng thn nguyn pht do tn thng cu trc hay chc nng ca v thng thn (bnh Addison) hoc th pht do tn thng vng di i hay thy trc tuyn yn. Suy thng thn th pht thng din tin m hn suy thng thn nguyn pht, c l do sinh tng hp mineralocorticoid vn c duy tr.

3.1.1 Suy thng thn cp

y l chng bnh nguy him c trng bi cc triu chng tiu ha (bun nn, nn, au bng) km theo mt nc, h Na+ huyt, tng K+ huyt, suy nhc, l , h huyt p. Bnh thng do ri lon tuyn thng thn hn l tuyn yn hay vng di i, cng c th gp sau khi ngng GC t ngt sau mt t iu tr ko di hay liu cao. iu tr: B nc v in gii: truyn IV dung dch NaCl 0,9% v glucose 5%. GC liu cao: tim IV nhanh 100 mg hydrocortison, sau truyn lin tc 100 mg mi 8h kt hp iu tr nguyn nhn gy bnh (nhim trng, chn thng, mt mu). Khi tnh trng bnh nhn n nh, c th gim liu hydrocortisone n 25 mg mi 6-8h IM hay PO. Bnh nhn c iu tr tip tc nh suy thng thn mn tnh.

3.1.2 Suy thng thn mn

Bnh nhn suy thng thn mn c nhiu biu hin ging cn suy thng thn cp nhng mc nh hn. Nguyn nhn c th nguyn pht do tn thng tuyn thng thn nh bnh t min, lao thng thn, suy gim min dch mc phi, xut huyt thng thn hay suy thng thn th pht.

Cc bnh nhn ny cn thc hin ch iu tr hng ngy vi GC: thng dng hydrocortisone 20 30 mg/ngy. Nu dng cortison acetat khng hot tnh, c chuyn ha nh enzyme 11-hydroxysteroid dehydrogenase 1 (11HSD1) thnh dng cortisol c hot tnh cn dng liu cao hn (25 37,5 mg/ngy). Nhm bt chc nhp tit cortisol hng ngy ca c th, thng dng 2/3 liu vo bui sng (~ 8h) v 1/3 liu vo bui chiu (~ 16h). Mc d 1 s bnh nhn suy thng thn nguyn pht c th n nh ch vi ch dng hydrocortison v n mui y , a s nhng bnh nhn ny vn cn phi iu tr thay th bng mineralocorticoid, thng dng fludrocortison 0,05 0,2 mg/ngy. Bnh nhn suy thng thn th pht khng cn b sung mineralocorticoid. Lu i vi bnh nhn b suy gim ton b chc nng tuyn yn, cn phi bt u iu tr bng GC trc khi khi u iu tr bng hormone thyroid trnh nguy c suy thng cp do hormone thyroid lm tng chuyn ha cortisol. Hiu chnh liu phi da trn lm sng v cc ch s sinh ha. Cn iu chnh liu GC khi bnh nhn dng km thuc tng tc vi GC (bng 2). Nu c ch nh phu thut th bnh nhn suy thng thn cn c ch nh liu GC cao hn: hydrocortison 80 100 mg IV mi 8h. Sau phu thut, liu GC c gim phn na mi ngy n khi t n liu duy tr bnh thng bng ng ung.

Bng 2: Mt s thuc tng tc vi glucocorticoid Thuc gy tng tc Thuc b tng tc Barbiturate Thuc nga thai PO Estrogen Hydantoin Ketoconazol Rifampin Cholestyramin hydrocortison corticosteroid C ch gim tc dng tng nng v gim o thi gim o thi gim tc dng do tng o thi gim o thi gim tc dng do tng o thi gim tc dng i khng tc dng ca thuc Thuc khng cholinesterase khng cholinesterase trong bnh nhc c nng Thuc chng ng PO Digitalis Corticosteroid Isoniazid Thuc li tiu thi K Salicylate Somatrem Theophylline Tng/ gim tc dng ca thuc chng ng nguy c tng c tnh ca digitalis do gim K+ huyt gim nng isoniazid trong mu h K+ huyt gim tc dng do lm gim nng salicylate trong mu c ch tc dng kch thch tng trng ca somatrem gim K+ huyt, thay i hot tnh ca theophylline

3.2 Cc ch nh ngoi mc ch thay th hormon

Cc ch phm GC tng hp cn c ch nh trong rt nhiu bnh l khc:

3.2.1 Bnh khp

GC c dng rng ri trong iu tri nhiu bnh khp v l nhm thuc chnh trong iu tr mt s bnh nghim trng nh lupus ban h thng, vim khp dng thp... GC thng c dng phi hp vi cc tc nhn c ch min dch khc nh cyclophosphamide, methotrexate nhm kim sot tt hn v lu di so vi dng steroid mt mnh. Cc GC tc dng trung bnh nh prednison v methylprednisone thng c a chung hn cc steroid tc dng di nh dexamethasone. Trong vim khp dng thp, GC c dng nh tc nhn lm chm tin trin v lm gim triu chng bnh n khi cc thuc tc dng chm hn nh methotrexate hay 9

thuc tc ng trn TNF pht huy tc dng. Khi u thng dng prednisone 5 10 mg/ngy. Trong cn vim cp, c th dng prednisone 20 40 mg/ngy hay tng ng, sau gim liu nhanh. Bnh nhn c triu chng gii hn mt s t khp c th c iu tr bng cch tim steroid vo khp. Ty kch thc khp c th dng triamcinolone acetonide 5 20 mg hay tng ng. i vi cc bnh thoi ha khp khng vim (nh vim xng khp) hay trong mt s hi chng au khu tr (nh vim gn hay vim ti thanh mc), c th tim GC ti ch trong giai on bng pht. Cc ln tim trong khp phi cch nhau t nht 3 thng nhm gim thiu tc dng ph gy ph hy khp.

3.2.2 Bnh thn

GC l thuc hng u iu tr cho bnh nhn b hi chng thn h nhim m. Liu khi u prednisone 1 2 mg/kg/ngy trong 6 tun, sau gim dn trong 6 8 tun.

3.2.3 Bnh d ng
Tc dng ca GC trong cc bnh d ng thng xut hin chm. Do , nhng bnh nhn d ng nng nh shock phn v cn c iu tr ngay lp tc bng epineprine. Cc biu hin d ng do ong t, my ay, ph mch c th c gii quyt bng liu thch hp GC ng PO. i vi cc bnh d ng nng, cn dng GC ng IV (methylprednisolone 125 mg IV mi 6h, hoc tng ng). Trong vim mi d ng, GC dng xt hin l chn la ca nhiu chuyn gia.

3.2.4 Hen ph qun

GC c dng t lu trong iu tr hen suyn di dng kh dung v c ng ton thn. GC dng ht dng phng nga hn l iu tr cn hen cp. Thuc c chn la l cc GC c hiu lc mnh, tc dng di nh beclomethasone dipropionate, fluticasone propionate, triamcinolone acetonide Trong cn hen cp, thng dng liu cao GC nh prednisolone 40 60 mg/ngy trong 5 ngy i vi ngi ln hay 1 2 mg/kg/ngy i vi tr em; gim liu trong 1 tun. Ch iu tr cch ngy vi prednisone PO kh ph bin trc y trong iu tr hen suyn mn nng nhng hin nay, phn ln bnh nhn hen c kim sot tt vi GC dng xng ht.

3.2.5 Trong thai k

PN mang thai sinh non hoc c nguy c sinh non (trc 37 tun) thng c ch nh GC nh beclomethasone 2 liu 12 mg IM mi 24h hay 4 liu dexamethasone IM mi 12h nhm lm gim nguy c suy kit h hp, xut huyt trong tht v t vong tr sinh non.

3.2.6 Bnh mt
Nh tc dng khng vim, GC c dng ti ch kim sot vim mt do d ng, nhim trng, vim sau phu thut. C th dng GC ng ton thn trong iu tr

10

vim thn kinh th gic hay tim GC vo thy tinh th trong iu tr thoi ha im vng do tui, bin chng vng mc do i tho ng.

3.2.7 Cc bnh d dy rut

GC c ch nh nhiu trong cc bnh vim rut nh bnh Crohn, vim lot i trng. Liu khi u thng dng l prednisone 40 60 mg/ngy, gim liu dn trong vi tun n vi thng. Dng thuc tht (hydrocortisone 100 mg/60 ml) hu ch vi bnh gii hn trc trng hay kt trng tri. Mt s bnh nhn khng p ng vi GC v c xem l khng steroid hay l thuc steroid.

3.2.8 Ung th
GC cho hiu qu cao trong iu tr bnh bch cu cp tr em v u lympho c tnh c ngi ln v tr em nh tc dng ph hy v c ch phn bo ca cc t bo lympho. GC cng c ch nh trong iu tr bnh Hodgkin v u lympho khng phi Hodgkin, u ty, ung th bch cu lympho mn v c bit hu dng trong kim sot thiu mu tiu huyt do t min v gim tiu cu do u lympho mn.

3.2.9 Ghp c quan

Prednisone, prednisolone v cc GC khc c dng n tr hay phi hp vi cc cht c ch min dch khc trong iu tr chng thi ghp v cc bnh t min.

3.2.10 Bnh da
GC c hiu qu vi cc bnh l da nh tc dng khng vim v c ch min dch. GC c th c dng ti ch vi cc ch phm cream bi da, ming dn da hay dng ng ton thn (PO/ IM/ IV).

11

Bng 3: Phn loi GC dng thuc bi da *

Nhm 1 Tn hot cht Bethamethason dipropionat Clobethasol propionat Halobethasol propionat Amcinonid Betamethasol dipropionat 2 Fluocinonid Halocinonid Betamethason dipropionat 3 Betamethason valerate Triamcinolon acetonid Amcinonid Flucinolon acetonid 4 Flucinolon acetonid Hydrocortison valerat Triamcinolon acetonid Betamethason dipropionat Betamethasone valerat 5 Flucinolon acetonid Hydrocortison valerat Triamcinolon acetonid Triamcinolon acetonid Aclomethason dipropionat 6 Desonid Flucinolon acetonid Dexamethason natri phosphat 7 Hydrocortison * Tim lc gim dn t 1 n 7 Dng ch phm, nng cream, thuc m 0,05% cream, thuc m 0,05% thuc m 0,05% thuc m 0,1% thuc m 0,05% cream, thuc m, gel 0,05% cream, thuc m 0,1% cream 0,05% thuc m 0,1% thuc m 0,1%, cream 0,5% cream 0,1% cream 0,2% thuc m 0,025% thuc m 0,2% thuc m 0,1% lotion 0,05% cream, lotion 0.1% cream 0,025% cream 0,2% cream 0,1% cream 0,025% cream, thuc m 0,05% cream 0,05% cream, dung dch 0,01% cream 0,1% cream, thuc m, lotion 0,5%, 1%, 2,5% Tn thng mi DIPROLEN TEMOVATE ULTRAVATE CYCLOCORT DIPROSONE LIDEX, FLUDEX HALOG DIPROSONE BETATREX ARISTOCORT CYCLOCORT SYNALAR-HP SYNALAR WESTCORT KENALOG DIPROSONE BETATREX SYNALAR WESTCORT KENALOG ARISTOCORT ACLOVAT TRIDESILON SYNALAR DECADRON DECADRON NUTRACORT PENECORT

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4 TC DNG PH V CCH KHC PHC

4.1 Tc dng ph do dng liu cao hoc dng ko di 4.1.1 Ri lon nc in gii
Nhim kim, h K huyt, tng gi Na+ v nc gy ph, tng huyt p. Cn c ch n t mui, b sung K. Nn chn cc ch phm t hot tnh mineralocorticoid nh triamcinolone, betamethasone.

4.1.2 Nhim khun

GC c tc dng c ch min dch nn lm tng nguy c nhim khun v lm bc l mt bnh lao tim tng. Do , ch dng GC khi bit chc khng c nhim khun hoc nu cn, phi phi hp vi thuc khng sinh hay khng nm thch hp.

4.1.3 Lot ng tiu ha

Kh nng gy lot mi ca GC hin vn cn l vn cn tranh lun. Tuy nhin, GC c th gy chy mu hoc lm thng lot hin c hay so lot c. V vy, ch dng GC cho bnh nhn khng c tin s hoc khng b lot ng tiu ha.

4.1.4 Nhc c, teo c

Thng xy ra vi cc c gn gc chi. c nhiu trng hp bnh nhn gp tai bin teo c i, phi chng nng hoc ngi xe ln. i vi bnh nhn cao tui, bnh nhn hen hoc COPD, thuc lm nhc c h hp c th lm nng thm tnh trng suy h hp.

4.1.5 Thay i tnh tnh

GC c th gy kch thch thn kinh trung ng gy lc quan nhng v sau lm bt rt, bn chn, lo u, kh ng. Khng loi tr kh nng GC c th lm bc l mt bnh tm thn tim n.

4.1.6 c thy tinh th

Nhiu khi gim liu hoc ngng iu tr, c thy tinh th vn tin trin. V vy, khi dng GC ko di vi liu tng ng prednison 10 - 15 mg/ngy, cn phi nh k kim tra mt.

4.1.7 Long xng

GC lm gim mt xng theo nhiu c ch: c ch hormone sinh dc, tng o thi Ca qua thn, gim hp thu Ca rut, tng huy ng Ca t xng vo mu do tc dng i khng vi vitamin D v c ch tc ng ca to ct bo. phng nga long xng do s dng GC, cn: nh k kim tra mt xng, nht l gai sng v c xng i. Ch n b sung Ca (1500 mg/ngy) v vitamin D (400 UI/ngy). Nu khng c chng ch nh, nn dng liu php hormone thay th cho ph n tin mn kinh hoc mn kinh, b sung testosterone cho nam gii khi c h testosterone mu. Dng cc thuc iu tr long xng nh alendronate hay etidronate. 13

4.1.8 Hoi t xng

y cng l mt tai bin thng gp. l loi hoi t v mch hoc v khun, thng b u xng i. au khp, cng khp thng l nhng triu chng sm. Hoi t xng thng tin trin dn dn v nhiu bnh nhn cui cng phi thay khp.

4.1.9 Chm pht trin tr em

Khi dng vi liu sinh l, cortisol kch thch tit hormone tng trng (grown hormone GH) nhng li c ch hormone ny khi dng liu cao. Tc dng gy chm ln tr em l hu qu ca s gim mc GH kt hp vi c ch s to xng v gim hot ng ca hormone tuyn gip. tui dy th, s c ch hot ng ca tuyn sinh dc cng l nguyn nhn gy chm ln v ri lon sinh dc. hn ch tc dng ph ny, cn c gng hn ch vic k n nhm thuc ny tr em v nu cn, nn dng cc GC t nhin nh cortisol, cortisone hay prednisolon; ch nn dng liu ti thiu c hiu qu v trong thi gian ngn nht c th. Khi phi dng ko di, nn chuyn sang ch dng thuc cch ngy gim bt hin tng c ch trin min tuyn thng thn, sinh dc v tuyn gip. Khuyn khch tr vn ng, chi th thao v c ch dinh dng giu m v Ca, tt nht l dng cc ch phm ch bin t sa.

4.1.10 Tha corticoid v bnh Cushing do thuc

Khi s dng GC ko di cng gy cc biu hin nh bnh Cushing. Tuy nhin, trong Cushing t pht th mc cortisol trong mu cao km tng ACTH, cn trong Cushing do thuc th ngc li: ACTH gim, cc triu chng ri lon ni tit do tha androgen cng t gp hn hoc t trm trng hn, ph do Na+ v nc ch gp khi s dng hydrocortisone v prednisolone. Khi thy c cc biu hin ca bnh Cushing do thuc, phi ngng iu tr. Lu l vn phi gim liu t t ch tuyt i khng ngng thuc t ngt. Sau khi ngng thuc, nu bnh ti pht th nn dng cc thuc c hiu iu tr triu chng tt hn l quay li dng GC.

4.2 Tc dng ph do ngng iu tr t ngt

Ngng GC t ngt sau t iu tr ko di (hn 2 tun) c th lm bnh bng pht tr li v gy suy thng thn cp do trc HPA b c ch. Mc v di ca suy thng thn sau khi iu tr bng GC ph thuc tng c th nn kh xc nh. Nhiu bnh nhn c th hi phc sau vi tun, vi thng, nhng c ngi phi mt n 1 nm hoc hn. lm gim nguy c suy thng thn cp do dng GC, cn gim thiu s c ch trc HPA bng cch: Dng cc thuc c t1/2 ngn nh hydrocortisone hay prednisolone. Dng 1 liu bui sng. Khi dng thuc ko di, nn dng ch dng thuc cch ngy to khong ngh cho tuyn thng thn v do , t gy c ch trc HPA hn. Phi gim liu t t trc khi ngng thuc, k c khi dng cc ch phm bi ngoi da. 14

4.3 Tc dng ph do dng GC ti ch

GC ng xng ht c th gy mt s tc dng ph nh kh pht m; nhim Candida hng (c th khc phc bng cch sc ming sau khi xt thuc). Hin tng bi nhim nm, vi khun, virus c th xy ra khi dng GC di dng ch phm nh mt mi. Do , khng nh mt/ mi cc ch phm cha GC khi c nhim virus hay nm. c thy tinh th v tng nhn p cng l cc tai bin thng gp khi dng dng thuc nh mt v do vy b chng ch nh trong cc trng hp ny. Tai bin thng gp khi dng cc ch phm ngoi da l teo da, x cng b, chm lin so, mn trng c hoc bi nhim nm, vi khun, virus, nht l khi iu tr ko di vi nhng ch phm GC c tim lc mnh. gim tc dng ph ny, cch tt nht l hn ch bi thuc ko di v khng t dng thuc.

5 CHNG CH NH V THN TRNG KHI S DNG

Cc trng hp nhim khun, nhim nm hay virus m cha c iu tr c hiu. Tim chng vaccine virus sng. Lot d dy t trng tin trin. Khng c chng ch nh tuyt i cho nhng trng hp iu tr ngn ngy hay iu tr cc bnh e da tnh mng. Thn trng khi s dng GC cho cc bnh nhn tm thn, i tho ng, tng huyt p, xp xng, suy gim chc nng gan, thn hoc suy tim Khng nn dng GC nu c th dng thuc khc v phi hiu chnh liu nu bt buc phi s dng.

6 NGUYN TC CHUNG KHI S DNG GLUCOCORTICOID

GC em li nhiu ch li gip kim sot tt bnh tt, nhng bn cnh thuc cng c nguy c gy nhiu tc dng ph nghim trng, lm gim cht lng sng, thm ch nguy him cho tnh mng bnh nhn. t hiu qu iu tr tt v gim thiu nguy c c tnh lin quan n GC, cn tun th mt s nguyn tc chung sau y: Lun cn nhc gia nguy c v li ch trc khi ch nh GC cho bnh nhn. Tun th cc chng ch nh ca thuc. Nn chn mc liu thp nht c hiu qu v trnh dng ko di do phn ln tc dng ph ca thuc t l vi liu dng v thi gian dng thuc. Nn chn loi GC c thi gian tc dng ngn hoc va (nh prednisolone) v nhng ch phm c tc dng cng ko di cng tng nguy c gp tc dng ph. Ch n: m bo cung cp K, Ca v vitamin D; tng protein; hn ch n mui, bt ng v cht bo. trnh nguy c suy thng thn cp do thuc, tuyt i khng ngng thuc t ngt sau mt t iu tr di ngy (> 2 tun), k c khi dng liu rt thp. gim nguy c c ch trc HPA, nn dng thuc 1 ln vo khong 8h sng, hoc nu dng liu cao th c th dng 2/3 liu bui sng v 1/3 cn li vo bui chiu. Ch dng thuc cch ngy rt hu ch i vi bnh nhn phi iu tr lu di vi GC nh trong trng hp bnh nhn vim lot rut kt, ghp thn, vim da 15

mn tnh, nhc c nng, hen v gim c ch trc HPA nn gim kh nng gy chm ln tr em v suy thng thn do thuc. Ch iu tr cch ngy nh sau: Khi mi bt u iu tr th phi dng thuc hng ngy, khi bnh tin trin tt v bt u n nh th chuyn sang ch dng thuc cch ngy. chun b chuyn sang ch dng cch ngy, trc ht phi gim liu t t n khi t mc liu tng ng prednisolon 15 20 mg/ngy ung 1 ln vo bui sng. Tuyt i khng ct ngay thuc ngy nh ngng m vn phi gim liu t t mi ln 10 20% liu ang dng cho n ht. Mi ln nh vy phi duy tr liu trong 3 ngy thm d phn ng ca bnh nhn. Nu trong thi gian , bnh nhn xut hin triu chng thiu nng thng thn nh mt mi, au c, au khp, bun nn, h huyt p th phi tng liu tr li. Bng 3: Cch gim liu chuyn sang ch iu tr cch ngy (Gi thit liu ban u l prednisolone 60 mg/ngy). Gim mi ln 5 mg, chu k 3 ngy cho ti khi t liu 20 mg/ngy.
Ngy 1 2 3 4 5 6 7 8 Liu (mg) 55 55 55 50 50 50 45 45 Ngy 9 10 11 12 13 14 15 16 Liu (mg) 45 40 40 40 35 35 35 30 Ngy 17 18 19 20 21 22 23 24 Liu (mg) 30 30 25 25 25 20 20 20

Gim mi ln 2,5 mg, chu k 3 ngy cho n 0 mg ngy nh ct thuc

Ngy Liu (mg) Ngy Liu (mg) Ngy Liu (mg)

25 26 27 28 29 30 31

20 17,5 20 17,5 20 17,5 20

41 42 43 44 45 46 47 16

20 12,5 20 10 20 10 20

57 58 59 60 61 62 63

20 5 20 5 20 2,5 20

32 33 34 35 36 37 38 39 40

15 20 15 20 15 20 12,5 20 12,5

48 49 50 51 52 53 54 55 56

10 20 7,5 20 7,5 20 7,5 20 5

64 65 66 67 68 69 70 71 72

2,5 20 2,5 20 0 20 0 20 0

(Theo Clin. Pharm. Ther. 1992)

Ti liu tham kho

1. Laurence Brunton, Keith Parker, Donald Blumenthal, Iain Buxton; Goodman Gilmans The Pharmacological Basis of Therapeutics, 11th ed, McGraw-Hill (2008). 2. PN Bennett, MJ Brown; Clinical Pharmacology, 9th ed, Churchill Livingstone (2003). 3. Joseph Dipiro, Robert Talbert, Gary Yee, Gary Matzke, Barbara Wells, Micheal Posey; Pharmacotherapy: A Pathophysiologic Approach; 7th ed, McGraw-Hill (2008). 4. Wayne Kradjan; Applied Therapeutics: The Clinical Use of Drugs; 8th ed, Lippincott Williams & Wilkins (2004). 5. o Vn Phan; Cc thuc gim au chng vim, NXB Y Hc (2004). 6. B mn Dc lm sng Trng i hc Dc H Ni; Dc lm sng, NXB Y Hc (2006). 7. Trn Th Thu Hng; Dc lc hc, 7th ed, NXB Phng ng(2005).

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TNH HUNG LM SNG THO LUN Tnh hung 1: B L. 43 tui ang ch ghp gan. B b vim khp gn 10 nm nay v hin ang dng prednisone kim sot cc triu chng vim. Gn y, b than phin v thng b sng au u gi tri, khng khi dng thuc. BS ch nh tng liu nhng tnh trng au vn khng ci thin. Xt nghim: Bilirubin ton phn 3,1 mg/dL ( 1 mg/dL) AST 93 U/L (< 45 U/L) ALT 65 U/L (< 45 U/L)

Cu hi: 1. V sao tnh trng vim khp ca b L. li tin trin nng hn? 2. Phi chn la thuc no kim sot bnh khp cho b L.? Tnh hung 2: ng A. 56 tui c tin s vim mng mch nho trc ti pht nhiu ln. Trc y chng bnh ny c kim sot tt vi thuc nh mt steroid v thuc khng cholinergic. Tuy nhin, ln mi y, mt ng p ng rt chm vi ch iu tr trn v BS phi ch nh tng liu steroid. 12 ngy sau khi tng liu, ng thy mt m v n BV khm. Thm khm cho thy ng b vim gic mc do Herpes simplex virus (HSV) v th lc gim 50%. Cu hi: 1. Yu t nguy c no dn n tnh trng nhim HSP ca ng A? 2. Nn x tr nh th no i vi tnh trng bnh ca ng A? Tnh hung 3: Mt PN 60 tui n BV vi triu chng ho v kh th trm trng. B ta than phin b kh th khi mi i c chng 1/3 on ng bnh thng v ho thng xuyn. Tin s: o i tho ng t 3 nm, kim sot tt bng ch n v tp th dc o HbA1C cch y 1 thng: 6,8% o COPD t 5 nm Khm LS: HA 130/ 70 mmHg Mch 120 ln/pht Nhp th 24 ln/pht Cn nng 81,5 kg

BN th kh kh, khng co ko c h hp ph, khng xanh tm Xt nghim: 18

ABG (Arterial Blood Gas) pH 7,46 PaO2 60 mmHg PaCO2 40 mmHg SaO2 88%

Spirometry FVC 3,2 FEV1 1,4

Thuc iu tr: o Albuterol khi cn o Prednisone 40 mg/ngy x 3 ngy gim liu trong 2 tun Vo ngy th 3, BN thng bo mc ng huyt o lc 4h l 350 mg/dl. Cu hi: 1. Nu nhng nguyn nhn gy tng ng huyt BN ny 2. Trnh by c im ca hin tng tng ng huyt do nguyn nhn trn 3. Trnh by chin lc iu tr thch hp cho BN ny Tnh hung 4: B B. 60 tui n phng khm do mt v yu. B ta ni thy cc triu chng mt mi tng dn trong vi nm nay nhng b ngh rng l do tui gi. Gn y, b thy mnh phi ngh ngi nhiu hn. B than phin thng b nn ma dn n gim cm gic ngon ming v st 4,55 kg trong vng 1 nm qua. B cng nhn thy cc vt so mi b sm mu li. Tin s bnh: o i tho ng type 1 t khi 5 tui, hin ang kim sot tt o Nhc gip, hin kim sot tt o Long xng (u gi) t 5 nm nay Tin s gia nh: khng r Tin s x hi: Th k v hu, khng ht thuc, ung ru hay dng thuc cm Thuc ang dng: o Insuline glargine 30UI khi i ng o Insulin Lispro 3 ln/ngy trong ba n tnh ton lng CH tiu th o Levothyroxine 75 g x 1 ln/ngy o Acetaminophen 1000 mg/8h khi cn gim gim au u gi o Cream capsaicin 0,075% x 3 ln/ngy gim au khp

19

Khm lm sng: o Sinh hiu: Ngi HA 108/70 mmHg Mch 74 ln/pht HA 96/68 mmHg ng Mch 86 ln/pht Nhp th 14 ln/pht Cn nng 68,18 kg Chiu cao 1,65 m

o Da: tng sc t np gp lng bn tay v gn nm v, so chn tri thm mu Xt nghim: Na+ 132 mEq/L (135 - 145) K+ 5,2 mEq/L (3,5 - 5) Cl98 mEq/L (98 - 108) HCO330 mEq/L (22 - 30) BUN 25 mg/dL (7 - 20) SCr 1,3 mg/dL (0,5 - 1,0) Glucose 120 mg/dL (76 - 120)

Cu hi: 1. B B c nhng biu hin v triu chng no gi suy thng thn? 2. Nhng biu hin ca b B c a ra gi no v nguyn nhn hay phn loi ca suy thng thn khng? 3. Cc xt nghim no cn thit xc nh nguyn nhn v khng nh chn on suy thng thn? Tnh hung 5: 1 b trai 6 thng tui c a vo bnh vin v tng cn bt thng t 3 thng nay. Khi nhp vin, b b bo ph phn thn trn, chn gy, da mng, c nhiu vt rn v nhiu mn dy ngc v lng. B m b cho hay gn y b hay b vim h hp ti pht. Nhit nch 37oC Hb 14,6 g/dL Urea huyt 25 mg/dL Na+ Huyt p 111/ 68 mmHg WBC 16600/mm3 SCr 0,4 mg/dL K+ Nhp tim 98 ln/pht Tiu cu 614000/mm3 Glucose huyt 91 mg/dL Cl-

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142 mEq/L Cortisol huyt (8AM) 0,66 g/dL

4 mEq/L ACTH huyt 7,1 pg/mL

105 mEq/L Cortisol sau khi IV 250 g/m2 ACTH 18,2 g/dL

Ba m b cho bit t mua pomade clobethasol propionate bi cho b 3 ln/ngy iu tr kh da t 3 thng nay. Tng cng b c bi 3 tube pomade 30g. ng b hon ton khng bit g v tc dng ph ca thuc. BS chn on b b hi chng Cushing do corticosteroid Cu hi: 1. Nu cc du hiu ca hi chng Cushing trn BN ny. 2. Chn la GC bi da thch hp cho i tng bnh ny. Tnh hung 6: 1 PN 32 tui nhp vin v au khp nng v th kh kh. Tin s: vim khp dng thp, au c, hen suyn Thuc ang dng: t 2 nm nay o Remicade (Infliximab) truyn IV mi 2 thng o Thuc gin ph qun dng ht o Prednisone 2 mg x 3 ln/ngy (PO) o Methotrexate 2,5 mg/tun. Nhp vin: o Ngng prednisone PO o Truyn IV Solumedrol (methylprednisolone) 20 mg x 2 ln/ngy x 4 ngy Xut vin: o Khng cn triu chng v BS khng ch nh li prednisone cho BN o 20 ngy sau, b n BV kim tra v au dai dng thng v o Xt nghim: Nhit 37,5oC WBC 42000/mm3 Na+ 134 mEq/L Huyt p 130/ 98 mmHg PMN 53% K+ 4,7 mEq/L 21 Mch 100 ln/pht Lymphocyte 41%

o Siu m ti mt cho thy tnh trng vim ti mt khng si. o BN c ch nh phu thut ct ti mt ngy hm sau. Khi gy m, BS pht hin BN c tin s dng GC lu di v mi ngng cch 21 ngy. ng ch nh tim bolus Solumedrol 40 mg IV 10 pht trc khi phu thut. Ca phu thut din ra tt p. 11 h sau phu thut: BN h huyt p v c chuyn xung phng hi sc ngoi (SICU). o pH mu 7,06 o HCO3- huyt tng 12 mEq/L BN khng p ng vi cc bin php truyn dch hi phc huyt p, hi sc tim phi v t vong 2h 30min sau . Khm nghim t thi cho thy tuyn thng thn ca BN b teo ng k. Cu hi: 1. Liu prednisone 2 mg x 3 ln/ngy gy suy thng thn? Ch nh ngng prednisone PO c hp l khng? 2. Nu cc du hiu gi suy thng thn BN ny khi nhp vin ln 2? 3. V sao IV Solumedrol 40 mg trc khi phu thut khng ngn nga tnh trng suy thng thn cp cho BN ny? 4. C nn ch nh phu thut cho BN ny hay khng? Nu bt buc phi phu thut, cn ch nh GC nh th no trc phu thut?

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