Drug Diabetic

I. TNG QUAN

Tuyn ty tng hp ra cc hormone bn cht peptid bao gm insulin, glucagon v somatostatin. Ba hormone trn ln lt c tit ra t t bo , , ca tiu o Langerhans. Nhng hormon ny c vai tr quan trng trong iu ha cc qu trnh chuyn ha, c bit l gi cho ng huyt n nh. S thiu ht insulin tng i hoc tuyt i trong i tho ng c th dn ti tnh trng tng ng huyt nghim trng. V lu di, bnh nhn khng c iu tr tt cc bin chng trn vng mc, thn kinh, thn v tim mch s xut hin. iu tr bng cc ch phm insulin hoc cc thuc iu tr i tho ng khc (Bng 1) s lm gim t l bin chng v t vong lin quan n i tho ng.II. B NH I THO NG

T l mc i tho ng ang gia tng chng mt ti M cng nh trn ton th gii, ngi ta c tnh c 25,8 triu ngi M v 347 triu ngi trn ton th gii ang phi lm bn vi cn bnh ny. i tho ng khng phi l mt bnh n thun m l mt nhm cc hi chng c c trng chung bi tnh trng tng ng huyt do thiu ht tng i hoc tuyt i insulin. Hip hi i tho ng M (ADA) phn i tho ng (T) thnh 4 nhm: T type 1, T type 2, T thai k v cc th c bit gy ra bi nguyn nhn khc nh di truyn, thuc. Bng 2 tm tt nhng im c trng ca i tho ng type 1 v type 2. i tho ng thai k c nh ngha l s ri lon dung np glucose khi pht hoc c chn on ln u trong lc mang thai. i tho ng thai k khng c kim sot tt c th dn ti sinh con to, kh sinh cng nh h ng huyt tr c sinh ra bi thai ph mc bnh. Ch n lnh mnh, tp th dc v/hoc s dng insulin c hiu qu tt cho nhng bnh nhn i tho ng thai k. Metformin v Glyburide c th s dng thay th insulin trong iu tr i tho ng thai k.

A. i tho ng type 1

T type 1 thng gp tr nh, thanh thiu nin hoc ngi tr tui, mt s th din tin chm, bnh c th xut hin la tui mun hn. T type 1 c c trng bi s thiu ht tuyt i insulin do t bo b ph hy. T bo b ph hy c th l kt qu ca qu trnh t min c khi mo bi tc nhn Virus hoc cc cht c t mi trng.

Thu c iu tr i tho ngTc gi: Karen Whalen - Trch trong Lippincott Illustrated Reviews: Pharmacology (Sixth Edition)Dch: V Tin Khoa

INSULINInsulin aspart NOVOLOGInsulin detemir LEVEMIRInsulin glargine LANTUSInsulin glulisine APIDRAInsulin lispro HUMALOGNPH insulin suspension HUMULIN N, NOVOLIN NRegular insulin HUMULIN R, NOVOLIN RAMYLIN ANALOGPramlintide SYMLINORAL AGENTSAcarbose PRECOSE

Glimepiride AMARYLGlipizide GLUCOTROLGlyburide DIAETA, GLYNASE PRESTAB

Metformin FORTAMET, GLUCOPHAGEMiglitol GLYSETNateglinide STARLIXPioglitazone ACTOSRepaglinide PRANDINRosiglitazone AVANDIASaxagliptin ONGLYZASitagliptin JANUVIATolbutamide TOLBUTAMIDEINCRETIN MIMETICExenatide BYETTA, BYDUREONLiraglutide VICTOZA

Linagliptin TRADJENTA

Alogliptin NESINABromocriptine CYCLOSET

INVOKANAColesevelam WELCHOL

nizol filgapaD FARXIGA

B ng 1Tm tt cc thuc s dng trong iu tr T

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Bnh i tho ng

T bo mt kh nng hot ng, tuyn ty khng iu ha c ng huyt v bnh nhn T type 1 c nhng triu chng in hnh ca thiu ht insulin: n nhiu, ung nhiu, tiu nhiu, gy nhiu. Bnh nhn T type 1 bt buc phi s dng insulin trnh nhng cn tng ng huyt nghim trng v nguy him tnh mng do nhim toan cetone.

1. Nguyn nhn: ngi bnh thng, sau khi n (postabsorptive) t bo lun tit ra mt lng insulin hng nh duy tr mc insulin nn. iu ny m bo qu trnh d ha lipid, protid v glycogen khng xy ra. Sau khi n khong 2 pht, t bo tit ra mt lng insulin p ng vi s tng glucose v acid amin trong mu. Qu trnh ny ko di khong 15 pht, tip sau l qu trnh tit insulin sau n. Tuy nhin, bnh nhn T type 1 t bo b ph hy v khng th m bo insulin nn cng nh lng insulin cn p ng vi thay i nng glucose trong mu (Bng 3).

2. iu tr: Bnh nhn T type 1 buc phi dng insulin trnh tng ng huyt, nhim toan cetone v duy tr HbA1C mc chp nhn c. Mc tiu iu tr vi insulin l duy tr ng huyt gn mc sinh l nht c th v trnh nhng thay i ln ca ng huyt. Khi iu tr vi insulin t kim tra ng huyt thng xuyn bng my o ng ti nh.

B. T type 2

T type 2 chim n hn 90% cc trng hp T. Bnh b nh hng bi cc yu t nh di truyn, tui, bo ph, khng insulin ngoi bin hn l qu trnh t min nh trong T type 1. Cc ri lon chuyn ha trong T type 2 khng rm r nh trong T type 1 (VD: bnh nhn T type 2 thng khng b nhim toan cetone) nhng cc bin chng mn tnh 2 th l tng t nhau.

1. Nguyn nhn: T type 2 c trng bi tnh trng khng insulin ( c quan ch khng thiu nhy cm vi insulin) (Bng 4). Trong T type 2 mc d t bo vn cn kh nng hot ng nhng lng in-sulin tit ra khng iu ha ng huyt (Bng 3) khi gp phi tnh trang khng insulin ngy cng tng ngoi bin. Khi lng t bo gim dn theo thi gian mc bnh. Tri vi T type 1, bnh nhn T type 2 thng bo ph. Bo ph l mt trong nhng yu t gp phn to ra tnh trng khng insulin - yu t c coi l nguyn nhn chnh gy T type 2.

2. iu tr: Mc tiu iu tr T type 2 l duy tr ng huyt trong gii hn bnh thng v ngn chn, tr hon tin trin ca cc bin chng mn tnh. Gim cn, tp th dc, iu chnh ch n lm gim khng insulin v gip mt s bnh nhn t mc ng huyt mc tiu tuy nhin hu ht cc bnh nhn u phi s cc thuc ung iu tr T. Theo din tin bnh, t bo dn suy kit, khi insulin thng c s dng a ng huyt v mc mc tiu (Bng 5).

Type 1

Thng gp tr em, ngi tr tui

Thng sau 35 tui

Gy Hay gp bo ph

5% - 10% 90% - 95%

Type 2

Tui khi pht

Th trng

T sut mc

Lin quan di truyn

Va phi Rt mnh

Thiu ht, khim khuyt in-sulin

T bo b ph hy, mt kh nng tit insulin

Ri lon tit in-sulin; khng insulin; cc ri lon khc

Bng 2So snh T type 1 v type 2

0 5 100

40

Pht

Ngi khe mnh

T type 2

80

Truyn glucose TM

T type 1

Bng 3Tit insulin ngi bnh thng v bnh nhn T khi truyn glucose tnh mch

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Insulin mu (U/ml)



Insulin v Insulin Analog

III. INSULIN V INSULIN ANALOGInsulin l hormone c bn cht peptid, cu to t hai chui peptid c ni vi nhau bng mt cu ni disulfide. T tin cht proinsulin khi b thy phn to thnh insulin v C-peptide, c hai u c tit ra t tuyn ty (Lu : Insulin b thi tr qua gan v thn do nng insulin trong mu khng phn nh chnh xc kh nng sn xut insulin ca tuyn ty. V vy nh lng C-peptide s cho nhng con s chnh xc hn v nng insulin). Insulin c bi tit ph thuc vo nng glucose, mt s acid amin, cc hormone khc v cc thuc ang s dng. Khi nng glucose mu cao s lm tng lng glucose vo t bo tuyn ty qua cc knh vn chuyn. Ti tuyn ty, glucose c phosphoryl ha bi enzyme glucosekinase - enzyme hot ng nh mt b phn nhn cm insulin. Glucose sau khi c phosphoryl ha s i vo chui h hp t bo v to ra ATP. Nng ATP tng cao s block knh K+, lm kh cc mng t bo, lm Ca2+ trn vo ni bo. Nng Ca2+ ni bo tng kch thch ty phng thch insulin theo nhp.

A. C ch tc dng

Cc loi insulin c s dng thay th insulin ni sinh trong T type 1 hoc b sung lng insulin thiu ht trong T type 2. Tc dng insulin ngoi sinh tng t nh ni sinh.

B. Dc ng hc

Insulin ngi c tng hp nh cng ngh ti t hp s dng cc chng E. Coli hoc nm men bin i gene. Khi thay i mt s acid amin trong insulin ngi s to ra cc loi insulin khc nhau (Insulin Analog) c c tnh dc ng hc khc bit so vi insulin ngi. im khc bit chnh gia cc ch phm insulin l thi gian bt u c tc dng v thi gian duy tr tc dng. V d: Insulin aspart, Insulin lispro, Insulin glulisine c thi gian khi pht v duy tr tc dng ngn hn so vi Insulin thng. Liu s dng, v tr tim, mc ti mu, nhit v cc hot ng th lc cng c th nh hng n thi gian khi pht v duy tr tc dng ca cc ch phm insulin. Do c bn cht polypeptid, nn cc isulin b thy phn trong ng tiu ha khi ung. V vy, insulin thng c tim di da, trong trng hp cp cu do tng ng huyt nng c th tim tnh mch insulin thng. Ngoi ra ngi ta cn s dng phng php truyn lin tc insulin di da (cn gi l bm insulin). Phng php ny kh tin li, n trnh phi tim nhiu mi insulin trong ngy. Cc loi bm insulin c lp trnh duy tr mc insulin nn. Ngoi ra n cng cung cp thm cho bnh nhn thm mt lng insulin nhanh x l lng carbonhydrate a vo khi n n hoc p ng khi glucose mu tng cao.

C. Tc dng ngoi ca insulinH ng huyt l tc dng ph nghim trng v thng gp nht ca insulin (bng 6). Cc tc dng ph khc bao gm tng cn, kch ng v lon dng m ch tim. Lon dng m c th c hn ch bng cch thay i v tr tim. Bnh nhn suy thn c th cn gim liu

Gan

C

Glucose

Tng tng hp glucose

Khng insulin ngoi bin

Gim thu nhn glucose

T bo tit insulinkhng y

Tuyn ty

Insulin

1

2

M M

Bng 4Cc yu t chnh gy tng ng huyt trong T type 2

Khng iu tr

n king

n king +

metformin

Din tin bnh nng dn

Phi hp thuc

Bnh thng

Ri lon dung np Glucose T type2

Insulin nhiumi

05 nm

515 nm

Trn 15 nm

Relative ability to secrete insulin

Bng 5Lng insulin ni sinh theo thi gian mc T type 2 v trnh t iu tr cho mi giai on

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namud.vn - Cng ng dc s Vit Nam

IV. CC CH PHM INSULIN TRONG IU TRInsulin c chia thnh: Insulin nhanh ( Rapid acting), Insulin thi gian duy tr tc dng ngn (Short acting), trung bnh (Intermediate acting) v di (Long acting). Bng 7 tm tt thi gian khi pht tc dng, t nh trong mu v duy tr tc dng ca cc loi insulin. i vi cc bc s, khi s dng insulin cn thn trng, c bit ch n lin dng v loi insulin, y l iu rt quan trng

A. Insulin nhanh v insulin thng

C 4 ch phm insulin thuc nhm ny: Insulin thng, Lispro insulin, Aspart insulin v Glulisine insulin (Aspart, Lispro, Glulisine l gc mui gn vo insulin thay i dc ng hc - dch gi). Insulin thng l loi insulin c thi gian duy tr tc dng ngn, tan c, c th to mui vi km. Ba insulin cn li thuc nhm insulin nhanh(rapid acting). Ngi ta thay i mt s acid amin trong insulin thng to ra cc Insulin alalog - chnh l cc insulin nhanh. VD: Lispro insulin khc insulin thng ch gc lysine v proline v tr 28 v 29 chui B hon i v tr cho nhau. S thay i ny lm cho thuc hp thu nhanh hn, tc dng xut hin nhanh hn v thi gian duy tr tc dng ngn hn sau khi tim di da. Thi gian t nh trong huyt tng ca Lispro insulin khong 30-50 pht so vi 50-120 pht ca insulin thng. Aspart v Glusine insulin c dc ng, dc lc tng t nh Lispro insulin. Nhm insulin ny c s dng m phng insulin gii phng ra trong khi n, qua kim sot ng huyt sau n ngoi ra cng c s dng h ng huyt nhanh khi cn. Nhm ny thng c dng phi hp vi cc loi insulin nn tc dng ko di ( loi ny dng kim sot ng huyt i). Insulin thng phi dng 30 pht trc khi n trong khi insulin nhanh c th dng 15 pht trc n hoc 15-20 pht sau khi bt u n. Insulin nhanh thng c s dng ngoi bm insulin, rt thch hp tim IV mc d insulin thng c dng bng ng ny nht khi cn

B. Insulin tc dng trung bnh - NPH insulin

NPH insulin l loi c thi gian tc dng trung bnh c tng hp bng cch thm km v protamine vo insulin thng. Do kt hp vi protamine di dng phc nn loi insulin ny t tan, kt qu l thuc hp thu chm, thi gian duy tr tc dng di hn. NPH insulin c s dng nh insulin nn trong T type 1 v 2, thng dng km vi insulin nhanh hoc insulin thng kim sot dng huyt sau n. NPH insulin ch dng tim di da, tuyt i khng tim tnh mch cng khng s dng h ng huyt tc th (nh trong nhim toan ceton).

C. Insulin tc dng ko di

im ng in ca insulin glargine thp hn so vi insulin ngi cho nn khi tim s to kt ta ti v tr tim, sau thuc c gii phng t t. Thi gian xut hin tc dng ca nhm ny chm hn NPH, AUC kh bng phng v khng c nh (Bng 7).

Triu chng h ng huyt

nh trng ngc L ln

Chng mt Tot m hi

Lon dng m Qu mn

AA

A

au u Hi hp

Run i cn co

Nhn m Mt mi r ri

Bng 6Tc dng ph ca insulin [Londng m l tnh trng teo hoc ph i m m ni tim]

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Nn

g

insulin

huy

t t

ng

0 6 12 18 24

Insulin glargine

Insulin detemir

Regular insulin

Insulin aspart, insulin lispro, Insulin glulisine

NPH insulin

Bng 7Thi gian xut hin v duy tr tc dng ca insulin ngi v cc loi insulin analog.

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Gi

Insulin detemir c chui acid bo bn cnh gip tng cng lin kt vi albumin, tc dng ko di tng t insulin glargine, y l kt qu ca s gii phng t t khi phc hp vi albumin. Tng t insulin NPH v glargine, insulin detemir c s dng lm insulin nn, Cc loi insulin khng c tc dng ko di thng c trn vi cc loi insulin ny trong cng mt liu tim nhm thay i c tnh dc lc ca thuc

D. Insulin phi hp ( cn gi l mixtard, trn sn - premix)Loi insulin ny c s dng rt nhiu ti Vit Nam vi l do tin li v gi thnh r, tuy nhin ADA khuyn co s dng phc MDI thay v s dng insulin trn sn (dch gi). Insulin trn sn (premix) l hn hp mt s loi insulin vi insulin thng theo t l nht nh, v d 70% NPH insulinv 30% insulin thng (bng 8) hoc 50% mi loi . S dng loi Insulin ny gip gim s ln tim trong mt ngy nhng kh iu chnh cc thnh phn n l trong hn hp tim

D. Phc iu tr c bn so vi iu tr tch cciu tr insulin c bn (thng s dng premix) thng s dng 2 mi tim/ngy. Tri li theo phc iu tr tch cc ( cn gi l MID - insulin nhiu mi) s dng 3 hoc nhiu hn s mi insulin trn ngy i km vi vic theo di ng huyt thng xuyn. ADA khuyn co mc tiu iu tr l a ng huyt trung bnh di 154mg/dL ( A1C di 7%), v iu tr tch cc thng t c mc tiu ny nhiu hn. [ Ch : ng huyt trung bnh ngi bnh thng l 115 md/dL hoc thp hn, ng vi A1C di 5,7%]. Tn sut cc cn h ng huyt, hn m, co git do h ng gp nhiu hn phc iu tr insulin tch cc (Bng 9A). Tuy nhin bnh nhn s dng phc iu tr tch cc gim ng k cc bin chng mch mu nh nh bin chng vng mc, thn, thn kinh so vi phc c bn (Bng 9B). Phc iu tr tch cc khng khuyn co cho cc bnh nhn mc bnh lu nm, xut hin bin chng mch mu nh, ngi cao tui, v nhng ngi b h ng huyt khng r nguyn nhn. iu tr tch cc khng lm gim bin chng mch mu ln bnh nhn i tho ng



V. NG VN AMYLIN

Amylin l hormone c tit ng thi cng insulin ti t bo khi n. N lm chm tc lm rng d dy, gim tit glucagon sau n v tng cm gic no. Pramlintide c tc dng tng t nh Amylin, ngun gc tng hp nhn to, c ch nh dng cng, h tr cho insulin ngay trc ba n bnh nhn T type 1 v 2. Pramlintide c tim di da trong ba n. Khi dng Pramlintide, cn gim khong 50% liu insulin trnh nguy c h ng huyt nghim trng. Tc dng ph ca thuc bao gm bun nn, nn, chn n. Pramlintide khng c trn chung vi insulin trong cng mt ng tim khi s dng v n cng khng c s dng cho bnh nhn i tho ng b lit d dy, qu mn vi thuc hoc h ng huyt khng r nguyn nhn

VI. CC THUC TNG T INCRETIN ( NG VN GLP-1)Ngi ta thy khi ung glucose s gy tit insulin nhiu hn so vi tim tnh mch. Hin tng ny gi l hiu ng Incretin v n b gim trong T type 2. Hiu ng ny xut hin do rut tit ra cc hormone incretin, ng ch l GLP - 1, mt polypeptide kch tit insulin ph thuc ng huyt. Cc hormone Incretin nh hng 60-70% lng in-sulin tit ra sau n. Exenatide v liraglutide l cc cht c tc dng tng t incretin (cn c gi l ng vn GLP-1) c s dng trong iu tr i tho ng type 2.

A. C ch tc dng

Nhm thuc ny tc dng bng cch gn v gy tc dng tng t nh GLP -1 khi gn ln th th tng ng. Chng lm tng tit insulin ph thuc ng huyt, lm chm tc tho rng d dy, gip tit thc tt hn do tng cm gic no, gim tit glucagon sau n, tng sinh t bo ( theo mnh bit th mi c bng chng trn ng vt - Dch gi ). Thuc gip gim cn, gim ng huyt sau n v HbA1C.

B. Dc ng hc

Do bn cht peptide nn cc thuc trong nhm u phi s dng bng ng tim di da. Liraglutide lin kt mnh vi protein huyt tng nn c t1/2di, do c th s dng mt ln/ngy khng ph thuc ba n. Exenatide thi tr qua thn v c t1/2 ngn do phi dng ngy 2 ln trong vng khong 60 pht trc ba n sng v n ti. Hin trn th trng c dng bo ch gii phng chm ca Exenatide dng 1 ln/tun. Exenatide trnh s dng cho bnh nhn suy thn nng

C. Tc dng ph

Cc tc dng ph hay gp bao gm nn, bun nn, ri lon tiu ha. Li-raglutide v Exenatide b cho l c lin quan n vim ty, do cn dng thuc v n bnh vin nu b au bng d di. Liraglutide gy ra khi u t bo C tuyn gip ng vt. Tuy nhin, vn cha r n c gy ung th tuyn gip trn ngi hay khng

Sng Chiu Ti m

Insu

lin ee

ct

B L

Thng Thng Thng

S Trc khi ng

NPH

Morning Afternoon Evening

Night

Insu

lin ee

ct

B S

Insu

lin ee

ct

B L S bedtime

Glargine or detemir

Morning Afternoon Evening Night

Lispro Lispro Lispro

Insulin trn sn ( Mixtard)NPH/Regular 70:30

Night

Bng 8V d v ba phc s dng thay th insulin tit sau ba n v insulin nn ngi. B = n sng; L = n tra; S = n ti. NPH = neu-tral protamine Hagedorn.

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Dch bi namud.vn - Cng ng dc s Vit Nam

VII. Cc thuc ung iu tr i tho ng type 2

Cc thuc ung c s dng cho cc bnh nhn tht bi vi ch n v tp luyn. Nhng bnh nhn mc i tho ng sau 40 tui v thi gian mc di 5 nm hu ht u p ng tt vi cc thuc ung. i vi bnh nhn lu nm cn phi hp nhiu loi thuc ung c th c hoc khng s dng insulin kim sot ng huyt. Bng 10 : thi gian tc dng ca mt s thuc ung, bng 11: mt s tc dng ph thng gp.

A. Nhm sulfonylurea

Nhm thuc ny kch thch t bo tit insulin do n c xp vo nhm kch tit insulin. Hin ti cc thuc trong nhm c s dng nhiu l cc Sulfonylurea th h 2, bao gm: Glyburide ( Gly-benclamide), Gliclazide, Glypizide v Glymepiride.

1. C ch tc dng: C ch tc dng chnh ca thuc l kch thch t bo tuyn ty tng tit insulin. Cc Sulfonylurea phong b knh K+ ph thuc ATP, gy kh cc mng t bo, lm m knh Ca2+, lm tng Ca2+

ni bo v gii phng Insulin t cc bc trong ni bo. Thm vo , thuc c th c tc dng gim sn xut glucose ti gan v tng nhy cm insulin m ngoi bin.

2. Dc ng hc: Sau khi ung, thuc lin kt vi protein huyt tng (hu ht cc thuc thuc nhm ny lin kt rt mnh vi protetin huyt tng - d tng tc - Dch gi), thuc c chuyn ha ti gan, thi tr qua nc tiu hoc phn. Thi gian tc dng ca cc SUs t 12 - 24h.

0

100

iu tr c bn

iu tr tch cc

iu tr tch cc vi insulin lm tng s c h ng huyt

C bn

Tch cc

Nm nghin cu

%bn

h nh

n c

bin

chn

g MM nh

0

30

60

0 1 2 3 4 5 6 7 8 9

A B Tuy c nguy c h ng huyt cao hn nhng nhiu nh lm sng tin rng iu tr tch cc lm gim ng k cc bin chng mch mu nh nh vng mc, thn, thn kinh

Figure 25.9A. H ng huyt hay gp hn cc bnh nhn i tho ng type 1 s dng phc insulin tch cc. B. Hiuqu trn cc bin chng mn tnh ca phc tch cc v c bn.

Metformin

Nateglinide

Repaglinide

Pioglitazone

Glipizide

Glimepiride

Glyburide

24 h

Acarbose

Miglitol

2 h

2 h

18 h

20 h

6 h

>24 h

6 h

6 h

Bng 10Thi gian tc dng ca mt s thuc ung

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S cn

h

ng hu

yt/

1000

BN/th

n



Thuc ung iu tr i tho ng

3. Tc dng ph: Tc dng ngoi chnh ca thuc bao gm tng cn, tng tit insulin qu mc, h ng huyt. Cn thn trng cc bnh nhn suy gan, suy thn cc i tng ny d b tch ly thuc v gy h ng huyt. Bnh nhn suy thn dng Glybiridethng gp cc tc dng ngoi , cc bnh nhn ny, thi gian tc dng ca thuc b ko di, lm tng nguy c h ng huyt. Glypizide v Glymepiride l cc la chn an ton hn cho bnh nhn suy thn v ln tui. Glypizide t qua nhau thai do c th s dng cng Insulin iu tr T thai k. Bng 12: Tm tt mt s nhm thuc tng tc vi Sulfonylureas

B. Nhm Glinide

Cc thuc thuc nhm ny bao gm Repaglinide v Netaglin-ide. Nhm Glinide cng c xp vo nhm kch tit Insulin

1. C ch tc dng: Tng t cc sulfonylurea, c ch tc dng ca nhm ny l kch thch tit insulin. Chng gn vo cc v tr c hiu trn t bo , lm ng knh K+ ph thuc ATP, bt u mt lot chui phn ng a n kt qu cui cng l gii phng Insulin. Khc vi Sulfonyluera, nhm ny khi pht tc dng nhanh v thi gian tc dng ngn. Chng c bit c hiu qu trong vic kch thch tit insulin pha sm sau khi n, chng thng c dng kim sot ng huyt sau n. Glinide khng s dng cng SUs trnh tc dng qu mc do cng c ch, dn n h ng huyt nghim trng.

2. Dc ng hc: Glinide thng ung trc ba n, hp thu tt. C hai thuc trong nhm u chuyn ha thnh cc sn phm khng hot tnh nh men CyP 450 3A4 ti gan v thi tr qua ng mt.

Ri lon tiu ha

Metformin,c ch -

Glucosidase

Bun nn

Metformin

Tng cn

Sulfonylurea,Glinides, TZD

H ng huyt

Glinide,Sulfonylureas

GLUCOSE

c ch DPP - 4

Vim ty

Bng 11Mt s tc dng ph thng gp ca cc thuc i tho ng

Cc thuc lm tng tc dng ca SUs dn ti nguy c h ng huyt Khng sinh khng nm Azole C h n b e t a C l o r a m p h e n i c a l C l a r i t h r o m y c i n c c h m o n o a m i n o x y d a s e Probenecide Salicylates Khng sinh Sulfamide

Cc thuc lm gim tc dng ca SUs dn ti kh kim sot ng huyt: Thuc iu tr ri lon tm thn Corticoide Li tiu Niacin Nhm Phenothiazin Nhm cng giao cm

Bng 12Cc thuc c tng tc vi nhm SU

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3. Tc dng ph: Mc d Glinide gy h ng huyt v tng cn nhng cc tc dng ph ny ca nhm thp hn cc Sulfonylurea [ Ch : Cc thuc c ch men Cytocrom P450 3A4 nh khng sinh khng nm Azole, Erythromycin, Azithromycin c th lm tng tc dng h ng huyt ca Glinide. Cc thuc hot ha men Cytocrom P450 3A4 nh Barbiturate, Carbamazepine, Rifampin c th lm gim tc dng ca thuc] Cc thuc h lipid mu nh Gemfbrizil c ch men chuyn ha ti gan , c th lm tng nguy c h ng huyt ca Glinide, do chng ch nh phi hp 2 thuc trn. Nhm thuc Glinide cn s dng thn trn cc bnh nhn suy gim chc nng gan.

C. Nhm biguanide

Metformin l thuc duy nht trong nhm cn c s dng, c xp vo nhm lm tng nhy cm Insulin (Nhm cn c Phenformin nhng b cm lu hnh do nguy c nhim toan lactic qu cao. Tuy nhin Vit Nam vn c hot cht ny trn th trng di dng thuc cp xut x Trung Quc - Dch gi).Thuc lm tng s dng glucose m ch do lm gim khng insulin. Tri vi SU, met-formin khng lm tng tit insulin. V vy, thuc khng gy tng tit insulin qu mc v nguy c h ng huyt thp hn SU rt nhiu

1. C ch tc dng: C ch tc dng chnh ca Metformin l gim sn xut glucose ti gan [Ch : Sn xut glucose qu mc ti gan l mt nguyn nhn quan trng lm tng ng huyt trong T type 2, nh hng ch yu ln ng huyt i]. Metformin cng lm chm qu trnh hp thu ng ti rut, lm tng bt gi v s dng glucose ngoi bin. Gim cn cng c th xut hin v Metformin lm mt cm gic ngon ming. ADA khuyn co Metformin l ch nh u tay trong iu tr T type 2. Metformin c th s dng n c hoc phi hp vi Insulin v cc thuc ung khc. H ng huyt c th xy ra khi s dng Metformin cng vi Insulin v cc thuc kch tit Insulin, v vy c th phi cn nhc iu chnh liu

2. Dc ng hc: Metformin hp thu tt qua ng ung, hu nh khng lin kt vi protein huyt tng, khng b chuyn ha, thi tr dng nguyn vn qua nc tiu

3. Tc dng ph: Hay gp nht l ri lon tiu ha. Metformin chng ch nh cho bnh nhn suy thn (eGFR di 60) do lm tng nguy c nhim toan lactic. Phi dng thuc khi c nhi mu c tim cp, t cp ca suy tim, nhim trng huyt hoc cc ri lon c th dn n suy thn. Cn s dng thn trng cho bnh nhn trn 80 tui, suy tim, nghin ru. Cn ngng thuc trn cc bnh nhn phi s dng thuc cn quang ng tnh mch. Nhim toan lactic him gp nhng t l t vong rt cao. Dng thuc ko di c th lm gim hp thu vitamin B12

4. Ch nh khc: Ngoi T type 2, Metformin cn c s dng iu tr hi chng bung trng a nang. N lm gim khng insulin trong hi chng ny, dn n rng trng v bnh nhn c th th thai.

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namud.vn - Cng ng hi dc s Vit Nam

D. Nhm thiazolidinedione (TZD)Cc TZD cng lm tng tnh nhy cm ca insulin. Hai thuc trong nhm bao gm: Pioglitazonev Rosiglitazone. Mc d insulin cn cho hot ng ca thuc nhng nhm thuc ny khng kch thch t bo tit insulin do khng c nguy c h ng huyt do tng tit qu mc insulin

1. C ch tc dng: Cc TZD lm gim khng insulin bng cch hot ng nh mt cht ng vn th th PPAR-, mt th th nm trong nhn t bo. Th th PPAR- c hot ha s lm thay i sao m ca mt s gene quy nh hot ng ca insulin, h qu l lm tng nhy cm ca insulin vi cc m m, gan, c xng. Ngi ta cn quan tm n tc dng ca thuc ln nng cholesterol. Rosigli-tazone lm tng triglyceride trong khi Pioglitazone lm gim triglyceride. C hai thuc u lm tng HDL - cholesterol. TZD c th dng n tr liu hoc phi hp vi cc thuc ung khc hoc insulin. Liu insulin cn gim khi s dng phi hp vi nhm thuc ny. ADA khuyn co Pioglitazone l la chn hng 2 hoc 3 trong iu tr T type 2. Rosiglitazone t c s dng do cc bin c nng trn tim mch.

2. Dc ng hc: Pioglitazone v Rosiglitazone u hp thu tt qua ng ung v lin kt mnh vi albumin huyt tng. C hai thuc u chuyn ha mnh qua cc isozym CYP450 khc nhau. Mt vi cht chuyn ha ca Pioglitazone cn hot tnh. Pioglitazone t thi tr qua thn, phn ln thuc v cc cht chuyn ha c thi tr qua dch mt trong phn. Cc cht chuyn ha ca Rosiglitazone c thi tr ch yu qua nc tiu. Khng cn chnh liu trn suy thn, tuy nhin trnh s dng nhm thuc ny cho ph n ang cho con b.

3. Tc dng ph:Mt vi trng hp nhim c gan c bo co khi dng thuc v theo di nh k chc nng gan khi dng thuc c khuyn co. Tng cn c th xut hin nhm ny do lm tng m di da v dch [Ch : Gi nc c th lm suy tim din tin xu hn, do cn trnh s dng nhm thuc ny cho bnh nhn suy tim nng]. TZD lin quan n nguy c mt xng v gy xng. Pioglitazone c th lm tng nguy c ung th bng quang. Mt vi phn tch gp xc nh Rosiglita-zone c th lm tng t l nhi mu c tim v t vong tim mch. Kt qu l vic s dng Rosiglitazone ch p dng cho cc i tng c bit. Sau khi xem xt thm cc d liu an ton, vic hn ch ny c d b.

4. Ch nh khc: Tng t nh Metformin, lm gim khng insulin c th lm trng rng tr li cc ph n b hi trng a nang bung trng trong thi k tin mn kinh.

E. Thuc c ch -glucosidase

Acarbose vMiglitol l hai thuc trong nhm s dng iu tr T type 2.

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1. C ch tc dng: Phn b nhiu b bn chi trong rut, -glucosidase thy phn carbonhy-drate thnh glucose v cc ng n khc m c th c th hp thu. Cc thuc trong nhm c ch -glucosidase. Khi dng cc thuc ny vo trc ba n s lm chm qu trnh tiu ha car-bonhydrate, do lm gim ng huyt sau n. Do khng kch tit insulin hay lm tng nhy cm insulin nn nhm thuc ny khng gy h ng huyt khi s dng n tr liu. Tuy nhin, khi phi hp vi nhm kch tit insulin, nguy c h ng huyt c th tng ln [Ch : mt iu quan trng l khi b h ng huyt c s dng nhm thuc ny, nn iu tr bng glucose hn l dng saccarose (ng ung) v saccarose cng khng hp thu c di tc dng ca nhm c ch -glucosidase]

2. Dc ng hc: Acarbose hp thu rt km. N c chuyn ha ch yu nh h vi khun ng rut, mt vi cht chuyn ha ca n c hp thu v thi tr qua nc tiu. Miglitol hp thu tt tuy nhin khng gy tc dng ton thn. N c thi tr nguyn vn qua nc tiu.

3. Tc dng ph: Tc dng ph thng gp bao gm y hi, tiu chy, au bng. Cc tc dng ph lm hn ch vic dng thuc trn lm sng. Bnh nhn vim ng rut, vim lot i trng hoc tc nghn ng rut khng nn s dng nhm thuc ny

F. Nhm c ch men DPP-4

Saxagliptin, Alogliptin, Linagliptin, Sitagliptin l cc thuc ung thuc nhm c ch men DPP -4 c dng trong iu tr i tho ng type 2.

1. C ch tc dng: Nhm thuc ny c ch men DPP-4, l men chu trch nhim bt hot cc hormone Incretin nh GLP-1. Do , thuc lm ko di thi gian hot ng ca hormone incretin, lm tng tit insulin ph thuc ba n v lm gim tit glucagon. Cc thuc c ch DPP-4 c th dng n tr liu hoc phi hp vi SUs, Metformin, TZD hoc Insulin. Khc vi nhm ng vn GLP -1, cc thuc trong nhm trung tnh vi cn nng

2. Dc ng hc: Cc thuc c ch DPP-4 hp thu rt tt qua ng ung. Thc n khng nh hng n hp thu thuc (do c th dng thuc bt k lc no trong ngy - dch gi). Alogliptin v sitagliptinhu ht thi tr qua nc tiu dng nguyn vn. Saxaglitin chuyn ha qua men CYP450 3A4/5, v cht chuyn ha vn cn hot tnh. Saxagliptin v cc cht chuyn ha ca n thi tr ch yu qua thn. Linagliptin thi tr ch yu qua mt. Tt c cc thuc trong nhm tr Linagliptin u phi chnh liu khi dng cho bnh nhn suy thn.

3. Tc dng ph: Nhn chung, thuc c ch DPP-4 dung np tt, cc tc dng ph thng gp bao gm au u v vim ng h hp trn. Mc d him nhng vim ty xut hin tt c cc thuc trong nhm. Cc thuc c ch CYP450 3A4/5 nh ritonavir, atazanavir, itraconazole v clarithromycin c th lm tng nng Saxagliptin, do cn chnh liu khi dng chung cc thuc trn.

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C ch tc dng nhm c ch DPP-4



G. Thuc c ch SGLT -2

Canagliflozin, Dapagliflozin v Empagliflozin l cc thuc trong nhm c s dng iu tr i tho ng type 2.

1. C ch tc dng: Knh SGLT-2 c mt ng ln gn m nhim vic ti hp thu glucose trong dch lc. Khi knh ny b c ch s lm gim lng ng ti hp thu, tng lng ng trong nc tiu, qua gip gim ng mu. c ch knh SGLT-2 cng lm gim ti hp thu Na, thuc c tc dng gy li tiu thm thu. V vy, thuc c th gip gim huyt p tm thu. Tuy nhin, n khong c ch nh trong iu tr cao huyt p

2. Dc ng hc: Cc thuc trn ung 1 ln/ngy vo bui sng. Canagliflozin nn ung vo trc ba n sng, Dapagliflozin v Canagliflozin u c glucuronide ha thnh dng bt hot. Canagliflozin thi tr ch yu qua phn, khong 1/3 liu dng thi tr qua thn. Cc thuc ny chng ch nh cho bnh nhn suy thn.

3. Tc dng ph: Tc dng ngoi thng gp l nhim nm sinh dc n, nhim trng ng tiu, i tiu nhiu. H huyt p cng c th gp, c bit ngi gi v ngi ang dng cc thuc li tiu.

H. Cc thuc khc

C thuc ng vn dopamine Bromocriptine v thuc gy ng acid mt CCCooollleeessseeevvveeelllaaammm u h A1C yu. C ch kim sot ng huyt ca hai thuc trn cha c bit r. Mc d c hai u c ch nh trn i tho ng type 2 nhng do hiu qu khng r rng, tc dng ph v gi thnh nn hai thuc trn t c s dng trong lm sng.

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C CH TC DNGNHM THUC

TC DNG

TRN INSULIN

HUYT TNG

NGUY C H NG HUYT

CH THCH

Biguanides

c ch -Glucosidase

GlimepirideGlipizideGlyburide Glyclazide

Metformin

AcarboseMiglitol

PioglitazoneRosiglitazone

Glinides

Nateglinide Repaglinide

Thiazolidinediones (glitazones)

DPP-4 inhibitors

Hiu qu tt

C th tng cn

H ng huyt thng gp khi phi hp vi cc thuc khc

Ung vo ba n. Thi gian tc dng ngn nn t h ng huyt. Hiu qu kim sot ng huyt sau n

Thuc c u tin trong iu tr T type 2. Hiu qu tt. C th gip gim cn. iu chnh liu khi suy th

Hiu qu cao trong gim khng insulin. Pioglitazone dng 1 ln/ngy. Kim tra chc nng gan trc khi dng thuc

Trnh s dng cho bnh nhn gan v suy tim

Ung cng ba n. Hay gp tc dng ph trn ng tiu ha

Kch thch tit in-sulin

Kch thch tit in-sulin

Gim sn xut ng ti gan

Gn vi receptor PPAR- c, m m, gan v lm gim tnh trng khng insulin

Gim hp thu glu-cose

C

C(Him)

Khng

Khng

Khng

AlogliptinLinagliptinSitagliptinSaxagliptin

S dng 1 ln/ngy. Ung bt k thi im no. Dung np tt. Nguy c vim ty

Tng tit isulin ph thuc gluose; gim tit glucagon Khng

ng vn GLP-1

ExenatideLiraglutide

Thuc tim. Exenatide phi tim 2 ln/ngy 60 pht trc n sng v n ti. Exenatidedng 1 ln/tun

Liraglutide dng 1 ln/ngy khng ph thuc ba n

Gim cnNguy c vim ty

Tng tit isulin ph thuc gluose;Gim tit glucagon; chm lm rng d dy; Tng cm gic no

Khng

Sulfonylureas

Dng 1 ln/ngy vo bui sng. Nguy c h ng huyt, tng K mu

Chng ch nh trn BN suy thn

KhngTng thi glucose qua nc tiu

SGLT2 inhibitors

CanagliozinDapaglifozin

Bng 25Tm tt cc thuc ung iu tr i tho ng = t hoc khng thay i. DPP-4 = dipeptidyl peptidase-4.

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Patient with Type 2 diabetes and HbA1c 7%

Metforminpreferred unless

contraindicationsor intolerance

The goal HbA1cis usually

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