THUC CHNG LON THN

ThS. BS. Nguyn Song Ch Trung

B mn tm thn

H Y dc TP.HCM

2

Si truc

Nang cha chat

dan truyen TK

Mang trc

xi-nap Khe xi-nap

Mang sau xi-nap

SINH L DN TRUYN

3

Men phan huy

CDTTK

Autoreceptor

trc xi-nap

Xung ong TK

Nang cha chat dn truyen TK

Bm tai hap thu

Chat dn truyen TK

Men phan huy

CDTTK

Thu the sau

xi-nap

P NG

SINH L DN TRUYN

C ch tc ng ca thuc CLT

Th th sau synapse: i vn, ng vn mt phn, ng vn ngc.

Hiu qu iu tr: dopamine, serotonin.

Tc dng ph: dopamine, i giao cm, giao cm, histamin.

C ch cp phn t cp lm sng?

5

He

TK

Tru

ng

ng

Giao cam

oi

giao cam

He TK

Somatic

Ach

(Nic rec)

NE

C xng

Tim

Cac tuyen

C trn

Tim

Cac tuyen

C trn

Ach

(Musc rec)

Ach

(Nic rec)

Ganglion

Ach

(Nic rec)

Ganglion

Ach: Acetylcholine NE: Norepinephrine

Nic rec: thu the Nicotinic Musc rec: thu the muscarinic

H THN KINH 1. Phn loi

6

H THN KINH H TK thc vt

Cc c im chung

Ch nh chnh: ri lon lon thn, bt k nguyn nhn.

Hiu qu ca thuc (tc dng chnh v ph) ph thuc vo c im di truyn ca tng bn v k mi trng.

t tc dng ph nguy him.

Tc dng ph i lc l c li c s dng v tc dng ph (ch nh off-label).

Khi nim lon thn (psychosis)

Psyche, -osis: tnh trng tinh thn bt thng.

Mt lin h vi thc t.

4 biu hin chnh:

o gic

Hoang tng

Ngn ng v t chc

Hnh vi v t chc

Ri lon lon thn nguyn pht

Tm thn phn lit

RL cm xc phn lit

Lon thn cp

RL hoang tng trng din

RL lng cc c biu hin lon thn

RL trm cm c biu hin lon thn

Lon thn o gic mn tnh

Ri lon lon thn th pht

Bnh thn kinh:

HC Parkinson

Sa st tr tu

ng kinh

Tai bin mch mu no

Di chng chn thng s no

Bnh lin quan s dng cht: ru, ma ty.

Bnh ni khoa: ni tit, tim mch, chuyn ha

Ch nh tm thn khc

Cn hng cm.

Trng thi kch ng bt k nguyn nhn (dng tim)

RL m nh cng ch (phi hp vi thuc chng trm cm)

RL tic (HC Tourette)

RL hnh vi trong RL pht trin lan ta (t k).

Mt ng (off-label).

Ch nh ngoi tm thn

Ma vn Hungtinton

Nn i (ha tr liu ung th)

Nc cc khng tr

Vim lot d dy (sulpiride)

Phn nhm thuc CLT

Thuc CLT th h th nht (thuc CLT c, c in, in hnh): haloperidol, chlorpromazine, levomepromazine, fluphenazine, sulpiride.

Thuc CLT th h th hai (thuc CLT mi, khng in hnh): risperidone, olanzapine, quetiapine, clozapine, amisulpride.

Cc dng trnh by

Dng vin thng

Phng thch chm XR (quetiapine)

Dng tim : IM (haloperidol, chlorpromazine, risperidone, olanzapine).

Dng tc dng ko di: IM mi 3-4 tun (haloperidol decanoate, fluphenazine decanoate, Risperdal Consta )

Thuc CLT th h th nht

Haloperidol (Haldol )

Chlorpromazine (Aminazin, Thorazine , Largactil )

Levomepromazine (Tisercin, Nozinan )

Sulpiride (Dogmatil )

Cyamemazine (Tercian )

Loxapine (Loxitane , Loxapac )

Zuclopenthixol (Clopixol )

Thuc CLT th h 1

Hiu qu cao trn o gic, hoang tng (TC dng tnh), km hiu qu trn TC m tnh hoc lm nng hn, nhiu TDP ngoi thp, t tc dng ph chuyn ha (so vi CLT th h 2).

Cc thuc ch khc nhau v tc dng ph, cn hiu qu trn triu chng lon thn l tng ng nhau.

Thuc CLT TH1 C ch

i vn th th D2 (dopamine), i lc cao (Dopamine receptor antagonist - DRA). Tc dng chnh: h thng trung no hi vin (mesolimbic). Tc dng ph:

Trung no hi vin: v cm, mt hng th. Nhn en th vn (nigrostriatal): triu chng ngoi thp Trung no v no (mesocortical): triu chng m tnh, nhn

thc. C - phu (tuberoinfundibular): tng prolactin mu.

An thn kinh (neurolepsis)

-lepsis: nm, gi, kim.

Neurolepsis: lm gim v chm li cc qu trnh tm thn vn ng, hnh vi bng quan, cm xc th .

Tc dng ph thn kinh ca thuc CLT.

i khi kh phn bit vi triu chng m tnh ca tm thn phn lit (triu chng m tnh nguyn pht th pht).

Hiu lc cao Hiu lc thp

Hiu lc (potency): lin quan n lng thuc cn s dng t hiu qu iu tr.

HL cao: 100mg/ngy (chlorpromazine, levomepromazine)

Hiu qu iu tr triu chng lon thn l nh nhau, ch khc nhau v tc dng ph

HL cao: TDP thn kinh. HL thp: TDP ngoi TK

So snh c ch thuc CLT hiu lc cao v thp

Hiu lc thp: - i vn D2 - i vn M1 (muscarinic anticholinergic) - i vn H1 (histamine) - i vn 1 (adrenergic)

Hiu lc cao: - i vn D2 - i vn 1

Triu chng ngoi thp (Extrapyramidal symptoms EPS)

HC Parkinson do thuc: cng c (bnh xe rng ca), chm vn ng, rung c kh phn bit vi HC Parkinson nguyn pht.

Lon trng lc c cp: vo c, cng hm, xon li, n cong ngi, mt hng ln trn, kh nut, ni kh.

ng ngi khng yn (akathisia).

Lon vn ng mun (tardive dyskinesia).

Lon vn ng mun

Xut hin tr, thng sau 6 thng iu tr CLT.

5% bn mi nm, 25% bn mi nm ngi ln tui.

Triu chng: c ng nhanh bt thng, khng t , th li, chu mi, nut, nhn mt, ma git vn tay chn.

C th khng hi phc c nu dng thuc CLT qu lu.

Hi chng c tnh do thuc ATK

Lm sng: st, cng c, khng ni, l ln, kch ng, mch nhanh, THA.

CLS: tng BC, CPK, men gan, suy thn.

iu tr:

Ngng thuc CLT

iu tr nng

iu tr triu chng

Tc dng ph thn kinh khc

Bun ng:

Thng gp thuc CLT hiu lc thp

Antihistamine H1

Dng ton b liu vo bui ti

i lc c ch nh trong mt ng

ng kinh:

Lm h ngng ng kinh

Thng gp thuc CLT hiu lc thp

Tc ng anticholinergic

i vn th th muscarinic M1.

Thng gp thuc CLT hiu lc thp.

H nhn en th vn: b tr li tc ng c ch dopamine gim TDP ngoi thp

Ngoi bin: nhn m, kh ming, tim p nhanh, kh tiu, tiu kh ch trn bn nam ln tui (u tuyn tin lit).

H huyt p t th

Thng gp thuc CLT hiu lc thp.

phng: o HA t th nm v ngi, trc v sau khi tim thuc CLT 1-2h.

X tr:

Nm u thp, chn nng cao

Thuc co mch norepinephrine, metaraminol (kch thch adrenergic)

Chng C epinephrine (kch thch adrenergic lm gin mch h HA nng hn)

Tc dng ph ni tit

H dopamine c - phu (tuberoinfundibular)

Tng nng prolactin mu

N: cng ngc, chy sa, ri lon kinh nguyt, khng rng trng, v sinh, mt kinh, gim estrogen mu (ch nguy c long xng)

Nam: n ha tuyn v, gim testosterone.

Tc dng ph trn tim

Ko di QT, PR, gy sng T dt, chnh ST gim.

Nguy c RL nhp tim xon nh trn BN c tin cn bnh tim.

Thng gp hn vi thuc CLT hiu lc thp, nhng c th gp vi tt c cc thuc CLT.

Thuc CLT th h 2

Clozapine (Leponex , Clozapyl, Zyrdex)

Risperidone (Risperdal , Docento, Sernal, Rileptid, Risperidon, Respidon).

Olanzapine (Zyprexa , Solan, Ozapine, Zapnex, Olanvipin, Onegpazin)

Quetiapine (Seroquel )

Amisulpride (Solian , Sullivan, Gayax)

Aripiprazole (Abilify )

CLT TH2 C ch

i vn dopamine v serotonin : SDA.

So vi thuc CLT TH1: i lc D2 thp hn, i lc 5-HT2A cao hn.

Aripiprazole: ng vn dopamine mt phn (partial dopamine agonist PDA) ci thin triu chng nhn thc, thng qua h thng trung no v no.

c im

t TDP ngoi thp (thn kinh) hn, nhng khi liu cao th nguy c TDP ny tng.

Hiu qu tng ng trn triu chng dng tnh.

Hiu qu hn trn triu chng m tnh, kh sc (v nhn thc?).

Nhiu tc dng ph chuyn ho hn.

Ch nh mi: RL lng cc.

Gi t hn (thuc mi)

Tc dng ph huyt hc

Clozapine: bin chng gim bch cu 1-2%

CTM trc khi bt u iu tr: WBC > 3500/mm3, Neutrophil > 2000/mm3.

6 thng u: CTM hng tun

6-12 thng: CTM mi 2 tun

Sau : CTM mi thng

Trong cc thuc CLT TH2, clozapine c v l hiu qu cao nht.

Ch nh: TTPL khng tr, c nh t t.

Tc dng ph chuyn ha

Gp nhiu nht vi olanzapine, nhng c th gp vi tt c thuc CLT TH2 v t hn vi thuc CLT TH1.

Tng glucose mu tng nguy c tiu ng

RL lipid mu.

Tng cn.

Olanzapine: thuc CLT c BN a chung nht.

Chn la thuc CLT no?

Ty i tng BN:

c im lm sng

Bnh l ni ngoi khoa km theo

(Kh nng chi tr)

Thuc CLT TH2 c u tin hn hin nay.

Aripiprazole l thuc t tc dng ph nht, khng c tc dng ph gy ng.