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Bai giang Tam Than
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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.
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