Adrenergic system

THUC TC NG LN H THN KINH TRUNG NGTHUC CHNG NG KINHPhan Th Nh Qunh, MSc.B mn Ha Dc-Ha L-Ha Hu CKhoa Dc, i hc Y Dc Hu

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John Hughlings Jackson, (04/04/ 1835 07/10/1911)John Hughlings Jackson: S phng lc thnh thong, bt thnh lnh, qu mc, nhanh chng ca t bo cht xmi cng2i cngCn ng kinh (seizures) L biu hin lm sng ca s phng lc bt thng v khng kim sot c ca cc neuron v noC th c yu t khi pht hay khngYu t khi pht: st, chn thng s no, ri lon in gii, h hay tng ng huytC ng kinh c yu t khi pht s t khi khi gii quyt c yu t khi pht3Dn truyn qua synapseTh th ca neuron k tipKch thchc chDn truyn TK bt thngKch thch >> c chMt vng ca noNhiu vng v noTon b noTon b noDn truyn qua neuronDn truyn qua neuron trong cn ng kinhC th lan ra nhiu vng khc ca no4Triu chng ca cn ng kinh:Vn ng: co git c ti mt vng c th hay ton thnCm gic: d cm t rn ti mt vng c th hay cc o gic gic quanGiao cm: bun nn, cm gic kh chu d dy, gin ng tTm thn: cc hnh vi bt thng, r lon tr nh, cc ng tc t ngi cngi cngBnh ng kinh (epilepsy)L s ti pht ca cc cn ng kinh khng yu t khi pht (> 2 cn)L tnh trng bnh l mn tnhC th c hay khng c nguyn nhnPhi iu tr bng thuc chng ng kinh6i cngCn ng kinhThnh phn ca bnh l cp tnh hay cc nguyn nhn tm thiChm dt khi gii quyt nguyn nhnV d: co git do st, chn thng s no, h ng huyt,Bnh ng kinhBnh l mn tnh v ti phtCn xy ra t ngt v khng c yu t khi phtC th c cn nguyn hay khng7Cn ng kinhTon th nguyn phtCc bn gin khng nh hng tri gicPhc tp nh hng tri gicVn ngCm gicGiao cmTm thnTon th ha th phtCn vng thc (cn nh)Cn git cCn co gitCn co cngCn mt trng lcCn co cng-co gitPhn loi Quc t8i cngng kinh cc b (Partial seizures): loi ng kinh m s phng in lc khi u ch xy ra mt phn khu tr ca mt bn cu i no.ng kinh cc b n thun (simple partial seizures): c ri lon v vn ng, cm gic v tm thn nhng khng c ri lon thcng kinh cc b phc tp (complex partial seizures): c tn thng thcng kinh cc b ton th th pht (secondary generalized seizures): xung lc lan trn khp no khin ng kinh cc b tin trin thnh co cng co git ton th th pht (secondary generalized tonic clonic)9i cngng kinh ton th (general seizures): lc khi u s phng in xy ra ng thi c hai bn cu i noCn vng thc (absence seizures) hay ng kinh cn nh (petit mal): thng gp tr em vi s mt thc t ngt trong vi pht km theo ri lon vn ng t s nhn chm ch vo khong khng n co gitCn vng thc in hnh (typical absence seizures): ch c ri lon thc khng c ri lon vn ngCn vng thc khng in hnh (atypical absence seizures): c ri lon vn ng. Khi u chm nhng ko di hn loi in hnh

10i cngng kinh ton th (general seizures)ng kinh co cng co git ton th nguyn pht (primary tonic-clonic seizures) hay ng kinh c ln (grand mal): c trng bng mt thc t ngt, sau l giai on co cng, ng xung v ngng th, giai on ny ko di di 1 pht. Tin n l giai on co git (2-3 pht), cui cng bnh nhn mt thc trong vi pht ri hi tnhng kinh git c (myoclonic seizures): c th git mt hay nhiu cTnh trng ng kinh lin tc (status epilepticus):ng kinh lin tc khng c hi tnh gia cc cnTnh trng cp cu v gy mt cn bng v mui trong c th c th dn n t vongTrong mi cn ng kinh, h hp b ngng li nn c th thiu oxygen

11i cngChn on:in no : EEG tiu chun vng trong chn on ng kinh (o trong cn ng kinh)MRICT scaniu tr: kim sot cn ng kinh vi tc dng ph thp nhtChn thuc ty vo loi cn v nhu cu BNDng n liu php trcDng thuc khng c tc dng an thn hay trn tm thnLiu lng thch hp, tng liu dni thuc hay phi hp khi cnChi ph

CT scan trong t/h ko thc hin c MRI, bnh l mch mu, chn thng s no12Thuc iu tr ng kinh3 c ch c bn cp t bo: iu bin cc cng in th knh ion (Na+, Ca2+ v K+)Tng dn truyn TK c ch iu ha bi GABA Lm gim dn truyn TK kch thch no, c bit l kch thch qua glutamateC ch tc dng.14 Cng in th knh Na+ L mc tiu phn t ca phenytoin, CBZ, lamotrigine v mt s thuc chng ng kinh mi nh oxcarbazepine, felbamate, v zonisamideGn vo v tr gn cng bt hot, ko di thi gian bt hot ca cng in th

1. Cc cng in th knh ionPhenytoin

LamotrigineCng in th knh Ca2+ iu ha tn hiu Ca2+ : gii phng cht dn truyn TK kch thch glutamate, duy tr hng nh ni mi t bo TK Dng Ca2+ i vo t bo qu mc s khi pht v din tin bnh ng kinh1. Cc cng in th knh ionKnh Ca2+ loi L: cn kh cc mnh hot ha l mc tiu phn t ca gabapentin v pregabalin

1. Cc cng in th knh ion

PregabalinGabapentinKnh Ca2+ loi T: cn kh cc yu hot ha l mc tiu phn t ca ethosuximide v zonisamide

1. Cc cng in th knh ion

EthosuximideZonisamideCng in th knh K+ C vai tr quan trng trong qu trnh ti cc mng t boThuc: levetiracetam

1. Cc cng in th knh ion

Levetiracetam Thuc lm tng sinh tng hp GABA Thuc c ch s phn hu GABA Thuc c ch s ti hp thu GABA Thuc gn vo v tr allosteric trn receptor GABAA lm tng dng ion i vo t bo2. Tc ng vo GABA receptor

Qu trnh sinh tng hp v chuyn ha GABAGabapentin, pregabalinVigabatrinAcid valproic21Thuc lm tng sinh tng hp GABA Gabapentin, pregabalin: hot ha GAD GABA

Acid valproic: c ch SSADH acid succinic c ch c ch feedback GABA

PregabalinGabapentin

Acid valproic Vigabatrin: -vinyl-GABAc ch khng thun nghch GABA-transaminase (GABA-T) GABAThuc c ch s phn hu GABA

23 GABA-transporter (GAT) vn chuyn GABA v GABAergic neuron hay cc t bo m Tiagabine c ch GAT1 GABAThuc c ch s ti hp thu GABA

Tiagabine Topiramate: thuc chng ng kinh ph rng tn sut m knh Cl-Thuc tc dng ln v tr allosteric trn GABA receptor

Topiramate L-glutamate v L-aspartate l nhng cht dn truyn TK kch thch quan trng nht no 2 nhm glutamate receptor:Receptor knh ionNMDA (N-methyl-D-aspartic acid) receptorAMPA (-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid) receptorReceptor gn vi G-protein3. Gim dn truyn TK kch thch no

27 Topiramate: iu ha AMPA receptor

Felbamate: gn vo v tr gn ca glycine ti NMDA receptor Thuc c ch receptor knh ion

Topiramate

Felbamate28 iu ha s gii phng acid glutamic, GABA v cc cht dn truyn TK quan trng khcThuc c ch receptor gn vi G-proteinMt s thuc chng ng kinhPhenytoinPhong b cc knh Na+ si trc trng thi bt hot s phng in lin tc, tn sut cao, v duy trCng l thuc chng lon nhp tim, thuc d phng trong ri lon lng ccHp thu qua ng ung thay i v chuyn ha qua gan ln u Theo di nng huyt tngCnh tranh gn kt protein huyt tng v cm ng P450 tng tc thucADRAn thn, mt iu ha, song th, mn, pht trin nha chu qu mc, rm lng, nhuyn xng, c tnh trn mu (gim bch cu ht, thiu mu hng cu khng l)Qui thai: Hi chng hydantoin thai nhi

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Hi chng hydantoin thai nhiPhenytoin32Carbamazepine

CarbamazepineC ch tng t PhenytoinHin l thuc c la chn iu tr au dy thn kinh sinh ba v thuc d phng trong ri lon lng ccCm ng P450 (bn thn chuyn ha bi P450)ADRAn thn, mt iu ha, song th (ng kinh khi qu liu), nhuyn xng, c tnh trn mu (gim bch cu ht, thiu mu hng cu khng l, thiu mu bt sn), gi nc (ADH), vim trc daQui thai: d dng s mt v nt t sng

33Acid valproic

Acid valproicNhiu c ch tc dngPhong b knh Ca2+ loi Tc ch GABA transaminasePhong b knh Na+ si trcS dng trong cc trng thi ng kinh, thuc d phng trong ri lon lng cc v iu tr au na uc ch P450 Tng tc thuc: Carbamazepine, PhenytoineADRRi lon tiu ha, c gan do to cc cht chuyn ha c, vim ty, rng tc, run, nhy cm nh sngQui thai: nc t sng

34Ethosuximide

EthosuximidePhong b dng ion Ca2+ qua knh Ca2+ loi T vng i thCh s dng cho ng kinh cn vngADRRi lon tiu ha, mt mi, ng lm(Him) Ri lon chc nng ngoi thp, vim trc da, v c tnh trn mu

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Phenobarbital Clonazepam Lorazepam Diazepam Barbiturate v BenzodiazepinePhenobarbital c tc dng chng ng kinh chn lc liu thp v thi gian bn hy di thch hp iu tr duy tr trong cc bnh ng kinhClonazepam thng l thuc d phng trong iu tr ng kinh cn vng v ng kinh kiu git c, thuc gy an thn r liu chng co git.Lorazepam v Diazepam (IV) c s dng trong trng thi ng kinh lin tc

36Cc c im chung khi s dng cc thuc chng co gitTc dng c ch CNS c tng cng xy ra vi cc thuc khc nh: khng histamine, ethanol, an thn gy ng, v cc opioidTrnh ngng thuc t ngt, c th dn n cn ng kinh di ngcLm gim tc dng ca cc thuc trnh thai ng ung do cm ng cc enzyme chuyn ha thuc

37Tm tt

C CH TC DNG39C CH TC DNG

40Thuc iu tr ng kinh

41Thuc iu tr ng kinh

42CC THUC CHNG NG KINH MI

Felbamate

Lamotrigine

Topiramate

Gabapentin

Tiagabine

Vigabatrin43Thank You !