Neuroleptic Malignant Syndrome (NMS)

1
Neuroleptic Malignant Syndrome (NMS)

• ???? ??????????? ?.?.
• ?????????????????? (??????????? ??????????)
• ??????????????????????????????????????????
  ???????????? ????????????????
• ??????????????????? ?????????????????????????
  ???????? 9
• ? ??????????? ???????? ?????????????
• ?????? 3 ??????? 2554

????????????????????????????????
2
Neuroleptic Malignant Syndrome (NMS)

• - ??????? chlorpromazine (CPZ) ????????
  1950
• - Syndrome malin des neuroleptiques
• (???????????????????????????????????????)
• ?????? ???????????????????? ??? (pallor)
• - 1968 neuroleptic malignant syndrome (NMS)
• - ?????? 1970 ???????????????????
• - 1980 ???????? NMS 60 ???
• - ????????? ??????????????? tardive dyskinesia
  (late) ??? NMS ??????
• - ????????? NMS ???????????????? ????????
  0.5 - 1
• ??????? NMS ????????? 30

3
Neuroleptic Malignant Syndrome (NMS)

• ???????????????????????? (Schizophrenia)
  ??????????????????? ????????????????????????????
  ????????? ??????????????????????????????????
  (side effect) ???/???? ?????????????????????
  (adverse effect)
• Neuroleptic drug Antipsychotic drug
• ????????????????????????????????????????????????
  ? ???? ?????????????? NMS

4
??????????????????????????????

• ??????????????????????????? dopamine receptor
  antagonist (DRA)
• ???? chlorpromazine (CPZ) ??????????????????????
  ????????
• (medication induce movement disorder) ?????? -
• 1. ????????????? (parkinsonism)
• 2. ?????????? neuroleptic malignant syndrome
  (NMS)
• ????????????????????????? (muscle
  rigidity)
• ?????? (hyperthermia)

5
?????????????????????????????? (??? 1)

• 3. ?????????????????????????????????????????????
  
• (acute dystonia) ??????? ?????????? ???????
  (muscle spasm)
• 4. ????????????????????????????? (acute
  akathisia)
• 5. ????? tardive dyskinesia (choreiform
  movement)
• 6. ??????????????????? (postural tremor)
• 7. Laryngeal pharyngeal dyskinesia
• ?????????? ????????????????? (laryngospasm)
  
• ???????????? ??????????????????????????????????
  ??
• ????????

6
?????????????????????????????? (??? 2)

• ???????????????????????????????????????
• ?????????????????????????????????????????????????
  ????? ???? 1. sedation 2. autonomic reaction
  3. ????????????????????? 4. ?????? 5.
  agranulocytosis 6. ??????????? 7. endocrine
  change ????
• ????????????????? ???????????????????????
• ??????????????/?????? ??????????
  
• ?????????????????? 8. cardiovascular
  effect ????????????????

7
?????????????????????????????? (??? 3)

• ?????????????????????????????????????
  ?????????????????????????????????????????????
• ?????????? neuroleptic malignant syndrome
  (NMS)

8
?????????????? ???????????????????????????????????
??(??????????) ?.?. 2544 - 2546
Code ICD 10 ?? ?????? ???????? ???????? ??????????? ??????????? ??????????? ??????????? ??????????? ??????????? ?????????? (????????) ?????????? (????????) ?????????? (????????)
Code ICD 10 ?? ?????? ???????? ???????? ??? ???? ??? ??? ???? ??? ??? ???? ???
F 20 2544 Schizophrenia 24,167 16,446 41,063 681 366 1,047 25,298 16,812 42,110
F 20 2545 Schizophrenia 23,044 15,815 38,859 663 441 1,074 23,707 16,226 39,933
F 20 2546 Schizophrenia 23,113 16,045 39,158 594 404 998 23,707 16,449 40,156
F 20 2544-2546 Schizophrenia 70,774 48,306 119,080 1,938 1,181 3,119 72,712 49,487 112,199
9
?????????????? ???????????????????????????????????
?(?????????) ?.?. 2544 - 2546
Code ICD 10 ?? ?????? ???????? ???????? ??????????? ward ??????????? ward ??????????? ward ?????????????? ?????????????? ?????????????? ????????? ????????? ?????????
Code ICD 10 ?? ?????? ???????? ???????? ??? ???? ??? ??? ???? ??? ??? ???? ???
F 20 2544 Schizophrenia 146 115 261 1,607 980 2,527 1,753 1,095 2,848
F 20 2545 Schizophrenia 130 122 252 1,632 1,070 2,702 1,762 1,192 2,954
F 20 2546 Schizophrenia 145 140 285 1,471 1,047 2,518 1,616 1,187 2,803
F 20 2544-2546 Schizophrenia 421 377 798 4,710 3,097 7,807 5,131 3,474 8,605
10
?????????? neuroleptic malignant syndrome (NMS)

• ??????????????????????????????????
  ????????????????????????????
• ??????????????????????????????? ???????????
  ??????????????????????????
• ???????????????????????????????????????
  (neuropsychiatric side effect)
• ????????????????????????? (adverse effect)
  ???????????????????????
• ??????????????????????????????????????
  ??????????????????????????
• dopamine receptor antagonist ???? ??
  chlorpromazine
• ??????????????? ???????????????????????
  ???????????????????????????? ???
• ???????????????????????????????????????
  (psychiatric emergency)

11
?????????? neuroleptic malignant syndrome (NMS)

• ????????????? ?????????????????????
  ?????????????? (depot antipsychotic
  medication) ??????????????????????????????????????
  ? NMS ??????????????????????? ?????????? NMS
  ??? ????????????????? ?????????????????????????
  ???????????????????????????????
• ?????????????????????????????????? 20 30

12
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
???????? ????? ?? ????????? ??? ??? ???? (??) ???? (??) ???? (??) First Post Diagnosis
???????? ????? ?? ????????? ? (???) ? (???) (15-19) (20-59) (60) First Post Diagnosis
1 ??.?. 45 - ?.?. 45 (2 ???) ????? 1 31 NMS e psychosis
2 ?.?. 45 ?.?. 46 (5 ???) ???????????? ???? 1 ? NMS.
3 ??????????????????? 1 ? Schizophrenia e NMS e seizure e hyponathemia
13
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
???????? ????? ?? ????????? ??? ??? ???? (??) ???? (??) ???? (??) First Post Diagnosis
???????? ????? ?? ????????? ? (???) ? (???) (15-19) (20-59) (60) First Post Diagnosis
4 ??? ?? 1 49 NMS e UTI e pneumonia
5 ??? ? 1 66 Schizophrenia (e Hypertension e fever) NMS
6 ??? ??? 1 27 NMS e psychosis
7 ??????? 1 37 NMS
14
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
???????? ????? ?? ????????? ??? ??? ???? (??) ???? (??) ???? (??) First Post Diagnosis
???????? ????? ?? ????????? ? (???) ? (???) (15-19) (20-59) (60) First Post Diagnosis
8 ?.?. 46 ?.?. 46 (9 ???) ????? 1 32 Schizophrenia e NMS c brain atrophy
9 ?????? 1 47 NMS e psychosis
10 ???????? 1 36 Schizo paranoid type e NMS
11 ????? 1 49 Schizo e NMS
12 ?????? 1 38 Schizo e NMS
13 ?????? 1 76 Schizo e NMS CVA, CPK, Dementia
14 ????? 1 52 NMS fever
15
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
???????? ????? ?? ????????? ??? ??? ???? (??) ???? (??) ???? (??) First Post Diagnosis
???????? ????? ?? ????????? ? (???) ? (???) (15-19) (20-59) (60) First Post Diagnosis
15 ?????? 63 NMS e renal failure
16 ???????? 1 50 NMS e antipsychotic drug
17 ??.?. 46 ?.?. 46 (5 ???) ????? 1 66 Schizo e NMS
18 ???????????? 1 70 NMS e Alzheimer CDM e hypertensio
19 ???????? 1 59 Schizo e NMS
20 ??????? 1 39 NMS e R/O Schizo
21 ????? 1 39 Schizo e NMS
16
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
???????? ????? ?? ????????? ??? ??? ???? (??) ???? (??) ???? (??) First Post Diagnosis
???????? ????? ?? ????????? ? (???) ? (???) (15-19) (20-59) (60) First Post Diagnosis
22 ?.?. 46 ?.?. 47 (6 ???) ????????? 1 66 NMS e behavioral change
23 ????? 1 66 NMS e psychosis e Dementia
24 ?????? 1 38 NMS e psychosis e delirium
17
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
???????? ????? ?? ????????? ??? ??? ???? (??) ???? (??) ???? (??) First Post Diagnosis
???????? ????? ?? ????????? ? (???) ? (???) (15-19) (20-59) (60) First Post Diagnosis
25 ?????? 1 21 Schizo e NMS
26 ????? 1 39 Schizo e NMS e hepatic Encephalopathy
27 ????? 1 56 Schizo e NMS
??? 27 ??.?. 45 ?.?.47 (27 ???) 15 12 0 18 7
??????????? (???) 2 ??? ??????????? (???) 2 ??? ??????????? (???) 2 ???
18
????? NMS ????????????????????????????????????????
????????????? ?.?. 2545 ??????????? ?.?.
2547
??? ?????? ??????? 15 12 1.25 1
???? ?????????????? ?????????????? 0
?????????????????? 2 ??? ??? 27 ??? 7 ???????????????? 25 ??? 93
????????????????? (20 59 ??) 18 ??? ??? 25 ??? 72
????????????????? (60 ????????) 7 ??? ??? 25 ??? 28
???? ??????????????? 40 ?? 14 ??? ??? 25 ??? 56
??????????????????? 40 ?? 11 ??? ??? 25 ??? 44
?????????????? NMS ??? SCHIZOPHRENIA 27 ??? 14 ??? 13 ??? ?? 27 ??? 48
NMS ?????????????? ? 14??? ?? 27 ??? 52
19
??????? (prevalence)

• ?????????? NMS ???????? 0.1 - 1
• ????????????????? ?????????????????? dopamine
  receptor antagonist (DRA) ?????????????? NMS
  ??????????????? 0.02 - 2.4
• ??????????????????????????????????????
  Serotonin dopamine antagonists (SDAs) ????
  ?? clozapine ??????????? NMS ???????????????

20
??????????? (incidence)

• ???????????????????????? NMS ?????????
• ???????????????????? NMS ????????
  ????????????????????????????? 10 - 30
  ????????????????????????????????????
  ??????????????? 20 - 30
• ????????? ????????????????? NMS ???????????
• ??????????????????????????? NMS ??????????
• ?????????????? ??????????? ???????????? NMS
  ????????????????

21
?????????? ??????????????????????????????? NMS
(risk factors)

• ??? ?????????? NMS ??????????????? 2 ??? 1
• ???? ??????????? 40 ?? ?????????????? NMS
  ?????? 80
• ??????????????? ?????????????? NMS
  ???????????????
• ?????????????????????????????? NMS ???????
  ?????????
• ????????????????????????????????
• ????????????????????? ? ???????????????????
• ????????????? (dementia)
• ??????????????? ?????????? (parkinsons diseases)
  ???????????????????????????????

22
?????????? ??????????????????????????????? NMS
(risk factors) (??? 1)

• ???????
• ????????????????? ?????????????????????????????
  ??
  ?????????????????????????? NMS
• ????????????????????? ?????????????????????????
  ????? NMS
• ?????????????????????????????????
• ??????????????????????????? (agitation)
• ?????????????????????
• ???????????????????????????? (critical time)
• ????????????? ???????????????????? NMS
  ???????????????????????????? ????? NMS ??????
• ????????????????????? ?????????????? ( affective
  disorder) ????????

23
?????????? ??????????????????????????????? NMS
(risk factors) (??? 2)

• ??????????????????????????? NMS
• ???????????????????????????????????????????????
  ?? ????????????????? ?
• ????????????????????????????????????????????????
  ??????????????
• ???????????????NMS ???? ??? ?????????????
• ????????????????? high potency ??????????????
  NMS ??????????
• ???????????? low-potency ????????????? NMS
  ???????????????
• ???????????????? ?? dopamine receptor
  antagonists (DRAS)??????
• NMS ??????????
• ?? serotonin dopa mine antagonists (SDAS)
  ????????? NMS ???? ????
• ?? clozapine

24
?????????? ??????????????????????????????? NMS
(risk factors) (??? 3)

• ???????????????????????????????????????
  ??????????????????
• ???????????????????????????????????????????????
  ???????????
• ?????????????????? antiparkinsonian agent
  ??????????????????
• ????????????????????????????????
• ?????????????????? clozapine ?????????
  lithium ???? NMS ???
• ??????? ??????????????????????????????????????
  ????????????????????? ??????????????????????????
  ???????????????? NMS???????????
  ?????????????????????????? ????????????????????
  NMS ?????? ????????????? clozapine ?????????
  lithium
• ?????????????????? risperidone ??????????? NMS
  ???

25
??????? NMS ?????????????????????????????????????
????? 5 ?? (?????? 2545 - ??????? 2549)
????????????????????????????????????????????? (???) ??????
1 40.5
2 16.7
3 9.5
4 7.1
5 2.4
6 2.4
7 2.4
???? NMS ???????????????????? admitted ??? 7 ??? ??????? ?????? 81 ??????????????????????????????????????????????????????????? ???? NMS ???????????????????? admitted ??? 7 ??? ??????? ?????? 81 ???????????????????????????????????????????????????????????
28 4.8

26
?????????????????????? NMS

• ????????????? 5 ?? (?????? 2545 ???????
  2549)
• ? ?????????????????????????????????

?????????????????????? NMS ??????
1. ???????????????????????????????? 85.7
2. ??????????? 81.0
3. ????????? 81.0
4. ????????????????? 71.4
5. ??????????????????????? 69.0
27
???????????????????? NMS ??????????

• ? ????? (fever)
• ? ????????????????????????????
• ? ??????????????????? ( muscle rigidity)
• ? ???????????????????????? ????
  ????????????????????????????????? (dystonia)
• ? ???????????????????????? (akinesia)
• ? ?????????????? ?????????????????? (mutism)
• ?????????????? ???????????????????????????????????
  ??
• (oscillation between obtundention and
  agitation)

28
???????????????????? NMS (???)

• ? ????????????????? (diaphoresis)
• ? ???????????????? ????????????? (dysphasia)
• ? ??????????? (tremor)
• ? ?????????????? ??????????????????????? (labile
  blood pressure )
• ? ???????????????????????? (incontinence)
• ? ??????? creatine phosphokinase
  (CPK)??????????????
• ( ???? CPK ???????? 60 - 280 IU/L
• ??????? 40 - 190 IU/L )
• ? ??????????????????????????????????????
  (leukocytosis)
• ? ???????????????????????????????????
  (myoglobinuria) ???????

29
???????????? NMS ????????? ? ??????

• ??????????????????????????
• ??????????? (delirium)
• ??????????????????? (diaphoresis) ???????????
  60
• ??????? extrapyramidal symptoms
• ?????????????????????????????????? (autonomic
  deregulation)
• ??????? CPK ??????? (elevated CPK) ???????
• ??????????????????????????????????????
  (leukocytosis)
• ?????????????????????????????? (rhabdomyolysis)

30
NMS ?????????????????????? (emergency
manifestation)

• ????????????????????? (muscle rigidity)
• ???????? (hyperthermia)
• ???????????????????????????????? (neurological
  signs)
• ????????????????????? ???????????????????
  (catatonic stupor)
• ?????????????????
• ????????????????????? ????????????? (autonomic
  instability)

31
????????????? (pathophysiology) ??? NMS

• ?????????????????? ????????? ???????
• 1. ?????????????
• ???????????????????????????????? ???????
  (dopamine
• receptor) ?????????????? (?????? basal
  ganglia ???
• hypothalamus) ?????????? ??????????????????????
  ???
• ???????????????????????????? post-ganglionic
  sympathetic
• neurons ?????????????????? (smooth muscle)

32
???????????????? NMS (???)

• ????????? ??????? (???)
• 2. ???????????????????????????????????????
• 3. ?????????????????? adrenergic tone ?????????
• 4. ??????????? non-dopamine monoamine ????
• ??????? selective serotonin reuptake
  inhibitors SSRIs
• ??????????? NMS ???
• 5. ???????????????????????
• 6. ???????????????? - norepinephrine (NE)
• - -Aminobutyric acid
  (GABA)
• - ????????? (5HT)
• ??? opioid neurotransmitter

33
??????????????? ????????????????? NMS

• ??????????????????????? hypothalamus
• ???????????? ?????????????????????????
• ( heat production)
• ????????????????????? ?????????????????????????
• ( heat dissipation )

34
????????????????????? ???????????????? (clinical
course and prognosis)

• ?????????? NMS ??????????????????????
  ???????????????????????? (emergency psychiatric
  medicine)
• ??????????????? NMS ?????????????????????
  ???? (rapid onset)
• ????????????? NMS ?????????????????????????????
  ? ??????????????????
• ????????
• ?????????? ??????????????????????????? NMS
  ?????? ??????????????? ????????? NMS
  ???????????????
• ???? ??????????????????????????????????????????
  ???????????????????? ?????? NMS ??????????

35
????????????????????? ???????????????? (clinical
course and prognosis) (???)

• ?????????????????????????? MNS
  ??????????????????????? ???????????????????????
• ????????????????????? ?????????????????????????
  ????????????? ??????????????????????
  (withdrawal) ????
• ?????????????????????????? (agitation)
• ???????????????????????? ??????????????????????
  ?????? (exacerbation of the psychosis)
• ??????????????????????????????????????????????
  ??????????????????????? NMS

36
????????????????????? ???????????????? (clinical
course and prognosis) (???)

• ?????????? NMS ????????? ? ?????????????????
  24 - 72 ???????
• ???????????????????? - ????????????? 10 - 14
  ???
• - ??????????????????? ?????? 10 - 30
• ??????????? NMS ???? ??????????????? 2
  ??????? ??????????????

37
??????? NMS ?????????

• - ?????????????????????
• - ?????????????????????????????
• - ????????????????????????????????????
• - ?????
• - ??????
• ????????????????????????????????
  ???????????????????????
• ???????????????

38
?????????????? NMS??????????????? NMS ??????
???????

• ??????????? NMS ???????????????? 30
• ?????????????? NMS??????????????? NMS ?????????
  ???????
• ????????????????? NMS ????????????

39
??????????????? NMS ???? ?????????????????????????
???????????????????????? ????????????????????????
??? NMS ?????????

• ? ????????? NMS ???????????????????? 2
  ???????
• ? ???????????????? - ????????????????? low
  potency
• - ???? ???????????????????? serotonin-
  dopamine antagonists (SDAS)
• ?????? clozapine ????? risperidone
  ?????????????????????????????????? NMS
• ????? clozapine ??????????????????? NMS
  ???????
• ? ?????????????? benzodiazepine ??? ???? ??
  diazepam
• ? ???????????????????????????
  Electroconvulsive therapy (ECT)

40
??????????? ???????????????? NMS

• ??????????????????? ??????????????????????????????
  ???????????????
• ???????????????? ?????????????? anticholinergic

41
???????????????????????? (management) ?????? NMS

• ????????????????????????NMS ???????????????????
• ?????????????????? ???????????? (organic workup)
• ????????????????? (septic workup)
• ????????????????????? ? ???????????????????????
  NMS ???
• ?????????????????????????? ??????????????????
• ?????????????????????????????????????
• ??????????????????????????? lithium ?????
  ??????????? lithium ????
• ??????????????????????? ????????????

42
??????????????????????????????????????????????????
??

• ????????????? NMS ??????????
• 1. ??????????????????????????
  ?????????????????
• 2. ???????????????????? (suspected drug)
  ????????????? ???????????? NMS ???????
• 3. ??????????????????????? ??????????????????????
  
• 4. ??????????? ??????????????????????????????????
  ? ????????????????? 8 ??????? ????????????????????
  ??????
• 5. ??????????????????????????
• 6. ????????????????????????????????????

43
??????????????????????????????????????????????????
?? (???)

• 7. ????????????? ??????????????
  ?????????????????????????????????????
• 8. ????????????????????????????????????????
• 9. ????????????????? ???????????????
• 9.1 ????? bromocriptine
• 9.2 ????? amantadin
• 9.3 ????? dantrolene
• 9.4 ????? caridopa-levadopa (Sinemet)
• 9.5 ????? lisuride
• 10. ???????????????????????????
  Electroconvulsive therapy (ECT)
  ??????????????????

44
???????? NMS

• ?????????? (first step)
• 1. ?????????????????????? ?????????dopamine
  receptor antagonist ?????
• 2. ????????????????????????????????? ????
  ??????????????????????????????
• 3. ?????????????????
• ?????????????????????????????????????
• 4. ??????????????????????
• 4.1 ?????????
• 4.2 electrolytes
• 4.3 ??????????????? ??????????????????????
  (fluid balance)
• 4.4 ????????????? ??????????????????????
  (renal output)

45
???????? NMS (??? 1)
??????????????????????? NMS ????
???????????????????????????????????
???????????????????????????????????????
???????????????????? ???????????????????????????
????????????????????
46
???????? NMS (??? 2)

• ???????????????????????????????????????
  ????????????????????????? low potency
  ???????????????????????
• ?????????????????????????????????????????????????
  ???????????
• ???????????????? ?????????????? ? ???????? 1.
  ????????? 2. ??????????? 3. ??????????????
  ???? extrapyramidal symptoms
• 4. ???????????? ??? ???????????????????????

47
???????? (NMS)

• ???????? Neuroleptic Malignant Syndrome ( NMS )
• ????????????????????? ????? ?????????????????????
  ?????
• ??? ????????????????????? ????????? ???????? 4
  text rev. (DSM IV - TR) ????????

??? 1 ?????????????????? ?? ?????
1.1 ???????????????????????????????? ? ?
1.2 ???????? ? ?
1.3 ????????????????????????? ? ?
48
???????? (NMS) (??? 1)
??? 2 ?????????????????????????? ???????????????????????????????? ?? ?????
2.1 ?????????????????????????? ????????????????????????? ? ?
2.2 ???????????????? ????????????? (mutism) ? ?
2.3 ???????????????? (dysphagia) ? ?
2.4 ?????????????????(diaphoresis) ? ?
2.5 ??????????? (tremor) ? ?
2.6 ???????????????????? (tachycardia) ? ?
49
???????? (NMS) (??? 2)
??? 2 ?????????????????????????? ???????????????????????????????? (???) ?? ?????
2.7 ????????????????????? ? ?? ? ?
2.8 ???????????????????? ?????????????????? (incontinence) ? ?
2.9 ???????????? ?????????????????? ??????????????????????? ?????????? CPK ??????? ??????? ? ?
2.10 ?????????????????????????????????????? (leukocytosis) ? ?
50
???????? (NMS) (??? 3)
??? 3 ?????????? 1?????? 2 ????????????????? ?? ?????
3.1 ??????????????????????? ? ???? ??? phencyclidine ? ?
3.2 ????????????????????????????????????????????? ? ? ?
??? 4 ?????????? 1 ??????2 ????????????????? ?? ?????
4.1 ???????????????????? ???? ?????????????????????? ????? catatonic ? ?
???? NMS ??????? ????????????????????????? ????????????????????????????????????? ?????????????????? ???? NMS ??????? ????????????????????????? ????????????????????????????????????? ?????????????????? ???? NMS ??????? ????????????????????????? ????????????????????????????????????? ??????????????????
51
???????? NMS ???????????????

• 1. ????? bromocriptine 2. ?????
  amantadin 3. ????? dantrolene 4. ?????
  azumolene 5. ????? clonazepam 6. ?????
  benztropine??? 7. ????????????????Electroconvuls
  ive therapy (ECT)

52
???????? NMS ????????????????????? (??? 1)

• 1. ????? bromocriptine
• ?????? dopaminergic agents ???? dopaminergic
  receptor agonist
• ??????????????????? 2 - 10 ??????????? 8 ???????
  ???????????????? (nasogastric tube )
• ??????????????????? bromocriptine ????? 20 -
  30 ????????? ?????? ??????????????????? 4
  ??????????
• (?? bromocriptine ?????????? central D2
  agonist
• ?????? bromocriptine ??????????????????????????
  ??????????????? )

53
???????? NMS ????????????????????? (??? 2)

• 2. ????? amantadin
• ?? amantadine ??????????? ????????
  bromocriptine ??? dopamine receptor agonist
• ????????????????????????? ????? dopamine
  receptor blockage ???????????????????????

54
???????? NMS ????????????????????? (??? 3)

• 3. ????? dantrolene
• ?? dantrolene sodium ???????????
  antispasticity agent ??
  dantrolene ??? ???????????????????????????????????
  ??????? ? (adjunctive therapy)
• ?????????????????????????????????????????
  ?????????
• ????? dantrolene ???????????????
  ??????????????????????? ???????????????????
• ??????? 0.3 - 1 ????????? ?????????????????????
  ???????????? ??? 6 ???????
• ??????????? ?????????? 0.5 - 2.5 ?????????
  ??????????????????????????
• ??????? 4 ???? ?????? ?????????? 100 ??? 400
  ???????????????
• ???????? dantrolene ??????????????????

55
???????? NMS ????????????????????? (??? 4)

• 4. ????? azumolene ?? azumolene ??????
  antispasticity compound
• ??????????????????? NMS

56
?????????????????????? ?????????????????????????
???????????????
???????? NMS
57
?????? ??? ??????