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1 서울대학교병원 장선주 만성정신질환자관리 Ⅰ

2 순서 Compliance vs. Adherence Antipsychotic agents

3 Role of the nurse Patient assessment Coordination of treatment modalities Drug administration the greatest daily impact, a key professional Monitoring drug effects and side effects

4 Role of the nurse Medication education patient collaboration, adherence a pivotal position Drug maintenance programs Clinical research drug trial Prescriptive authority(aprns) Adherence 연속선상의개념 (Lask, 1998)

5 서울대학교병원 장선주 만성정신질환자관리 Ⅰ

6 순서 Role of the nurse Antipsychotic agents

7 Compliance vs. Adherence Compliance 수동적역할 충실히따름 순종적임 치료진조언대로행동 치료진이계획 2000년전히포크라테스 Chin(1997) Adherence 능동적역할 자발적이며협력 상호수용적인과정 선택할수있음 계획, 수행에대상자도관여 *Concordance: negotiated agreement. misleading, inaccurate!(aronson, 2007)

8 Compliance vs. Adherence Barofsky(1978 ) compliance adherence alliance coercion conformity negotiation Compliance: 가부장적, 강압적순응아니면불순응 Adherence: 대상자의책임과자율성강조 Self efficacy 이론

9 정신과환자의약물불이행 40%(Kent&Yellowlees,1994), 80%(Corrigan et al.,1990) 신체질환자에비해약물불이행도 (Cramer&Rosenheck,1998) 약물이행증진간호사가적격자 적격자 (Pearce, 2003) 약에대한환자의신념은진단에대한이해만큼이행에영향, 간호사의역할강조 1997) 강조 (Kemp et al.,

10 Drug adherence Multifaceted and complex No single causative factor Multidimensional phenomenon

11 Multifaceted model

12 Multidimensional phenomenon 환자환자환자환자의료인의료인의료인의료인처방내용처방내용처방내용처방내용질병특성질병특성질병특성질병특성신체적신체적신체적신체적건강건강건강건강정신적정신적정신적정신적건강건강건강건강경제적경제적경제적경제적자원자원자원자원문화적문화적문화적문화적신념신념신념신념자기효능감자기효능감자기효능감자기효능감사회적지지사회적지지사회적지지사회적지지기술기술기술기술지식지식지식지식태도태도태도태도대인관계대인관계대인관계대인관계유용성유용성유용성유용성사정기술사정기술사정기술사정기술의사소통기술의사소통기술의사소통기술의사소통기술전문기술전문기술전문기술전문기술복용횟수복용횟수복용횟수복용횟수약종류약종류약종류약종류약크기약크기약크기약크기약맛약맛약맛약맛보관방법보관방법보관방법보관방법투약방법투약방법투약방법투약방법부작용부작용부작용부작용효과효과효과효과비용비용비용비용증상증상증상증상기간기간기간기간심각성심각성심각성심각성낙인낙인낙인낙인 (Williams, 1999)

13 약물이행도증진전략 Fenton et al. (1997) Psychoeducation Cognitive and behavioral approach Motivational interviewing Coombs et al. (1997) Side effect monitoring Recognition Treatment Drug adherence

14 약물이행도증진전략 Cobb(1996) Yellow card 87% Hynes et al.(2001) More thorough client instruction Counselling Reminders Close follow-up Supervised self-monitoring and rewards for success

15 Rating of Medication Influence ROMI scale(weiden et al. 1994) 4 subscales Denial of illness Rejection of label Logistical problems Negative therapeutic relationship Non-adherence 영향요인

16 약물이행증진을위한간호사의역할 Happell, Manias, Pinikahana(2002) Patient education Patient advocacy Patient support and reassurance Family support Liason with other professionals

17 약물이행증진을위한간호사의역할 Nurse s close proximity to clients a key role in monitoring of medication a key role in providing education 수많은문헌에서 education program이 adherence relapse 보고

18 약물이행증진을위한간호사의역할 방해요인 간호사스스로지식부족, 자신감부족보고 61.5%(Millar et al., 1999) task and time focused rituals Drug reps 으로만정보얻기도하는상황 extensive, current information 필요 self-initiated learning

19 Issues Depot preparation Haloperidol, Risperidone, Palliperidone Soluble tablets Risperidone 부작용체중증가측면관리

20 Central Nervous System 뇌세포중뉴런은 1/10 공군의 pilot에해당 뉴런 : 500억-1000억개로신경전달물질 (50-100개 ) 이중복될수밖에없음. dirty drug 각뉴런마다특정신경전달물질담당 질환 : too much / little transmission

21 순서 Role of the nurse Compliance vs. Adherence

22 5 symptom dimensions Positive symptom Negative symptom: 5As Cognitive symptom Aggressive and Hostile symptom - poor impulsive control Depressive and Anxious symptom 5A affective flattening, alogia, avolition, anhedonia, attention impairment

23 schizophrenia 5 가지 symptom dimensions positive symptoms negative symptoms anx/dep aggressive symptoms cognitive symptoms

24 Dopamine Pathway Nigrostriatal dopamine pathway Mesolimbic dopamine pathway Mesocortical dopamine pathway Tuberoinfundibular dopamine pathway 어떻게하면 mesolimbic pathway DA 활동성을감소시키면서동시에 mesocortical pathway DA 활동성을증가시킬수있을까? Atypical antipsychotics

25 DOPAMINE PATHWAYS Substantia nigra Basal Nucleus Ganglia accumbens a b d c hypothalamus Tegmentum

26 작용 1. mesolimbic pathway - 양성증상 Nucleus accumbens Tegmentum 즐거움, 보상, 행동강화, 약물남용

27 mesolimbic overactivity = positive symptoms of psychosis

28 부작용 2. mesocortical pathway 음성증상, 인지적증상 Limbic cortex Tegmentum

29 primary dopamine deficiency D2 receptor blockade secondary dopamine deficiency increase in negative symptoms mesocortical pathway

30 부작용 3. nigrostriatal pathway - 운동조절 Basal Ganglia Substantia nigra DA 차단시 EPS

31 부작용 4. tuberoinfundibular pathway PRL 분비 Pituitary gland Hypothalamus DA 차단시 PRL level

32 pure D2 blocker D2

33 pure D2 blocker

34 Mesocortical pathway Increase in negative symptoms

35 Nigrostriatal pathway EPSs

36 Blockade of receptors in the nigrostriatal dopamine pathway causes them to upregulate This up-regulation may lead to tardive dyskinesia

37 Tuberoinfundibular pathway Prolactin levels rise

38 M1 H1 1 conventional antipsychotic drug D2

39 = acetylcholine = dopamine DA - Ach 억제 Nigrostriatal pathway

40 = D2 blocker EPS 발생 Nigrostriatal pathway

41 = anticholinergic

42 M1 INSERTED constipation blurred vision LAXATIVE dry mouth drowsiness

43 H1 INSERTED drowsiness weight gain

44 1 INSERTED decreased blood pressure dizziness drowsiness

45 1 1 haloperidol D2 1.5mg 12 원, 5mg 30 원

46 Atypical antipsychotics Serotonin-dopamine antagonist SDAs Typical 보다적은 EPS Conventional 만큼양성증상향상시킴 CZP, OZP, RSP, QTP, ZPRS, APPZ

47 5HT2A SDA D2

48 Nigrostriatal pathway 에서 5HT-DA Interactions brake Substantia nigra brake raphe nucleus 그러므로 5HT 2A antagonism DA 증가 Ach 억제 low EPS

49 Nigrostriatal pathway dopamine D2 receptor DA neuron postsynaptic neuron 5HT2A receptor 5HT neuron

50 Nigrostriatal pathway no dopamine release serotonin

51 Nigrostriatal pathway D2 receptor SDA

52 Nigrostriatal pathway 5HT2A receptor Disinhibition 탈억제 SDA는 DA 뉴런을탈억제시켜 EPS, TD 줄여준다

53 5HT2A receptor pituitary lactotroph prolactin D2 receptor dopamine serotonin

54 5HT2A receptor serotonin pituitary lactotroph prolactin 5HT와 DA은 PRL 분비에있어상호규제

55 D2 antagonist pituitary lactotroph D2 receptor prolactin

56 5HT2A receptor pituitary lactotroph D2 receptor prolactin SDA

57 5HT1A 5HT2A 5HT2A 1 M1 H HT1D SRI 5HT2C NRI SDA D2 5HT3 5HT6 atypical antipsychotic D4 D3 D2 D1 5HT7

58 single selective mechanisms = loss of side effects multiple mechanisms = side effects Haloperidol chlorpromazine risperidone quetiapine olanzapine clozapine SDA multiple therapeutic mechanisms = improved efficacy Are Antipsychotics with Multiple Therapeutic Mechanisms Better than Selective Dopamine 2 Antagonists?

59 5HT1A 5HT2A 5HT2C 5HT3 5HT6 M1 H1 1 clozapine D4 D3 D2 1 D1 2 2 Agranulocytosis 0.5-2% Sz Sedation 음성증상의호전가장많은체중증가 H1, 5HT2C 최고의효능 vs. 최고의부작용 TD 치료 25mg 274원, 100mg 685원 5HT7 가장복잡한포트폴리오중하나

60 5HT2A 고용량에서는 typical(eps) 기분장애개선 TD 적음 Atypical 중가장간단체중증가가적음 (H1 막지않음 ) 0.5mg 520원, 1mg 758원, 2mg 1143원 risperidone D2 5HT7

61 5HT2A 5HT2C 5HT3 5HT6 M1 H1 1 olanzapine D4 D3 D2 1 D1 항상 EPS 없다비싸다체중증가 PRL 상승적음 TD 적음 Bipolar의 1차치료인지기능개선 2.5mg 1286원, 5mg 2368원, 10mg 4462원

62 5HT2A 5HT6 H1 quetiapine D EPS 없다 PRL 상승없다체중증가렌즈에서콜레스테롤생합성 X 백내장기분장애에서효과적인지기능개선 25mg 495원, 100mg 1216원, 200mg 1825원 5HT7

63 5HT1A 5HT2A 5HT1D 5HT2C ziprasidone 1 1 SRI NRI Low EPS QTc Prolongation PRL 상승거의없다체중증가전혀없는것같다 5HT2C 막지만 H1 막지는않음 SRI, NRI 유일 Strong 5HT1A agonist 항우울제, 항불안제로도 20mg 2157원, 40mg 2226원 D3 D2 5HT7

64 Aripiprazole partial agonist dopamine stabilizer 10mg 4406 원, 15mg 4406 원 $$$ APPZ 10mg 4406 원 = 15mg 4406 원??!!

65 Amisulpride partial agonist dopamine stabilizer 100mg 845 원 200mg 1265 원 400mg 2204 원

66 The Goldilocks antipsychotics

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<4D F736F F F696E74202D204E494345BCADC8ABBFF8B0ADC0C7B7CF34205BC8A3C8AF20B8F0B5E55D> 신경전달물질 (Neurotransmitter; Introduction to CNS Pharmacology) 한림대학교의과대학약리학교실, 서홍원 학습목적 중추신경계정보전달기전을학습하므로신경정신질환에사용되는중추신경계치료제들의기본적이고체계적인약리학적응용지식을습득한다. 학습목표 : 1. 신경전달물질, 신경호르몬, 신경조정인자, 신경매개인자, 신경영향인자의정의와각각의예를열거한다.