향정신약물의 정신과적 부작용(II)

윤도준 대한정신약물학회 2002 대한정신약물학회지 Vol.13 No.1

The psychotropic effects of the original psychotropics currently in use, such as chlorpromazine, iproniazide, imipramine, lithium, and clozapine, have been applied to clinical practice through fortuitous discoveries of their psychiatric side effects(PSE). The etiopathophysiology of various psychiatric disorders have been deduced from the action mechanism of original psychotropics, and the designed drugs which selectively act on those neurotransmitters involved in the therapeutic effects of the original drugs are being developed as novel drugs. Psychiatric side effects cannot be considered to necessarily anti-therapeutic, as seen throughout the history of psychopharmacology. The clinical and pathophysiological significance of PSE deduced from their analyses according to the psychiatric symptoms manifested as PSEs are as follows: 1) PSEs are manifested according to the biological characteristics of the patient across diagnosis. This reflects the lack of biological basis in the current diagnostic system. 2) Psychotropics are important as in vivo pharmacological probes or challenges which, upon administration, allow for the biological characterization of the patient brain, i.e. pharmaco-biological typing of the patient may be performed based on the patient responses to the agent (both therapeutic and adverse effects). Such data may be of importance in subsequent prescription of the patient. 3) The hierarchy of a psychiatric disorder may be modified by drug administration, converting the disorder into that of a lower rank and thus into what is more easily treated. 4) A pharmacological approach, rather than a diagnosis-based one, is required. Consequently, more research into the still unknown psychotropic effects of each psychotropic is desired. In the process, clinically significant psychotropic effects currently undefined from the point of diagnosis-based approach may be discovered. 현재 사용 중인 원조 향정신약물 chlorpromazine, iproniazide, imipramine, lithium, clozapine의 향정신효과는 우연히 발견된 이들 약물의 정신과적 부작용을 임상에 응용하게 된 것이다. 다양한 정신질환의 원인병태생리는 이들 약물의 작용기전의 유추에 의한 것이며, 원조 약물의 치료적 효과에 관련되는 신경전달물질에만 선택적으로 작용하게 디자인한 약물이 신약으로 소개되고 있다.정신약물학의 역사를 통해 볼 때, 정신과적 부작용을 반치료적이라고만 할 수 없다. 정신과적 부작용으로 나타나는 정신증상에 따른 분석 결과 정신과적 부작용의 임상적 그리고 병태생리학적 의미는 다음과 같이 요약된다. (1) 정신과적 부작용은 진단을 떠나 환자의 생물학적 특성을 잘 반영한다. 현 진단 체계의 생물학적 근거가 결여되었음을 반영한다. (2) 생체 약물학적 소식자로서 향정신약물은 투여된 환자 뇌의 생물학적 특성을 알 수 있게 한다. 즉 약물에 대한 모든 반응(치료적 및 부작용)에 따라 환자를 약물-생물학적 분류가 가능하게 된다. 이와 같은 자료는 해당 환자의 향후 처방에 중요하다. (3) 정신질환의 서열이 투여된 약물에 의해 보다 치료하기 용이한 하위 서열로 변화될 수 있다. (4) 진단보다는 약물 중심의 접근이 강조된다. 나아가 현재 사용 중인 향정신약물의 아직 우리가 모르고 있는 향정신 효과에 대한 연구가 필요하다. 이런 과정을 통해 진단 중심의 접근에서 규명되지 못한 임상적으로 유용한 향정신 효과들이 밝혀질 것이다.

滴疾重叠症의 臨床的 考察

尹道竣,韓弘武 대한신경정신의학회 1982 신경정신의학 Vol.21 No.2

An attempt was made to study the problems and preventive measures on the therapeutic managem ent of the status epilepticus, which is one of the em ergency diseases in the neuropsychiatry. The author reviewed the clinical records of 51 inpatients with status epilepticus who have been hospitalized in the neuropsychiatric ward of Kyung-Hee University Hospital during a period from Oct. 1971 to Aug. 1981. T he results were summarized as follows; 1. The rate of status epilepticus out o f the total epileptic inpatients o f 240 in the period was 21.3 %. 75% of them were in the age above 21. Male to female ratio was 29 : 22. More than half of the patients belonged to the lower socioeconomic class. 2. Age of onset in the initial status epileptic patients was between 11 and 20, whereas that in the intercurrent status epileptic patients was between 21 and 30. The interval between first seizure and first intercurrent status epilepticus was mostly less than 10 years and that in more than half of them was less than 1 year. 3. More than half of those with intercurrent status epilepticus had been managed with the herb practice, folk therapy, and superstitious measures, and the remaining patients have been treated with anticonvulsant medication, though in general, on irregular basis. 4. It was found that a majority of the patients had precipitating factors. The more frequent prec ipitating factors were irregular medication, high fever, alcohol drinking, and hypoglycem ia, in that order. 5. 94% of them showed grand mal type seizure. 35.3% was sym ptom atic type and 64.7%, idiopathic. Most of them experienced at least 4 times of seizure attacks, and about half of them, more than 10 times. The duration o f unconsciousness was mostly less than 24 hours. 55% of the seizures occured during sleep, especially early in the morning, and 41% of them occured in winter. The overall mortality rate was A%t and the cause of death was respiratory failure. 6. 81% o f the patients showed EEG abnormalities. In 54% of the patients were found focal sites, and most of the focal sites were in the fronto-temporal areas. 7. In the therapeutic management of status epilepticus, intensive follow-up measures including regular administration of anticonvulsant drugs and prevention of possible precipitating factors are thought to be important.

구강 편평세포암종 세포주에서 섬유모세포 자극에 의한 Cathepsin D 의 발현 증가

윤도준,정현정,차충민,이은주,김진 대한구강악안면병리학회 2005 대한구강악안면병리학회지 Vol.29 No.6

Epitheli a l mesenchymal interaction(EMl) is well known to be essential in eznbryonic deve]opment. wound hea]jng a nd ca rci nogenes is. Th is study was a i med to design in vi tro model for the investigation of protein analysis in epithe li al a ncl mesenchyma l i nteract ion(EMI) . This stucly usecl oral squamous cell carcinoma cell line(YD-lOB) . 1'0 investigate the clifference 0 1' protei n ex press ion of cancel‘ cells influencecl by variable in vitro conditions. three different models were des ig necl ; Collagen gel- basecl ca ncer cell culture model devoid of fibroblasts(C) , Direct coτulture moclel(M2) composed of ca ncer cells beneath co ll agen gel embeclded with Swiss 31'3 fibroblasts ‘ and Indi rect co-culture model(Ml) with collagen layer betwecn cancel‘ cells and collagen gel with f lbroblasts Two-dimensional electrophoresis was performed to compa re t he diffe r ence of protein express ion pattern of ca ncer cells aznong three znodel systems. Protein identification was done by MALDI-TOF. As res ults ‘ pl'O te in express ion pat tem of cancel' cells was quite different between znonolayer cul ture and coll agen gel based cultu re. Aclditiona ll y. protein expression was different between culture models with fi broblasts and without fibroblasts a ncl between ind irect contact and direct contact of two cell types ‘ Among differentia l prot ei n spots. catheps in D WäS iuenLifï ed by MALDl• TOF Cathepsin D exprcssion was increased from C model to 11띠 and M2 model by West em blott ing. suggest ing that cathe psi n D expression may be activated by direct and indirect stimulation of stromal fï broblas ts F' rom these resul ts ‘ these models could be appropriate for EMI study and cathepsin D mi ght be incluced by fi broblasts s timulation

정신과약물의 부작용 : 분류 및 개요

尹道埈 대한의학협회 1995 대한의학협회지 Vol.38 No.10

항정신병약물에 의한 인두-후두 근긴장이상증 2예

윤도준 경희대학교 1992 慶熙醫學 Vol.8 No.4

의학적 치료

尹道埈 대한의학협회 1994 대한의학협회지 Vol.37 No.7

정신의학(精神醫學)에서 행동모형(行動模型)(I) : 우울증과 불안

윤도준,Yoon, Doh Joon 대한생물정신의학회 1995 생물정신의학 Vol.2 No.1

Behavioral models are used very widely to investigate or illuminate aspects of human psychopathology. However, the extent to which it is possible to extrapolate from animals to people, and, therefore, the value of information derived from a behavioral model, will depend to a large extent on the validity of the models. This article outlines some behavioral models of depression and anxiety.

항정신병약물의 임상치료지침

윤도준,Yoon, Doh-Joon 대한생물정신의학회 1994 생물정신의학 Vol.1 No.1

I will try to serve as the basis for the development of a clinical therapeutic guideline of antipsychotic drugs. Knowing that many patients fail standard treatment recommendations, either because of insufficient efficacy or intolerance to adverse effects, led us to emphasize the importance of the guideline. The clinicians continually assimilate new information about recent advances, including : novel agents targeted to impact specific components of various neurotransmitter systems ; combination strategies ; alternative uses of existing agents ; and specialized requirements of a growing number of identified diagnostic subtypes. The cost to benefit ratio must always be considered when developing a therapeutic guideline.

항우울제와 관련된 조증

윤도준 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.3

To examine the causative agents, clinical characteristics, management, risk factors, and neurochemical mechanism of the antidepressant-associated mania, MEDLINE searches were conducted. Mania can occur by chance during antideressant treatment or withdrawal, particularly in patients predisposed to mood disorder. Antidepressant-associated mania, especially withdrawal mania, appears to be milder and a more time-limited syndrome than a spontaneous mania and may represent a distinct clinical entity. MAOI, especially RIMA, or bupropion may be associated with milder and less manic inductions than either TCA or SSRI. The possible risk factors for antidepressant-induced mania are female, mood disorder, especially bipolar type I, past and family history of mood disorder, especially bipolar type I, long-term treatment, high dose, and combined therapy in treatment-resistant depression, the possible for withdrawal mania are female, mood disorder, especially major depressive disorder, past and family history of mood disorder, especially major depressive disorder, long-term treatment, high dose, abrupt discontinuation or dose reduction, TCA or MAO(except RIMA?). Antidepressant-induced mania can result from dysfunction of mechanisms that maintain noradrenaline/acetylcholine balance associated with the antidepressant-induced activation of noradrenaline system. The mechanism of withdrawal mania with TCA is cholinergic-monoaminergic interaction theory, and with MAOI is related a hyperdopaminergic state due to loss of drug-induced subsensitivity of dopamine autoreceptors. The prevention of these side effects will require further well-designed study on risk factors.

기분장애에서 risperidone의 양면성

윤도준,Yoon, Doh Joon 대한생물정신의학회 1997 생물정신의학 Vol.4 No.2

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.