untitled

대한소아소화기영양학회지 : 제 12 권부록 1 호 2009 최신지견 복통의약물요법 - 복통과연관된기능성위장관질환을중심으로 서울의료원소아과 신지연 Pharmacological Treatment for Functional Abdominal Pain in Children Jee Youn Shin, M.D. Department of Pediatrics, Seoul Medical Center, Seoul, Korea Functional gastrointestinal disorders are among the most common medical problems in children. Abdominal pain-related functional gastrointestinal disorders can be categorized as functional dyspepsia, irritable bowel syndrome, abdominal migraine and childhood functional abdominal pain according to the Rome III criteria for pediatric functional gastrointestinal disorders. The aim of this paper was to examine the evidence supporting the use of the range of therapeutic options available for functional gastrointestinal disorders. [Korean J Pediatr Gastroenterol Nutr 2009; 12(Suppl 1): 103 110] Key Words: Chronic abdominal pain, Functional abdominal pain, Children 서 소아에서복통은병원에내원하게되는흔한증상중하나이다. 급성복통은계획에없던병원방문의 5% 에이르는부분을차지하고있고 1) 만성복통은소아에서유병률이 10 15% 에이른다고보고되고있다 2 4). 복통의원인은해부학적, 감염성, 비감염성염증성, 생화학적기질적질환을포함하여다양한원인이있어 론 접수 :2009 년 10 월 31 일, 승인 :2009 년 11 월 6 일책임저자 : 신지연, 135-740, 서울시강남구삼성 1 동 171-1 서울의료원소아청소년과 Tel: 02-3430-0394, Fax: 02-567-0685 E-mail: jeeyouns@gmail.com 서복통을주소로내원한환자의경우적절한진단이치료방향결정에중요하다. 이중흔한비수술적복통의원인으로위장관염, 변비, 기능적위장관질환과관련된복통, 염증성장질환, 담관질환, 췌장염, 간염, 급성위염, 십이지장염, 소화성궤양, 알러지성자반증, 일차성복막염, 장중첩증, 기타 ( 폐렴, 신우신염, 월경통등 ) 등을들수있다. 여기에서는비교적만성복통의흔한원인이되는기능적위장관질환과관련된복통을약물치료에중점을두어다루고자한다 (Table 1). 기능성위장관질환은적절한설명, 안심시켜주는것과더불어약이처방되는경우가많으나약제의효과와안정성에대한연구는부족한실정이다. 한프랑스의연구에따르면 87% 의과민성장증후군환자가약을처방 103

104 ㆍ대한소아소화기영양학회지 : 제 12 권부록 1 호 2009 Table 1. Available Drugs for Functional Abdominal Pain in Korea H2 blocker: Famotidine ( 파모티딘정, 가스터정외 ) 0.5 mg/kg/dose bid max, 20 mg bid Ranitidine ( 라니티딘정, 잔탁정 ) 2 4 mg/kg/d max.150 mg bid PPI: Omeprazole ( 오메프라졸정, 로섹캅셀, 오엠피정등 ) 0.8 mg/kg/d Lansoprazole ( 란스톤정, 란프라정등 ) 0.8 mg/kg/d Prokinetics: Domperidone ( 돔페리돈정, 모리리움정, 돔페리돈현탁액, 하미돈현탁액 1 mg/ml) 1 2 mg/kg/d #3 Metoclopramide ( 멕소롱액, 맥페란정, 멕페란주, 멕쿨주 ) iv,po. 0.033 0.1 mg/kg/dose q8hr Erythromycin ( 아이로손시럽 25 mg/ml, 에리스로캡슐 ) 20 mg/kg/d #2 4 Octreotide ( 산도스타틴주, 목트스타틴주 ) 50 mcg/dose 2/d SC ( 성인 ) Ondansetron ( 조프란정, 조프란주, 온세트론정, 온세트론주, 유니온단정, 온단세트론정 ) 4 8 mg q 8 12 hr Antispasmodics: Pinaverium bromide ( 디세틸정, 피린정, 디스텐정, 베리움정, 트인텔정, 핀베린정 ) 50 mg tid ( 성인용량 ) Trimebutine ( 말레인산트리메부틴정 ) 100 200 mg tid ( 성인용량 ) Cimetropium bromide 50 mg tid ( 성인용량 ) Laxatives: Lactulose syrup ( 듀파락시럽, 모니락시럽 ) 1 3 ml/kg/d Polyethylene glycol 3350 ( 마이락스산 ) 0.75 1.5 g/kg/d Antidiarrheal agents: Loperamide ( 로페라미드, 록펠, 페라민캅셀 ) 2 5 yr: 1 mg tid / 6 8 yr: 2 mg bid / 8 12 yr: 2 mg tid 0.1 mg/kg dose after each loose stool (max. initial dose) Others: Propranolol ( 프로프라놀롤정, 인데놀정, 테프라정, 프라놀정 ) 10 20 mg 2 3/d( 성인 ) Sumatriptan ( 수마트란정, 슈그란, 이미그란에프디필름코팅정, 이미그란정 ) 성인 1 회 50 mg Amitriptyline 25 mg qd 증량 ( 성인 ) 받지만그에반도못미치는환자만이약이효과적이었다고보고하였다고하였다 5). 약제효과판단에기능성장질환에서위약효과가큰편이라는점도고려되어야한다 6). 과민성장증후군과기능성소화불량증에서 5% 에서 85% 까지위약효과가있다는보고가있다 7,8). 따라서약물의진정한효과를판별하기위해서는위약효과를배제하기위해 randomized controlled trial이되어야하는데실제로이렇게구성된연구는많지않고, 더군다나소아에서의정보는부족한상황이다. 기능성복통에효과적이라고알려진 cisapride, tegaserod, alosetron 등의약이부작용으로허가받은수년만에 FDA에서제한을받게된예를보더라도기능성위장관질환에서의약물의안정성에대하여서도더많은연구가필요한실정이다. 본론 1. 기능성복통의병태생리 9,10) 기능성복통은단순히사회적인모델링이나부모통증의모방또는원치않는경험 ( 학교기피, 꾀병 ) 을피하기위한수단이아니라, 실재하는통증이라고받아들여지고있다. 기능성복통의원인과병태생리는잘밝혀져있지는않으나뇌-장관상호작용의와해에기인한다는생각이지배적이다. 운동장애와장신경의과민성이가장중요한기전으로보이는데, 장신경과민성이란정상아이에서는통증이라고받아들이지않는감각을만성기능성장질환을가진아이들에서는예민하게통증으로느끼게되는현상을이른다. 운동이상과장관과민성을초래하는유발인자로서는신체적 ( 특정음식이나 Helicobacter위염, 약물, 대변정체와같은물리적자극등 ), 정신적스트레스가있다. 또다른가능

신지연 : 복통의약물요법 - 복통과연관된기능성위장관질환을중심으로ㆍ 105 성으로전반적인자율신경계의이상도관련이있다고생각되고있다. 또한유전적인소인도관련이있는것같다. 소아의기능적복통의원인이어른과다른지에대한근거는부족하나, 소아에서는기능성복통이호전되는경향이있어자기제한적인 (self-limiting) 발달인자가소아의병태생리에관여하는것으로보인다 9). 기능성장질환의하나인기능성소화불량증은증상을설명할기질적질환이없이위-십이지장에서기인하는임상증후군으로, 복통, 복부불편감, 이른포만감, 상복부팽만감 (bloating), 혹은구역이포함되어있다 11). 기능성소화불량증의원인은위및소장운동지연, 식후위용적변화나조절 (accommodation) 의감소, 장신경의과민성이라고보고있다 12). 2. 기능성복통의치료 11) 기능성복통은 Rome III criteria에따라크게기능성소화불량증, 과민성장증후군, 복성편두통, 소아기능성복통의네가지로분류된다 (Table 2, 3). 1) 기능성소화불량증 (functional dyspepsia) 13,14) : 비스테로이드성항염증성약물, 증상을악화시키는음식 ( 카페인, 맵고기름진음식 ) 을피한다. H2 blocker나 proton pump inhibitor는통증이주증상인경우에, prokinetcs는불편감이주증상인경우에도움이되는경향이있다. Randomized controlled trial로 See 등 5) 은 25명의소아를대상으로 famotidine 0.5 mg/kg/dose bid를투여시증상이호전됨을보고하였다 15). Table 2. The Functional Gastrointestinal Disorders 11) H. Functional disorders: children and adolescents H1. Vomiting and aerophagia H1a. Adolescent rumination syndrome H1b. Cyclic vomiting syndrome H1c. Aerophagia H2. Abdominal pain related FGIDs H2a. Functional dyspepsia H2b. Irritable bowel syndrome H2c. Abdominal migraine H2d. Childhood functional abdominal pain H2d1. Childhood functional abdominal pain syndrome H3. Constipation and incontinence H3a. Functional constipation H3b. Nonretentive fecal incontinence 성인대상의연구에서 2006년 Cochrane collaboration 14) 에서는 7개의 prokinetic trial에서전반적인경향은통계적으로유의하게호전되지는않았다고분석하였고 cisapride가 domperidone과 metoclomide에비해더효과적으로보고되고있다. (1) 항분비약물 (Antisecretory agents); H2 receptor blocker의연구에서구역질 (dysmotility symptom) 에는 H2 blocker가통계적으로유의한도움이되지않았으나, 통증 (reflux symptom) 은유의하게호전을보였다 14). 3개의 proton pump inhibitor와위약의비교연구에서삶의질이유의하지호전되지는않은경향을보였다고분석하였다. H2 antagonist와 proton pump inhibitor의비교에서는상반된결과가보고되고있다 14). Bismuth salts 의경우위약에비해호전된정도에약간의통계적유의성을보였으나장기간처방시신경독성과관련이있어주의를요한다. (2) 위장관조절제 (prokinetic drugs) 16,17) 1 콜린성약제 : Choline derivatives인 bethanechol과 Acetylcholinesterase inhibitor인 neostigmine이있다. Choline derivatives는위장관기능이약한데비해서맥, 설사, 홍조, 경련, 침분비, 흐린시야등의부작용이있어흔히쓰이지않는다. 2 도파민수용체항길항제 : 근육층신경얼기에서 Ach분비를억제시켜하부식도괄약근과위내강압을감소시킨다. 구토와연관이있는 chemoreceptor trigger zone에있는도파민수용체에도길항효과를나타내구토호전에도움을준다. Domperidone은뇌-혈관장벽을통과하는양이적어신경계부작용은적으나유즙분비와같은부작용이있고 1세이하에서는뇌-혈관장벽이성숙하지않아추체외로계증상이나타날가능성이높으므로주의하여투약해야한다. 부정맥을일으킬수있는약으로미국에서는금기약물이되었고현재우리나라유럽에서는시판중인약제이다. Metoclopramide는좀더추체외로계증상의부작용이높고, 수개월에서수년에걸쳐사용시비가역적인 Tardive dyskinesia가올수있다. 그외 levosulpride, Itopride는소아에서의임상연구가필요한실정이다. 3 세로토닌수용체약제 : 세로토닌 (5-hydroxytryptamine, 5-HT) 는위장관내점막에있는 enterochromaffin

106 ㆍ대한소아소화기영양학회지 : 제 12 권부록 1 호 2009 Table 3. Abdominal Pain-related Pediatric Functional Gastrointestinal Disorders. 11) H2a. Diagnostic Criteria* for Functional Dyspepsia Must include all of the following: 1. Persistent or recurrent pain or discomfort centered in the upper abdomen (above the umbilicus) 2. Not relieved by defecation or associated with the onset of a change in stool frequency or stool form (ie, not IBS) 3. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject's symptoms *Criteria fulfilled at least once per week for at least 2 months before diagnosis H2b. Diagnostic Criteria* for Irritable Bowel Syndrome Must include all of the following: 1. Abdominal discomfort (an uncomfortable sensation not described as pain) or pain associated with 2 or more of the following at least 25% of the time: a. Improved with defecation b. Onset associated with a change in frequency of stool c. Onset associated with a change in form (appearance) of stool 2. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject's symptoms *Criteria fulfilled at least once per week for at least 2 months before diagnosis H2c. Diagnostic Criteria* for Abdominal Migraine Must include all of the following: 1. Paroxysmal episodes of intense, acute periumbilical pain that lasts for 1 hour or more 2. Intervening periods of usual health lasting weeks to months 3. The pain interferes with normal activities 4. The pain is associated with 2 or more of thefollowing: a. Anorexia b. Nausea c. Vomiting d. Headache e. Photophobia f. Pallor 5. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process considered that explains the subject's symptoms *Criteria fulfilled 2 or more times in the preceding 12 months H2d. Diagnostic Criteria* for Childhood Functional Abdominal Pain Must include all of the following: 1. Episodic or continuous abdominal pain 2. Insufficient criteria for other FGIDs 3. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject's symptoms *Criteria fulfilled at least once per week for at least 2 months before diagnosis H2d1. Diagnostic Criteria* for Childhood Functional Abdominal Pain Syndrome Must include childhood functional abdominal pain at least 25% of the time and 1 or more of the following: 1. Some loss of daily functioning 2. Additional somatic symptoms such as headache, limb pain, or difficulty sleeping *Criteria fulfilled at least once per week for at least 2months before diagnosis 세포와근육층신경얼기의신경에작용한다. 호르몬처럼작용하여장의유동운동을유발하고, 근육층신경얼기에서신경전달물질로서억제 interneurone의 5-HT 3 수용체에작용하여길항효과를내고, 흥분세포의 5-HT 4 수용체에작용하여평활근수축을일으킨다. Cisapride는 5-HT 4 수용체를자극하고 5-HT 3 antagonistic 기능으로평활근을자극하여위십이지장운동 을촉진하는효과가있으나 herg K + channel에도작용하여 QT interval을늘릴수있는부작용때문에사용이중단되었다. Tegaserod는 5-HT 4 에작용하여위장관조절제의기능뿐아니라내장감수성을감소시키는효과가있어변비형과민성장증후군의치료제로 FDA 승인을받았으나 11,600명의환자중 13명에서심각한허혈성심장

신지연 : 복통의약물요법 - 복통과연관된기능성위장관질환을중심으로ㆍ 107 Therapy Antispasmodics Laxatives D2 receptor antagonists Antidepressants Behavioural therapy Serotonergic agents Table 4. Drugs for Irritable Bowel Syndrome 7) Finding Level II evidence does not support improvement of global IBS symptoms Limited evidence for improvement of abdominal pain/discomfort Level II evidence for improvement of constipation with fibre, but no evidence to indicate improvement of global IBS symptoms No evidence to support use of other laxative types in IBS patients No evidence to support use in IBS Level II evidence to support improvement of abdominal pain/discomfort with TCAs Insufficient evidence for improvement of global IBS symptoms with TCAs Insufficient evidence to support efficacy of SSRIs Level II evidence indicates some degree of improvement of individual IBS symptoms Level I evidence (alosetron, tegaserod) Level II evidence (ondansetron) Further data required (cilansetron, renzapride) Level I: evidence from mainly high-quality (quality score >10) RCTs that reached statistical significance for the primary end point, with adequate sample sizes and appropriate design. Level II: evidence from mainly low-(quality score 1 5) or intermediate-quality (quality score 6 10) RCTs that either failed to reach statistical significance forthe primary end point, and/or had an inadequate sample size and/or important trial design limitations. 부작용이있어 2007년부터는제한하게되었다. Alosetron은 5-HT 3 수용체길항체로설사형과민성장증후군의약제로사용되었으나허혈성대장염을일으키는것으로알려져시판이중단되었다. Mosapride는 5-HT 4 수용체에대한작용하며대사물질은 5-HT 3 수용체에결합하여길항작용을하며, 하부식도괄약근의수축을도와주나소아에서의안정성은아직확립되어있지않다 18). 4 Motilin 수용체작용제 : Motilin은 22개아미노산펩타이드로호르몬으로위장관의 M 세포와상부위장관일부 enterochromaffin 세포에위치한다. 주로위장관근위부에영향을미치고공복시나타나는 phase III migrating motor complex를유도한다. Erythromycin이주로위와소장에작용하는데항생제로서의기능이있고장기간투여시 motilin 수용체가하향조절 (down-regulation) 되면서내성을나타낼수있다. 5 Somatostatin analog: Octreotide는 serotonin, gastrin, vasoactive intestinal polypeptide, insulin, secretin 등의호르몬억제에관여하여소장운동을자극하고위의운동, 담낭수축을억제한다. 십이지장에서기인하는 phase III 활동을유발하지만위에서의 phase III 활동은억제한다. 소장의세균과증식 (bacterial overgrowth) 호전에도움을준다. 부작용으로구역, 팽만감, 주사부위통증, 담석, 저혈당증, 고혈당증이있을수있다. 6 기타 : Trimebutine (3,4,5-trimethoxybenzoic acid 2- (dimethylamino)-2-phenylbutylester) 은위장관에서말초 μ, κ, δ opiate 수용체에작용하며위장관에서 motilin, VIP, gastrin, glucagon의분비를조절한다. 위배출을촉진하고, Migrating motor complex를유도하며대장의수축력을조절한다 19). 2) 과민성장증후군 (Table 4) 7,13,20,21) : 정확한진단, 통증에대한설명, 안심시키는것자체가중요한치료이다. (1) 진경제 (antispsmodics); 장관평활근육에직접작용하는기전으로작용하는약물 (papaverine-like agents and mebeverine) 과항콜린성, 항무스카린성으로작용하는약물 (dicyclomine, hyoscyamine, cimetropium, bromide, otilonium bromide, octylonium bromide and prifinium bromide), 또는 calcium channel-blocking property 로작용하는약물 (pinaverium bromide) 로분류된다. 진경제가복통경감에는효과가있다는보고들이있는데비하여과민성장증후군전체증상에는유의하게도움이된보고는적은편이며이들대부분의논문이적은환자수를대상으로하였기때문에이를바탕으로진경

108 ㆍ대한소아소화기영양학회지 : 제 12 권부록 1 호 2009 Table 5. Dosing Guidelines for Antidepressants and Anxiolytics for FGIDs 35) Antidepressants Treatment (6 8 wk) (mg) Starting dose (mg) Tricyclic antidepressants Imipramine 100 10 Desipramine 100 10 Clomipramine 75 2.5 10 SSRIs/SNRIs Sertraline 50 12.5 25 Paroxetine 20 5 10 Fluoxetine 20 2 5 Escitalopram 10 5 Citalopram 20 10 Fluvoxamine 50 25 Venlafaxine 75 18.75 High-potency benzodiazepinesa Alprazolam 2 0.25 0.5 3 times daily Clonazepam 1 0.25 0.5 twice daily Some patients may still benefit from dosages lower than indicated. For treatment of major depression or anxiety disorders, dosages are at least double what is indicated. anot useful as antidepressants. 제가도움이된다는결론을내기는힘들다고보고있다 22). 부작용으로 atropine과유사한부작용이있을수있기때문에변비증상이주도적인과민성장증후군환자에서는주의를요한다. (2) 설사제 (laxatives); 과민성장증후군환자에서 bulking agent는일부도움이되나 osmotic, stimulant, surfactant laxatives에대한 randomized controlled trial은부족하다. (3) 지사제 (antidiarrhoeal agents); 설사형과민성장증후군에서장통과시간을늦추기위해투여되곤한다. Loperamide는중추신경계에영향이없는 synthetic opioid derivative이다. 설사횟수빈도와양상에는도움이되는것으로보이나복통은유의한호전을보이지않았다 23 25). 3세미만의소아와중등도이상의탈수가있을때에는주의를요한다 26). (4) 위장관조절제 (Prokinetics) 1 D2 수용체길항제 : Domperidone의과민성장증후군통증경감효과에대해서는도움이된다는보고 27) 와유의한증상의변화가없다는상반되는결과가있다 28). (5) 항우울증약제 (Table 5, Fig. 1) 29) ; 통증인지에변화를주고, 기분, 수면, 정신과적문제에도움을준다. 장관의통증자극의구심성신호전달에영향을주고, Fig. 1. Algorithm for use of treatment with psychotropics for psychiatric symptoms in FGIDs in clinical practice 35). BZ: benzodiazepines, SNRI: serotonin-norepinephrine reuptake inhibitor, TCA: tricyclic antidepressant.

신지연 : 복통의약물요법 - 복통과연관된기능성위장관질환을중심으로ㆍ 109 위장운동과분비에영향을준다. 대표적으로 TCA (tricyclic antidepressants) 와 SSRI (Selective serotonin reuptake inhibitors) 가과민성장증후군에쓰이고있다. TCA는장관통과시간을늘려설사를호전시키는작용이있고 SSRI는장관통과시간을감소시켜변비형증상에도움을준다. 증상호전에는 4 6주가소요되는데비해부작용은 1 2주에나타나므로적은용량으로시작하여조절한다. TCA의부작용으로는졸음, 항콜린성증상 ( 변비, 빈맥, 요저류 ) 중추신경계부작용 ( 불면, 악몽 ) 이있을수있다. SSRI는선택적으로 5HT의재흡수를억제하고 5HT transporter protein을막아시냅스내 5HT 농도를높게해주게된다. SSRI의부작용으로설사, 적대감, 자살이있을수있다. SSRI로치료받은청소년에서자살위험성이높다는보고가있어처방에주의를요한다 30). 3) 복성편두통 13) : 가족, 형제중에편두통의병력이있는경우가많다. 카페인, nitrite, amine 포함음식, 여행, 오랜금식, 수면패턴의변화, 깜박이는빛같은유발인자를피한다. 예방적으로 pizotifen, propranolol, cyproheptadine, sumatriptan을투여할수있다 31 33). Symon 등 2) 은 14명의소아에서매일 pizotifen 0.25 mg을투여했을때복통의중증도가호전되었다고보고하였으나 34) 값비싼약가와졸음, 식욕변화, 위장관장애등의부작용을고려할필요가있다. 결론소아에서기능성장질환은병원에내원하게되는가장흔한원인중하나이다. 가장중요한치료의근간은보호자와환아를이해시키고안심하도록하는것이지만많은경우약물을필요로하게된다. 약물치료에있어소아에관련된정보는부족한실정이다. 향후소아에서의약물의효용성과안정성을입증하기위한연구가필요하며, 충분히효용성과안정성이입증된약물을투여할때도주의깊은부작용의모니터링이필요하다하겠다. 참고문헌 1) Scholer SJ, Pituch K, Orr DP, Dittus RS. Clinical outcomes of children with acute abdominal pain. Pedatrics 1996;98:680-5. 2) Apley J, Naish N. Recurrent abdominal pains: a field survey of 100 school children. Arch Dis Child 1958;50: 429-36. 3) Faull C, Nicol AR. Abdominal pains in six-year olds: an epidemiological study in a new town. J Child Psychol Psychiatry 1986;27:251-60. 4) Jeffrey S, Hyams MD, Burke G, Patricia M, Davis RN, Rzepski B, et al. Abdominal pain and irritable bowel syndrome in adolescents: A community-based study. J Pediatr 1996;129:220-6. 5) Dapoigny M, Bellanger J, Bonaz B, Bruley des Varannes S, Bueno L, Coffin B, et al. Irritable bowel syndrome in France: a common, debilitating and costly disorder. Eur J Gastroenterol Hepatol 2004;16:995-1001. 6) Enck P, Klosterhalfen S. The placebo response in functional bowel disorders: perspectives and putative mechanisms. Neurogastroenterol Motil 2005;17:325-31. 7) Tack J, Fried M, Houghton LA, Spicak J, Fisher G. Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective. Aliment Pharmacol Ther 2006;24:183-205. 8) Allescher HD, Bockenhoff A, Knapp G, Wienbeck M, Hartung J. Treatment of non-ulcer dyspepsia: a metaanalysis of placebo-controlled prospective studies. Scand J Gastroenterol 2001;36:934-41. 9) Walker WA, Olivier G, Kleinman RE. Pediatric gastrointestinal disease. 4th ed. Hamilton: BC Decker; 2004. 10) 정수진. 소아만성복통의진단적평가 - 기능성복통과의감별점을중심으로. 대한소아소화기영양학회지 2008;11(Suppl 2):S19-S28. 11) Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130: 1527-37. 12) Chitkara DK, Di Lorenzo C. Pharmacotherapy for functional gastrointestinal disorders in children. Current Opinion in Pharmacology 2006;6:536-40. 13) Huertas-Ceballos A, Logan S, Bennett C, Macarthur C. Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev 2008(1):CD003017. 14) Moayyedi P, Soo S, Deeks J, Delaney B, Innes M,

110 ㆍ대한소아소화기영양학회지 : 제 12 권부록 1 호 2009 Forman D. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006(4):CD001960. 15) See MC, Birnbaum AH, Schechter CB, Goldenberg MM, Benkov KJ. Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment. Dig Dis Sci 2001;46:985-92. 16) 서지현. 소아의기능성장질환에서사용하는소화기계약물의종류 : 위장관조절제. 대한소아소화기영양학회지 2008;11(Suppl 1):S30-S37. 17) Sanger GJ, Alpers DH. Development of drugs for gastrointestinal motor disorders: translating science to clinical need. Neurogastroenterol Motil 2008;20:177-84. 18) Ruth M, Hamelin B, Rohss K, Lundell L. The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1998;12:35-40. 19) Delvaux M, Wingate D. Trimebutine: mechanism of action, effects on gastrointestinal function and clinical results. J Int Med Res 1997;25:225-46. 20) Brandt LJ, Bjorkman D, Fennerty MB, Locke GR, Olden K, Peterson W, et al. Systematic review on the management of irritable bowel syndrome in North America. Am J Gastroenterol 2002;97(11 Suppl):S7-S26. 21) Goettsch WG, van den Boom G, Breekveldt-Postma NS, Smout AJ, Herings RM. Treatment patterns and health care costs of mebeverine-treated IBS patients: a casecontrol study. Pharmacoepidemiol Drug Saf 2004;13: 803-10. 22) Quartero AO, Meineche-Schmidt V, Muris J, Rubin G, de Wit N. Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2005(2):CD003460. 23) Cann PA, Read NW, Holdsworth CD, Barends D. Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 1984;29:239-47. 24) Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol 1987;130:81-4. 25) Efskind PS, Bernklev T, Vatn MH. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 1996;31:463-8. 26) Pulling M, Surawicz CM. Loperamide use for acute infectious diarrhea in children: safe and sound? Gastroenterology 2008;134:1260-2. 27) Milo R. Use of the peripheral dopamine antagonist, domperidone, in the management of gastro-intestinal symptoms in patients with irritable bowel syndrome. Curr Med Res Opin 1980;6:577-84. 28) Fielding JF. Domperidone treatment in the irritable bowel syndrome. Digestion 1982;23:125-7. 29) Grover M, Drossman DA. Psychotropic agents in functional gastrointestinal disorders. Curr Opin Pharmacol 2008;8:715-23. 30) Jick H, Kaye JA, Jick SS. Antidepressants and the Risk of Suicidal Behaviors JAMA 2004;292:338-43. 31) Russell G, Abu-Arafeh I, Symon DN. Abdominal migraine: evidence for existence and treatment options. Paediatr Drugs 2002;4:1-8. 32) Worawattanakul M, Rhoads JM, Lichtman SN, Ulshen MH. Abdominal migraine: prophylactic treatment and follow-up. J Pediatr Gastroenterol Nutr 1999;28:37-40. 33) Sadeghian M, Farahmand F, Fallahi GH, Abbasi A. Cyproheptadine for the treatment of functional abdominal pain in childhood: a double-blinded randomized placebocontrolled trial. Minerva Pediatr 2008;60:1367-74. 34) Symon DN, Russell G. Double blind placebo controlled trial of pizotifen syrup in the treatment of abdominal migraine. Arch Dis Child 1995;72:48-50. 35) Camilleri M, Bueno L, de Ponti F, Fioramonti J, Lydiard RB, Tack J. Pharmacological and Pharmacokinetic Aspects of Functional Gastrointestinal Disorders. Gastroenterology 2006;130:1421-34.