차세대 완하제
New Generation Laxatives
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초록
만성 변비는 서구의 경우 성인의 2-27%, 우리나라에서는16.5%의 유병률을 보일 정도로 많은 환자에서 삶의 질을 떨어뜨리는 흔한 질환이다[1,2]. 인터넷을 이용한 설문 연구에서 만성 변비 환자의 68%가 완하제를 사용하고 있었으며,28%는 전통적 완하제 치료에 전혀 만족하지 못하고 새로운치료에 관심이 있다고 응답했다[3]. 현재 주로 사용되고 있는 완하제는 부피형성 완하제, 삼투성 완하제, 자극성 완하제, 기타 완하제 등으로 구분할 수있다. 그러나 세로토닌(5-hydroxytryptamine, 5-HT)이 장의 평활근을 자극하여 직접적으로 장운동을 촉진시키고, 염소 통로(chloride channel)가 장 분비를 조절하는 데 중요한 역할을하는 것이 밝혀지면서 이러한 수용체에 특이적으로 작용하는 차세대 완하제가 개발되었고, 전통적 완하제에 반응이 없는 변비 환자의 치료에 새로운 장을 열고 있다. 본고에서는최근 국내에 도입되어 사용 중인 세로토닌 4형(5-hydroxytryptaminetype 4, 5-HT4) 수용체 작용제인 prucalopride의 실제 임상 사용에 대해 알아보고, 아직 국내에 도입되지 않았지만 서구에서 사용되고 있는 선택적 제2형 염소 통로(type-2chloride channel) 자극제인 lubiprostone과 guanylate cyclase C작용제인 linaclotide에 대해 작용기전과 연구 결과를 중심으로 효과를 고찰해 보고자 한다.
Abstract
A significant proportion of chronic constipation patients are dissatisfied with their treatment. Recently, a number of new medicationshave been introduced for patients refractory to conventional laxatives, such as prucalopride, lubiprostone, linaclotide, andelobixibat. Prucalopride is a novel gastrointestinal prokinetic agent that acts as a 5-hydroxytryptamine type 4 (5-HT4) agonist. Compared with older nonselective 5-HT4 agonists, the higher selectivity of prucalopride for 5-HT4 receptors can reduce the risk ofsignificant adverse cardiovascular events. Prucalopride improves stool frequency and consistency, and reduces the need for rescuemedications. Lubiprostone, a chloride channel activator, increases the secretion of intestinal fluid, improves the stool frequency andconsistency, and reduces straining. Linaclotide, a guanylate cyclase-C agonist, is effective in treating patients with chronic constipationand its effect on visceral sensitivity, as shown mainly in animal studies, provides an attractive pharmaceutical option for patients with irritable bowel syndrome with constipation. Elobixibat is an ileal sodium-dependent bile acid transporter inhibitor thatblocks the enterohepatic circulation of bile acids, increasing the bile acid concentration in the intestine, which accelerates colonictransit and softens the stool. A phase III trial of the treatment of chronic constipation and irritable bowel syndrome with constipationis underway. The clinical application of new-generation laxatives will contribute to the management of chronic constipation refractoryto conventional laxatives.
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