설사와변비 2013. 3. 28 이숙향, PharmD, PhD 아주대학교, 약학대학
설사 - 정의 Abnormally frequent watery stool 3 or more loose unformed Imbalance between absorption and secretion of water and electrolytes 정상소화관기능 fluid movement 9 L/d 가소장을거침, 8 L 는소장에서흡수 1.0-1.5 대장을거침, 0.9-1.4 L/d 대장흡수 1 일대변수분량은약 100ml/d 2
수분과전해질균형 Villi- 흡수, crypt cell - 분비 소장점막 -semipermeable membrane Na 과같은전해질에따른수동적통과 Na 가장많은양소장에존재하는물질 능동적이동 Na-K pump coupled transport: glucose, Na 대장점막 소장과유사한과정으로 Na, water 의이동 3
대장의운동 분절운동 Segmental contraction 부수고소화액과혼합 연동운동 Peristalsis 장내에서하향운동으로움직임 배변운동 Massive movements 상당히긴장내의거리를움직임 배변운동과관련 신경, 호르몬의조절 4
배변운동 배변자극 : 위의포만등이장운동자극 massive movement 직장의팽창에따른배변의욕 대부분아침식사후 내, 외부항문괄약근의이완으로배변 5
설사 삼투성 Osmotic diarrhea increased osmolality 분비성 Secretory diarrhea Intestinal ion secretion 운동기능 Altered intestinal motility 염증성 Exudative diarrhea Inflammatory and ulcerative processes 6
Osmotic diarrhea 장내흡수되지않은 solute 에의한수분의장내저류 peristalis 운동이자극됨 장내물질의이동이증진 주요인 lactase deficiency malabsorption Mg antacids poorly soluble carbohydrate 환자가먹지않으면멈추는점이특징 7
Secretory diarrhea 장내물질이세포내 camp 를자극하여 Na-K pump 의억제 물, 필요한물질흡수억제 원인 병원균의 enterotoxin: 예 E. coli, traveler s diarrhea stimulant laxatives hormone: serotonin, calcitonin, PGE1, Vasoactive intestinal peptide Thyroid cancer Large stool volume(>1l/d) Fasting does not change the stool 8
Altered intestinal motility 소장 :Reduction of contact time premature emptying of the colon 원인 irritable bowel syndrome diabetic neuropathy intestinal resection or bypass surgery short bowel syndrome drugs: decrease GI transit time metoclopramide cisapride 9
Exudative diarrhea Release of mucus, serum proteins, blood into lumen 수분과전해질의흡수 주원인 ulcerative colitis Crohn s disease shigellosis 10
증상및진단 Acute acute 대체로 self limiting, 대부분큰합병증이없이완화 Chronic 장기간지속되며정밀진단필요 Na/water 결핍 : 체중감소, 기립성저혈압, poor skin turgor, sunken eyes, oliguria, tachycardia, severe shock, coma bicarbonate loss: metabolic acidosis 11
환자의병력 Duration Description stool large vs. small, consistency, color, odor Frequency Associated symptoms fever, vomiting, muscle cramps Underlying illness/medical history Travel history Risk patients infants, young child, elderly, debilitated patients 12
기존질환과설사증상 Blood inflammatory,infectious,neoplastic Pus/Exudate/mucus inflammation, infection blood tinged mucus without odor shigellosis Green soupy stools: salmonella Nonbloody mucus with intermittent diarrhea and constipation: irritable bowel syndrome Fecal incontinence/nocturnal diarrhea 신경이상에의한 rectal sphincter dysfunction 13
급성 Acute diarrhea 음식에의한설사, intolerance Lactase deficiency Enzyme: Lactaid, Dairy Ease, Lactrase 지나치게기름지거나자극성음식 약물에의한설사 광범위항생제 : tetracycline, clindamycin 등 자극성하제, Mg 함유제산제 methyldopa, reserpine, guanethidine cholinergics: betanechol. Neostigmine quinidine, digitalis MMF, metformin, acarbose, misoprostol 14
Infectious diarrhea 원인균 viral bacteria protozoa Rotavirus Shigella Girdia lamblia Norwalk virus Salmonella Entamoeba Enteric adenovirus E. coli Cryptosporium Astrovirus Yersina Conavirus C. difficile Herpes simplex Bacillus Cytomegalovirus T. pallidum 15
Infectious diarrhea- 감염원 Day care center shigella, campylobacter, rotavirus 최근항생제치료, 항암요법 Clostridium difficile Swimming pool: Giardia, Cryptosporidium 외국여행 : traveller s diarrhea Shellfish: Vibrio Hamburger: E.coli 16
치료 Diarrhea history, PE Acute <3d chronic >14d no fever systemic sx fever systemic sx 원인분석, infection inflammation, drug fluid/electro loperamide diet WBC feces check microbiology stool culture sigmoidoscopy biopsy negaive symptom tx positive antibiotics symptom tx hydration tx for specific causes 17
치료 Goal 수분, 전해질, acid-base 장애방지 증상의완화 기존질병의치료 Rehydration mild loss of water 2-3 L clear water: tea, 이온음료 24 시간정도후부드러운음식에서정상식이 Moderate: oral rehydration severe: IV hydration +dextrose 18
지사제 Attapulgite natural hydrous Mg aluminium silicate adsorbent: 약 8 배무게의물흡수 부작용 : 변비 처음사용후각 loose stool 마다복용 소아 >3 세 제품 : Kaopectate, Donnagel 300, 600, 750 mg tablet, 용액 Kaolin/pectin polycarbophil 약 60 배무게의물흡수 Equalactin, Mitrolan, FiberCon, Fiber-Lax, Fiberall 19
지사제 Loperamide 장운동억제 부작용 : 복통, 변비, 졸림, 피로, 구강건조, N/V 비감염 traveler s diarrhea 48시간내증상완화가없으면중단 주의 : 간질환자에서 first pass effect 감소 6세이하의어린이사용추천하지않음 Imodium AD, Kaopectate II, 1, 2mg 20
지사제 Bismuth subsalicylate antisecretory effect, antimicrobial 변의색이잠시흑색 부작용 간대성경련, 혼수, 운동장애 색소침착 3세이하소아사용추천하지않음 nitrate 염 : 아질산중독 : 혈압강하, 빈혈, 피부홍조 여행자설사의예방, 치료에효과 21
지사제 Diphenoxylate with atropine 장운동저하 부작용 : 졸림, 어지러움, 두통, N/V, 복통 고용량에서의존성 소아 not recommended <2 세 2.5 mg/ tab, 5 ml liquid Diphenoxin Lidamidine Lactobacillus not proven suppress pathogenic bacteria 22
치료 - 소아 Rehydration 초기 high sodium(70-90 meq) solution, Rehydralyte 수분공급의유지 : low sodium: Pedialyte, Resol 당분이많은용액은피함 운동음료, juice 23
여행자설사 High risk area: 남미, 동남아 증상 N/V, 복통, 설사 예방 doxycycline 100 mg/d x21d Bactrim 160/800 bid x21d ciprofloxacin 500 mg qd x14d Bismuth 2 tab qid x21d 24
치료 수분보충 Bismuth 2tab q30-60 min, max 8 dose/24h Bactrim bid x3 d cipro 500 mg bid x3d norfoxacin 400mg bid x3d ofloxacin 300 mg qd x 3d loperamide 감염성에는사용하지않음 Absorbent 는효과적이지않음 소아 : erythromycin 여행자설사 25
변비 이숙향, Pharm.D. 숙명여자대학교, 임상약학대학원
변비 - 정의 배변횟수의감소 정상인 : 1일 3회- 1주 3회 Difficult passage of hard dry stools 병인 low fiber lack of exercise, immobility decrease fluid intake lack of muscle tone in the colon drug induced 27
약물에의한변비 제산제 : calcium, aluminum containing Anticholinergics Barium sulfate Bismuth Calcium channel blocker(verapamil, diltiazem) Diuretics Iron Opiates Phenothiazines Tricyclic antidepressants 28
Endocrine disorders Medical problem associated diabetes mellitus Hyperparathyroidism hypothyroidism hypokalemia porphyria Uremia GI disorders anorectal (anal fissures, hemorrhoids) Carcinoma of colon or rectum Ischemic bowel disease hypomotility disorders Neurologic/psychiatric disorders autonomic neuropathy Stroke multiple sclerosis Parkinson s disease anxiety depression psychosis 29
Symptoms Abdominal distress, distension Lassitude 무력감 Headache Low back pain Loss of appetite 30
Patient history/data collection 변비의기간 배변횟수 변의양태 증상 Medical history/surgeries Pregnancy Normal bowel habits Diet and daily fluid intake Daily activity, exercise Current medications 31
Treatment Non-drug treatment Increase daily fiber intake Increase exercise/physical activities Increase fluid intake Correction of underlying disease states Medical treatment 32
팽윤제 Non-absorbable polysaccharides, cellulose derivatives 장내에서수분을흡수하여팽윤됨 변의양과수분을증가하여연동운동자극함 작용발현시간 : 12-24 hours up to 3 days 부작용 : flatulence, intestinal or esophageal obstruction 주의대상환자 장내 ulceration, stricture, megacolon sodium, sugar 함량 ; HTN, DM 환자 33
팽윤제 대부분안전하여 1차치료제로사용 즉각적인반응이요구되는경우는피함 적절한용량을충분한물과함께복용 맛이좋은음료수와함께복용 Methylcellulose 보리맥아 Citrucel Malt supex Polycarbophil psyllium Fibercon Metamucil Equalactan Konsyl Mitrolan Modane Fiberall Perdiem 34
삼투성사하제 Glycerin 장내삼투압의증가로수분의증가와변을유화시킴 작용발현시간 : 15-30 분 ( 좌제, 관장제 ) 부작용 : rectal irritation, burning glycerin 좌제, Fleets babylax liquid 35
삼투성사하제 Lactulose 비흡수된이당류, 장내균에의하여 lactic acid, formic and acetic acid 의형성과삼투압증가 작용발현시간 : 24-48 시간 SE: flatulence, 복통, 설사, 전해질불균형, 탈수 주의사항 : galactose, lactose 의함유, 당뇨환자, 임산부, 소아 Cephulax, Chronulac, Cholac, Enulase, Duphalac 36
계면활성제, stool softner 계면활성제로서장내수분의 wetting efficiency 의증가 작용발현시간 : 12-72 시간 배변의어려움을피하기위한경우 rectal surgery, MI, rectal disease, pregnancy SE: 복통, throat irritation(docusate) 주의사항 : not effective in hypotonic constipation facilitating absorption of poorly absorbed drugs Colace, Modane Soft, Surfak, Dialose 37
윤활제 Lubricants (Mineral oil) Coats and softens feces Prevents colonic absorption of water Onset: 6-8 h SE: repeated/prolonged use foreign body reaction in lymphoid tissue lipid pneumonia 주의사항 do not give at bed time, to debilitated pts absorption of fatty vitamins impaired not for pregnancy do not take with meals: decrease gastric emptying time use with caution in pts on anticoagualnt therapy 38
염류성하제 Saline laxatives Non absorbable cations and anions Onset: oral 30 min -6 h, enema 3-5 min SE: dehydration, electro imbalance 주의사항 : Na content, Mg in renal dysfunction Enema prep for endoscopic exam elimination of parasites fecal impaction Mg sulfate, citrate, hydroxide. Sodium phosphate 39
자극성하제 Stimulant laxatives Most frequently used/ abused well Stimulate peristalsis; mucosal irritation, modify permeability of cells Anthroquinones cassanthranol, senna, cascara sagrada onset 6-8 h alkaline urine -discolor reddish violet chrysophanic acid in senna, cascara sagrada acidic urine-discolor yellow brown, cascara sagrada 40
자극성하제 Stimulant laxatives Diphenylmethane onset: 6-8 h phenolphthalein alkaline urine; pink - red feces is discolored allergic reaction; skin rash Alophen, Ex Lax, Feen A Mint Bisacodyl,Dulcolax onset: oral 6-10 h, rectal 15-60 min very irritating- enteric coated suppostitory - burning sensation 41
자극성하제 Stimulant laxatives SE: 심한복통, 전해질불균형, 영양분섭취불량 주의사항 임산부, 소아, 사하제남용 1치치료제로사용하지않음 1 주이상치료하지않음 42
기타 Castor oil metabolized in GI to ricinoleic acid stimulate secretory process decrease glucose absorption promote GI motility onset 1-3 h 강한하제로일반적치료제로사용치않음 Cisapride: GI prokinetic agent PEG-ELS; polyethylene glycol electrolyte lavage solution- colon cleansing solution, 4 L over 3 hr 43
Drugs and Dose Drugs/Doses Effective in 1-3d Bulkforming agents Methylcellulose 4-6 g/d Polycarbophil 4-6 g/d Psyllium varies Emollients Docusate sodium 50-360mg/d Lactulose 15-30 ml po Sorbitol 30-50 g/d po Mineral oil 13-30 ml po Effective Mg citrate Mg hydroxide Mg sulfate Sodium phosphate Bisacodyl in 1-6 h, waterly evacuation 18 g 300 ml water 2.4-4.8 g po 10-30 g po varies 10 mg rectally Drugs/Doses Effective in 6-12 h Bisacodyl (po) 5-15 mg po Phenolphtalein 30-270mg po Cascara sagrada varies Senna varies Magnesium sulfate (low dose) <10 g po 44