Download Stimulant laxatives

만성변비의 진단과 내과적 치료
이창균
경희대학교 의학전문대학원
경희대학교 병원 소화기내과
Egyptian papyrus
“The body is poisoned by material released
from decomposing waste in the intestines…”
“Autointoxication theory”
the 16th century BC
1920s: advertisement for a “candy cathartic”
An abdominal massage machine
Rectal dilators for constipation, 1938
Total colectomy for as a cure of
“autointoxication”
Constipation related to “civilization”
Misconceptions 1
• Daily bowel movements are important
for overall health.
• Chronic constipation may result in poor
general health because of failure to
empty toxins from the colon in a timely
fashion.
Dietary fiber hypothesis and
“Western diseases”
Don’t forget fiber in your diet !
- Dr. Denis Burkitt
Geographic prevalence of
constipation
Jump forward to 2011
• High prevalence
– 15% in adults (9% in children)
• High health care burden
– 6.3 million patient visits to medical centres
– total costs of $1.7 billion (in US)
Let’s start to talk about
current management of constipation.
What causes constipation?
Rome Criteria
* ≥25% of defecations
Dynamics of defecation
3 types of functional constipation
Normal transit constipation
Slow transit constipation
Pelvic floor dysfunctions
Diagnostic algorithm
Colonic transit time
7th day
Rt
Initial screening
test:
Lt
Normal- or slow transit constipation
vs
Pelvic floor dysfunction
RS
Radioopaque marker
(KolomarkTM)
Diagnosis of pelvic floor
dysfunctions
Balloon expulsion test
Anorectal manometry
Defecography
Balloon Expulsion Test
• Balloon expulsion test is a simple,
office-based screening test for
defecatory disorders.
• After insertion of the latex balloon into
the rectum, 50 ml of water or air is
instilled into the balloon, and the
patient is asked to expel the balloon
into a toilet.
• Inability to expel the balloon within 2 or
3 minutes suggests a defecatory
disorder.
Lembo A et al. NEJM 2003;349:1360-8
Anorectal manometry
Normal Defecogram
102˚
129˚
Anismus
What are the medical therapy
for constipation?
Basic advice
Laxative agents
Prokinetic agents
Normal or
Slow transit C
Biofeedback treatmentPelvic
floor
dysfunctions
Basic advice
Correct position for defecation
Increasing dietary fiber intake
Increasing water intake
Adequate exercise
Bulk-forming laxatives
Correct position for defecation
“semi-squatting” position << natural squatting position ?
Basic advice
Misconceptions 2
• Constipation is the result of a diet poor
in fiber, low fluid intake, and/or lack of
exercise.
Stepwise approach
Basic advice
Bulk-forming
Osmotic
Stimulant
• Dietary fiber
laxatives
laxatives
laxatives
• Water ingestion
• Psyllium
• Magnesium salts
• Senna
• Bran
• Sorbitol
• Bisacodyl
• Methylcellulose
• Lactulose
• Calcium
• Polyethylene
polypcarbophil
뮤타실 (일양)
아기오 (부광)
웰콘 (건일)
glycol
산화 마그네슘
(삼천당)
락티톨
두팔락(중외)
아락실 (부광)
둘코락스 (베
링거)
Bulk-forming laxatives
Laxative
Usual Adult Dose
Onset of
Action
Psyllium
Up to 1 tsp TID
12-72 h
Methylcellulose
Up to 1 tsp TID
12-72 h
Calcium
2-4 tablets/day
24-48 h
polycarbophil
Osmolar agents
Laxative
Usual Adult Dose
Onset of
Action
Polyethylene glycol
8.5-34 g in 240 mL
2-4 days
liquids
Lactulose
15-30 mL QD or BID
24–48 h
Sorbitol
120 mL of 25%
24-48 h
solution QD
Glycerine
3 g suppository QD
15-60 min
Magnesium sulfate
15 g QD
0.5-3 h
Magnesium citrate
200 mL QD
0.5-3 h
Stimulant laxatives
Laxative
Usual Adult Dose
Onset of
Action
Bisacodyl
Senna
10-20 mg PO QHS
6-10 h
10 mg suppository QD
15-60 min
2-4 tablets QHS
6-12 h
Misconceptions 3
• Chronic use of currently available
stimulant laxatives is unsafe because
they may damage the colon when used
chronically.
Bisacodyl
• Category I drug by the US-FDA
• Category I
– “Safe and effective”
Misconceptions 4
• Stimulant laxatives induce habituation
and tolerance or physical dependence
and addiction.
Better strategy
for use of laxatives
Non-stimulant laxatives on a daily basis
+
Stimulant laxatives twice or thrice weekly
Probiotics in constipation
Monitoring response to
treatment
• Spontaneous bowel movement (SBM)
• Complete SBM
• Bristol stool chart
Enterokinetic agents
• Historical agents
– Cisapride: withdrawal
– Metoclopramide: no effect
– Erythromycin: no effect
New prokinetic agents
1. Tegaserod
– non-selective serotonin (5-HT4) receptor agonist
2. Prucalopride
– selective, high-affinity 5-HT4 receptor agonist
3. Lubiprostone
– chloride channel activator
Role of Serotonin
Serotonin and EC Cells in
Constipation
• Serotonin stimulates small intestine and colonic
motility and accelerates transit1
• A study in 10 patients with chronic laxative use
demonstrated a reduced number of serotonin
immunoreactive cells, P<.052
• Reduced number of serotonin cells in slow transit
constipation contributes to reduced motility of the
colon with consequent constipation2
1Talley
2El-Salhy
, Aliment Pharm Ther 1992; 6: 273
et al, Scand J Gastroenterol 1990; 10: 1007
Serotonin and Motor Activity
Proximal
Orad
motor neurons
(contraction)
ACh / SP
Distal
Interneurons in
the Myenteric
Plexus
CGRP
Movement of gut
content
Caudad
motor neurons
(relaxation)
VIP / NO
Submucosal IPAN
5-HT4 receptor
5-HT1p receptor
. ... ... .. 5-HT (serotonin)
Enterochromaffin cells in GI tract release 5-HT
Adapted from Grider et al, Gastroenterology 1998; 115: 370
Adapted from Gershon, Rev Gastroenterol Dis 2003; 3: S25
How prucalopride works?
A placebo-controlled trial of prucalopride
for severe chronic constipation
N Engl J Med 2008;358(22):2344–54.
Misconceptions 5
• Are enterokinetic agents a major advance
in treating constipation?
• Are enterokinetic agents cost-effective in
most constipated patients in the primary
care setting?
Biofeedback
Pelvic floor rehabilitation
Sensory and muscular training
Treatment of choice
for pelvic floor dysfunction
Protocol for biofeedback therapy
Evidence-based summary for the
treatment of constipation
Surgical treatment
• Severe refractory slow-transit constipation
• Colonic inertia
• Subtotal colectomy with ileorectal
anastomosis
When to refer for specialist care
• Alarm symptoms
• Psychological treatment for irritable bowel syndrome
• Painful anorectal conditions
– anal fissure, haemorrhoids, abscess, or fistula
• Obstructed defecation
• Paradoxical puborectalis contraction
• Solitary rectal ulcer syndrome
• Rectocoele
• Rectal intussusception and rectal prolapse
Acute
on chronic constipation
SEMS in Acute colonic malignant obstruction
Stercoral ulcers
Take home messages
Basic understanding of pathophysiology
Stepwise approach of laxatives
Biofeedback treatment for pelvic floor dysfunction
Specialist referral for refractory cases
Educational web resources
• 대한소화기학회 (www.gastrokorea.org)
– 변비 치료에 관한 임상진료지침 (2011)
• Rome Foundation (www.romecriteria.org)
• British Society of Gastroenterology
(www.bsg.org.uk)
• Core (www.corecharity.org.uk)
Enjoy your summer vacation!