Adult and Children Constipation

The role of laxative therapy

Chudahman Manan
Indonesian Society of Gastroenterology

Introduction (1) :
Chronic constipation and irritable bowel
syndrome (IBS), the most prevalent
functional bowel disorders in North
America (20-70%)
Symptoms related to these motility
disorders are chronic, sometimes severe,
and can profoundly and negatively affect
patients QOL
Chronic constipation and IBS often leading
to polypharmacy and a significant burden
on healthcare resources.

Introduction (2) :
oData from RSCM-Jakarta during
1998-2005, 2.397 colonoscopy exam ,
216 (9%) indication for constipation
o Gender comparative women and men
(4 : 1)

LIFE
Genetics
Environment
Social Context

Drossman, DA; Gastro 2006

Epidemiology Constipation :

Irritable bowel syndrome: a global perspective, WGO Global

Guideline 2009.

Data in Indonesia, of
the 304 cases of
digestive disorders is
incorporated in Asian
studies Functional
Gastrointestinal
Disorders Study
(AFGID) in 2013,
reported incidence of
5.3% functional
constipation and
constipation type IBS
incidence of 10.5%.

Constipation Increases With Age

and Is More Common in Women

10

Harari, et al
Population: NHIS 1989
Criteria: self-report

8
6
4
2

25

Prevalence of
Constipation (%)

Prevalence of
Constipation (%)

12

Study 1
N = 42,375

Men

20
15
10
5
0

Study 2

N = 5,430
Drossman

Age Group (years)

NHIS = National Health Interview Survey
Higgins PDR, et al. Am J Gastroenterol. 2004;99:750-759.

Women

Study 3

N = 1,149
Pare

Sex

Study 4

N = 10,018
Stewart

How Do We Define Constipation?

o The American College of Gastroenterology (ACG)
definition of constipation:
o Unsatisfactory defecation characterized by infrequent
stools, difficult stool passage, or both. Difficult stool
passage includes straining, a sense of difficulty passing
stool, incomplete evacuation, hard/lumpy stools,
prolonged time to pass stool, or need for manual
maneuvers to pass stool

o The ACG Chronic Constipation Task Force also

clarified what is meant by chronic:
o Chronic constipation is defined as the presence of
these symptoms for at least 3 months

American College of Gastroenterology Chronic Constipation Task Force. Am J Gastroenterol. 2005;100(S1):1-4.

Myths and Misconceptions About

Chronic Constipation
Misconception

Reality

Diseases arise from

autointoxication by
retained stools

No evidence to support this theory

Fluctuations in hormones
contribute to constipation

Fluctuations in sex hormones during the menstrual

cycle have minimal impact on constipation, but are
associated with changes in other GI symptoms
Changes in hormones during pregnancy may play
a role in slowing gut transit

A diet poor in fiber causes

constipation

A low fiber diet may be a contributory factor in a

subgroup of patients with constipation
Some patients may be helped by an increase in
dietary fiber, others with more severe constipation
may get worse symptoms with increased dietary
fiber intake

Increasing fluid intake is a

successful treatment for
constipation

No evidence that constipation can be treated successfully

by increasing fluid intake unless there is evidence of
dehydration

Muller-Lissner S, et al. Am J Gastroenterol. 2005;100:232-242.

Heitkemper M, et al. Am J Gastroenterol. 2003;98(2):420-430.

More Misconceptions About Chronic

Constipation
Misconception

Reality

Stimulant laxatives
damage the enteric
nervous system and
increase the risk of
cancer

Unlikely that stimulant laxatives at recommended

doses are harmful to the colon
No data support the idea that stimulant laxatives are
an independent risk factor for colorectal cancer

Laxatives cause
electrolyte
disturbances

Laxatives can cause electrolyte disturbances, but

appropriate drug and dose selection can minimize
such effects

Laxatives induce
tolerance

Tolerance is uncommon in most laxative users,

however tolerance to stimulant laxatives can occur in
patients with severe constipation and slow colonic
transit

Laxatives are
addictive

No potential for addiction to laxatives, but laxatives

may be misused

Muller-Lissner S, et al. Am J Gastroenterol. 2005;100:232-242.

Abdominal Pain: Salient Feature

Absent in Chronic Constipation

(-) Abdominal Pain

Chronic
constipation

(+) Abdominal Pain

IBS with
constipation

Presence or absence of abdominal pain is the

major differentiating feature
Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.

Primary Constipation
Slow-transit Constipation

Characterized by prolonged
intestinal transit time
Altered regulation of enteric
nervous system
Decreased nitric oxide
production
Impaired gastrocolic reflex
Alteration of neuropeptides
(VIP, substance P)
Decreased number of
interstitial cells of Cajal in the
colon

Irritable Bowel Syndrome

(IBS) with Constipation
Alterations in brain-gut axis

Stress-related condition
Visceral hypersensitivity
Abnormal brain activation
Altered gastrointestinal
motility
Role for neurotransmitters,
hormones
Presence of non-GI sympt
Headache, back pain,
fatigue, myalgia,
dyspareunia,

urinary symptoms,
dizziness

ROME III CLASSIFICATION

Symptom onset at least 6 months before
diagnosis
Recurrent abdominal pain or discomfort at
least 3 days a month in the past 3 months,
associated with two or more of the
following
Improvement with defecation
Onset associated with a change in frequency of
stool
Onset associated with a change in form
(appearance) of stool

Clinical CC & IBS-C :

Functional Gastrointestinal diseases
(FGID)
Patomechanism motility disorders
The same clinical symptoms but IBS-C
with abdominal pain
CC slow & weak motility but IBS-C
segmental spasm
IBS-C strongly related to QOL
Psychological factors influence of IBS-C

Ask the Right Questions

o Define the meaning of constipation
o How long have you experienced these
symptoms?
o Frequency of bowel movements?
o Abdominal pain?
o Other symptoms?
o What is most distressing symptom?
o Manual maneuvers to assist with defecation?
o Any limitation of daily activities?
o Are you taking any medications?
o What treatment have you tried?
o What investigations have been done?
Locke GR III, et al. Gastroenterology. 2000;119:1761-1778.

Any Alarm Symptoms?

Are Diagnostic Tests Needed?
Hematochezia
Family history of colon cancer
Family history of inflammatory bowel disease
Anemia
Positive fecal occult blood test
Unexplained weight loss 10 pounds
Severe, persistent constipation that is
unresponsive to treatment
o New-onset constipation in an elderly patient
o
o
o
o
o
o
o

Locke GR III, et al. Gastroenterology. 2000;119:1761-1778.

Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.

Diagnosis :
Diagnosis of IBS-C based on Rome
criteria
Diagnosis of CC depend on
longstanding constipation without
typical clinical symptom

Consider Secondary Causes

Psychological
Depression
Eating disorders

Surgical

Abdominal/pelvic surgery
Colonic/anorectal surgery

Lifestyle

Inadequate fiber/fluid
Inactivity

Metabolic/
Endocrine

Hypercalcemia
Hyperparathyroidism
Diabetes mellitus
Hypothyroidism
Hypokalemia
Uremia
Addisons
Porphyria

Drugs

Opiates
Antidepressants
Anticholinergics
Antipsychotics
Antacids (Al, Ca)
Ca channel blockers
Iron supplements

Constipation
Gastrointestinal

Neurological

Parkinsons
Multiple sclerosis
Autonomic neuropathy
Aganglionosis
(Hirschsprungs, Chagas)
Spinal lesions
Cerebrovascular disease

Candelli M, et al. Hepatogastroenterology. 2001;48:1050-1057.

Locke GR, et al. Gastroenterology. 2000;119:1761-1766.

Systemic
Amyloidosis
Scleroderma
Polymyositis
Pregnancy

Colorectal: neoplasm,
ischemia, volvulus,
megacolon,
diverticular disease
Anorectal: prolapse,
rectocele, stenosis,
megarectum

Treatment CC & IBS-C :

According to pathophysiology
Clinical diagnosis very important to choose
the treatment
Wrong choice of treatment will be worse
clinical symptoms
Treatment of CC with prokinetic or
stimulant laxative
Treatment of IBS-C with anti spasmodic

Definition PK :
Pharmacokinetics
is currently defined as the study of the
time course of drug absorption,
distribution, metabolism, and excretion.
Clinical pharmacokinetics
is the application of pharmacokinetic
principles to the safe and effective
therapeutic management of drugs in an
individual patient.

Definition PD :
Pharmacodynamics
refers to the relationship between drug
concentration at the site of action and the
resulting effect, including the time course
and intensity of therapeutic and adverse
effects
The effect of a drug present at the site of
action is determined by that drugs binding
with a receptor.

Relationship of
pharmacokinetics and
pharmacodynamics and factors that affect
each.

Mode of action different laxatives

Lissner, AGH 2012; 3:(1)

Classification of laxatives :

Bisacodyl pharmacodynamics
Bisacodyl, a stimulant laxative, is
hydrolyzed by intestinal brush border
enzymes and colonic bacteria to form an
active metabolite [bis-(p-hydroxyphenyl)
pyridyl-2 methane; (BHPM)] that acts
directly on the colonic mucosa to produce
colonic peristalsis.

Bisacodyl pharmacokinetics :
The osmotic activity of HalfLytely solution
results in no net absorption or excretion of
ions or water

Treating Constipation With Laxatives

Laxative

Description

Bulking Agents

Absorbs liquids in the intestines and swells to form a soft, bulky

stool; the increase in fecal bulk is associated with accelerated
luminal propulsion

Osmotic
Laxatives

Draws water into the bowel from surrounding body tissues

providing a soft stool mass and improved propulsion
[saline, poorly absorbed mono- and disaccharides, polyethylene
glycol]

Stimulant
Laxatives

Cause rhythmic muscle contractions in the intestines, increase

intestinal motility and secretions

Lubricants

Coats the bowel and the stool mass with a waterproof film; stool
remains soft and its passage is made easier

Stool Softeners

Helps liquids mix into the stool and prevent dry, hard stool masses;
has been said not to cause a bowel movement but instead allows
the patient to have a bowel movement without straining

Combinations

Combinations containing more than 1 type of laxative; for example,

a product may contain both a stool softener and a stimulant
laxative

Gallagher P, et al. Drugs Aging. 2008;25:807-821.

Laxatives
Laxative
Type
Bulk-forming

Lubricating

Stool
Softeners
Saline

Stimulant

Osmotic

Generic Name

Brand Name(s)

Methylcellulose

Citrucel

Polycarbophil

FiberCon, Fiber-Lax

Psyllium

Metamucil, Konsyl

Glycerin

Glycerin suppository (generic)

Mineral oil

Mineral oil (generic)

Magnesium hydroxide (milk of magnesia) and mineral

oil

Phillips M-O

Docusate sodium

Colace, Dulcolax Stool Softener, Phillips

Liqui-Gels

Magnesium hydroxide (milk of magnesia)

Ex-Lax Milk of Magnesia Laxative/Antacid

Phillips Chewable Tablets
Phillips Milk of Magnesia

Bisacodyl

Ex-Lax Ultra, Dulcolax Bowel Prep Kit

Sodium bicarbonate and potassium bitartrate

Ceo-Two Evacuant

Sennosides

Ex-Lax Laxative Pills

Castor oil

Purge

Senna

Senokot

Polyethylene glycol 3350

GlycoLax, MiraLAX

Lactulose

Kristalose

Aim of bisacodyl study:

oTo observe Complete Spontaneous Bowel
Movements (CSBM) every week during 4 weeks
treatment
oTwo condition related to bowel movement :
Spontaneous Bowel Movement (SBM):
spontaneous defecation
Complete Spontaneous Bowel Movement (CSBM):
spontanneous defecation with good sensation

Study result:
Complete Spontaneous bowel movement at first day
& 4 weeks after treatment :
Placebo

Bisacodyl

Total patients

117

239

First step evaluation

1.1

1.1

4 weeks evaluation

2.0

5.2

Different result between

bisacodyl & placebo

3.3

95% Confidence interval

(2.6 , 4.0)

p-value

<0.0001

Significant difference the end result from 2 groups , bisacodyl

more superior than placebo

Patients self assesment for quality of life (QOL)

Percentageof patients

60
50
40
PBO
BIS

30
20
10
0
Good

Satisfactory

Not
satisfactory

Bad

Bisacodyl increase QOL from patients with constipation

recovery bowel habit every day . 80% patients have satisfied with
Bisacodyl.

Suggested Management Algorithm for

Chronic Constipation
Bleeding, anemia,
weight loss,
sudden change in
stool caliber,
abdominal pain

Alarm
Symptoms

No Alarm
Symptoms
Lifestyle, OTC, stimulant laxative

Directed testing
Refer to a specialist
as needed

+ Response

Continue
regimen

No response

OTC = over-the-counter therapies (probiotics, herbal medications, stool softeners

[docusate sodium], psyllium, methylcellulose, calcium polycarbophil, bisacodyl, senna)

Conclusions (1) :
Chronic Constipation is a functional GI
disorder consists of 2 types CIC and IBS-C
Differences in clinical symptoms of IBS-C
and CC are abdominal pain in IBS-C
Pathophysiology is a motility disorder, CC
with hipomotility and IBS-C with
segmental spasm
Diagnosis is based on history of illness
refer to Rome criteria

Conclusions (2) :
Treatment for CC with prokinetic or
stimulant laxative & IBS-C with
antispasmodic as primary drug
Reassured he patient that the disease is
not harmful & need longstanding
treatment to improve QOL
Development of new treatments not
medically further research is still needed

Paediatric constipation

Constipation Prevalence

Journal of Pediatrics 2005;146:359-63

Classification of Pediatric constipation

Delayed passage of meconium

Intestinal Obstruction / Anatomical
Malformation
Hirschsprungs Disease
Meconium Ileus
Functional Ileus
Small left colon
Maternal Drugs
Hypothyroidism

Normal Frequency of Bowel Movements

Evaluation and Treatment of Constipation in Infants and Children: Recommendations

of the North American Society for Pediatric Gastroenterology, Hepatology and
Nutrition.

Journal of Pediatric Gastroenterology & Nutrition. 43(3):e1-e13, September 2006.

Functional vs. Organic -- Functional

Over 95% of Constipated children has functional
constipation
Functional: persistent, difficult, infrequent, or
seemingly incomplete defecation without evidence of
underlying structural or metabolic defect
Most commonly due to with-holding after a painful bowel
movement
Presents most commonly at three age periods
At introduction of cereals and solid foods
At toilet training
At the start of school

Functional Constipation
Classic History
Child has a painful bowel movement
When urge to have a bowel movement happens, the
child consciously withholds stool by contracting their
external anal sphincter and gluteal muscles
The child might rise on their toes, rock back and forth, stiffen
their buttocks and legs, assume unusual postures, and often
will hide in a corner
Eventually, the rectum habituates to the stimulus of the
enlarging fecal mass, the urge to defecate subsides, and
the retentive behavior becomes almost second nature or
subconscious
Can develop soiling (encopresis)

Evaluation of Constipation
Evaluation and Treatment of
Constipation in Infants and Children:
Recommendations of the North
American Society for Pediatric
Gastroenterology, Hepatology and
Nutrition.
Journal of Pediatric Gastroenterology & Nutrition. 43(3):e1-e13, September 2006.

Overall approach to management

Determine whether fecal impaction
present
Treat impaction if present

Initiate treatment with oral medications

Provide parental education
Close follow up
Adjust medications as necessary

SPS untuk Konstipasi Kronis Pada Anak*

Efikasi SPS Pada Konstipasi Anak

90
80

% pasien

70
60
50
40
30
20
10

Sangat efektif

Efektif

Tidak efektif

Keterangan:
Sangat efektif : Defekasi terjadi dalam sehari
Efektif: Defekasi terjadi dalam 2 hari
Tidak efektif: Tidak terjadi defekasi setelah 3 hari atau
lebih

*sodium picosulfate cocok untuk anak di atas 4 tahun

Kozaki T. Journal of New Remedies and Clinics. 1976;25(6): 1009-1012.

Sodium picosulfate (SPS)

efektif mengatasi
konstipasi pada anak
pada lebih dari 83%
pasien. Dengan bentuk
tetes, tidak berwarna,
tidak berbau, dan tidak
berasa, sodium
picosulfate lebih mudah
untuk diberikan pada
pasien anak-anak.

Toilet Hygiene
Dynamics
of the
Anorectal
Angle

Twice a day for 10-15

minutes after breakfast
and dinner
Gastrocolic reflex

Sit up straight
Thighs parallel to ground
Good foot support
Valsalva maneuver to
increase abd pressure
Blow up balloon

Anorectal Angle in Action

No distractions
Reasonable reward system

Enema
Fleets Phosphosoda enema

< 2 YO not recommended

2 4 YO = 33.75 ml (1/2 of a Pediatric Fleets enema
<Pedia Lax>)
5-11 YO = 67.5 ml (full Pediatric Fleets enema
<Pedia-Lax>)
12 YO and up 118 ml (adult Fleet enema)

Retention of enema

Hyperphosphatemia
Hypocalcemia

Never give more than one enema per day

If enema not evacuated, do not give a second enema

Lactulose
Second line in infants < 6 mo not responding to
juice
Limited role in those over 6 mo secondary to
success of PEG 3350
Comes 10 g / 15 ml
Dose = 1-3 ml/kg/day in single or divided doses
Usually start to 1 teaspoon a day and increase as needed

Side effects
Cramps, flatulence, colicky behavior

PEG 3350
Safe for use down to 6 months of age
Comes 17 grams in a cap
Roughly 4 teaspoons is in one cap (1 teaspoon =
roughly 4 to 5 grams of PEG 3350
Easier to dose by teaspoon in infants

Typical dose for maintenance is roughly 0.7 g/kg/day

In older children typically start at max of 17 grams twice a
day but can increase if needed
Technically no max dose
If not responding to 34 grams a day in older child or
roughly 1 g/kg/day in younger child, consider adding a
stimulant laxative, re-education, or referral

Sample Treatment regimen for

older child (non infant)
Start Miralax at discussed doses
Increase or decrease dose by small amounts until
desired effect is reached
Follow up within 1 month
Aggressive Approach
After 8 weeks of soft daily bowel movements, begin to taper by
small amounts every couple of weeks (1/4 of dose at a time is a
good guide) until BM achieved without laxative
If stools become hard again during taper, increase to the last
effective dose and maintain for another 8 weeks

Conservative approach
Continue laxatives for 6 months of soft daily bowel movements,
then wean slowly

Long Term Outcome of Constipation

Gastroenterology 2003;125:357-363

Stimulants
Senna

Comes 8.8 mg/5ml or 8.8 mg tabs

2-6 YO 2.5 to 7.5 ml a day
6-12 YO 5-15 ml a day

Try to limit to periodic dosing

With regular use drug can lose effectiveness
Anecdotal evidence

Bisacodyl

0.2 mg/kg/dose, max 10 mg per dose

Comes in 5 and 10 mg tabs
Use intermittently or for short periods
Has very high side effect profile

Cramping, diarrhea, abdominal pain, nausea

Summary
Functional constipation mostly found in
children
Kind of laxative use depend on age of child
Training must be done beside laxative
drugs
Laxative therapy is the initial step further
toilet training should be conducted on an
ongoing basis

Thank you very much

for your kind attention