Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation. Severe constipation includes obstipation (failure to pass stools or gas) and fecal impaction, which can progress to bowel obstruction and become life-threatening. Constipation is a symptom with many causes. These causes are of two types: obstructed defecation and colonic slow transit (or hypo mobility). About 50 percent of people evaluated for constipation at tertiary referral hospitals have obstructed defecation. This type of constipation has mechanical and functional causes. Causes of colonic slow transit constipation include diet, hormonal disorders such as hypothyroidism, side effects of medications, and rarely heavy metal toxicity. Because constipation is a symptom, not a disease, effective treatment of constipation may require first determining the cause. Treatments include changes in dietary habits, laxatives, enemas, biofeedback, and in particular situations surgery may be required. Constipation is common; in the general population rates of constipation varies from 2–30 percent. In elderly people living in care homes the rate of constipation is 50–75 percent.[4] In the United States expenditures on medications for constipation are greater than US$250 million per year. The definition of constipation includes the following: infrequent bowel movements (typically three times or fewer per week) difficulty during defecation (straining during more than 25% of bowel movements or a subjective sensation of hard stools; straining in this context is a strong effort to push out stool often by holding one's breath and by pushing the respective muscles in the abdominal area hard), or the sensation of incomplete bowel evacuation. The Rome III criteria are widely used to diagnose chronic constipation, and are helpful in separating cases of chronic functional constipation from less-serious instances. Another definition states that less than three bowel movements per week and straining on more than 75% of occasions represents constipation in clinical surveys.

1. Chronic Constipation
DR SREEJOY PATNAIK
Chronic Constipation
DR SREEJOY PATNAIK
DOCTOR !
Please help
me
DOCTOR !
Please help
me

2. No organ in the body is so misunderstood, so
slandered and maltreated as the colon!
Sir Arthur Hurst, 1935
OLD SAYING…. NOT TRUE
ANYMORE

3. 3
 Constipation is one of the most common gastrointestinal
disorders encountered in clinical practice.
 Up to one-fifth of the general population suffers from chronic
constipation during their lifetime.
Am J Gastroenterology 2012;107:18-25.
It is estimated that 130 million Indians suffer from
constipation
Special report from World Gastroenterology Organization
Prevalence

4. Prevalence in Children
Normal Bowel Habits
 First week of life – 4-5 soft/liquid stools/day
 First three months – 3-4 soft stools/day
 3 months - 2 years – 2-3 soft stools
 Above 2 years – 1-2 formed stools
 Prevalence 3%-30% across the World
 Not uncommon in Indian subcontinent
 Common in toddlers and preschool children
 Starts in 17-40% cases in first year of life
02/10/17 4

5. 5
Diagnostic Criteria

6. Common Patient Descriptions (adults)
Physicians think:
< 3 BM per week
Straining Hard or
lumpy
stools
Incomplete
emptying
Abdominal
fullness or
bloating
< 3 BM
per
week
81
72
54
39 37 36
0
10
20
30
40
50
60
70
80
90
Stools
cannot be
passed
N = 1149
Pare P, et al. Am J Gastroenterology. 2001;96:3130-3137.

7. Difficult to define
 delay or difficulty in defecation
 distressful faecal incontinence
 retentive posturing
 withholding behaviour
 painful defecation
 passage of hard stools in large volumes
02/10/17 7
Common Patient Descriptions (Children)

8. Rome III Diagnostic Criteria* for Adults
Chronic constipation must include 2 or more of the following
StrainingStraining
Lumpy or
hard
stools
Lumpy or
hard
stools
Sensation
of
incomplete
evacuation
Sensation
of
incomplete
evacuation
Sensation of
Ano-rectal
obstruction
&blockage
Sensation of
Ano-rectal
obstruction
&blockage
Manual
maneuvers
to facilitate
defecations
Manual
maneuvers
to facilitate
defecations
< 3
defecations
per week
< 3
defecations
per week
(During at least 25% of defecations)
Loose stools are rarely present without the use of laxatives
 Insufficient criteria for irritable bowel syndrome
*Criteria fulfilled for the last 3 months with symptom onset at least 6 months
prior to diagnosis

9. (0-4 years)
(Criteria fulfilled for at least one month)
Must include two or more of the following:
Two or fewer defecations in toilet per week
One of more episodes of faecal incontinence/wk after
acquiring toilet training
History of excessive stool retention
History of painful or hard bowel movements
Presence of large faecal mass in rectum
History of large diameter stools which may obstruct the
toilet
02/10/17 9
Rome III Diagnostic Criteria* for Children

10. (4-12 years)
(Criteria fulfilled for at least once per week and must be present
since last two months)
Must include two or more of the following:
Two or fewer defecations in toilet per week
One of more episodes of faecal incontinence/week
History of retentive posturing
History of painful or hard bowel movements
Presence of large faecal mass in rectum
History of large diameter stools which may obstruct the toilet
Insufficient criteria for irritable bowel syndrome
02/10/17 10
Rome III Diagnostic Criteria* for Children

11. 11
Used in Clinical Trials
Correlates with symptoms of
straining and difficult evacuation
Also correlates with colonic transit
Majority of “constipated”
pts have stools that are Type 1-3
University of Bristol, Scand J Gastroenterology, 1997

12. 12
Quality of Life (adults)
Social and mental health particularly
affected
Impact as severe as
Diabetes,
IHD,
Rheumatoid Arthritis
Systematic review: Belsey et al
Impact of constipation on quality of life
in adults

13. 02/10/17 13
In Children

14. 14
Causes of Ch. Constipation

15. ADULTS

17. Normal to constipated child
02/10/17 17
 Pain
 Unfamiliar surroundings
 Too playful child
 Starts going to play/formal
school
 Transition to solid diet
 Toilet training
 Faulty sitting position
Organic causes
 Motility retiled – Hirsch sprung disease
 Congenital anomalies – Anal stenosis, spinal cord
abnormalities
 Neurological – cerebral palsy, mental retardation
 Endocrine/metabolic –hypothyroidism, DM, DI,
hypercalcemia
 Drugs – anticonvulsants, codeine
Causes in children

18. 18
Faecal Impaction
The typical presenting symptoms of faecal impaction are
A retrospective review by Gurll and Steer revealed that 39% of
patients with faecal impaction had a history of prior impactions
 Constipation
 Rectal discomfort
 Anorexia
 Nausea
 Vomiting
 Abdominal pain
 Paradoxical diarrhoea
 Faecal incontinence
 Urinary frequency
 Urinary overflow incontinence

19. 19
Etiologies of Faecal Impaction
Chronic constipation
Anatomic
Metabolic
Dietary
Medications
Neurogenic
Anatomic anorectal abnormalities
Mega-rectum
Anorectal stenosis
Neoplasm
Functional anorectal abnormalities
Increased rectal compliance
Abnormal rectal sensation

20. 20
Rescue therapy
1.Enemas
2.Stimulant laxatives
Chronic Constipation
Management Pyramid
Can J Gastroenterology 2011;25 (suppl B):22B-28B

21. Polyethylene Glycol
HO-CH2-(CH2-O-CH2-)n-CH2-OH
PEG are the polymers of ethylene oxide with a
molecular mass between 300 to 20,000 Dalton
PEG 3350 and 4000 are the mainly used as
laxatives. Most of the marketed preparations
world wide have PEG 3350
02/10/17 21

22. Biological Properties of PEG +E
 High water binding capacity (dose-dependent)
 Allows a controlled water transport into the colon
 No fermentation or relevant absorption in the colon (inert macromolecule)
Other Benefits
 Iso-osmotic by nature
 Negligible net gain/loss of electrolytes
02/10/17 22

23. Mechanism of Action
Being Iso-osmotic in nature, prevents the excess
absorption of the water from the colon
Maintains the required amount of hydration in the
colon.
Retained water is taken up by the fecal matter.
Feces becomes soft and bulky.
Fecal bulk stretches the bowel wall and triggers the
defecation reflex.
02/10/17 23

24. 02/10/17 24

25. 25
Available Clinical Data in Adults

26. Ram Kumar and Rao Study
26
Am j Gastroentrol 2005;100:936-971
• Literature search - Pubmed and Medline to
identify studies from 1966 - 2003
• Studies were assigned a quality score based on
methodology and the following were
evaluated:
Randomisation
Blinding
Completeness of follow up
Maximum score 5

27. Ram Kumar and Rao Study
27
Am j Gastroentrol 2005;100:936-971
Evaluation
Levels of Evidence
Good Level I
Fair Level II
Poor Level III
Classification of
Recommendations
Grade A - Good evidence
Grade B - Moderate
Grade C - Poor
Grade D - Moderate
against
Grade E - Good against

28. 28
Laxative Level Grade
Osmotic
Lactulose II B
Polyethylene Glycol I A
Sorbitol III C
Milk of magnesia III C
Stimulant
(Bisacodyl/Sodium Picosulphate)
III C
Bulk laxatives
(Psyllium/Methycellulose)
III C
Stool Softner (Sodium docusate) III C
Tegaserod I A
RESULTS
Banned Drug

29. 29
Laxative Recommendations
Quality Level
Psyllium Effective B
Sodium Docusate Insufficient C
Milk of Magnesia Effective C
Polyethylene Glycol Effective A
Lactulose Effective B
Stimulant laxative
(long term use)
No Evidence _
Domperidome Insufficient D
Tegaserod Effective A
Biofeedback Effective B
Recommendations on Ch. Constipation
Can J Gastroenterology 2007;21 (suppl B):3-22
Banned Drug

30. 30
Polyethylene Glycol
GRADE A

31. Clinical Efficacy and Safety
Polyethylene glycol + Electrolytes (PEG +
E)
31
 PEG + E vs Bulk Laxative
 PEG +E vs Lactulose
 PEG + E in Fecal Impaction
PEG + E in IBS-C

32. PEG +E vs Bulk Laxative
Objective: To compare the efficacy and safety of MOVICOL
with ispaghula husk in the treatment of
constipation.
Design:
 Randomised, controlled, open label, parallel group study.
 Patients were randomised to MOVICOL®
13.8g twice a day
or ispaghula husk 3.5g twice a day for 2 weeks.
Author: Wang, et al. 2004
Journal: Clinical Drug Investigations 2004;24(10):569-576
32

33. PEG + E vs Bulk Laxative
Number of Patients & Inclusion Criteria
 126 pts in total (63 in each group), 18-75 years old
 In-patients or out-patients with all of the following:
 Constipated for at least 3 months
 2 or less defecations/week
 Bristol Stool Chart Type 1-3 stools
Author: Wang, et al. 2004
Journal: Clinical Drug Investigations 2004;24(10):569-576
02/10/17 06:41 33

34. PEG + E vs Bulk Laxative
 By day 5,6 or 7 of treatment, 84.1 % of the pts in Movicol group
compared with 52.4% pts in the ispaghula group had stools of
normal shape and consistency as defined by Bristol Stool Scale
 On overall efficacy measure, Movicol was considered effective
in 92% and highly effective in 79% patients
 Time from treatment to first defecation was significantly less
with MOVICOL. 50% of patients on MOVICOL had a bowel
movement within 24 hours, and most had a bowel movement
within 48 hours.
Author: Wang, et al. 2004
Journal: Clinical Drug Investigations 2004;24(10):569-576
34

35. PEG + E vs Bulk Laxative
Author: Wang, et al. 2004
Journal: Clinical Drug Investigations 2004;24(10):569-576
35

36. PEG + E vs Bulk Laxative
Safety & Tolerability
 No serious adverse events
 Only 11.7% of patients on MOVICOL and 8.3% of those on
ispaghula husk reported any adverse events
 No changes in electrolytes in either group
Author: Wang, et al. 2004
Journal: Clinical Drug Investigations 2004;24(10):569-576
36

37. PEG + E vs Lactulose
Objective: To evaluate the efficacy of MOVICOL® compared to
lactulose in the treatment of chronic constipation.
Design:
 Multi-centre randomized, open-label study, comparing
MOVICOL with lactulose over a 4-week period (part A).
 At the end of the 4-week period patients were given the
opportunity to continue with the MOVICOL for further 2 months
to determine the long term efficacy and safety of the treatment
(part B).
Author: Attar et al. 1999
Journal: Gut 1999;44:226-230
37

38. PEG + E vs Lactulose
Number of patients & inclusion criteria
115 patients (27% from geriatric institutions) with chronic
idiopathic constipation.
Author: Attar et al. 1999
Journal: Gut 1999;44:226-230
38

39. PEG + E vs Lactulose
Author: Attar et al. 1999
Journal: Gut 1999;44:226-230
Assessment Criteria Movicol Lactulose P Value
No. of stools/wk 9.1 6.3 < 0.005
Straining Score 0.5 1.2 < 0.001
Overall improvement (VAS) 7.4 5.2 < 0.001
Mean no. sachets/day in first 2 wks 1.8 1.9 NS
Mean no. sachets/day in last 2 wks 1.6 2.1 < 0.001
39

40. PEG + E vs Lactulose
Author: Attar et al. 1999
Journal: Gut 1999;44:226-230
At the end of the 4 weeks treatment with MOVICOL
 65 patients were treated in the open phase of whom 61
completed the additional 2 months.
 Mean sachets reduced to 1.5/day
 No loss of efficacy (stool frequency remained 9.1/wk)
40

41. Safety and TolerabilityPEG + E vs Lactulose
Author: Attar et al. 1999
Journal: Gut 1999;44:226-230
41

42. PEG + E in Fecal Impaction
Objective: To investigate the efficacy and tolerability of
polyethylene glycol/electrolyte solution therapy in
patients with faecal impaction and severe constipation.
Patients:
 16 inpatients (aged 26 to 87 yr) and 14 outpatients
(aged 17 to 61 yr) with a history of chronic
constipation, who had not had a bowel motion for 5 or
more days and had faecal loading confirmed by clinical
examination
Author: Culbert et al
Journal: Clinical Drug Invest 1998; 16 (5): 355-60
42

43. PEG + E in Fecal Impaction
Intervention
 Each daily treatment consisted of 1 litre of polyethylene
glycol/electrolyte solution, administered as two 500 ml portions
to be taken within 4 to 6 hours, up to 3 days
Results
 Efficacy
43
Author: Culbert et al
Journal: Clinical Drug Invest 1998; 16 (5): 355-60
Duration
Complete resolution of
constipation or impaction
(Number of patients)
After 1 day 13
After 2 days 11
After 3 days 1

44. PEG + E in Fecal Impaction
Results
 Tolerability
Only symptom significantly associated with the treatment was
abdominal rumbling, evidence of the action of the drug in
stimulating colonic motility
Conclusion
44
Author: Culbert et al
Journal: Clinical Drug Invest 1998; 16 (5): 355-60
When used as a bolus treatment of eight
sachets (1 litre) daily for up to 3 days, the
PEG/electrolyte solution, was a highly effective
and acceptable oral therapy for faecal impaction

45. 45
PEG+E, administered orally at a dose equivalent to eight 13.8 g
sachets (1 L) per day over three days, was a highly effective and well
tolerated therapy for the treatment of severe constipation and faecal
impaction.
56 patients (aged 17 to 88 years) with H/O of cc and presenting with
no bowel movement for 3-4 days (severe constipation), or no bowel
movement for at least five days (faecal impaction), were enrolled at
3 centres in Taiwan.
Based on bowel movement data recorded by the pts, an excellent
response rate was obtained: 50/56 pts had a successful response
to treatment (there were 39 complete responders and 11 patients
showed improvement.
Chen et al
CURRENT MEDICAL RESEARCH AND OPINION
VOL. 21, NO. 10, 2005, 1595–1602

46. PEG + E in Fecal Impaction
Objective: To assess the efficacy and safety of MOVICOL in
treating refractory constipation with accumulation
of stools in the rectal ampulla in elderly patients.
Design:
 Open trial.
 Treatment was with 8 sachets of MOVICOL for 3 days.
Author: Alix et al. 1999
Journal: La Revue de Geriatrie 2001;26(1):65-72
46

47. PEG + E in Fecal Impaction
Number of patients & inclusion criteria
 11 of the initial 30 elderly hospitalized patients were
included. Patients had multiple diseases and used multiple
medications
 Median age was 83 years (range 65 - 88 years).
Author: Alix et al. 1999
Journal: La Revue de Geriatrie 2001;26(1):65-72
47

48. PEG + E in Fecal Impaction
 81% of patients reported complete relief. 19% felt that
they had improved but still felt uncomfortable
 The cumulative % of complete resolution was 100% by day
3 of treatment with MOVICOL
 Abdominal pain and rumbling decreased in the majority of
patients
Author: Alix et al. 1999
Journal: La Revue de Geriatrie 2001;26(1):65-72
48

49. 49
Available Clinical Data in Children

55. 55
Professor David Candy,
St Richard’s Hospital, Chichester, UK
Treatment of faecal impaction with PEG+E followed by a double-
blinded
comparison of PEG+E vs Lactulose as maintenance therapy
(Journal of paediatric gastroenterology and nutrition 2006; 43: 65-70)
Objectives
To assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E)
as oral mono-therapy in the treatment of faecal impaction in children (2 to 11
years).
To compare PEG + E with lactulose as maintenance therapy in a randomized
trial.

62. 62
Irritable Bowel Syndrome
Diagnostic criterion*
Recurrent abdominal pain or discomfort** at least 3 days/month in the last
3months 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
* Criterion fulfilled for the last 3 months with symptom onset at least 6 months
prior to diagnosis
** “Discomfort” means an uncomfortable sensation not described as pain.
In pathophysiology research and clinical trials, a pain/discomfort frequency of
at least 2 days a week during screening evaluation is recommended for subject
eligibility.

63. 63
 3-20% of the general
population
 Twice as prevalent in
women as men
 Predominantly in
those aged < 45 yrs
Irritable Bowel Syndrome
Neurogastroenterology & Motility 2005; 17: 317-24
Am J Gastroenterol. 2013 Jul 9

64. PEG + E in IBS-C
• Objectives: To compare the efficacy and safety of PEG
3350+E vs. placebo in adult patients with IBS-C
• Methods: Patients with confirmed IBS-C were randomized
to receive PEG 3350+E (N=68) or placebo (N=71)
for 28 days
Primary endpoint was mean number of spontaneous bowel
movements (SBMs) per day in the last treatment week
Author: Chapman et al. 2013
Journal: Am J Gastroenterol. 2013 Jul 9.
64

65. PEG + E in IBS-C
Author: Chapman et al. 2013
Journal: Am J Gastroenterol. 2013 Jul 9.
65

66. PEG + E in IBS-C
Conclusions:
PEG 3350+E is a well-established and effective treatment
that should be considered suitable for use in IBS-C.
Author: Chapman et al. 2013
Journal: Am J Gastroenterol. 2013 Jul 9.
66

67. Pregnancy
67

68. Causes of Constipation in Pregnancy
Multifactorial
68

69. Pharmacology of PEG 3350
69

70. Macrogol 4000 Study
Neri I et al.
Polyethylene glycol electrolyte solution (Isocolon) for
constipation during pregnancy: An observational open-label
study. J Midwifery Womens Health 2004; 49:355-358
70

71. • Constipation resolved in 73% women
• Significant improvement in: number of evacuation episodes;
defaecation pain; abdominal pain; presence of anal injury
• 22% reported side effects such as nausea, asthenia and
severe/prolonged abdominal pain
71
RESULTS

72. 72
PEG is an ideal laxative in pregnancy: effective, not
absorbed (non-teratogenic), well tolerated, and low
risk.
American Gastroenterological Association Institute
Technical Review on the Use of Gastrointestinal
Medications in Pregnancy
GASTROENTEROLOGY 2006;131:283–311

73. Novel targets (emerging)
73
Drug Mode of action
Prucalopride Highly selective 5-HT4 receptor
agonist with minimal activity on 5-
HT3 and hERG receptors
Renzapride 5-HT4 agonist and 5-HT3 antagonist
Methylnaltrexon
e & Alvimopan
Opioid (Mu receptor)antagonist
Lubiprostone &
Linocotide
Chloride channel activator

74. 74
THANKS