CONSTIPATION PPT.DR SREEJOY PATNAIK

Chronic ConstipationDR SREEJOY PATNAIK

DOCTOR ! Please help

me

No organ in the body is so misunderstood, so slandered and maltreated as the colon!

Sir Arthur Hurst, 1935

OLD SAYING…. NOT TRUE ANYMORE

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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

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

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Diagnostic Criteria

Common Patient Descriptions (adults)

Physicians think: < 3 BM per week

Straining Hard orlumpystools

Incompleteemptying

Abdominalfullness orbloating

< 3 BM per

week

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30

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50

60

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80

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Stools cannot be

passed

N = 1149Pare P, et al. Am J Gastroenterology. 2001;96:3130-3137.

Difficult to define

delay or difficulty in defecation distressful faecal incontinence retentive posturing withholding behaviour painful defecation passage of hard stools in large volumes

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Common Patient Descriptions (Children)

Rome III Diagnostic Criteria* for Adults

Chronic constipation must include 2 or more of the following

StrainingLumpy or

hard stools

Sensation of

incomplete evacuation

Sensation of Ano-rectal obstruction &blockage

Manual maneuvers to facilitate defecations

< 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

(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 weekOne of more episodes of faecal incontinence/wk after acquiring toilet trainingHistory of excessive stool retentionHistory of painful or hard bowel movementsPresence of large faecal mass in rectum History of large diameter stools which may obstruct the toilet

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Rome III Diagnostic Criteria* for Children

(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 weekOne of more episodes of faecal incontinence/weekHistory of retentive posturingHistory of painful or hard bowel movementsPresence of large faecal mass in rectum History of large diameter stools which may obstruct the toilet

Insufficient criteria for irritable bowel syndrome

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Rome III Diagnostic Criteria* for Children

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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

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Quality of Life (adults)Social and mental health particularly

affectedImpact as severe as

Diabetes, IHD, Rheumatoid Arthritis

Systematic review: Belsey et al Impact of constipation on quality of life in adults

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In Children

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Causes of Ch. Constipation

ADULTS

Normal to constipated child

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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

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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

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Etiologies of Faecal Impaction

Chronic constipationAnatomicMetabolicDietaryMedicationsNeurogenic

Anatomic anorectal abnormalitiesMega-rectumAnorectal stenosisNeoplasm

Functional anorectal abnormalitiesIncreased rectal complianceAbnormal rectal sensation

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Rescue therapy 1.Enemas2.Stimulant laxatives

Chronic Constipation Management

PyramidCan J Gastroenterology 2011;25 (suppl

B):22B-28B

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

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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

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Mechanism of ActionBeing 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.

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Available Clinical Data in Adults

Ram Kumar and Rao Study

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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

Ram Kumar and Rao Study

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Am j Gastroentrol 2005;100:936-971

Evaluation

Levels of Evidence

Good Level IFair Level IIPoor Level III

Classification of Recommendations

Grade A - Good evidenceGrade B - ModerateGrade C - PoorGrade D - Moderate

againstGrade E - Good against

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Laxative Level GradeOsmotic Lactulose II BPolyethylene Glycol I ASorbitol III CMilk of magnesia III CStimulant(Bisacodyl/Sodium Picosulphate)

III C

Bulk laxatives (Psyllium/Methycellulose)

III C

Stool Softner (Sodium docusate) III C

Tegaserod I A

RESULTS

Banned Drug

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Laxative RecommendationsQuality Level

Psyllium Effective BSodium Docusate Insufficient CMilk of Magnesia Effective CPolyethylene Glycol Effective ALactulose Effective BStimulant laxative (long term use)

No Evidence _

Domperidome Insufficient DTegaserod Effective ABiofeedback Effective B

Recommendations on Ch. ConstipationCan J Gastroenterology 2007;21 (suppl B):3-22

Banned Drug

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Polyethylene Glycol

GRADE A

Clinical Efficacy and Safety

Polyethylene glycol + Electrolytes (PEG + E)

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PEG + E vs Bulk Laxative PEG +E vs Lactulose PEG + E in Fecal ImpactionPEG + E in IBS-C

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. 2004Journal: Clinical Drug Investigations 2004;24(10):569-576

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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


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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.


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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


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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. 1999Journal: Gut 1999;44:226-230

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PEG + E vs Lactulose

Number of patients & inclusion criteria

115 patients (27% from geriatric institutions) with chronic idiopathic constipation.

Author: Attar et al. 1999Journal: Gut 1999;44:226-230

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PEG + E vs LactuloseAuthor: 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 < 0.00139

PEG + E vs LactuloseAuthor: 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)

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Safety and TolerabilityPEG + E vs LactuloseAuthor: Attar et al. 1999

Journal: Gut 1999;44:226-230

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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 alJournal: Clinical Drug Invest 1998; 16 (5): 355-60

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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

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DurationComplete resolution of

constipation or impaction (Number of patients)

After 1 day 13After 2 days 11After 3 days 1


Results Tolerability

Only symptom significantly associated with the treatment was abdominal rumbling, evidence of the action of the drug in stimulating colonic motility

Conclusion

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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

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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 alCURRENT MEDICAL RESEARCH AND OPINIONVOL. 21, NO. 10, 2005, 1595–1602


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. 1999Journal: La Revue de Geriatrie 2001;26(1):65-72

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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).


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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


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Available Clinical Data in Children

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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)

ObjectivesTo 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.

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Irritable Bowel SyndromeDiagnostic 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 defecationOnset associated with a change in frequency of stoolOnset 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.

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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: 317-24Am J Gastroenterol. 2013 Jul 9

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. 2013Journal: Am J Gastroenterol. 2013 Jul 9.

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PEG + E in IBS-C


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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.


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Pregnancy

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Causes of Constipation in Pregnancy

Multifactorial

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Pharmacology of PEG 3350

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Macrogol 4000 StudyNeri 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

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• 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

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RESULTS

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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

Novel targets (emerging)

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Drug Mode of actionPrucalopride Highly selective 5-HT4 receptor

agonist with minimal activity on 5-HT3 and hERG receptors

Renzapride 5-HT4 agonist and 5-HT3 antagonist

Methylnaltrexone & Alvimopan

Opioid (Mu receptor)antagonist

Lubiprostone & Linocotide

Chloride channel activator

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THANKS

CONSTIPATION PPT.DR SREEJOY PATNAIK

Health & Medicine

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