Curriculum Vitae

Nama Tempat & Tanggal lahir Alamat Pekerjaan Riwayat pendidikan : : : : : Dr. dr. H. CHUDAHMAN MANAN SpPD-KGEH , FINASIM Jakarta, 1 Juni 1951 Jl. Taman Golf 6, BG 1, No. 7, Cipondoh Tangerang. (15515) Staf Senior Divisi Gastroenterologi, Dept. Ilmu .Penyakit .Dalam FKUI/RSUPNCM, Fakultas Kedokteran UI, tahun 1976 Spesialis Penyakit Dalam FKUI tahun 1986 JICA Program in Gastroenterology, Tokyo,1989 Konsultan Gastroentero-Hepatologi, th. 1996 S3 , Sains Veteriner, IPB 2012 Kepala Puskesmas Kota Agung, Lahat, Sum-Sel 1976-1980 Kepala RSUD Kabupaten Lahat, Sum-Sel 1980-1981. Pendidikan Spesialis Penyakit Dalam FKUI/RSCM, 1981-1986 Spesialis P.Dalam RS Sekupang Batam 1986 Koordinator Pelayanan Masyarakat, Bag.I.P.Dalam FKUI/RSCM 1998-2000 Ketua Divisi Gastroenterologi, Dept.I.P.Dalam FKUI/RSUPNCM 2001-2008 Anggota Ikatan Dokter Indonesia (IDI) Anggota Perhimpunan Ahli Penyakit Dalam Indonesia Advisory PB PGI/PEGI Anggota Perhimpunan Peneliti Hati Indonesia (PPHI) Anggota Perkumpulan Onkologi Indonesia Councillor Asian Pasific Association of Gastroenterology Councillor Asian Pacific Association of Digestive Endoscopy Member OMED (Word organization of Digestive Endoscopy) Dalam dan Luar Negeri

Riwayat pekerjaan

Organisasi

Publikasi

Patophysiology & management of chronic constipation

Chudahman Manan
Indonesian Society of Gastroenterology

Epidemiology
oConstipation problem most finding in western country. oIn USA constipation prevalence 2-27% with physician consultation about 2.5 million and hospitalized patients about 100.000 pts. oData from RSCM-Jakarta during 1998-2005, 2.397 colonoscopy exam , 216 (9%) indication for constipation oGender comparative women and men (4 : 1)
Sumber: buku konsensus nasional penatalaksanaan konstipasi di Indonesia oleh PGI

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.

Differentiating Between Occasional and Chronic Constipation

Occasional Constipation Chronic Constipation Present for at least 3 months and may persist for years

Infrequent
Occasional or short-term condition that may temporarily interrupt usual routine May be brought on by patients behavior, change in diet, lack of exercise, illness, or medication May be relieved by diet, exercise, and over-the-counter (OTC) medication

Long-term condition that may dominate personal and work life

Not only related to patients behavior, change in diet, lack of exercise, or medication May need medical attention and prescription medication

Overlap Between Common Disorders

Bloating Belching Constipation

Chronic Constipation Dyspepsia

Discomfort

IBS GERD
Abdominal Pain Regurgitation

Heartburn

Brandt L, et al. Am J Gastroenterol. 2005;100(S1):5-22.

Abdominal Pain: Salient Feature Absent in Chronic Constipation

(-) Abdominal Pain

(+) Abdominal Pain

Chronic constipation

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.

Prevalence of Functional Gastrointestinal Disorders

45 40 Population (%)
40

35
30 25 20 15 10
8 8 25-40 2-28 25 3-20 6-18 28

5
0
Chronic DyspepsiaFunctional GERD Heartburn Constipation IBS Hyper- Migraine Asthma Diabetes tension

Wong WM, Fass R. Curr Treat Options Gastroenterol. 2004;7(4):273-278. Corazziari E. Best Pract Res Clin Gastroenterol. 2004;18(4):613-631. Higgins PD, Johanson JF. Am J Gastroenterol. 2004;99(4):750-759. Brandt L, et al. Am J Gastroenterol. 2002;97(suppl11):S7-26.

Wolf-Maier K, et al. JAMA. 2003;289:2363-2369. Lawrence EC. South Med J. 2004 Nov;97(11):1069-1077. CDC. MMWR Morb Mortal Wkly Rep. 2004;53:145-148. CDC. MMWR Morb Mortal Wkly Rep. 2003;52:833-837.

Constipation Increases With Age and Is More Common in Women

12

Prevalence of Constipation (%)

8 6 4 2 0

Prevalence of Constipation (%)

10

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

Study 1 N = 42,375

25 20 15 10

Men

Women

5
0

N = 5,430 Drossman

Study 2

N = 1,149 Pare

Study 3

N = 10,018 Stewart

Study 4

Age Group (years)

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

Sex

Normal Physiology of Defecation

o Increased abdominal pressure or propulsive colorectal contractions o Relaxation of internal anal sphincter (autonomic) o Relaxation of external anal sphincter (voluntary) o Straightening of pelvic musculature (levator ani, puborectalis)
At rest With straining

Lembo A, Camilleri M. N Engl J Med. 2003;349:1360-1368. Muller-Lissner S. Best Pract Res Clin Gastroenterol. 2002;16:115-133.

Chronic Constipation Interferes with Daily Lives of the Aging Population

100
Mean MOS Score 8 0 6 0 4 0 2 0 0 Constipation No GI symptoms

Physical Role Functioning Functioning

Social Functioning

Mental Health

Health Perception

Bodily Pain

MOS = medical outcomes survey

Impact of chronic constipation on quality of life in Olmsted County, MN, residents aged 65 years Lower score indicates worse quality of life

Adapted from Talley NJ. Rev Gastroenterol Disord. 2004;4(suppl 2):S3-S10.

Primary Causes of Chronic constipation :

o Normal-transit constipation

o Slow-transit constipation
o Defecatory dysfunction o IBS with constipation

Bosshard W, et al. Drugs Aging. 2004;21:911-930. Hadley S.K, et al. Journal of Am Fam Physician. 2005;72:2501-2506.

Stool Form Correlates With Intestinal Transit Time

The Bristol Stool Form Scale
Slow Transit

Type 1 Type 2

Separate hard lumps

Sausage-like but lumpy Sausage-like but with cracks in the surface Smooth and soft Soft blobs with clear-cut edges Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces

Type 3
Type 4 Type 5 Type 6
Fast Transit

Type 7

ODonnell LJD, et al. BMJ. 1990;300:439-440.

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

Primary Constipation(1):
Normal-transit Constipation
Intestinal transit and stool frequency are within the normal range Most frequent type of constipation

Bosshard W, et al. Drugs Aging. 2004;21:911-930. Gallagher P, et al. Drugs Aging. 2008;25(10):807-821.

Primary Constipation(2):
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

Lembo A, Camilleri M. N Eng J Med. 2003;349:1360-1368.

Primary Constipation(3):
Defecatory Dysfunction
More common in older women childbirth trauma Pelvic floor dyssynergia Contributing factors include anal fissures, hemorrhoids, rectocele, rectal prolapse, posterior rectal herniation Excessive perineal descent Pathogenesis may be multifactorial structural problem Abnormal anorectal manometry and/or defecography

Bosshard W, et al. Drugs Aging. 2004;21:911-930. Hadley S.K, et al. Journal of Am Fam Physician. 2005;72:2501-2506.

Primary Constipation(4):
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 symptoms Headache, back pain, fatigue, myalgia, dyspareunia,
urinary symptoms, dizziness

Videlock E, Chang L. Gastroenterol Clin N Am. 2007;36:665-685. Hadley SK, et al. Journal of Am Fam Physician. 2005;72:2501-2506.

Rome III Criteria for IBS-C

Recurrent abdominal pain or discomfort (an uncomfortable sensation not described as pain) at least 3 days per month in the last 3 months associated with 2 or more of the following: 1. Improvement with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form of stool

Criteria must be fulfilled for the last 3 months, with symptom onset at least 6 months prior to diagnosis
In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening for patient eligibility
Longstreth G, et al. Gastroenterology. 2006;130:1480-1491.

Rome III Diagnostic Criteria* for Functional Constipation

Chronic constipation must include 2 or more of the following:
During at least 25% of defecations
Sensation of incomplete evacuation

Straining

Lumpy or hard stools

Sensation of anorectal obstruction/ blockage

Manual maneuvers to facilitate defecations

<3 defecations per week

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

Longstreth GF, et al. Gastroenterology. 2006;130:1480-1491.

Patient Care :
o Through patient history o Physical/abdominal/digital rectal exams o Evaluate symptoms in terms of diagnostic criteria Chronic constipation/IBS-C o Assessment for red flags/alarm features o Need for additional testing o Treatment/Management plan

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.

90 80 Percent of Patients 70 60 50 40 30 20 10 0

Common Patient Descriptions of Constipation

81 72 54 Physicians think: < 3 BM per week

39

37

36 28

Straining

Hard or Incomplete Stool Abdominal < 3 BM lumpy emptying per cannot fullness or stools bloating week be passed

Need to press on anus

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

Supportive exam :

Colonoscopy

Sumber: konsensus nasional penatalaksanaan konstipasi di Indonesia oleh PGI

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.

Mediators of Gl Function
Motility Visceral Sensitivity
Serotonin Acetylcholine Nitric oxide Substance P Vasoactive intestinal peptide Cholecystokinin Corticotropin releasing factor Serotonin Tachykinins Calcitonin gene-related peptide Neurokinin A Enkephalins Corticotropin releasing factor

Secretion

Serotonin Acetylcholine

Kim DY, Camilleri M. Am J Gastroenterol. 2000;95(10):2698-2709.

Combined Risk Factors for Constipation in the Elderly Population

Reduced fiber intake Reduced liquid intake Reduced mobility associated with functional decline Decreased functional independence Pelvic floor dysfunction Chronic conditions Parkinsons disease Dementia Diabetes mellitus Depression o Polypharmacy (both over the counter and prescription medications, such as NSAIDs, antacids, antihistamines, iron supplements, anticholinergics, opiates, Ca channel blockers, diuretics, antipsychotics, anxiolytics, antidepressants) o o o o o o

Common Changes with Aging that Increase the Risk for Constipation
o o o o o o o Decreased total body water Decreased colonic motility* Deterioration of nerve function Increased pelvic floor descent Decreased rectal compliance Decreased rectal sensation Age-related changes to the internal and external anal sphincter

*Demonstrated in some, but not all studies

Gallagher P, et al. Drugs Aging. 2008;25(10):807-821. Schiller L. Gastroenterol Clin N Am. 2001;30:497-515.

Consider Secondary Causes

Psychological
Depression Eating disorders Abdominal/pelvic surgery Colonic/anorectal surgery

Surgical

Inadequate fiber/fluid Inactivity

Lifestyle

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

Drugs

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

Hypercalcemia Hyperparathyroidism Diabetes mellitus Hypothyroidism Hypokalemia Uremia Addisons Porphyria

Metabolic/ Endocrine

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

Systemic
Amyloidosis Scleroderma Polymyositis Pregnancy

Candelli M, et al. Hepatogastroenterology. 2001;48:1050-1057. Locke GR, et al. Gastroenterology. 2000;119:1761-1766.

Chronic Constipation Secondary to Diabetes

Special Considerations o Constipation occurs in 20% of patients with diabetes o Related to duration of diabetes > 10 years o Diabetic autonomic neuropathy o Gastrocolic reflex may be absent, delayed, blunted o Constipation may be severe and can lead to megacolon Treatment Strategy* 1. Optimize diabetes care 2. Stepwise pharmacologic therapy

Exclude slow transit Bulking agents, osmotic laxatives, Cl channel activators, stimulant laxatives

*Treatment strategy based on clinical experience

Verne GN, et al. Gastroenterol Clin North Am. 1998;27:861-874.

Myths and Misconceptions About Chronic Constipation

Misconception
Diseases arise from autointoxication by retained stools Fluctuations in hormones contribute to constipation

Reality
No evidence to support this theory 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 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 No evidence that constipation can be treated successfully by increasing fluid intake unless there is evidence of dehydration

A diet poor in fiber causes constipation

Increasing fluid intake is a successful treatment for constipation

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
Stimulant laxatives damage the enteric nervous system and increase the risk of cancer Laxatives cause electrolyte disturbances Laxatives induce tolerance Laxatives are addictive

Reality
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 can cause electrolyte disturbances, but appropriate drug and dose selection can minimize such effects Tolerance is uncommon in most laxative users, however tolerance to stimulant laxatives can occur in patients with severe constipation and slow colonic transit No potential for addiction to laxatives, but laxatives may be misused

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

Lifestyle Modifications
Modification
Increase fluid intake

Targeted Mechanism
Increase stool volume by augmenting luminal fluid

Efficacy
Limited; majority of fluid is absorbed before reaching the colon and is expelled via urine Moderate; some evidence suggests this is beneficial; however, not sufficient to treat Limited benefit compared with placebo

Increase exercise

Improve motility by decreasing transit time through the GI tract

Increase dietary fiber

Increase water and bulk stool volume

Chung BD, et al. J Clin Gastroenterol. 1999;28:29-32. Dukas L, et al. Am J Gastroenterol. 2003;98:1790-1796. ACG Chronic Constipation Task Force. Am J Gastroenterol. 2005;100(suppl 1):S1-S4.

Are Patients Satisfied With Laxatives and Fiber?

100
OTC laxatives (n = 146) Prescription laxatives (n = 42) 71 75 79 67 52 Fiber (n = 268) 80

Dissatisfied Patients (%)

80
66 60 50 44 50 50

60

40

20

0
Ineffective Relief Ineffective Relief of of Constipation Multiple Symptoms Lack of Predictability Ineffective Relief of Bloating

Johanson JF and Kralstein J. Aliment Pharmacol Ther. 2007;25:599-608.

Treating Constipation With Laxatives

Laxative
Bulking Agents

Description
Absorbs liquids in the intestines and swells to form a soft, bulky stool; the increase in fecal bulk is associated with accelerated luminal propulsion 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] Cause rhythmic muscle contractions in the intestines, increase intestinal motility and secretions Coats the bowel and the stool mass with a waterproof film; stool remains soft and its passage is made easier 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 containing more than 1 type of laxative; for example, a product may contain both a stool softener and a stimulant laxative

Osmotic Laxatives Stimulant Laxatives Lubricants Stool Softeners

Combinations

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

Laxatives
Laxative Type
Methylcellulose

Generic Name
Citrucel

Brand Name(s)

Bulk-forming

Polycarbophil Psyllium Glycerin

FiberCon, Fiber-Lax Metamucil, Konsyl Glycerin suppository (generic) Mineral oil (generic) Phillips M-O

Lubricating

Mineral oil Magnesium hydroxide (milk of magnesia) and mineral oil

Stool Softeners
Saline

Docusate sodium

Colace, Dulcolax Stool Softener, Phillips Liqui-Gels

Ex-Lax Milk of Magnesia Laxative/Antacid Phillips Chewable Tablets Phillips Milk of Magnesia Ex-Lax Ultra, Dulcolax Bowel Prep Kit Ceo-Two Evacuant Ex-Lax Laxative Pills Purge Senokot GlycoLax, MiraLAX Kristalose

Magnesium hydroxide (milk of magnesia) Bisacodyl Sodium bicarbonate and potassium bitartrate

Stimulant

Sennosides Castor oil Senna Polyethylene glycol 3350 Lactulose

Osmotic

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

Material & Method :

o Adult patients total 368 pts o Diagnosis chronic constipation o Bisacodyl tab (Dulcolax)R vs. placebo; during 4 weeks o Center of study Germany & UK

Study result:
Complete Spontaneous bowel movement at first day & 4 weeks after treatment :
Placebo Total patients 117 Bisacodyl 239

First step evaluation

4 weeks evaluation Different result between bisacodyl & placebo 95% Confidence interval p-value

1.1
2.0 3.3

1.1
5.2

(2.6 , 4.0) <0.0001

Significant difference the end result from 2 groups , bisacodyl more superior than placebo

Result :
Complete spontaneous bowel movement after 4 weeks

** ** ** **

Significant diff in CSBM between Bisacodyl mand placebo

Result :
Avarage Spontaneous Bowel Movement after 4 weeks
**

**
** **

Significant diff between Bisacodyl & plasebo to increase SBM

Patients self assesment for quality of life (QOL)

60
Percentageof patients

50 40 30 20 10 0 Good Satisfactory Not satisfactory Bad PBO BIS

Bisacodyl increase QOL from patients with constipation recovery bowel habit every day . 80% patients have satisfied with Bisacodyl.

Patients symptoms improvement after bisacodyl treatment

o Regular bowel habit everyday o Decreased constipation symptoms o Decreased bloating symptoms o Decreased abdominal discomfort

Bisacodyl relief clinical symptoms due to constipation

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

+ Response

Directed testing Refer to a specialist as needed

Continue regimen

No response

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

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

Summary
o Chronic constipation is a common condition mostly in the elderly o Quality of life pts with constipation especialy in elderly patients is negatively affected by the symptoms of chronic constipation o Identify risk factors and secondary causes for constipation o Be vigilant for red flags or alarm symptoms; directed tested may be necessary

Summary contd
o Main objective of treatment for chronic constipation is to improve patients symptoms, restore normal bowel function ( 3 bowel movements per week), improve quality of life o Bisacodyl have good therapeutic effect and minimal side effect with good safety profile

Thank you very much for your kind attention