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Transcript of Boehringer Simp Obst Kronik Ukrida 070413 (Chudahman Manan)
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Curriculum Vitae
N a m a : Dr. dr. H. CHUDAHMAN MANAN SpPD-KGEH , FINASIMTempat & Tanggal lahir : Jakarta, 1 Juni 1951Alamat : Jl. Taman Golf 6, BG 1, No. 7, Cipondoh
Tangerang. (15515)
Pekerjaan : Staf Senior Divisi Gastroenterologi, Dept. Ilmu .Penyakit .DalamFKUI/RSUPNCM,
Riwayat pendidikan :Fakultas Kedokteran UI, tahun 1976Spesialis Penyakit Dalam FKUI tahun 1986JICA Program in Gastroenterology, Tokyo,1989Konsultan Gastroentero-Hepatologi, th. 1996S3 , Sains Veteriner, IPB 2012
Riwayat pekerjaan :Kepala Puskesmas Kota Agung, Lahat, Sum-Sel 1976-1980Kepala RSUD Kabupaten Lahat, Sum-Sel 1980-1981.Pendidikan Spesialis Penyakit Dalam FKUI/RSCM, 1981-1986Spesialis P.Dalam RS Sekupang Batam 1986Koordinator Pelayanan Masyarakat, Bag.I.P.Dalam FKUI/RSCM 1998-2000Ketua Divisi Gastroenterologi, Dept.I.P.Dalam FKUI/RSUPNCM 2001-2008
Organisasi :
Anggota Ikatan Dokter Indonesia (IDI)Anggota Perhimpunan Ahli Penyakit Dalam IndonesiaAdvisory PB PGI/PEGIAnggota Perhimpunan Peneliti Hati Indonesia (PPHI)Anggota Perkumpulan Onkologi IndonesiaCouncillor Asian Pasific Association of GastroenterologyCouncillor Asian Pacific Association of Digestive EndoscopyMember OMED (Word organization of Digestive Endoscopy)
Publikasi : Dalam dan Luar Negeri
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Patophysiology & management
of chronic constipation
Chudahman Manan
Indonesian Society of Gastroenterology
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EpidemiologyoConstipation problem most finding in
western country.
oIn USA constipation prevalence 2-27% with
physician consultation about 2.5 million andhospitalized 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
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How Do We DefineConstipation?
o The American College of Gastroenterology (ACG)definition of constipation:
o Unsatisfactory defecation characterized by infrequentstools, difficult stool passage, or both. Difficult stoolpassage includes straining, a sense of difficulty passingstool, incomplete evacuation, hard/lumpy stools,prolonged time to pass stool, or need for manualmaneuvers to pass stool
o The ACG Chronic Constipation Task Force alsoclarified what is meant by chronic:
o Chronic constipation is defined as the presence of thesesymptoms for at least 3 months
American College of Gastroenterology Chronic Constipation TaskForce. Am J Gastroenterol. 2005;100(S1):1-4.
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Differentiating BetweenOccasional and Chronic Constipation
Occasional Constipation Chronic Constipation
InfrequentPresent for at least 3 monthsand may persist for years
Occasional or short-term
condition that may temporarilyinterrupt usual routine
Long-term condition that maydominate personal and work life
May be brought on by patientsbehavior, change in diet, lack ofexercise, illness, or medication
Not only related to patientsbehavior, change in diet, lack ofexercise, or medication
May be relieved by diet, exercise,and over-the-counter (OTC)medication
May need medical attention andprescription medication
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Belching
Dyspepsia
IBS
GERD
Chronic
Constipation
Constipation
Heartburn Regurgitation
Bloating
AbdominalPain
Discomfort
Overlap Between CommonDisorders
Brandt L, et al.Am J Gastroenterol. 2005;100(S1):5-22.
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Chronicconstipation
(-)Abdominal Pain
IBS withconstipation
(+)Abdominal Pain
Presence or absence of abdominal pain is themajor differentiating feature
Abdominal Pain: Salient FeatureAbsent in Chronic Constipation
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Prevalence of FunctionalGastrointestinal Disorders
25
25-40
40
3-20
2-28
05
10
15
20
25
30
35
40
45
DyspepsiaFunctionalHeartburn
ChronicConstipation
GERD IBS
Populatio
n(%)
28
8 8
6-18
Hyper-tension
Migraine Asthma Diabetes
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.
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.
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Higgins PDR, et al.Am J Gastroenterol. 2004;99:750-759.
Age Group (years)
Prevalence
of
Constipation
(%)
0
2
4
6
8
10
12
Study 1N = 42,375
Harari, et alPopulation: NHIS 1989
Criteria: self-report
NHIS = National Health Interview Survey
Constipation Increases With Ageand Is More Common in Women
Prevalence
of
Constipation
(%)
Sex
N = 5,430Drossman
N = 1,149Pare
N = 10,018Stewart
Study 2 Study 3 Study 4
Men Women
0
5
10
15
20
25
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Normal Physiology of Defecation
o
Increased abdominal pressure or propulsive colorectalcontractions
o Relaxation of internal anal sphincter (autonomic)
o Relaxation of external anal sphincter (voluntary)
o Straightening of pelvic musculature (levator ani,puborectalis)
With strainingAt rest
Lembo A, Camilleri M. N Engl J Med. 2003;349:1360-1368.Muller-Lissner S. Best Pract Res Clin Gastroenterol. 2002;16:115-133.
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Chronic Constipation Interferes withDaily Lives of the Aging Population
100
8
0604020
0
MeanMOSScore
PhysicalFunctioning
HealthPerception
MentalHealth
SocialFunctioning
RoleFunctioning
BodilyPain
No GI symptoms
Constipation
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.
MOS = medical outcomes survey
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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 Causes of Chronic constipation :
o Normal-transit constipation
o Slow-transit constipation
o Defecatory dysfunction
o IBS with constipation
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Stool Form Correlates WithIntestinal Transit Time
ODonnell LJD, et al. BMJ. 1990;300:439-440.
Slow Transit
Fast Transit
Separate hard lumps
Type 2
Type 1
Type 3
Type 4
Type 5
Type 6
Type 7
Sausage-like but lumpy
Sausage-like but withcracksin the surfaceSmooth and soft
Soft blobs with clear-cut edges
Fluffy pieces with raggededges,a mushy stoolWatery, no solid pieces
The Bristol Stool Form Scale
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Primary Constipation Slow-transit Constipation
Characterized by prolongedintestinal transit time
Altered regulation of entericnervous system
Decreased nitric oxideproduction
Impaired gastrocolic reflex
Alteration of neuropeptides(VIP, substance P)
Decreased number ofinterstitial 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
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Bosshard W, et al. Drugs Aging. 2004;21:911-930.Gallagher P, et al. Drugs Aging. 2008;25(10):807-821.
Primary Constipation(1):
Normal-transit ConstipationIntestinal transit and stool frequency are within the
normal range
Most frequent type of constipation
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Lembo A, Camilleri M. N Eng J Med. 2003;349:1360-1368.
Primary Constipation(2):
Slow-transit ConstipationCharacterized 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
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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.
Primary Constipation(4):
Irritable Bowel Syndrome (IBS) withConstipation
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
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Rome III Criteria for IBS-C
Recurrent abdominal pain or discomfort (anuncomfortable sensation not described as pain) at least3 days per month in the last 3 months associated with 2or more of the following:
1. Improvement with defecation2. Onset associated with a change in frequency of
stool3. Onset associated with a change in form of stool
Criteria must be fulfilled for the last 3 months, withsymptom onset at least 6 months prior to diagnosis
In pathophysiology research and clinical trials, a pain/discomfort frequency ofat least 2 days a week during screening for patient eligibility
Longstreth G, et al. Gastroenterology. 2006;130:1480-1491.
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Manualmaneuversto facilitatedefecations
Sensation ofanorectal
obstruction/blockage
Loose stools are rarely present without the use of laxatives
Insufficient criteria for irritable bowel syndrome
Longstreth GF, et al. Gastroenterology. 2006;130:1480-1491.
*Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
During at least 25% of defecations
Sensationof
incompleteevacuation
StrainingLumpy or
hardstools
< 3defecations
per week
Rome III Diagnostic Criteria*for Functional Constipation
Chronic constipation must include 2 or more of the following:
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Patient Care :
o Through patient historyo Physical/abdominal/digital rectal examso
Evaluate symptoms in terms of diagnosticcriteria Chronic constipation/IBS-Co Assessment for red flags/alarm featuresoNeed for additional testing
o Treatment/Management plan
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Ask the Right Questions
o Define the meaning of constipationo 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.
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Pare P, et al.Am J Gastroenterol. 2001;96:3130-3137.
N = 1149
Stoolcannot
bepassed
PercentofPatients
Physicians think:
< 3 BM per week
Straining Hard orlumpystools
Incompleteemptying
Abdominalfullness orbloating
< 3 BMper
week
Need topress on
anus
81
72
54
3937 36
28
0
10
20
30
40
50
60
7080
90
Common Patient Descriptionsof Constipation
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Any Alarm Symptoms?Are Diagnostic Tests Needed?
Locke GR III, et al. Gastroenterology. 2000;119:1761-1778.Brandt LJ, et al.Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
o Hematochezia
o Family history of colon cancer
o Family history of inflammatory bowel disease
o Anemia
o Positive fecal occult blood test
o Unexplained weight loss 10 pounds
o
Severe, persistent constipation that isunresponsive to treatment
o New-onset constipation in an elderly patient
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Mediators of Gl Function
Visceral SensitivitySerotoninTachykininsCalcitonin gene-related peptideNeurokinin A
EnkephalinsCorticotropin releasing factor
Kim DY, Camilleri M.Am J Gastroenterol. 2000;95(10):2698-2709.
SecretionSerotonin
Acetylcholine
MotilitySerotonin
AcetylcholineNitric oxideSubstance P
Vasoactive intestinal peptideCholecystokininCorticotropin releasing factor
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Combined Risk Factors forConstipation in the Elderly Populationo
Reduced fiber intakeo Reduced liquid intakeo Reduced mobility associated with functional declineo Decreased functional independenceo Pelvic floor dysfunctiono
Chronic conditions Parkinsons disease Dementia Diabetes mellitus Depression
o Polypharmacy (both over the counter andprescription medications, such as NSAIDs, antacids,antihistamines, iron supplements, anticholinergics,opiates, Ca channel blockers, diuretics,antipsychotics, anxiolytics, antidepressants)
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Consider Secondary Causes
Constipation
GastrointestinalColorectal: neoplasm,
ischemia, volvulus,megacolon,
diverticular diseaseAnorectal: prolapse,
rectocele, stenosis,megarectum
Drugs
OpiatesAntidepressantsAnticholinergicsAntipsychotics
Antacids (Al, Ca)Ca channel blockersIron supplements
Metabolic/EndocrineHypercalcemia
HyperparathyroidismDiabetes mellitusHypothyroidismHypokalemia
UremiaAddisonsPorphyria
PsychologicalDepression
Eating disorders
NeurologicalParkinsons
Multiple sclerosisAutonomic neuropathy
Aganglionosis(Hirschsprungs, Chagas)
Spinal lesionsCerebrovascular disease
LifestyleInadequate fiber/fluid
Inactivity
SurgicalAbdominal/pelvic surgeryColonic/anorectal surgery
SystemicAmyloidosisSclerodermaPolymyositisPregnancy
Candelli M, et al. Hepatogastroenterology. 2001;48:1050-1057.Locke GR, et al. Gastroenterology. 2000;119:1761-1766.
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Chronic Constipation Secondary to Diabetes
Special Considerationso Constipation occurs in 20% of patients with diabeteso Related to duration of diabetes > 10 yearso Diabetic autonomic neuropathyo Gastrocolic reflex may be absent, delayed, blunted
o Constipation may be severe and can lead tomegacolon
Treatment Strategy*1. Optimize diabetes care2. Stepwise pharmacologic therapy
Exclude slow transit Bulking agents, osmotic laxatives, Cl channel activators,
stimulant laxatives
Verne GN, et al. Gastroenterol Clin North Am. 1998;27:861-874.
*Treatment strategy based on clinical experience
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Myths and Misconceptions AboutChronic Constipation
Misconception Reality
Diseases arise fromautointoxication byretained stools
No evidence to support this theory
Fluctuations in hormonescontribute to constipation
Fluctuations in sex hormones during the menstrualcycle have minimal impact on constipation, but are
associated with changes in other GI symptomsChanges in hormones during pregnancy may playa role in slowing gut transit
A diet poor in fiber causes
constipation
A low fiber diet may be a contributory factor in asubgroup of patients with constipation
Some patients may be helped by an increase in
dietary fiber, others with more severe constipationmay get worse symptoms with increased dietaryfiber intake
Increasing fluid intake is asuccessful treatment forconstipation
No evidence that constipation can be treated successfullyby increasing fluid intake unless there is evidence ofdehydration
Muller-Lissner S, et al.Am J Gastroenterol. 2005;100:232-242.Heitkemper M, et al.Am J Gastroenterol. 2003;98(2):420-430.
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More Misconceptions About ChronicConstipation
Muller-Lissner S, et al.Am J Gastroenterol. 2005;100:232-242.
Misconception RealityStimulant 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 colonictransit
Laxatives are
addictive
No potential for addiction to laxatives, but laxatives
may be misused
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Modification Targeted Mechanism Efficacy
Increase fluidintake
Increase stool volume by augmentingluminal fluid
Limited; majority of fluidis absorbed beforereaching the colon and isexpelled via urine
Increase exercise Improve motility by decreasing transit timethrough the GI tract
Moderate; someevidence suggests this isbeneficial; however, notsufficient to treat
Increase dietaryfiber
Increase water and bulk stool volume Limited benefit comparedwith placebo
Lifestyle Modifications
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.
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Ineffective Reliefof Constipation
Johanson JF and Kralstein J.Aliment Pharmacol Ther. 2007;25:599-608.
Ineffective Relief ofMultiple Symptoms
Lack ofPredictability
Ineffective Reliefof Bloating
D
issatisfiedPatients(%)
OTC laxatives Prescription laxatives Fiber(n = 268)(n = 42)(n = 146)
44
60
7167
50 50
75
5250
66
79 80
0
20
40
60
80
100
Are Patients Satisfied WithLaxatives and Fiber?
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Treating Constipation With Laxatives
Laxative Description
Bulking Agents
Absorbs liquids in the intestines and swells to form a soft, bulkystool; the increase in fecal bulk is associated with acceleratedluminal propulsion
Osmotic
Laxatives
Draws water into the bowel from surrounding body tissuesproviding a soft stool mass and improved propulsion
[saline, poorly absorbed mono- and disaccharides, polyethyleneglycol]
StimulantLaxatives
Cause rhythmic muscle contractions in the intestines, increaseintestinal motility and secretions
LubricantsCoats the bowel and the stool mass with a waterproof film; stoolremains 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 allowsthe 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 stimulantlaxative
Gallagher P, et al. Drugs Aging. 2008;25:807-821.
Laxatives
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LaxativesLaxative
TypeGeneric Name Brand Name(s)
Bulk-forming
Methylcellulose Citrucel
Polycarbophil FiberCon, Fiber-Lax
Psyllium Metamucil, Konsyl
Lubricating
Glycerin Glycerin suppository (generic)
Mineral oil Mineral oil (generic)
Magnesium hydroxide (milk of magnesia) and mineral
oil Phillips
M-O
StoolSofteners
Docusate sodiumColace, DulcolaxStool Softener, PhillipsLiqui-Gels
Saline Magnesium hydroxide (milk of magnesia)Ex-Lax Milk of Magnesia Laxative/AntacidPhillips Chewable TabletsPhillips Milk of Magnesia
Stimulant
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
Osmotic Polyethylene glycol 3350 GlycoLax
, MiraLAX
Lactulose Kristalose
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Aim of bisacodyl study:
oTo observe Complete Spontaneous Bowel
Movements (CSBM) every week during 4 weeks
treatment
o
Two condition related to bowel movement : Spontaneous Bowel Movement (SBM):
spontaneous defecation
Complete Spontaneous Bowel Movement (CSBM):
spontanneous defecation with good sensation
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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
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Result :Complete spontaneous bowel movement after 4 weeks
**
** ** **
Significant diff in CSBM between Bisacodyl mand placebo
R l
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Result :
**
**
**
**
Avarage Spontaneous Bowel Movement after 4 weeks
Significant diff between Bisacodyl & plasebo to increase SBM
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Patients symptoms improvement afterbisacodyl 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
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Summary
o Chronic constipation is a commoncondition mostly in the elderly
o Quality of life pts with constipationespecialy in elderly patients is
negatively affected by the symptomsof chronic constipation
o Identify risk factors and secondary
causes for constipationo Be vigilant for red flags or alarm
symptoms; directed tested may benecessary
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Summary contd
o Main objective of treatment forchronic constipation is to improvepatients symptoms, restore normal
bowel function ( 3 bowelmovements per week), improvequality of life
o Bisacodyl have good therapeuticeffect and minimal side effect withgood safety profile
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Thank you very muchfor your kind attention