adult and children constipation the role of laxative therapy - chudahman manan
TRANSCRIPT
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
1/54
Chudahman Manan
Indonesian Society of Gastroenterology
Adult and Children Constipation
The role of laxative therapy
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
2/54
Introduction (1) :
Chronic constipation and irritable bowelsyndrome (IBS), the most prevalentfunctional bowel disorders in NorthAmerica (20-70%)
Symptoms related to these motilitydisorders are chronic, sometimes severe,and can profoundly and negatively affectpatients QOL
Chronic constipation and IBS often leadingto polypharmacy and a significant burdenon healthcare resources.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
3/54
oData from RSCM-Jakarta during
1998-2005, 2.397 colonoscopy exam ,
216 (9%) indication for constipationoGender comparative women and men
(4 : 1)
Introduction (2) :
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
4/54
Drossman, DA; Gastro 2006
LIFEGenetics
Environment
Social Context
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
5/54
Irritable bowel syndrome: a global perspective, WGO GlobalGuideline 2009.
Data in Indonesia, ofthe 304 cases ofdigestive disorders isincorporated in Asian
studies FunctionalGastrointestinalDisorders Study(AFGID) in 2013,reported incidence of
5.3% functionalconstipation andconstipation type IBSincidence of 10.5%.
Epidemiology Constipation :
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
6/54
Higgins PDR, et al.Am J Gastroenterol. 2004;99:750-759.
Age Group (years)
Prevalence
of
Constipation
(%)
0
2
4
68
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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
7/54
How Do We Define Constipation?
oThe 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 passing
stool, incomplete evacuation, hard/lumpy stools,prolonged time to pass stool, or need for manualmaneuvers to pass stool
oThe ACG Chronic Constipation Task Force alsoclarified what is meant by chronic:
o Chronic constipation is defined as the presence ofthese symptoms for at least 3 months
American College of Gastroenterology Chronic Constipation TaskForce.Am J Gastroenterol. 2005;100(S1):1-4.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
8/54
Myths and Misconceptions AboutChronic Constipation
Misconception RealityDiseases 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.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
9/54
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 colonic
transit
Laxatives are
addictive
No potential for addiction to laxatives, but laxatives
may be misused
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
10/54Brandt LJ, et al.Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
Chronicconstipation
(-)Abdominal Pain
IBS withconstipation
(+)Abdominal Pain
Presence or absence of abdominal pain is themajor differentiating feature
Abdominal Pain: Salient FeatureAbsent in Chronic Constipation
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
11/54
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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
12/54
ROME III CLASSIFICATION
Symptom onset at least 6 months beforediagnosis
Recurrent abdominal pain or discomfort atleast 3 days a month in the past 3 months,
associated with two or more of thefollowing
Improvement with defecation
Onset associated with a change in frequency ofstool Onset associated with a change in form
(appearance) of stool
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
13/54
Clinical CC & IBS-C :
Functional Gastrointestinal diseases(FGID)
Patomechanism motility disorders
The same clinical symptoms but IBS-Cwith abdominal pain
CC slow & weak motility but IBS-C
segmental spasm IBS-C strongly related to QOL
Psychological factors influence of IBS-C
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
14/54
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.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
15/54
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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
16/54
Diagnosis :
Diagnosis of IBS-C based on Romecriteria
Diagnosis of CC depend onlongstanding constipation withouttypical clinical symptom
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
17/54
Consider Secondary Causes
Constipation
Gastrointestinal
Colorectal: 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.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
18/54
Treatment CC & IBS-C :
According to pathophysiology
Clinical diagnosis very important to choosethe treatment
Wrong choice of treatment will be worseclinical symptoms
Treatment of CC with prokinetic or
stimulant laxative Treatment of IBS-C with anti spasmodic
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
19/54
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 effectivetherapeutic management of drugs in anindividual patient.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
20/54
Pharmacodynamics
refers to the relationship between drugconcentration at the site of action and the
resulting effect, including the time courseand intensity of therapeutic and adverseeffects
The effect of a drug present at the site ofaction is determined by that drugs bindingwith a receptor.
Definition PD :
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
21/54
Relationship of pharmacokinetics andpharmacodynamics and factors that affecteach.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
22/54
Mode of action different laxatives
Lissner, AGH 2012; 3:(1)
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
23/54
Classification of laxatives :
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
24/54
Bisacodyl pharmacodynamics
Bisacodyl, a stimulant laxative, ishydrolyzed by intestinal brush borderenzymes and colonic bacteria to form an
active metabolite [bis-(p-hydroxyphenyl)pyridyl-2 methane; (BHPM)] that actsdirectly on the colonic mucosa to produce
colonic peristalsis.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
25/54
Bisacodyl pharmacokinetics :
The osmotic activity of HalfLytely solutionresults in no net absorption or excretion ofions or water
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
26/54
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.
L ti
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
27/54
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 mineraloil PhillipsM-O
StoolSofteners
Docusate sodiumColace, DulcolaxStool Softener, PhillipsLiqui-Gels
Saline Magnesium hydroxide (milk of magnesia)Ex-LaxMilk of Magnesia Laxative/AntacidPhillipsChewable TabletsPhillipsMilk of Magnesia
Stimulant
Bisacodyl Ex-Lax Ultra, Dulcolax Bowel Prep Kit
Sodium bicarbonate and potassium bitartrate Ceo-Two Evacuant
Sennosides Ex-LaxLaxative Pills
Castor oil Purge
Senna Senokot
Osmotic Polyethylene glycol 3350 GlycoLax
, MiraLAX
Lactulose Kristalose
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
28/54
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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
29/54
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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
30/54
Patients self assesment for quality of life (QOL)
Bisacodyl increase QOL from patients with constipationrecovery bowel habit every day . 80% patients have satisfied withBisacodyl.
0
10
20
30
40
50
60
Good Satisfactory Not
satisfactory
Bad
Percentageofpatients
PBO
BIS
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
31/54
No AlarmSymptoms
AlarmSymptoms
Directed testing
Refer to a specialistas needed
Continue
regimen
+ Response
Suggested Management Algorithm forChronic Constipation
OTC = over-the-counter therapies (probiotics, herbal medications, stool softeners[docusate sodium], psyllium, methylcellulose, calcium polycarbophil, bisacodyl, senna)
Bleeding, anemia,weight loss,sudden change instool caliber,abdominal pain
No response
Lifestyle, OTC, stimulant laxative
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
32/54
Conclusions (1) :
Chronic Constipation is a functional GIdisorder consists of 2 types CIC and IBS-C
Differences in clinical symptoms of IBS-Cand CC are abdominal pain in IBS-C
Pathophysiology is a motility disorder, CCwith hipomotility and IBS-C with
segmental spasm
Diagnosis is based on history of illnessrefer to Rome criteria
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
33/54
Treatment for CC with prokinetic orstimulant laxative & IBS-C withantispasmodic as primary drug
Reassured he patient that the disease isnot harmful & need longstandingtreatment to improve QOL
Development of new treatments notmedically further research is still needed
Conclusions (2) :
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
34/54
Paediatric constipation
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
35/54
Constipation Prevalence
Journal of Pediatrics 2005;146:359-63
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
36/54
Classification of Pediatric constipation
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
37/54
Delayed passage of meconium
Intestinal Obstruction / AnatomicalMalformation
Hirschsprungs Disease
Meconium Ileus Functional Ileus
Small left colon
Maternal Drugs Hypothyroidism
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
38/54
Normal Frequency of Bowel Movements
Journal of Pediatric Gastroenterology & Nutrition. 43(3):e1-e13, September 2006.
Evaluation and Treatment of Constipation in Infants and Children: Recommendationsof the North American Society for Pediatric Gastroenterology, Hepatology and
Nutrition.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
39/54
Functional vs. Organic -- Functional
Over 95% of Constipated children has functionalconstipation
Functional: persistent, difficult, infrequent, or
seemingly incomplete defecation without evidence ofunderlying structural or metabolic defect
Most commonly due to with-holding after a painful bowelmovement
Presents most commonly at three age periods
At introduction of cereals and solid foodsAt toilet training
At the start of school
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
40/54
Functional Constipation
Classic History Child has a painful bowel movement
When urge to have a bowel movement happens, thechild 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 oftenwill hide in a corner
Eventually, the rectum habituates to the stimulus of the
enlarging fecal mass, the urge to defecate subsides, andthe retentive behavior becomes almost second nature orsubconscious
Can develop soiling (encopresis)
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
41/54
Evaluation of Constipation
Evaluation and Treatment ofConstipation in Infants and Children:
Recommendations of the North
American Society for PediatricGastroenterology, Hepatology and
Nutrition.
Journal of Pediatric Gastroenterology & Nutrition. 43(3):e1-e13, September 2006.
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
42/54
Overall approach to management
Determine whether fecal impactionpresent
Treat impaction if present
Initiate treatment with oral medications
Provide parental education
Close follow up
Adjust medications as necessary
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
43/54
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
44/54
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
45/54
SPS untuk Konstipasi Kronis Pada Anak*
Kozaki T. Journal of New Remedies and Clinics. 1976;25(6): 1009-1012.
0
10
20
3040
50
60
70
80
90
Sangat efektif Efektif Tidak efektif
%pasien
Efikasi SPS Pada Konstipasi Anak
Keterangan:
Sangat efektif : Defekasi terjadi dalam sehariEfektif: Defekasi terjadi dalam 2 hariTidak efektif: Tidak terjadi defekasi setelah 3 hari ataulebih
Sodium picosulfate (SPS)efektif mengatasi
konstipasi pada anakpada lebih dari 83%
pasien. Dengan bentuktetes, tidak berwarna,tidak berbau, dan tidak
berasa, sodiumpicosulfate lebih mudahuntuk diberikan pada
pasien anak-anak.
*sodium picosulfate cocok untuk anak di atas 4 tahun
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
46/54
Toilet Hygiene
Dynamics
of the
AnorectalAngle
Anorectal Angle in Action
Twice a day for 10-15minutes after breakfastand dinner
Gastrocolic reflex
Sit up straight Thighs parallel to ground
Good foot support
Valsalva maneuver toincrease abd pressure
Blow up balloon No distractions
Reasonable reward system
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
47/54
Enema
Fleets Phosphosoda enema < 2 YO not recommended 24 YO = 33.75 ml (1/2 of a Pediatric Fleets enema
)
5-11 YO = 67.5 ml (full Pediatric Fleets enema) 12 YO and up118 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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
48/54
Lactulose
Second line in infants < 6 mo not responding tojuice
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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
49/54
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 orroughly 1 g/kg/day in younger child, consider adding astimulant laxative, re-education, or referral
S l T t t i f
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
50/54
Sample Treatment regimen forolder child (non infant)
Start Miralax at discussed doses
Increase or decrease dose by small amounts untildesired 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 agood 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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
51/54
Long Term Outcome of Constipation
Gastroenterology 2003;125:357-363
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
52/54
Stimulants
Senna Comes 8.8 mg/5ml or 8.8 mg tabs
2-6 YO2.5 to 7.5 ml a day 6-12 YO5-15 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
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
53/54
Summary
Functional constipation mostly found inchildren
Kind of laxative use depend on age of child
Training must be done beside laxativedrugs
Laxative therapy is the initial step furthertoilet training should be conducted on anongoing basis
-
7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan
54/54
hank you very much
for your kind attention