adult and children constipation the role of laxative therapy - chudahman manan

7/23/2019 Adult and Children Constipation the Role of Laxative Therapy - Chudahman Manan

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Chudahman Manan

Indonesian Society of Gastroenterology

Adult and Children Constipation

The role of laxative therapy


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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.


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oData from RSCM-Jakarta during

1998-2005, 2.397 colonoscopy exam ,

216 (9%) indication for constipationoGender comparative women and men

(4 : 1)

Introduction (2) :


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Drossman, DA; Gastro 2006

LIFEGenetics

Environment

Social Context


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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 :


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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


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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.


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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.


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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 colonic

transit

Laxatives are

addictive

No potential for addiction to laxatives, but laxatives

may be misused


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


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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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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


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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


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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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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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Diagnosis :

Diagnosis of IBS-C based on Romecriteria

Diagnosis of CC depend onlongstanding constipation withouttypical clinical symptom


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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.


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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


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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.


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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 :


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Relationship of pharmacokinetics andpharmacodynamics and factors that affecteach.


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Mode of action different laxatives

Lissner, AGH 2012; 3:(1)


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Classification of laxatives :


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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.


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Bisacodyl pharmacokinetics :

The osmotic activity of HalfLytely solutionresults in no net absorption or excretion ofions or water


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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.

L ti


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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 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


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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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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


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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


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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


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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) :


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Paediatric constipation


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Constipation Prevalence

Journal of Pediatrics 2005;146:359-63


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Classification of Pediatric constipation


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Delayed passage of meconium

Intestinal Obstruction / AnatomicalMalformation

Hirschsprungs Disease

Meconium Ileus Functional Ileus

Small left colon

Maternal Drugs Hypothyroidism


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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.


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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


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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)


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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.


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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


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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


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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


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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


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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


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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


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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


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Long Term Outcome of Constipation

Gastroenterology 2003;125:357-363


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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


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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


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hank you very much

for your kind attention

adult and children constipation the role of laxative therapy - chudahman manan

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