Transcript GAPNA Chapter Meeting Content Chronic Constipation and IBS-C

Practical Approaches Towards Improving
Patient Outcomes for Chronic Constipation
and Irritable Bowel Syndrome With
Constipation (IBS-C) Among Older Adults
Educational Learning Objectives
•
Describe the elements of proper diagnosis and follow-up management of
chronic constipation (CC) in older adults
•
Demonstrate awareness of the prevalence of irritable bowel syndromeconstipation (IBS-C) in older adults and the elements of differential
diagnosis from CC
•
Discuss how management of CC and IBS-C varies based upon underlying
etiologies and across the spectrum of older adults, from the active
community dweller to the compromised long term care resident with multiple
comorbidities
•
List common patient perceptions of constipation and describe how these
may impact progress towards practitioners' clinical goals in CC and IBS-C
•
Identify patient education and counseling strategies that will allow advanced
practice nurses (APN) to collaborate with patients and family members in
the successful management of CC and IBS-C in older adults
How Do We Define Constipation?
• The American College of Gastroenterology (ACG)
definition of constipation:
– 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
• The ACG Chronic Constipation Task Force also
clarified what is meant by chronic:
– 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.
GI Symptoms Are Common
in the Older Population
• 35% to 40% of geriatric patients will have at least 1 GI
symptom in any year
– Constipation, fecal incontinence, diarrhea, irritable bowel
syndrome, reflux disease, and swallowing disorders
• Prevalence rates for constipation in the older adult
population range from approximately 19% to 40%
– Day Hospitals/Living at Home: 25–40%
– Nursing Homes/Geriatric Hospitals: 60–80%
• Irritable bowel syndrome presents in ~10% of the older
population
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
Ginsberg D, et al. Urol Nursing. 2007;27:191-200.
Morley J. Clin Geriatr Med. 2007;23:823-832.
Overlap Between Common Disorders
Bloating
Belching
Constipation
Chronic
Constipation
Dyspepsia
IBS
Discomfort
GERD
Heartburn
Brandt L, et al. Am J Gastroenterol. 2005;100(S1):5-22.
Abdominal
Pain
Regurgitation
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
40
Population (%)
35
30
25
25-40
2-28
28
25
3-20
20
6-18
15
10
8
8
5
0
Chronic
Dyspepsia Functional
GERD
Heartburn Constipation
IBS
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.
Hyper- Migraine Asthma Diabetes
tension
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
10
25
Harari, et al
Population: NHIS 1989
Criteria: self-report
20
8
6
4
2
Prevalence of
Constipation (%)
Prevalence of
Constipation (%)
12
Study 1
N = 42,375
0
NHIS = National Health Interview Survey
Higgins PDR, et al. Am J Gastroenterol. 2004;99:750-759.
Women
15
10
5
0
Age Group (years)
Men
Study 2
Study 3
Study 4
N = 5,430
Drossman
N = 1,149
Pare
N = 10,018
Stewart
Sex
Chronic Constipation Interferes with
Daily Lives of the Aging Population
Constipation
No GI symptoms
Mean MOS Score
100
80
60
40
20
0
Physical
Role
Functioning Functioning
Social
Functioning
Mental
Health
Health
Perception
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.
Bodily
Pain
Economic Impact of Constipation
• 2.5 million office visits annually
• 92,000 hospital admissions
• 85% are given prescriptions for laxatives or cathartics
• $400 million dollars spent in annually for prescription laxatives
• $2253 average cost per long term care resident
Economic Burden of Irritable Bowel Syndrome
• IBS care: > $20 billion direct and indirect expenditures
• Patients with IBS consume > 50% more health care costs than
matched controls without IBS
Tariq S. J Am Med Dir Assoc. 2007;8:209-218.
Ginsberg D, et al. Urol Nursing. 2007;27(3):191-201.
ACG IBS Task Force. Am J Gastroenterol. 2009;104:S1-S35.
Normal Physiology of Defecation
•
•
•
•
Increased abdominal pressure or propulsive colorectal contractions
Relaxation of internal anal sphincter (autonomic)
Relaxation of external anal sphincter (voluntary)
Straightening of pelvic musculature (levator ani, puborectalis)
At 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.
With straining
Mediators of Gastrointestinal Function
Motility
Serotonin
Acetylcholine
Nitric oxide
Substance P
Vasoactive intestinal peptide
Cholecystokinin
Corticotropin releasing factor
Visceral Sensitivity
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.
Rome III Diagnostic Criteria*
for Functional Constipation
Chronic constipation must include 2 or more of the following:
During at least 25% of defecations
Straining
Lumpy or
hard
stools
Sensation
of
incomplete
evacuation
Sensation of
anorectal
obstruction/
blockage
Manual
maneuvers
to facilitate
defecations

Loose stools are rarely present without the use of laxatives

Insufficient criteria for irritable bowel syndrome
<3
defecations
per week
*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.
Primary Causes of
Chronic Constipation
• Normal-transit constipation
• Slow-transit constipation
• Defecatory dysfunction
• 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.
Primary Constipation
• 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
• 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
• 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
[Role for biofeedback therapy]
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
• 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.
% Hard or Lumpy Stools
Subtypes of IBS
100
75
50
IBS-C
IBS-M
25
IBS-U
0
IBS-C: IBS with constipation
IBS-U: Unsubtyped IBS
IBS-M: IBS mixed
IBS-D: IBS with diarrhea
IBS-D
25
50
75
% Loose or Watery Stools
Longstreth G, et al. Gastroenterology. 2006;130:1480-1491.
100
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
–
–
–
–
Parkinson’s disease
Dementia
Diabetes mellitus
Depression
• Polypharmacy (both over the counter and prescription
medications, such as NSAIDs, antacids, antihistamines,
iron supplements, anticholinergics, opiates, Ca channel
blockers, diuretics, antipsychotics, anxiolytics,
antidepressants)
Common Changes with Aging that
Increase the Risk for Constipation
•
•
•
•
•
•
•
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.
Patient Care
• Thorough patient history
• Physical/abdominal/digital rectal exams
• Evaluate symptoms in terms of diagnostic criteria
– Chronic constipation/IBS-C
• Assessment for red flags/alarm features
– Need for additional testing
• Treatment/Management plan
Ask the Right Questions
•
•
•
•
•
•
•
•
•
•
•
Define the meaning of “constipation”
How long have you experienced these symptoms?
Frequency of bowel movements?
Abdominal pain?
Other symptoms?
What is most distressing symptom?
Manual maneuvers to assist with defecation?
Any limitation of daily activities?
Are you taking any medications?
What treatment have you tried?
What investigations have been done?
Locke GR III, et al. Gastroenterology. 2000;119:1761-1778.
90
Common Patient Descriptions
of Constipation
81
Percent of Patients
80
72
Physicians think:
< 3 BM per week
70
60
54
50
39
40
37
36
28
30
20
10
0
Straining
Hard or Incomplete
lumpy
emptying
stools
N = 1149
Pare P, et al. Am J Gastroenterol. 2001;96:3130-3137.
Stool Abdominal < 3 BM
per
cannot fullness or
bloating
week
be
passed
Need to
press on
anus
Stool Form Correlates With
Intestinal Transit Time
The Bristol Stool Form Scale
Slow Transit
Fast Transit
Type 1
Separate hard lumps
Type 2
Sausage-like but lumpy
Type 3
Sausage-like but with cracks
in the surface
Type 4
Smooth and soft
Type 5
Soft blobs with clear-cut edges
Type 6
Fluffy pieces with ragged edges,
a mushy stool
Type 7
Watery, no solid pieces
O’Donnell LJD, et al. BMJ. 1990;300:439-440.
Consider Secondary Causes
Psychological
Depression
Eating disorders
Drugs
Surgical
Abdominal/pelvic surgery
Colonic/anorectal surgery
Lifestyle
Inadequate fiber/fluid
Inactivity
Constipation
Metabolic/
Endocrine
Hypercalcemia
Hyperparathyroidism
Diabetes mellitus
Hypothyroidism
Hypokalemia
Uremia
Addison’s
Porphyria
Opiates
Antidepressants
Anticholinergics
Antipsychotics
Antacids (Al, Ca)
Ca channel blockers
Iron supplements
Gastrointestinal
Neurological
Parkinson’s
Multiple sclerosis
Autonomic neuropathy
Aganglionosis
(Hirschsprung’s, Chagas)
Spinal lesions
Cerebrovascular disease
Candelli M, et al. Hepatogastroenterology. 2001;48:1050-1057.
Locke GR, et al. Gastroenterology. 2000;119:1761-1766.
Systemic
Amyloidosis
Scleroderma
Polymyositis
Pregnancy
Colorectal: neoplasm,
ischemia, volvulus,
megacolon,
diverticular disease
Anorectal: prolapse,
rectocele, stenosis,
megarectum
Digital Rectal Exam
• Place patient in left lateral recumbent position
• Visually inspect the perianal region
– Fissures, hemorrhoids, masses, skin tags, or evidence of
previous surgery, skin lesions
• Stroke the perianal skin to elicit a reflex contraction of
the external anal sphincter
• Assess for paradoxical pelvic floor contraction
(suggestive of pelvic floor descent)
• Perform a digital assessment
– Strictures, masses, a rectocele, and hemorrhoids
– Examine stool for color and consistency
– Check for occult blood
Rao SSC. Gastroenterol Clin North Am. 2003;32:659-683.
Locke GR III, et al. Gastroenterology. 2000;119:1761-1778.
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
New-onset constipation in an elderly patient
Locke GR III, et al. Gastroenterology. 2000;119:1761-1778.
Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
ACG Task Force Recommendations
on Diagnostic Testing
• ACG task force does not recommend diagnostic testing
in patients without alarm signs or symptoms
– BUT routine colon cancer screening recommended for all
patients aged ≥ 50 years (African Americans aged ≥ 45 years)
• Diagnostic studies are indicated in patients with alarm
signs or symptoms
• Thyroid function tests
• Measurements of
– Calcium
– Electrolytes
Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
Agrawal S, et al. Am J Gastroenterol. 2005;100:515-523.
Diagnostic Tests That
May Be Performed After a Referral
Test
Anorectal
manometry
Balloon
expulsion
Defecography
Colonic transit
study
Colonoscopy
Use
Assesses the internal and external anal sphincters, pelvic floor, and
associated nerves
Screening test of choice for dyssynergic defecation
Detects defecatory disorders
Simple, office-based screening test
Detects structural abnormalities of the rectum
Operator dependent, poor reliability, not widely available
Measures rate at which fecal mass moves through colon
Provides a visual diagnosis while performing biopsies with detection
and removal of polyps
Rao SSC, et al. Am J Gastroenterol. 2005;100:1605-1615.
Lembo A, Camilleri M. N Engl J Med. 2003;349:1360-1368.
Winawer S, et al. Gastroenterol. 2003;124:544-560.
Differentiating Between
Occasional and Chronic Constipation
Occasional Constipation
Chronic Constipation
Infrequent
Present for at least 3 months and
may persist for years
Occasional or short-term
condition that may temporarily
interrupt usual routine
Long-term condition that may
dominate personal and work life
May be brought on by patient’s
behavior, change in diet, lack of
exercise, illness, or medication
Not only related to patient’s
behavior, change in diet, lack of
exercise, or medication
May be relieved by diet, exercise,
and over-the-counter (OTC)
medication
May need medical attention and
prescription medication
Lifestyle Modifications
Modification
Targeted Mechanism
Efficacy
Increase fluid
intake
Increase stool volume by augmenting
luminal fluid
Limited; majority of fluid
is absorbed before
reaching the colon and is
expelled via urine
Increase
exercise
Improve motility by decreasing transit time
through the GI tract
Moderate; some
evidence suggests this is
beneficial; however, not
sufficient to treat
Increase dietary
fiber
Increase water and bulk stool volume
Limited benefit compared
with placebo
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.
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
Osmotic Laxatives
[saline, poorly absorbed mono- and disaccharides, polyethylene
glycol]
Stimulant
Laxatives
Cause rhythmic muscle contractions in the intestines, increase
intestinal motility and secretions
Lubricants
Coats the bowel and the stool mass with a waterproof film; stool
remains 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 allows
the 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 stimulant
laxative
Gallagher P, et al. Drugs Aging. 2008;25:807-821.
Laxatives
Laxative Type
Bulk-forming
Lubricating
Stool Softeners
Saline
Stimulant
Osmotic
Generic Name
Brand Name(s)
Methylcellulose
Citrucel®
Polycarbophil
FiberCon®, Fiber-Lax®
Psyllium
Metamucil®, Konsyl®
Glycerin
Glycerin suppository (generic)
Mineral oil
Mineral oil (generic)
Magnesium hydroxide (milk of magnesia) and mineral
oil
Phillips’® M-O
Docusate sodium
Colace®, Dulcolax® Stool Softener, Phillips’
Liqui-Gels®
Magnesium hydroxide (milk of magnesia)
Ex-Lax® Milk of Magnesia Laxative/Antacid
Phillips’® Chewable Tablets
Phillips’® Milk of Magnesia
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®
Polyethylene glycol 3350
GlycoLax®, MiraLAX
Lactulose
Kristalose®
Bulk Laxatives:
Review of Efficacy
Laxative
Psyllium
Studies
• 5 RCTs:
– 3 placebo
controlled
– 1 well
designed
Bran
• 3 RCTs:
– 1 placebo
controlled
– All poorly
designed
Evidence
• 2 trials: greater stool
frequency, better stool
consistency, and greater
ease of defecation
Summary and
Recommendation
Psyllium appears to
improve stool
frequency and
consistency
• 1 trial: no improvement
• Stool frequency was
significantly greater with
bran than placebo if
placebo was given first,
but not if bran was given
first
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
GRADE B
Insufficient data to
make a
recommendation
Stool Softeners and Stimulant Laxatives:
Review of Efficacy
Laxative
Docusate
Studies
• 4 RCTs:
– 2 placebo
controlled
– 3 well
designed
Stimulant
laxatives
• 4 RCTs:
– None
placebo
controlled
– Low-quality
study design
Evidence
Summary and
Recommendation
• 1 trial: greater stool
frequency
Insufficient data to make
recommendation
• 1 trial: greater stool
frequency and global
symptom assessment
Docusate may be inferior
to psyllium in increasing
stool frequency
• 2 trials: no improvement (1 vs
placebo, 1 vs psyllium)
• In 3 studies, no difference
Not possible to make a
between stimulant laxative
recommendation about
and control in stool frequency efficacy
or consistency
• 1 trial: less efficacy compared
with lactulose at increasing
stool frequency
RCT = randomized controlled trial
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
Osmotic Laxatives:
Review of Efficacy
Laxative
Lactulose
Polyethylene
Glycol (PEG)
Studies
• 3 RCTs:
Evidence
• All trials favor lactulose
– All placebo
controlled
• Significantly improved
stool consistency
– 2 well
designed
• Mean number of BM/day
significantly greater vs
placebo
• Increased stool
frequency and
improvement in stool
consistency vs. placebo
• 5 placebocontrolled
RCTs
• 2 RCTs
comparing
PEG and
lactulose
• Stool frequency greater,
straining less often,
overall effectiveness
higher vs. lactulose
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
Summary and
Recommendation
Effective at improving
stool frequency and
stool consistency
GRADE A
Effective at improving
stool frequency and
stool consistency
GRADE A
PEG 3350 – 12-Month Study
An Open-Label, Single Treatment Multi-Centre Study of
311 Patients (117 aged 65 and older)
100
completely relieved
somewhat relieved
unchanged
Percentage of Patients
90
80
70
60
46
50
52
49
50
40
40
30
20
10
0
Visits
16
15
14
11
10
4
3
3
1
1
2 months
N = 250
4 months
N = 217
6 months
N = 203
9 months
N = 185
12 months
N = 180
PEG 3350 was determined safe and effective for treating constipation in adult older
patients for periods up to 12 months, with no signs of tachyphylaxis
Di Palma J. Ailment Pharmacol Ther. 2006;25;703-708.
Adverse Effects of Laxatives
• Bulking agents
– Bloating
– Severe adverse events: esophageal and colonic obstruction,
anaphylactic reactions
• Osmotic laxatives
– Possible electrolyte abnormalities, hypovolemia
– Diarrhea (2% to 40% of PEG-treated patients)
– Excessive stool frequency, nausea, abdominal bloating,
cramping, flatulence
• Stimulant laxatives
– Abdominal discomfort, electrolyte imbalances, allergic reactions,
hepatotoxicity
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
Dangers of Saline Laxatives
in the Elderly
• Oral sodium phosphate products [Visicol®, OsmoPrep®,
Fleet* Phospho-soda] for bowel cleansing
• Black box warning for Visicol®, OsmoPrep®
• Acute phosphate nephropathy
• Patients with identifiable risk factors
–
–
–
–
–
Age > 55
Baseline kidney disease
Hypovolemic, reduced intravascular volume
Bowel obstruction, active colitis
Using medications that affect renal perfusion or function
*Withdrawn from the market
Available at: http://www.fda.gov/cder/drug/infopage/OSP_solution/default.htm. Accessed April 2009.
Are Patients Satisfied With
Laxatives and Fiber?
Dissatisfied Patients (%)
100
OTC laxatives
(n = 146)
Prescription laxatives
(n = 42)
80
71
75
Fiber
(n = 268)
80
79
66
67
60
60
50
50
52
50
44
40
20
0
Ineffective Relief
of Constipation
Ineffective Relief of
Multiple Symptoms
Lack of
Predictability
Johanson JF and Kralstein J. Aliment Pharmacol Ther. 2007;25:599-608.
Ineffective Relief
of Bloating
Lubiprostone:
A Chloride Channel Activator
• Gastrointestinal-targeted bicyclic
functional fatty acid
• Activates ClC-2 chloride channels
– Movement of Cl-, Na+, H2O follow
– Increased luminal fluid secretion
– Shortened colonic transit time
• Indicated for:
– Treatment of chronic idiopathic
constipation (24 µg BID) in the adult
population including age > 65 years
(FDA approval 2006)
– Treatment of irritable bowel syndrome
with constipation (8 µg BID) in women
≥ 18 years (FDA approval 2008)
Cuppoletti J, et al. Am J Physiol Cell Physiol. 2004;287:C1173-C1183.
Amitiza PI. Available at: http://www.fda.gov/cder/foi/label/2008/021908s005lbl.pdf. Accessed April 2009.
Lubiprostone: Stool Frequency in Patients
Over 65 with Chronic Constipation
Nonelderly lubiprostone 48 µg
Elderly (≥ 65 years) lubiprostone 48 µg
Nonelderly placebo
Elderly placebo
Change from Baseline
in SBM Frequency
6
5
*
*
†
*
†
*
*P ≤ 0.03
†P < 0.0001
†
4
N = 57 (patients aged
≥ 65 years vs placebo)
3
2
1
0
Week 1
Week 2
Week 3
Week 4
SBM = spontaneous bowel movement
Ueno R, et al. Annual Meeting of the American College of Gastroenterology;
October 2006; Las Vegas, NV. Johanson J, et al. Am J Gastroenterol. 2008;103:170-177.
Safety Profile of Lubiprostone
• Well tolerated in 4 week and 6-12 month trials
• Nausea, diarrhea, and headache
• No clinically significant changes in serum
electrolyte levels
• Low likelihood of drug-drug interactions
– Non-absorbed; works intraluminally and does not
result in measurable blood levels
Available at: http://www.fda.gov/cder/foi/label/2008/021908s005lbl.pdf. Accessed April 2009.
Suggested Management Algorithm for
Chronic Constipation
Bleeding, anemia,
weight loss, sudden
change in stool
caliber, abdominal
pain
Alarm
Symptoms
Directed testing
Refer to a specialist as
needed
No Alarm
Symptoms
Lifestyle, OTC, stimulant laxative
No Response
+ Response
Trial of lactulose
or PEG 3350
No response
+ Response
Trial of lubiprostone
No response
+ Response
OTC = over-the-counter therapies (probiotics, herbal medications, stool softeners
[docusate sodium], psyllium, methylcellulose, calcium polycarbophil, bisacodyl, senna)
Continue
regimen
Treatment for IBS-C
Treatment
Recommendation
Psyllium
Moderately effective; single study reported improvement
with calcium polycarbophil
Wheat or corn
bran
No more effective than placebo in relief of global IBS
symptoms; Not recommended for routine use
Polyethylene
glycol
Shown to improve stool frequency, but not abdominal pain
in 1 small study
No publications of placebo-controlled, randomized studies
of laxatives in IBS-C
Antibiotics
Short-term course of a non-absorbable antibiotic is more
effective than placebo for global improvement of IBS and
for bloating. No data to support long-term safety and
effectiveness
Probiotics
In single organism studies, lactobacilli do not appear
effective for patients with IBS; bifidobacteria and some
probiotic combinations demonstrate some efficacy
ACG IBS Task Force. Am J Gastroenterol. 2009;104:S1-S35.
Treatment for IBS-C
Treatment
Antispasmodics
(hyoscine,
cimetropium,
pinaverium,
peppermint oil
Recommendation
Certain antispasmodics may provide short-term relief of
abdominal pain/discomfort
Evidence for long-term efficacy is not available; safety and
tolerability evidence is limited
Lubiprostone
8 µg BID is more effective than placebo in relieving global
IBS symptoms in women with IBS-C
Tricyclic
antidepressants
Selective serotonin
reuptake inhibitors
More effective than placebo at relieving global IBS
symptoms;
Appear to reduce abdominal pain
Limited data on safety and tolerability
Tricyclic antidepressants may worsen constipation
Psychotherapy
Cognitive therapy, dynamic psychotherapy, hypnotherapy
(not relaxation therapy) are more effective than usual care
in relieving global symptoms of IBS
ACG IBS Task Force. Am J Gastroenterol. 2009;104:S1-S35.
Lubiprostone for IBS-C
Data From 2 Phase 3 Studies
Placebo N = 385
Lubiprostone (8 µg BID) N = 769
Response Rate (%)
20
15
P = 0.001
Note the different dose!
For chronic constipation
lubiprostone: 24 µg BID
10
5
0
Combined intent to treat population
Monthly responder for ≥ 2/3 months during treatment
Drossman D, et al. Aliment Pharmacol Ther. 2009;29:329-341.
Lubiprostone – Symptom Change IBS-C
Mean Change from Baseline
Baseline Score
2.08
0
2.19
2.19
2.76
2.33
-0.2
-0.4
-0.6
-0.8
*
-1.0
-1.2
-1.4
*
Abdominal
Discomfort/Pain§
§Score:
†Score:
*
Bloating§
*
*
Constipation
Severity§
Stool
Consistency†
0 (absent); 1 (mild); 2 (moderate); 3 (severe); 4 (very severe)
0 (very loose/watery); 1 (loose); 2 (normal); 3 (hard); 4 (very hard/little balls)
Drossman D, et al. Aliment Pharmacol Ther. 2009;29:329-341.
Straining§
Nonresponder
Responder
* P < 0.001
When to Change/Add Therapy for an
Unresponsive Patient?
• No studies have examined this question1
• Stepped Treatment Of Older adults on Laxatives
(STOOL) trial was designed to investigate the efficacy of
adding a second agent when the first constipation
therapy failed2
– It closed early with only 19 enrolled participants
• In general, the prescribing clinician may elect to combine
therapy depending on the patient’s response and
lingering symptoms; recommended more often for
patients with severe symptoms
• Combine agents with different mechanisms of action,
such as lubiprostone with senna, or an antispasmodic
with a laxative for IBS-C
1. Gartlehner G, et al. Available at: http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/constip/pdfconstip.pdf. 2007.
Accessed April, 2009.
2. Mihaylov S, et al. Health Technol Assess. 2008;12(13).
Post-Stroke Patient
Special Considerations
• Recent studies have reported constipation in 55% of patients at the
acute stage (4 weeks)1, and in 30% ≥ 3 months2 following stroke
• Patient limitations
– Positioning problems
– Reduced peristalsis
– Immobility
Treatment Strategy*
1. Appropriate assessment of bowel function, frequency, consistency
2. Tailor a specific bowel management program to facilitate/initiate
defecation
3. Careful documentation with a bowel diary
4. Glycerin suppositories, laxatives, motility agents to promote
defecation
*Treatment strategy based on clinical experience
1.
2.
Su Y, et al. Stroke. 2009;40:1304-1309.
Bracci F, et al. World J Gastroenterol. 2007;13(29):3967-3972.
Patient With Dementia
Contributing Factors
•
•
•
•
•
•
•
•
•
•
Immobility
Dehydration
Inadequate food intake
Depression
Cognitive deficits
Cannot find the bathroom
Inability to undress
Cannot ask for help
Cannot sense the urge to defecate
Use of psychotropic drugs
Treatment Strategy*
1.
2.
3.
4.
5.
6.
Appropriate assessment of bowel function
Establish a bowel routine, regular toileting program
Suppositories, stool softeners, bulking agents
Careful documentation (bowel diary, effectiveness of treatments, etc.)
Involve family or health care team (in a nursing facility)
Address nutritional/fluid needs
*Treatment strategy based on clinical experience
Patients Treated With Opiates
Special Considerations
• Opioids inhibit GI propulsive motility and secretion
• GI effects of opioids are mediated primarily by µ-opioid receptors within the
bowel
• Constipation is a common and troubling side effect
• Patients do not develop tolerance to the effects of opiates on the bowel
Treatment Strategy*
1. Laxative therapy should be initiated proactively with start of opiate use
2. Magnesium hydroxide, senna, lactulose, bisacodyl, stool softener
3. A combination of a stimulant and stool softener is often required
4. Laxative doses may need to be increased along with increased doses of
opioids
5. Titrate doses of laxatives according to response prior to changing to an
alternative laxative
6. When laxative therapy is inadequate, consider methylnaltrexone
*Treatment strategy based on clinical experience
Tamayo A, Diaz-Zuluaga P. Support Care Cancer. 2004;12:613-618.
Shaiova L, et al. Palliat Supp Care. 2007;5:161-166.
A Role for Peripheral µ-opioid
Receptor Antagonists?
• Methylnaltrexone
– Novel, quaternary µ-opioid receptor antagonist
– Does not antagonize the central (analgesic) effects of opioids or
precipitate withdrawal
– FDA approved for treatment of opioid-induced constipation in
patients with advanced illness, receiving palliative care, when
laxative therapy has been inadequate
– Subcutaneous injection; one dose (0.15 mg/kg) every other day
as needed, no more than 1 dose in a 24 hr period
– Abdominal pain and flatulence most common adverse events
Foss JF. Am J Surg. 2001;182 (5ASuppl):19S-26S.
Thomas J, et al. New Engl J Med. 2008;358:2332-2343.
Relistor [package insert]. Available at:
http://www.wyeth.com/content/showlabeling.asp?id=499. Accessed April 2009.
Neurologic Disorders: Parkinson’s Disease
Special Considerations
• Constipation occurs in at least 2/3 of patients
• Multifactorial:
– Slow colonic function
– Defecatory dysfunction
– Enteric and central nervous system
– Antiparkinsonian medications
 Anticholinergic agents
 Dopaminergic agents
• Underlying illness is chronic and uncorrectable
Treatment Strategy*
1. Adjust medications if possible
2. Initiate pharmacologic therapy
– May need to use medications from several classes
– Osmotic laxatives, Cl channel activators, stimulant laxatives
*Treatment strategy based on clinical experience
Stark ME. Am J Gastroenterol. 1999;94:567-574.
Chronic Constipation
Secondary to Diabetes
Special Considerations
• Constipation occurs in 20% of patients with diabetes
• Related to duration of diabetes > 10 years
• Diabetic autonomic neuropathy
• Gastrocolic reflex may be absent, delayed, blunted
• 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.
Complications of
Chronic Constipation
• Fecal impaction1,2
– Identified in up to 40% of elderly adults hospitalized in United
Kingdom
• Intestinal volvulus/obstruction2
• Urinary and fecal incontinence2
• Stercoral ulceration/ischemia2
• Bowel perforation2
• Possible increased risk of colorectal cancer
(controversial)3,4
1.
2.
3.
4.
Read NW, et al. J Clin Gastroenterol. 1995;20:61-70.
De Lillo AR, Rose S. Am J Gastroenterol. 2000;95:901-905.
Roberts MC, et al. Am J Gastroenterol. 2003;98:857.
Dukas L, et al. Am J Epidemiol. 2000;151:958-964.
Fecal Impaction
Recognition/Identification
• Maintain high level of vigilance for institutionalized patients or
patients in the hospital
– Absence of bowel movement, absence of bowel sounds
– Fecal soiling, fecal incontinence of liquid stool
• Assessment
– Digital rectal exam
– Abdominal x-ray
Treatment Strategy*
1. Prevention!!
2. Treat from below
• Enema, suppository
• Manual disimpaction with prior pain medication
3. Treat from above
• Osmotic laxatives
4. Institution of preventative measures
• Diet, laxatives, bowel regimen
*Treatment strategy based on clinical experience
Emerging Therapies
Prucalopride
–
–
–
–
Selective 5-HT4 agonist
Does not interact with 5-HT3 or 5-HT1B receptors
Increases colonic motility and transit
Phase 3 studies have demonstrated efficacy of 2 or 4 mg prucalopride
in patients with severe chronic constipation
– Adverse events included headache, abdominal pain, nausea, diarrhea
Linaclotide
– Guanylate cyclase agonist
– Induces intestinal fluid secretion
– Pilot study showed improved spontaneous bowel movement frequency
and improved symptoms in patients with chronic constipation
– Also being studied in patients with IBS-C
Camilleri M, et al. New Engl J Med. 2008;358:2344-2354.
Quigley E, et al. Aliment Pharmacol Ther. 2009;29:315-328.
Tack J, et al. Gut. 2009;58:357-365.
Johnston J, et al. Am J Gastroenterol. 2009;104:125-132.
Myths and Misconceptions About
Chronic Constipation
Misconception
Reality
Diseases arise from
autointoxication by retained • No evidence to support this theory
stools
Fluctuations in hormones
contribute to constipation
• 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 diet poor in fiber causes
constipation
• 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
Increasing fluid intake is a
successful treatment for
constipation
• No evidence that constipation can be treated successfully
by increasing fluid intake unless there is evidence of
dehydration
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
Reality
Stimulant 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
Muller-Lissner S, et al. Am J Gastroenterol. 2005;100:232-242.
Patient and Caregiver Education
• Provide reassurance
• Engage patients/caregivers in a discussion of constipation
• Discuss medicines that can contribute to chronic
constipation
• Discuss criteria for diagnosis, share a diagnostic algorithm
• Utilize patient questionnaire/symptom log
• Discuss treatment options, including
– Common side effects
– How long a treatment might take to work
– Is it appropriate to request an alternative treatment?
• Answer questions!
• Emphasize the goals of treatment
– Improve symptoms
– Restore normal bowel function
– Improve quality of life
Summary
• Chronic constipation is a common condition in the elderly
• Quality of life in elderly patients is negatively affected by
the symptoms of chronic constipation and IBS-C
• Identify risk factors and secondary causes for constipation
• Be vigilant for red flags or alarm symptoms; directed
tested may be necessary
• 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
Summary (cont)
• Evidence-based therapeutic options for chronic constipation include
psyllium, lactulose, polyethylene glycol, and lubiprostone
• Psyllium, polyethylene glycol, antibiotics, probiotics, antispasmodics,
antidepressants, lubiprostone and psychotherapy are treatments for
IBS-C with varying degrees of efficacy
• Long-term safety and efficacy data needed for therapeutic options
for both chronic constipation and IBS-C, particularly in older (> 65)
adults
• Careful recognition, assessment, treatment, and monitoring can lead
to more effective patient-specific interventions that can reduce the
burden of chronic constipation or IBS-C