Practical Approaches Towards Improving Patient Outcomes for Chronic Constipation and Irritable Bowel Syndrome With Constipation (IBS-C) Among Older Adults
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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 syndrome-constipation (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.
Belching Dyspepsia
IBS
GERD
Chronic Constipation
Constipation
Heartburn Regurgitation
Bloating
Abdominal Pain
Discomfort
Overlap Between Common Disorders
Brandt L, et al. Am J Gastroenterol. 2005;100(S1):5-22.
Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
Chronic constipation
(-) Abdominal Pain
IBS with constipation
(+) Abdominal Pain
Presence or absence of abdominal pain is the major differentiating feature
Abdominal Pain: Salient Feature Absent in Chronic Constipation
Prevalence of Functional Gastrointestinal Disorders
25
25-40
40
3-20
2-28
0
5
10
15
20
25
30
35
40
45
Dyspepsia Functional Heartburn
Chronic Constipation
GERD IBS
Popu
latio
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.
Higgins PDR, et al. Am J Gastroenterol. 2004;99:750-759.
Age Group (years)
Prev
alen
ce o
f C
onst
ipat
ion
(%)
0 2 4 6 8
10 12
Study 1 N = 42,375
Harari, et al Population: NHIS 1989
Criteria: self-report
NHIS = National Health Interview Survey
Constipation Increases With Age and Is More Common in Women
Prev
alen
ce o
f C
onst
ipat
ion
(%)
Sex
N = 5,430 Drossman
N = 1,149 Pare
N = 10,018 Stewart
Study 2 Study 3 Study 4
Men Women
0
5
10
15
20
25
Chronic Constipation Interferes with Daily Lives of the Aging Population
100
80
60
40
20
0
Mea
n M
OS
Scor
e
Physical Functioning
Health Perception
Mental Health
Social Functioning
Role Functioning
Bodily Pain
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
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)
With straining 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.
Mediators of Gastrointestinal Function
Visceral Sensitivity Serotonin Tachykinins Calcitonin gene-related peptide Neurokinin A Enkephalins Corticotropin releasing factor
Kim DY, Camilleri M. Am J Gastroenterol. 2000;95(10):2698-2709.
Secretion Serotonin Acetylcholine
Motility Serotonin Acetylcholine Nitric oxide Substance P Vasoactive intestinal peptide Cholecystokinin Corticotropin releasing factor
Manual maneuvers to facilitate defecations
Sensation of anorectal
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
Sensation of
incomplete evacuation
Straining Lumpy or
hard stools
< 3 defecations
per week
Rome III Diagnostic Criteria* for Functional Constipation
Chronic constipation must include 2 or more of the following:
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
• Normal-transit constipation
• Slow-transit constipation
• Defecatory dysfunction
• IBS with constipation
Bosshard W, et al. Drugs Aging. 2004;21:911-930. Gallagher P, et al. Drugs Aging. 2008;25(10):807-821.
Primary Constipation
• Normal-transit Constipation – Intestinal transit and stool frequency are within the normal range – Most frequent type of constipation
Lembo A, Camilleri M. N Eng J Med. 2003;349:1360-1368.
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
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 • 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]
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 • 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
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.
Subtypes of IBS
Longstreth G, et al. Gastroenterology. 2006;130:1480-1491.
IBS-C IBS-M
IBS-U IBS-D
0 25 50 75 100
25
50
75
100
% Loose or Watery Stools
% H
ard
or L
umpy
Sto
ols
IBS-C: IBS with constipation IBS-U: Unsubtyped IBS IBS-M: IBS mixed IBS-D: IBS with diarrhea
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
Gallagher P, et al. Drugs Aging. 2008;25(10):807-821. Schiller L. Gastroenterol Clin N Am. 2001;30:497-515.
• 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
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.
Pare P, et al. Am J Gastroenterol. 2001;96:3130-3137.
N = 1149
Stool cannot
be passed
Perc
ent o
f Pat
ient
s Physicians think:
< 3 BM per week
Straining Hard or lumpy stools
Incomplete emptying
Abdominal fullness or
bloating
< 3 BM per
week
Need to press on
anus
81 72
54
39 37 36 28
0
10
20
30
40
50
60
70
80
90
Common Patient Descriptions of Constipation
Stool Form Correlates With Intestinal Transit Time
O’Donnell 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 with cracks in the surface
Smooth and soft
Soft blobs with clear-cut edges
Fluffy pieces with ragged edges, a mushy stool
Watery, no solid pieces
The Bristol Stool Form Scale
Consider Secondary Causes
Constipation
Gastrointestinal Colorectal: neoplasm,
ischemia, volvulus, megacolon,
diverticular disease Anorectal: prolapse, rectocele, stenosis,
megarectum
Drugs Opiates
Antidepressants Anticholinergics Antipsychotics
Antacids (Al, Ca) Ca channel blockers
Iron supplements
Metabolic/ Endocrine Hypercalcemia
Hyperparathyroidism Diabetes mellitus Hypothyroidism
Hypokalemia Uremia
Addison’s Porphyria
Psychological Depression
Eating disorders
Neurological Parkinson’s
Multiple sclerosis Autonomic neuropathy
Aganglionosis (Hirschsprung’s, Chagas)
Spinal lesions Cerebrovascular disease
Lifestyle Inadequate fiber/fluid
Inactivity
Surgical Abdominal/pelvic surgery Colonic/anorectal surgery
Systemic Amyloidosis Scleroderma Polymyositis Pregnancy
Candelli M, et al. Hepatogastroenterology. 2001;48:1050-1057. Locke GR, et al. Gastroenterology. 2000;119:1761-1766.
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?
Locke GR III, et al. Gastroenterology. 2000;119:1761-1778. Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
• 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
Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21. Agrawal S, et al. Am J Gastroenterol. 2005;100:515-523.
• 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
ACG Task Force Recommendations on Diagnostic Testing
Diagnostic Tests That May Be Performed After a Referral
Test Use Anorectal manometry
Assesses the internal and external anal sphincters, pelvic floor, and associated nerves Screening test of choice for dyssynergic defecation
Balloon expulsion
Detects defecatory disorders Simple, office-based screening test
Defecography Detects structural abnormalities of the rectum Operator dependent, poor reliability, not widely available
Colonic transit study Measures rate at which fecal mass moves through colon
Colonoscopy 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
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
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.
Treating Constipation With Laxatives Laxative Description
Bulking Agents Absorbs liquids in the intestines and swells to form a soft, bulky stool; the increase in fecal bulk is associated with accelerated luminal propulsion
Osmotic Laxatives
Draws water into the bowel from surrounding body tissues providing a soft stool mass and improved propulsion [saline, poorly absorbed mono- and disaccharides, polyethylene glycol]
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 Generic 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
Stool Softeners Docusate sodium Colace®, Dulcolax® Stool Softener, Phillips’ Liqui-Gels®
Saline Magnesium hydroxide (milk of magnesia) Ex-Lax® Milk of Magnesia Laxative/Antacid Phillips’® Chewable Tablets Phillips’® 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®
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
Laxative Studies Evidence Summary and Recommendation
Psyllium • 5 RCTs: – 3 placebo
controlled – 1 well
designed
• 2 trials: greater stool frequency, better stool consistency, and greater ease of defecation
• 1 trial: no improvement
Psyllium appears to improve stool frequency and consistency
GRADE B Bran • 3 RCTs:
– 1 placebo controlled
– All poorly designed
• Stool frequency was significantly greater with bran than placebo if placebo was given first, but not if bran was given first
Insufficient data to make a recommendation
Bulk Laxatives: Review of Efficacy
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
Laxative Studies Evidence Summary and
Recommendation Docusate • 4 RCTs:
– 2 placebo controlled
– 3 well designed
• 1 trial: greater stool frequency • 1 trial: greater stool frequency
and global symptom assessment
• 2 trials: no improvement (1 vs placebo, 1 vs psyllium)
Insufficient data to make recommendation Docusate may be inferior to psyllium in increasing stool frequency
Stimulant laxatives
• 4 RCTs: – None
placebo controlled
– Low-quality study design
• In 3 studies, no difference between stimulant laxative and control in stool frequency or consistency
• 1 trial: less efficacy compared with lactulose at increasing stool frequency
Not possible to make a recommendation about efficacy
Stool Softeners and Stimulant Laxatives:
Review of Efficacy
RCT = randomized controlled trial
Laxative Studies Evidence Summary and
Recommendation Lactulose • 3 RCTs:
– All placebo controlled
– 2 well designed
• All trials favor lactulose • Significantly improved
stool consistency • Mean number of BM/day
significantly greater vs placebo
Effective at improving stool frequency and stool consistency
GRADE A
Polyethylene Glycol (PEG)
• 5 placebo-controlled RCTs
• 2 RCTs comparing PEG and lactulose
• Increased stool frequency and improvement in stool consistency vs. placebo
• Stool frequency greater, straining less often, overall effectiveness higher vs. lactulose
Effective at improving stool frequency and stool consistency
GRADE A
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
Osmotic Laxatives: Review of Efficacy
PEG 3350 – 12-Month Study
2 months N = 250
4 months N = 217
6 months N = 203
9 months N = 185
12 months N = 180
An Open-Label, Single Treatment Multi-Centre Study of 311 Patients (117 aged 65 and older)
Perc
enta
ge o
f Pat
ient
s
Visits
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.
Brandt LJ, et al. Am J Gastroenterol. 2005;100:S5-S21.
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
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.
Ineffective Relief of Constipation
Johanson JF and Kralstein J. Aliment Pharmacol Ther. 2007;25:599-608.
Ineffective Relief of Multiple Symptoms
Lack of Predictability
Ineffective Relief of Bloating
Dis
satis
fied
Patie
nts
(%)
OTC laxatives Prescription laxatives Fiber (n = 268) (n = 42) (n = 146)
44
60
71 67
50 50
75
52 50
66
79 80
0
20
40
60
80
100
Are Patients Satisfied With Laxatives and Fiber?
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.
• 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)
Lubiprostone: A Chloride Channel Activator
Lubiprostone: Stool Frequency in Patients Over 65 with Chronic Constipation
6
5
4
3
2
1
0
N = 57 (patients aged ≥ 65 years vs placebo)
Week 1 Week 4 Week 3 Week 2
Cha
nge
from
Bas
elin
e in
SB
M F
requ
ency
* * * *
*P ≤ 0.03 †P < 0.0001
Nonelderly lubiprostone 48 µg Nonelderly placebo
Elderly (≥ 65 years) lubiprostone 48 µg Elderly placebo
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.
† † †
SBM = spontaneous bowel movement
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.
No Alarm Symptoms
Alarm Symptoms
Directed testing Refer to a specialist as
needed Trial of lactulose or PEG 3350
Trial of lubiprostone
No Response
Continue regimen
+ Response
+ Response
+ Response
Suggested Management Algorithm for Chronic 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 in stool caliber, abdominal pain
No response
No response
Lifestyle, OTC, stimulant laxative
Treatment for IBS-C
ACG IBS Task Force. Am J Gastroenterol. 2009;104:S1-S35.
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
Treatment for IBS-C Treatment Recommendation
Antispasmodics (hyoscine, cimetropium, pinaverium, peppermint oil
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
Drossman D, et al. Aliment Pharmacol Ther. 2009;29:329-341.
0
5
10
15
20
Res
pons
e R
ate
(%)
Placebo N = 385
Lubiprostone (8 µg BID) N = 769
Combined intent to treat population Monthly responder for ≥ 2/3 months during treatment
P = 0.001
Note the different dose! For chronic constipation lubiprostone: 24 µg BID
Lubiprostone – Symptom Change IBS-C
Drossman D, et al. Aliment Pharmacol Ther. 2009;29:329-341.
§Score: 0 (absent); 1 (mild); 2 (moderate); 3 (severe); 4 (very severe) †Score: 0 (very loose/watery); 1 (loose); 2 (normal); 3 (hard); 4 (very hard/little balls)
Responder Nonresponder
Abdominal Discomfort/Pain§
Constipation Severity§
Baseline Score
Stool Consistency†
2.19 2.08 2.19 2.76 2.33 0
-0.4
-0.6
-0.8
-1.0
-1.4
-0.2
-1.2
Mea
n C
hang
e fr
om B
asel
ine
Bloating§ Straining§
* * *
*
*
* 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
1. Su Y, et al. Stroke. 2009;40:1304-1309. 2. Bracci F, et al. World J Gastroenterol. 2007;13(29):3967-3972.
*Treatment strategy based on clinical experience
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. Appropriate assessment of bowel function 2. Establish a bowel routine, regular toileting program 3. Suppositories, stool softeners, bulking agents 4. Careful documentation (bowel diary, effectiveness of treatments, etc.) 5. Involve family or health care team (in a nursing facility) 6. 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
Tamayo A, Diaz-Zuluaga P. Support Care Cancer. 2004;12:613-618. Shaiova L, et al. Palliat Supp Care. 2007;5:161-166.
*Treatment strategy based on clinical experience
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
Stark ME. Am J Gastroenterol. 1999;94:567-574.
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
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
Verne GN, et al. Gastroenterol Clin North Am. 1998;27:861-874.
*Treatment strategy based on clinical experience
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. Read NW, et al. J Clin Gastroenterol. 1995;20:61-70. 2. De Lillo AR, Rose S. Am J Gastroenterol. 2000;95:901-905. 3. Roberts MC, et al. Am J Gastroenterol. 2003;98:857. 4. 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 stools
• No evidence to support this theory
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
Muller-Lissner S, et al. Am J Gastroenterol. 2005;100:232-242.
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
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
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