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PHARMACOLOGY
ANCC
Contact
Hours
Constipation Treatment
A Review
Emily Lammers  Sneha Baxi Srivastava
Constipation seems like a ubiquitous condition, something
people of all ages experience and many complain about. It is
often associated with infrequent bowel movements; however,
in reality, constipation has a wide array of symptoms includ
ing hard stools, feeling of incomplete evacuation, abdominal
discomfort, bloating, distension, excessive straining, sensation
of anorectal blockage, or need for manual maneuvers during
defecation. Determining the cause of the constipation is
essential to ensure the appropriate treatment approach. The
patient evaluation consists of collecting subjective and objec
tive information. Constipation has many different treatment
options, with many treatments available as over-the-counter
products as well as prescription medications. For most types
of constipation, nonpharmacological and dietary changes are
typically recommended as first-line treatment. Prescription
medications are available with indications for specific types of
constipation. Both nonpharmacological and pharmacological
interventions have a key role, and follow-up is important to
ensure treatment is appropriate and adequate.
C
onstipation seems like a ubiquitous condition,
something people of all ages experience and
many complain about. It is often associated
with infrequent bowel movements; however, in
reality, constipation has a wide array of symptoms in
cluding hard stools, feeling of incomplete evacuation,
abdominal discomfort, bloating, distension, excessive
straining, sensation of anorectal blockage, or need for
manual maneuvers during defecation. Constipation is
categorized into 3 subgroups based on the assessment
of colonic transit and anorectal function. Determining
the type of constipation is very important as it ensures
how it should be further evaluated and treated.
Determining the cause of the constipation is essen
tial to ensure the appropriate treatment approach. The
patient evaluation consists of collecting subjective and
objective information. This includes learning what
symptoms the patient is experiencing, medications pa
tient may be taking, and exploring red flag symptoms
such as rectal bleeding or sudden weight loss. Learning
what the patient has done so far to address the constipa
tion is key as well. In addition, to further explore symp
toms, patients may use the Bristol Stool Chart to docu
ment their stool history or bowel movement diaries,
which are available on paper as well as apps. Depending
on the findings, patients may be referred for a digital
rectal examination and diagnostic tests such as a colo
noscopy. In addition, guidelines recommend addressing
the biopsychosocial components of constipation.
General Treatment Approach
Constipation has many different treatment options,
with many treatments available as over-the-counter
(OTC) products as well as prescription medications. In
some kinds such as medication induced, a risk versus
benefit analysis will be considered to determine whether
the medication causing constipation can be changed to
avoid further constipation or whether the constipation
is an unfortunate side effect of the continued medica
tion. Common medication classes that may cause con
stipation include anticholinergics, antidepressants, an
tihistamines, calcium channel blockers, diuretics, iron
supplements, nonsteroidal anti-inflammatory drugs,
and opioids. For most types of constipation, nonphar
macological and dietary changes are typically recom
mended as first-line treatment. This includes increasing
fiber with food if possible and with bulk-forming agents
as necessary, physical activity, hydration, creating rou
tines for bowel movements, and considering way to use
a toilet closer to the floor or elevating the feet.
First-Line Agents to Treat
Constipation-Generally
BULK FORMING
Common bulk-forming agents include psyllium,
methylcellulose, and wheat dextrin. These agents work
Emily Lammers, PharmD, PGY-1 Community-Based Pharmacy Resident,
Albertsons Company-Jewel Osco Division, and Adjunct Pharmacy
Faculty, Rosalind Franklin University of Medicine and Science, Chicago, IL.
Sneha Baxi Srivastava, PharmD, BCACP, CDE, DipACLM-Certified Lifestyle
Medicine Practitioner, and Associate Professor, Department of Pharmacy
Practice, Rosalind Franklin University of Medicine and Science, Chicago, IL.
The authors have disclosed that they have no financial interests to any
commercial company related to this educational activity.
Correspondence: Sneha Baxi Srivastava, PharmD, BCACP, CDE,
Department of Pharmacy Practice, Rosalind Franklin University of
Medicine and Science, 3333 Green Bay Rd, North Chicago, IL 60064
(sneha.srivastava@rosalindfranklin.edu).
DOI: 10.1097/NOR.0000000000000657
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Page 2
by absorbing water and increasing fecal mass, which
will increase the frequency and soften the stool. By
doing this, it will make it easier for a patient to have a
bowel movement. It is imperative to start adding fiber
slowly and working up to the recommended 25-30 g/day
because, at first, fiber can cause bloating, distension,
flatulence, and cramping. By incorporating fiber into the
diet slowly, these side effects can be avoided or mitigated.
SURFACTANTS
Surfactants are another option for treatment commonly
used by patients, but evidence is lacking for the use of
surfactants in patients with chronic constipation. An ex
ample of a surfactant is docusate sodium. If used, this
medication class works to lower the surface tension of
stool, making it easier for water to enter the stool.
Surfactant medications present minimal side effects but
may not be as efficacious as other treatment options.
STIMULANT
Stimulant laxatives work via alteration of electrolyte
transport by the intestinal mucosa and increase intesti
nal motor activity. Stimulant laxatives include bisacodyl
and senna products. Studies have shown that stimulant
laxatives are more efficacious than placebo in the treat
ment of constipation by having more complete sponta
neous bowel movements and an increase in quality-of
life scores. Long-term use of stimulant laxatives may
cause electrolyte imbalances, so long-term use must be
discussed with a healthcare provider (Brenner, 2012).
OSMOTIC
Osmotic agents produce an osmotic effect in the colon
with resultant distension that promotes peristalsis. This
class of medications causes water retention in the stool
and increases stool frequency. This class of medications
includes polyethylene glycol (PEG), lactulose, milk of
magnesia (MOM), and magnesium citrate. Polyethylene
glycol is considered superior to other medications in
this class, and the OTC dose is 17 g dissolved in 4-8 oz
of any type of liquid one-time daily (Wald, 2019a).
LAXATIVES
Laxatives come in many different forms such as powder,
tablet, liquid, and suppositories. Suppositories are
mainly used for defecatory dysfunction and work to liq
uefy stools by altering the water and electrolyte secre
tion, producing intestinal fluid accumulation and laxa
tion to aid in bowel movements. Suppositories work
locally and can be used daily to aid in bowel movements.
Laxatives may be indicated in people 6 years and older;
however, it is recommended that, especially when used
in pediatric cases, people with certain chronic condi
tions and people inappropriately using laxatives chroni
cally be further evaluated. Any person 6 years and older
can use suppositories if needed.
Opioid-Induced Constipation
Opioid-induced constipation (OIC) is a common side
effect of patients using opioid pain medications for
their moderate to severe pain. The prevalence of consti
pation is estimated to be around 25% but can be as high
as 64% in some patients (Veiga et al., 2018). To diag
nose a patient with OIC is difficult as there is not a clear
diagnosis for the condition. When making the diagno
sis, providers must consider many factors such as his
tory of constipation, physical examinations including a
rectal examination, diagnostic tests, and patient medi
cation therapy. Other things to consider are a change in
opioid therapy, increase in dose of therapy, or initiation
of new opioid therapy that could cause new or worsen
ing symptoms of constipation. To make a diagnosis of
OIC, two or more of the following symptoms must be
present:
1. Straining during more than one fourth of def
ecations;
2. Lumpy or hard stools in more than one fourth
of defecations;
3. Sensation of incomplete evacuation in more
than one fourth of defecations;
4. Sensation of anorectal obstruction/blockage in
more than one fourth of defecations;
5. Manual maneuvers to facilitate more than one
fourth of defecations (e.g., digital evacuation,
support of the pelvic floor); and
6. Fewer than three spontaneous bowel move
ments per week.
For patients who may be starting on long-term opi
oid therapy or believe they are at risk for developing
constipation, there are ways to try to prevent constipa
tion from occurring. Risk factors for developing OIC
include increased age, immobility, poor diet, hypercal
cemia, and others (Portenoy et al., 2019). If a patient
has risk factors and/or is on long-term opioid therapy,
an option is to use prophylactic laxative therapy. Other
options include increased fluid intake, increased mobil
ity, and/or a high-fiber diet to decrease the chances of
constipation. All options are viable and should be cho
sen on the basis of patient-specific risk factors and pa
tient preference.
Many different treatment options exist for OIC de
pending on the severity. For most patients, first-line
therapy will be laxative therapy. Options for laxative
therapy have been discussed earlier and are listed in
Table 1. For refractory OIC, which is when a patient
does not respond to first-line laxative therapy, prescrip
tion treatment should be considered. A simple and vali
dated tool used when evaluating constipation is the
Bowel Function Index, and prescription therapy is gen
erally considered when a score of 30 or more points is
recorded. Prescription therapy for OIC provides differ
ent options including peripherally acting mu-opioid re
ceptor antagonists (PAMORAs) and Type 2 chloride
channel activators.
TREATMENT OF OIC: PAMORA
The PAMORAs include methylnaltrexone, naloxegol,
naldemedine, and alvimopan. The class of medications
includes opioid receptor antagonists blocking the opioid
receptor binding at the mu receptors. Methylnaltrexone
is a quaternary derivative of naltrexone with limited
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Page 3
TABLE 1. MEDICATION THERAPY FOR CONSTIPATION
Medication
Brand Name
Mechanism of Action
Onset of Action
Adverse Effects (>5%)
FDA Approval
Methylnaltrexone
Relistor
Peripherally acting opioid receptor antagonist that
Time to peak: SubQ: 30
Abdominal pain, flatulence,
Tablets and injection: OIC with
blocks opioid binding at the mu receptors in the GI
minutes
nausea, dizziness, diarrhea,
chronic noncancer pain
tract to improve GI motility and GI transit time; does
Oral: 1.5 hours (delayed
hyperhidrosis
Injection: OIC with advanced
not affect opioid analgesic effects
with high fat meal)
illness
Naloxegol
Movantik
Mu-opioid receptor antagonist functioning peripherally
Time to peak: <2 hours
Abdominal pain, diarrhea,
OIC in noncancer pain
in tissues of the GI tract
nausea, flatulence, vomiting
Naldemedine
Symproic
Opioid antagonist that blocks binding at mu, delta, and
Time to peak: 0.75 hours;
Abdominal pain, diarrhea
OIC in noncancer pain
kappa receptors
2.5 hours with food
Alvimopan
Entereg
Opioid receptor antagonist that blocks binding at the
Time to peak: 2 hours
Hypokalemia, dyspepsia,
Postoperative ileus, used only
mu receptor; selectively and competitively binds to
anemia
in the hospital setting
the GI tract mu-opioid receptors; does not affect opi
oid analgesic effects or induce withdrawal symptoms
Lubiprostone
Amitiza
Locally acting chloride channel activator on the GI tract
24-48 hours
Headache, nausea, diarrhea,
Chronic idiopathic constipation,
to increase intestinal fluid secretion and improve
abdominal pain, flatulence,
irritable bowel syndrome with
fecal transit
abdominal distension
constipation, OIC
Linaclotide
Linzess (Linzess,
Agonist of guanylate cyclase-C on the luminal surface of
12-24 hours
Diarrhea, abdominal pain, flat-
Chronic idiopathic constipa
2017)
intestinal epithelium, resulting in increases in intesti-
ulence, upper respiratory
tion, irritable bowel syn
nal fluid and GI transit acceleration
tract infection
drome with constipation
Plecanatide
Trulance (Trulance,
Agonist of guanylate cyclase-C on the luminal surface of
12-24 hours
Diarrhea
Chronic idiopathic constipa
2018)
intestinal epithelium, resulting in increases in intestinal
tion, irritable bowel syn-
fluid and GI transit acceleration
drome with constipation
Psyllium
Metamucil
Soluble fiber that absorbs water in the intestine to
12-72 hours
Gas, bloating, fluid overload
Constipation, dietary fiber
promote peristalsis and reduce transit time
supplement
Methylcellulose
Citrucel
Soluble fiber that absorbs water in the intestine to
12-72 hours
Gas, bloating, fluid overload
Constipation
promote peristalsis and reduce transit time
Wheat dextrin
Benefiber
Soluble fiber that absorbs water in the intestine to pro-
24-48 hours
Gas, bloating
Dietary fiber supplement
mote peristalsis and reduce transit time
Docusate sodium
Colace
Lowers the surface tension of stool, making it easier for
24-72 hours
Throat irritation
Constipation
water to enter the stool
Polyethylene
MiraLAX
Osmotic agent that causes water retention in the stool
1-4 days
Diarrhea, flatulence, nausea,
Constipation
glycol
and increased stool frequency
abdominal pain
Lactulose
Enulose, Constulose
Osmotic effect in the colon resulting in distension pro-
24-48 hours
Dehydration, hypernatremia,
Constipation, portal systemic
moting peristalsis
hypokalemia, cramps, flatu-
encephalopathy
lence, nausea, vomiting
Milk of magnesia
Phillips Milk of
Osmotic retention of fluid distending the colon with in-
0.5-3 hours
Watery stools and urgency,
Antacid, constipation
Magnesia
creased peristaltic activity; reacts with hydrochloric
caution in renal insufficiency
acid in the stomach to form magnesium chloride
Bisacodyl
Dulcolax
Stimulates peristalsis by irritating the smooth muscle of
6-10 hours
Abdominal cramps
Constipation
the intestine; alters water and electrolyte secretion, pro
ducing net intestinal fluid accumulation and laxation
Senna
Senokot, Ex-Lax,
Stimulate peristaltic activity on the intestine by direct
6-12 hours
Diarrhea, nausea, vomiting
Constipation
Geri-kot, Senna
action on the intestinal mucosa or nerve plexus,
Lax, Senexon
therefore increasing motility
Note. FDA = Food and Drug Administration; GI = gastrointestinal; OIC = opioid-induced constipation; SubQ = subcutaneously.
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Page 4
ability to cross the blood-brain barrier. Therefore, it
functions as a peripheral acting opioid antagonist with
actions in the gastrointestinal (GI) tract to inhibit opi
oid-induced decreased GI motility and delay in GI tran
sit time. This is how it works to decrease OIC but does
not affect opioid analgesic effects. Methylnaltrexone
requires dosage adjustments for both renal and hepatic
impairments ("Methylnaltrexone bromide oral," n.d.).
Naloxegol works similarly to methylnaltrexone as it has
limited ability to cross the blood-brain barrier and
works peripherally in the GI tract to reduce the symp
toms of OIC. A decreased dose of this medication is re
quired with a creatinine clearance of less than 60 ml per
minute and has not been studied in hepatic impairment,
so avoid its use. Naloxegol is contraindicated for con
comitant use with strong CYP3A4 inhibitors such as
clarithromycin or ketoconazole ("Naloxegol oxalate
oral," n.d.). Naldemedine works by blocking opioid
binding at the mu, delta, and kappa receptors. It func
tions as a PAMORA, including actions in the GI tract to
inhibit delay in GI transit time to decreasing constipat
ing effects of opioids. There is no required dosage ad
justment for renal impairment or moderate hepatic im
pairment. Naldemedine has not been studied in severe
hepatic impairment, so its use should be avoided
("Naldemedine oral," n.d.). Alvimopan works by selec
tively and competitively binding the mu-opioid recep
tors in the GI tract and antagonizes the effects of opioid
on GI motility and secretion without affecting the anal
gesic effects of opioids. This medication is specifically
used for short-term hospitals use and a maximum of 15
doses (180 mg) can be given to a patient. There are no
dosage adjustments needed for moderate renal or he
patic impairment. Its use should be avoided in severe
renal and hepatic impairments ("Alvimopan oral," n.d.).
TREATMENT OF OIC: TYPE 2 CHLORIDE CHANNEL
ACTIVATOR
The type 2 chloride channel activator that is commonly
used for OIC is lubiprostone. This medication works by
inducing secretion of fluid into the intestines and bowel,
allowing stool to pass more freely. It does this by acting
locally on the apical membrane of the GI tract to in
crease intestinal fluid secretion and improve fecal tran
sit. Lupiprostone bypasses the antisecretory effects of
opiates, which suppress secretomotor neuron excitabil
ity. The dose when used for OIC is 24 microg twice daily.
Dosing of this medication changes on the basis of indi
cation. No dosage adjustments are needed for renal im
pairment or mild hepatic impairment. For moderate
hepatic impairment, dosing should be decreased to
16 microg twice daily and for severe impairment dosing
should be 8 microg twice daily initially ("Amitiza," 2018).
Chronic Idiopathic Constipation
Chronic idiopathic constipation (CIC) is diagnosed on
the basis of the absence of physical abnormalities or
other causes of constipation and the presence of the fol
lowing in 25% of defecations-at least two of the follow
ing with straining: lumpy/hard stools, sensation of in
complete evacuation or obstruction, need for manual
maneuvers, and less than three spontaneous bowel
movements per week in addition to the rare presence of
loose stools without laxative and insufficient criteria for
irritable bowel syndrome (IBS).
CHRONIC IDIOPATHIC CONSTIPATION: TREATMENT
OPTIONS
First-line therapy for CIC typically begins with nonphar
macological options: increasing fiber, fluid intake, phys
ical activity, and behavioral changes such as having a
routine for bowel movements. The American
Gastroenterological Association next recommends os
motic agents such as MOM or PEG and then adding a
stimulant laxative such as bisacodyl or senna. If the
nonpharmacological and/or nonprescription therapies
are not adequate, there are four prescription drugs cur
rently on the market: lubiprostone, linaclotide, plecana
tide, and prucalopride. Lubiprostone was the first medi
cation on the market, and it works by selectively
activating the ClC-2 chloride channel in the intestinal
lumen, which leads to an efflux of chloride ions, fol
lowed by sodium ions into the small intestine. This, in
turn, enhances intestinal fluid secretion and motility in
intestine, facilitating the passage of stool. Lubiprostone
is indicated in CIC, OIC, and IBS with predominant
constipation (IBS-C), but the dose varies depending on
the condition it is treating. The most common side ef
fects are nausea and headache, and the medication
should be taken with food and water. Both linaclotide
and plecanatide are guanylate cyclase-C (GC-C)
agonists-They bind to CG-C and act on the luminal
surface of the intestinal epithelium. This causes an in
crease in the intra/extracellular cGMP, stimulates secre
tion of chloride and bicarbonate into the intestinal
lumen, and ultimately increases intestinal fluid, acceler
ating transit. Linaclotide capsules are supposed to be
swallowed whole on an empty stomach at least 30 min
utes prior to the first meals. These capsules can be
opened and gently swirled in bottled water or room tem
perature applesauce. The most common adverse effects
include diarrhea, abdominal pain, flatulence, abdomi
nal distension, upper respiratory tract infections, and
sinusitis. Plecanatide tablets are also supposed to be
swallowed whole or can be crushed and mixed with ap
plesauce or water. Both are indicated in CIC and IBS-C
as well. The last medication indicated for CIC is pruca
lopride, a selective serotonin Type 4 agonist, which stim
ulates colonic peristalsis and increases bowel motility.
This is only indicated for CIC and can be taken with or
without food, and adverse effects include headache, ab
dominal pain, diarrhea, and abdominal distension.
Irritable Bowel Syndrome
Irritable bowel syndrome is a chronic disorder of the GI
tract that may present as altered bowel habits and/or ab
dominal pain without cause. There are approximately
10%-15% of adults and adolescents who have signs and
symptoms consistent with IBS. Irritable bowel syndrome
is broken down into different subtypes including IBS-C,
IBS with predominant diarrhea (IBS-D), IBS with mixed
bowel habits (IBS-M), and IBS unclassified (Wald,
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Page 5
2019b). This article focuses on IBS-C. There are many
nonpharmacological treatment options for IBS-C includ
ing changes in diet, lactose avoidance, gluten avoidance,
food allergy testing, physical activity, and fiber.
IRRITABLE BOWEL SYNDROME: TREATMENT OPTIONS
Psyllium
In a study conducted by Ford et al. (2014), psyllium has
been associated with improvements in symptoms of
IBS-C over placebo. Psyllium is a soluble fiber that
works by absorbing water in the intestine to form a vis
cous liquid that promotes peristalsis and reduces transit
time (Ford & Talley, 2012). If patients fail a trial of psyl
lium, the next option is PEG for alleviation of constipa
tion. Studies have shown that PEG does not show much
benefit in improving abdominal pain in patients with
IBS-C, but patients did have significantly more sponta
neous bowel movements, improvement in bowel con
sistency, and reduction in severity of straining ("Psyllium
oral," n.d.). If the patient fails a trial of PEG, other op
tions for treatment of IBS-C include lubiprostone, lina
clotide, or plecanatide. Lupiprostone is dosed at 8 microg/
day when used for IBS-C, which is different from OIC
dosing. Linaclotide and plecanatide work by binding
and agonizing GC-C on the luminal surface of intestinal
epithelium, increasing concentrations of intracellular
and extracellular cGMP concentrations resulting in
chloride and bicarbonate secretions into the intestinal
lumen. This increases GI transit time and thus may re
duce constipation (Brown et al., 2016). Medication ther
apy for IBS-C is discussed in Table 1.
Conclusion
Constipation is a common condition where symptoms
present in a decreased frequency of bowel movements
alongside other symptoms. Evaluating the patient is key
to determining the cause of the constipation to ensure
the appropriate treatment is recommended. Both non-
pharmacological and pharmacological interventions
have a key role, and follow-up is important to ensure
treatment is appropriate and adequate.
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For additional continuing nursing education activities on orthopaedic
nursing topics, go to nursingcenter.com/ce.
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