Drug Therapy For IBS Essay

Jordan is a 35-year-old woman who presents with intermittent diarrhea with cramping that is relieved by defecation. The diarrhea is not bloody or accompanied by nausea and vomiting. Review of past medical history includes some childhood “stomach issues”, HTN, and a recent cholecystectomy. She works in the environmental department of a large hotel. . She denies alcohol and cigarette.Drug Therapy For IBS Essay

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Diagnosis: Irritable Bowel Syndrome (IBS)

I. Discuss the epidemiology of IBS?

II. What is your treatment goals for this patient?

III. Discuss First line and second line drug therapy for IBS. Please include pharmacotherapeutic information.

Please I need at least 300 words

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disorder without structural or biochemical abnormalities.
Chronic abdominal pain altered bowel habits (constipation,
diarrhea) and bloating are the classic symptoms.Drug Therapy For IBS Essay
1-4 (see
Table 1: Rome III & Manning criteria) Symptoms of this
benign disorder cycle through phases of exacerbations and
remissions.5-7 The one-year prevalence rate in Canadian
adults is around 12% 6
. Most cases are diagnosed before
age 45. Females are twice as likely as men to suffer from
IBS.2, 8 Patients often experience significant emotional
distress and ~50-90% suffer from co-morbid mental health
disorders, such as anxiety or depression. Surgical
procedures (e.g. hysterectomy, appendectomy) are more
common in this population impacting quality of life. 9

The exact cause of IBS is unknown.1, 3 There are three
interrelated factors thought to affect symptoms to varying
degrees: altered gut motility, increased gut sensitivity and
dysregulation of the brain-gut axis.1, 8
Table 1: Criteria for IBS Diagnosis & Alarm features
Rome III Drossman 27:IBS if at ≥3months, with onset ≥ 6months previously of
recurrent abdominal pain or discomfort not described as pain assoc. with ≥2 of:
• Improve with defecation; &/or onset assoc. with a change in frequency
of stool; &/or change in form appearance of stool (present ≥3days/month)
Manning Cayley, BMJ 2005Diagnose IBS if ≥3 are present*:
• Abdominal pain, relief of pain on defecation, increased stool
frequency with pain, looser stools with pain, mucus in stools,
feeling of incomplete evacuation
“Red Flag” / ALARM signs for further evaluation:Drug Therapy For IBS Essay
• weight loss, blood in stools, anaemia, fever; onset after age 50;
recent antibiotic use; family history of colon cancer or
inflammatory bowel disease; physical findings (abdominal mass,
stool +ve for occult blood, enlarged lymph nodes), extra-GI
symptoms ( arthritis, skin abnormalities, lymphadenopathy)
* average sensitivity 60% & specificity 80%; diagnostic accuracy ↑ if younger & female
IBS Subtypes/Findings
IBS can be broken down into three main subtypes:
IBS-C with constipation, IBS-D with diarrhea
, or IBS-M mixed
constipation & diarrhea changes over hours or days, plus IBS-U unsubtyped.
Subtypes are based on the single classification of stool
consistency from the Bristol Stool Scale.28 (Type 1-7)
However, it is recommended that treatment is sought for
symptoms, not subtypes – which can change over time.3,
6, 8 The goal of therapy is to improve abdominal pain,
bloating and altered bowel habits.8
Unfortunately, there
is no single drug that targets all of the IBS symptoms.6, 10
IBS General Management Considerations
Provide Patient Education
Often patients who seek medical care are concerned that
their symptoms may represent life-threatening disorders.
Despite having an impact on quality of life, IBS does not
have an effect upon life expectancy, nor has it been linked
to structural diseases such as diverticular disease, cancer
or inflammatory bowel disease.4,6,7,12 The importance of
providing education and reassurance to all IBS patients
should not be overlooked.Drug Therapy For IBS Essay
Encourage Lifestyle Modification
Lifestyle changes (e.g. identifying food triggers, diet
modification, stress management) typically offer more
benefit than medications do.6
Encourage patients to keep
a diary record of their symptoms for at least a two week
period to help identify possible triggers (e.g. fat, alcohol,
caffeine, sorbitol, meal size).
1,5 When possible, refer patients to
a dietitian to assist with dietary recommendations.
Treat Co-morbid Psychiatric Disorders
For patients with underlying mental health issues (e.g.
depression, anxiety and stress), addressing the
psychosocial issues may provide IBS symptom relief.
Investigate Possible Drug-Induced Causes
Check for medications that may cause or contribute to the
primary IBS symptom complaint.
Table 2: Drugs that can cause IBS symptoms
Constipation anticholinergics (especially tricyclic
antidepressants: amitriptyline > imipramine
> nortriptyline, desipramine), opioids,
anticonvulsants, iron and calcium
supplements, calcium channel blockers
(esp. verapamil), Al++ containing antacids,
high dose diuretics, loperamide
Diarrhea Mg++ containing antacids/supplements,
NSAIDs, antibiotics, chemotherapy,
antiarrhythmics, laxatives, herbal
medications and teas that contain senna
Abdom. pain NSAIDs, corticosteroids, antibiotics, iron
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Drug Treatment Drug Therapy For IBS Essay
Drug therapy may be initiated when IBS symptoms start
to diminish the patient’s quality of life.5, 8 Evidence to
support chronic drug therapy is lacking, however trials of
medications targeting the predominant symptoms may be
used empirically during exacerbations.10
Limitations with the Evidence 8, 10-14
There are several limitations with the available literature.
These lead to conflicting results between trials, metaanalysis and systematic reviews.
Table 3: IBS Study design limitations
• small sample size; lack of sample size calculations
• short durations
• inconsistently reported IBS subtype classification
• criteria to identify IBS patients not always used (e.g.
Manning, ROME, ROME II, ROME III criteria)
• some endpoints inadequately designed, outcomes varied
• compliance seldom measured
• placebo response rate high (40-70%)
• often in gastroenterology and not primary care setting
Diarrhea
Loperamide IMODIUM is the antidiarrheal of choice for
treating IBS related diarrhea and is the only drug in this
class to be evaluated for this indication. It has a better
safety profile, since it does not cross the blood brain barrier
like other opiates.5, 10, 12
Loperamide, when scheduled for short periods of time (i.e.
<5 weeks), has been shown to decrease stool frequency
from 1.9/day to 1.3/day, and decrease the incidence of
urgency from 2.4 days/week to 1.1 days/week when
compared to placebo (p<0.05 for both).15 When studied in
patients suffering from painless diarrhea, all patients
(100%) noted an improvement in stool frequency and stool
consistency (versus 40% and 50%, respectively, in the
placebo group, p<0.001).16 The doses used in these trials
ranged from 2-12mg daily in divided doses.15-17 Patients
were allowed to titrate the dose up or down to balance
relief of symptoms with adverse events.
Loperamide has not been shown to relieve global IBS
symptoms, abdominal pain or bloating.8, 10, 18 In fact,
loperamide may increase nighttime abdominal pain.10
Therefore, loperamide is recommended in patients with
painless diarrhea.Drug Therapy For IBS Essay
Despite being used in trials, most recommendations
suggest that loperamide should be limited to PRN use.2,5 It
can be used intermittently to reduce postprandial urgency
or to help prevent predictable episodes of diarrhea,
especially for important events.2,3,5,10 However, if the
diarrhea is severe, a short-term course of scheduled dosing
may be needed.2
Avoid in patients with constipation, and
use with caution in patients suffering from IBS alternating
between diarrhea and constipation.2,5,12
Cholestyramine (QUESTRAN) may be useful when there
is a component of bile-salt diarrhea, especially pertinent in
post-cholecystectomy IBS.
Constipation
Non-pharmacological measures, like increasing dietary
fruits and vegetables, exercise and fluid intake should be
recommended in all patients suffering from constipation.3

If constipation continues despite these lifestyle
modifications, fibre supplementation can be tried. There
are two types of fibre – soluble (e.g. bulking agents –
psyllium, calcium polycarbophil, oats) and insoluble (e.g.
wheat bran).Drug Therapy For IBS Essay
Patients who are on fibre supplementation
are 1.5 times more likely to experience relief from their
constipation compared to those who are not (RR 1.56,
95% CI 1.21-2.02).19 Fibre will not improve abdominal
pain or bloating, and insoluble fibre may actually
worsen these symptoms – especially if introduced too
quickly.19, 20 {Fibre supplementation has also been
evaluated in diarrhea-predominant IBS patients as well.
However, due to previously listed literature limitations,
current evidence only supports the use of fibre
supplementation for treating constipation.11, 19, 20}
There is little randomized controlled trial evidence for
laxative use in this population.8
If fibre supplementation
fails, other laxatives are sometimes necesary.2, 3, 5
Osmotic laxatives (such as Mg++ Citrate, PEG solution,
sorbitol) are somewhat safer in the long term.
Occasionally a stimulant is necessary and in such cases an
agent such as bisacodyl may be used.
Abdominal Pain
Both antispasmodics and antidepressants have been
investigated for relieving abdominal pain associated with
IBS. Most recommendations suggest avoiding opioid
analgesics, due to concerns involving adverse events, the
abuse potential, and the lack of evidence in this
population.5
Antispasmodics
Antispasmodics are thought to relieve abdominal pain by
reducing intestinal smooth muscle contractions.1, 2, 10, 12
The published reviews assessing the efficacy of
antispasmodics in IBS patients have yielded conflicting
summaries.8, 10-14 Some of the reviews included up to
eleven different antispasmodic agents – however, only
three of these are available in Canada with an official
indication for irritable bowel syndrome: dicyclomine
BENTYLOL, pinaverium DICETEL and trimebutine
MODULON.
6, 21 Therefore, these medications may be
trialed empirically in patients suffering from abdominal
pain. They can be used as-needed for acute attacks of
abdominal pain or scheduled before meals in patients with
postprandial symptoms.2
Use with caution in patients
with constipation, as antispasmodics may worsen this
symptom. Drug Therapy For IBS Essay
Antidepressants
Antidepressants are used for their analgesic properties, as
well as their ability to alter gastrointestinal transit and
treat psychiatric co-morbidity.1, 2 Only tricyclic
antidepressants (TCAs) and selective serotonin reuptake
inhibitors (SSRIs) have been investigated for IBS, with
the bulk of the studies involving TCAs. There is only one
trial comparing a TCA (imipramine) to a SSRI
(citalopram). Unfortunately, neither agent was
superior to placebo for improving global IBS
symptoms or abdominal pain.

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22
Tricyclic Antidepressants (TCA)
As with the antispasmodics, the reviews assessing the
efficacy of TCA use for relieving IBS-related abdominal
pain have lead to inconsistent conclusions.8, 11, 12, 14 A
physiological study showed that a TCA (imipramine)
prolonged intestinal transit time.23 The anticholinergic
properties of TCAs, along with this finding, support the
use of these agents for treating diarrhea. Therefore,
patients suffering from IBS-related abdominal pain may
benefit from a TCA when a diarrhea component is also
present, or when indicated for a co-morbid mental health
disorder. Avoid using in patients with constipation, as
TCAs may provoke or aggravate constipation.2, 10, 12
Selective Serotonin Reuptake Inhibitor (SSRI)
No systematic reviews or meta-analysis, for this
indication, have been conducted with the SSRIs, largely
due to the small number of trials involving these agents.
Although the clinical significance has yet to be
determined, the above mentioned physiological study also
showed that a SSRI (paroxetine) accelerated intestinal
transit time – thus suggesting that SSRIs would be more
suited for treating constipation. 23 A study involving
fluoxetine in IBS patients suffering from pain and
constipation (ROME II criteria) strengthened this notion.
In this trial, 44 patients (61% ♀, mean age 34.9 [±10
years]) were randomized to fluoxetine 20mg po OD x 12
weeks or placebo, in a tertiary setting. By week 4,
abdominal discomfort, bloating, hard stool consistency,
frequency of bowel movements <3 times a week and
change in bowel habit were all significantly improved in
the fluoxetine group (p<0.05 for each). This effect
continued to week 12. Four weeks after the study
medications were discontinued, all of the above endpoints
– except change in bowel habit, were still significantly
less in the fluoxetine group.Drug Therapy For IBS Essay
In other words, in patients suffering from IBS-related
abdominal pain and constipation may benefit from a
SSRI. The SSRIs have also been investigated in patients
suffering from diarrhea-predominate IBS. However, until
additional evidence is available, reserve this class of
antidepressants for co-morbid mental health disorders in
these patients.
Only three SSRI antidepressants have been studied in IBS
patients to date – fluoxetine PROZAC, paroxetine
PAXIL and citalopram CELEXA.
22, 24, 25 {For studied
doses in IBS, see Comparison Chart.}
Abdominal Bloating
Alleviating constipation, if present, may help reduce
bloating. If using fiber supplementation to treat
constipation, use cautiously as fibre may worsen
bloating.5
Fluoxetine has been shown to relieve
constipation, abdominal pain and bloating in patients
suffering from constipation-predominant IBS and
associated pain.24 Otherwise, medications are not useful
for bloating.
Herbal Medications, Probiotics & Alternatives
A Cochrane review assessed the effectiveness and safety
of Chinese herbal medicines in IBS patients, but
concluded that there is limited evidence to suggest using
herbal agents at this time.26 Currently, there is
insufficient data to recommend any probiotics for IBS.
Hypnosis, yoga, meditation, tai chi & acupuncture has no
or limited evidence, but anecdotal cases of success.
Cognitive behavioral therapy, standard psychotherapy and
hypnotherapy 32 may help selected IBS patients.
Agents on the Horizon
Asimadoline (a peripheral kappa-opioid agonist),
cilansetron (competitive type 3 serotonin 5-HT3 receptor
antagonist), renzapride (a novel benzamide related to
cisapride) & talnetant (a neurokinin-3 receptor-specific
antagonists) are four examples of potentially promising
agents for IBS.Drug Therapy For IBS Essay

The etiology of IBS has not yet been identified. Examination of the large and small bowels has revealed altered GI motility. This delays meal transit in patients who report constipation but accelerates transport in patients who report diarrhea. Patients with IBS also have visceral hyperalgesia. Microscopically, some bacterial overgrowth and microscopic inflammation has been identified in patients who have IBS.8

In addition, IBS is associated with psychopathology. Patients with IBS tend to have a higher incidence of anxiety disorder, catastrophizing, major depression, panic disorder, and somatoform disorders than the general population.1,9 A major concern in patients with IBS is suicidal attempts or ideation.10 Clinicians should heighten awareness around this risk.

IBS Management
Patients need to know 2 things: Symptoms tend to be chronic and exacerbate from time to time, and individuals need to avoid stressors and triggers.4 Patients with IBS need 3 types of support.Drug Therapy For IBS Essay

First, they need support to address the common psychological comorbidities. Cognitive behavioral therapy and judicious use of antidepressants may reduce symptoms or strengthen coping skills.3,6,10

Second, they need advice about dietary measures that can ameliorate or prevent symptoms. Fiber supplementation can improve constipation and diarrhea, but it may cause bloating or distention. Clinicians should note that a Cochrane systematic review of bulking agents and fiber in IBS found that these medications had no benefit.11 Regardless, many patients report improvement.Drug Therapy For IBS Essay

Third, additional dietary recommendations include staying adequately hydrated, limiting fermentable oligo-, di-, and monosaccharides and polyols, and supplementing calcium for patients who avoid lactose entirely.12,13

Pharmacologic Management
Pharmacologic treatment is considered adjunct to lifestyle management and must be symptom directed.6 Clinicians can choose among anticholinergics, antidiarrheals, bulk-forming laxatives, chloride channel activators, guanylate cyclase C agonists, prokinetics, serotonin receptor antagonists, and tricyclic antidepressants. The choice of the drug(s) used depends on the patient’s symptoms, preference, and previous responses.6 The Figure shows the typical approach to treatment; note that the stepwise approach is deceptively simple, and no comparative effectiveness studies support its structure.6 For many patients, it will take time and trial and error to find the most successful strategy.Drug Therapy For IBS Essay

In the past several years, the FDA has approved many agents to treat IBS. Table 2 describes the newer agents.15-20

Conclusion
With recent developments, the likelihood of successful treatment for patients with any type of IBS is greater than ever before. Pharmacists need to take note of specific indications, the most common adverse reactions, and potential drug interactions. Given time and trial of multiple interventions, most patients will learn to live successfully with IBS and control its exacerbations. Drug Therapy For IBS Essay