Transcript OTC Agents for Constipation, Diarrhea, hemorrhoids and heartburn

Spring 2015
 Constipation is the difficulty or infrequent passage of
stool. Normal frequency ranges from 2-3 times daily to 23 times weekly.
 Patients may experience abdominal bloating, headaches
or a sense of rectal fullness from incomplete evacuation
of feces.
 The normal frequency of bowel movements varies with
age. Newborn infants frequently defecate an average of
two to 2.9 times a day. This frequency gradually declines
over time, and the average number of stools is 1.8 in
children who are one to three years of age and 1 stool per
day in children who are older than three years of age.
However, there is wide variation in these numbers.
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 Although there is no universally accepted definition of
constipation in clinical practice, the following have
been proposed: difficulty in passing feces or fewer than
three evacuations per week. The Rome III
classification refers to functional constipation when
patients have no organic causes but present with two
or more of the symptoms listed in the following table.
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Rome III diagnostic criteria for functional constipation (criteria fulfilled at least
once per week for at least two months before diagnosis):
Must include two or more of the following in a child with a developmental age of at least
four years, with insufficient criteria for the diagnosis of irritable bowel syndrome:
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Two or fewer defecations in the toilet per week.
At least one episode of fecal incontinence per week.
History of retentive posturing or excessive volitional stool retention.
History of painful or hard bowel movements.
Presence of a large fecal mass in the rectum.
History of large diameter stools that may obstruct the toilet.
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Usually, constipation is not a sign of serious illness
but rather “functional constipation” or
“withholding constipation.” Functional constipation
is constipation without an organic cause.
More than 95% of children over the age of one year with
constipation have functional constipation. Most
commonly, it is due to a painful bowel movement which
then leads to voluntary withholding. However, a small
percentage may have a more serious illness such as
gastrointestinal diseases (e.g., Hirschsprung’s disease),
metabolic causes (e.g., electrolyte abnormalities),
diabetes mellitus or insipidus, cystic fibrosis, or
neurological diseases
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PATHOPHYSIOLOGY
The primary action of the muscles within the gut wall is
to mix bowel contents, enhancing enzymatic and
bacterial breakdown of food into reabsorbable nutrients
and water and to propel the contents (peristalsis)
towards the anus. In the large bowel, mass movements
of peristalsis last 10–30 minutes and occur only 1–3 times
a day, particularly during the first hour after breakfast.
They are triggered by gastric distension, i.e. meals and
physical activity
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The propulsion of feces into the rectum brings about the
desire to defecate and stimulates defecation reflexes.
These reflexes act both locally in the nerves of the bowel
wall (mysenteric plexus) and also via the spinal cord.
They lead to distal colonic as well as rectal peristalsis.
Hence, once defecation is initiated with the aid of
abdominal muscle contraction, peristalsis in the rest of
the colon brings more stool to the rectum to be expelled
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Common Causes of Constipation.
 Insufficient dietary fibers.
 Lack of exercise.
 Poor bowel habits.
 Medications.
 Organic problems such as IBS, hypothyroidism,
Parkinson’s disease, intestinal obstruction and tumors.
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Treatment.
Non-Pharmacological.
 The key to treating most patients with constipation is
correction of dietary deficiencies. These generally
involve increasing fiber and fluid intake and
decreasing the use of constipating agents, such as milk
products, coffee, tea, and alcohol.
 Increase exercise.
 Bowel training to increase regularity.
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Dietary fiber is available in diverse natural sources, such as
fruits, vegetables, and cereals. It is nutritionally superior
to supplementation with purified fiber. However, advising
patients to eat more fruits and vegetables is frequently
unsuccessful, at least in American patients. Conversely,
American patients respond reasonably well to
prescriptions and often seek them. Prescribing a fiber
supplement, such as wheat, psyllium, or methylcellulose,
is often useful.
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Fluid intake
 Fluid intake is the key to treatment. Patients should be
advised to drink at least 8 glasses of water daily. Counseling
may be required to achieve this goal.
 Milk and milk products should be minimized if these prove
constipating.
 In some patient populations, most consumed fluids consist of
coffee, tea, and alcohol. Patients should understand that this
practice is counterproductive because of the diuretic effects of
these products. The author usually recommends that patients
decrease consumption of coffee, tea, and alcohol as much as
possible, and they should consume an extra glass of water for
every drink of coffee, tea, or alcohol.
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Pharmacological treatment for functional constipation can
be divided into disimpaction and maintenance
treatment.
Disimpaction, if necessary, can be performed manually
(physical removal of stool) or pharmacologically. In children,
disimpaction is most often performed with medication so as
to avoid traumatizing the child.
The goals in treating constipation are to produce soft,
painless stools and to prevent the reaccumulation of feces.
These outcomes are achieved through a combination of
education, behavioural modification, daily maintenance
stool softeners and dietary modification. Fecal disimpaction
may be necessary at the outset of treatment.
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 Disimpaction can be achieved by either oral or rectal
medication. In a double-blind uncontrolled study, it
was shown that the three-day administration of
polyethylene glycol (PEG) 3350 at a dose of 1 g/kg/day
to 1.5 g/kg/day (maximum dose 100 g/day) successfully
disimpacted 95% of children, and was well tolerated.
Another study showed that a regimen of daily enemas
for six days was equally as effective as PEG 3350 (1.5
g/kg/day) in relieving disimpaction, but may be less
well tolerated. High-dose mineral oil has also been
shown to be effective.
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 Children with severe impaction may need to be
admitted to hospital or an outpatient medical unit for
nasogastric lavage with PEG solution if the volume
required is intolerable orally. This is usually continued
until the rectal effluent is clear.
 Digital disimpaction cannot be recommended based
on available information, and may have harmful
effects
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Pharmacologic Treatment.
 Laxatives are classified based on their mechanisms of
action into:
 1) Bulk-forming laxatives. These are natural or synthetic
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polysaccharide derivatives that adsorb water to soften the stool and
increase bulk, which stimulates peristalsis.
They work in both small and large intestines.
The onset of action is slow (12 up to 72 hrs).
Used to prevent rather than treat acute constipation.
Must be given with at least 8 oz water.
Shouldn’t be given to patients with obstructive bowel lesions or Crohn’s
disease.
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1) Natural bulk-forming laxatives.
 a) Psyllium. Adult dose is 3.5g in 8 oz water 1-3 times daily.
Child dose is half the adult dose.
 b) Malt soup extract. 8-16 g 2-4 times daily. Child dose is 16 g
1-2 times daily.
Synthetic bulk forming laxatives.
 a) methylcellulose. 1-2 g given 1-3 times daily.
 b) Polycarbophil. 1g given 1-4 times daily. Ca-polycarbophil
may interact with tetracyclines and fluoroquinolone
antibiotics.
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 Many of the available products vary substantially in their
potency. For instance, sugar-free Metamucil has twice
the potency of standard Metamucil on a volume basis
because the latter is half sugar. Pharmaceutical
companies may argue that one type of fiber is better
tolerated or more effective than another. This may not
make much difference in treatment or in fiber tolerance
in most patients as long as the fiber supplementation
doses start low and are slowly titrated upward.
 Theoretical considerations suggest that the use of a
fermentable fiber, which increases short chain fatty acid
concentrations in the colonic lumen, may have other
health benefits (as opposed to methylcellulose).
However, this remains controversial and awaits further
exploration.
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 Because no convincing reason exists to pick one product
over another, a single brand of choice should be prescribed
until the patient's constipation resolves. The patient may
then switch to generic or other brands with appropriate
dose adjustments. Some patients have preferences based
on the taste of the product or other subjective reasons. In
particular, rare patients who cannot tolerate fermentable
fiber supplementation because of resulting gas or bloating
may do better with methylcellulose, while others find the
quality of the stool, taste preferences, or both favoring
psyllium supplementation.
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 To avoid patient noncompliance due to the development
of cramping and bloating that accompany changes in
dietary fiber, fiber supplementation should be started at a
low subtherapeutic dose and titrated upwards on a weekly
basis until the desired effect is achieved. Patients should
continue to increase the dose on a weekly basis until they
experience daily bowel movements with no straining or
until they achieve the maximum dose.
 Patients should be cautioned that these products are not
laxatives, will not induce a bowel movement, and must be
taken daily regardless of their perceived need.
 Patients may increase or decrease their dose on a week-to-
week basis.
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2) saline and osmotic laxatives.
 Work by creating an osmotic gradient to pull water into the
small and large intestines which leads to distention of the
intestinal lumen and increase in peristalsis.
 They also increase the activity of cholecystokininpancreozymin, an enzyme that increases the secretion of
fluids into the GI tract.
 Onset of action varies depending on the ingredient and
dosage form; rectal formulations (suppositories and
enemas) have an onset of action of 5-30 minutes. Oral
preparations work within 3-6 hrs.
a) Saline laxatives. Include sodium and magnesium salts.
 About 20% of magnesium may be absorbed so should use
cautiously in pts with renal impairment.
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 Use cautiously in pts with hypertension or heart failure.
 Magnesium citrate: adult ½ bottle, children 6-12 years ¼ bottle taken at
once.
 Magnesium hydroxide. Adults 30 ml. children 6-12 years 15 ml. children 2-6
years 5-15 ml taken at once.
 Magnesium sulfate. Adults 5-10 ml with 8 oz water.
 Sodium phosphate. Adults 20-45 mls.
b) Osmotic laxatives.
 Glycerin: through rectal route. Adults 3 g suppositories. Children 1.5 g
suppositories.
 Lactulose. Also used to decrease blood ammonia levels in patients with
hepatic encephalopathy. May cause flatulence and cramping and should be
taken with fruit juice or milk to improve palatability. Adult dose is 15-30 ml
given 1-2 times daily.
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 Sorbitol. A nonabsorbable sugar, similar in efficacy to
lactulose. Administeredd orally (70% solution) or rectally
(25% solution). Adult dose is 15 ml orally or 120 ml rectally.
 Polyethylene glycol 3350. more effective than lactulose and
sorbitol. Used if other treatments failed. Can be used for
more than one week.
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3) stimulant laxatives.
Oral preparations have an onset of action of 6-10 hrs. rectal 3060 minutes. Should not be used for more than a week. Can
cause cathartic colon if used regularly which resembles
symptoms of ulcerative colitis.
 Sennosides. Adults 12-50 mg twice daily.
 Cascara anthraquinones
 Bisacodyl. Enteric coated tablets. Should not be taken within
1 hr of milk or antacid. Oral dose is 5-15 mg daily. Rectal dose
is 10 mg (1 suppository) daily.
 Castor oil. Onset of action 2-6 hrs. strong cathartic action.
Adult dose is 15-60 ml. Pregnancy Risk Category X
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4) emollient laxatives.
Act as surfactants by allowing absorption of water into the stool,
which makes the softened stool easier to pass. Have slow onset of
action (24-72 hrs). Laxatives of choice for post MI patients.
 They are salts of docusate. Na, K and Ca salts.
 Dose for Na docusate is 50 mg twice daily.
 May increase the absorption of mineral oil.
5) Lubricant laxatives.
Mineral oil works by increasing water retention in the stool to
soften the stool. Onset of action is 6-8 hrs. adult dose is 15-45 ml
daily. Can decrease absorption of fat soluble vitamins.
 Shouldn’t be given to elderly, children less than 6 or pts with
rectal bleeding or appendicitis.
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Summary of Guidelines: Adults
 The first step to treat most cases of constipation is to
provide more fiber, either as a high-fiber diet or as
supplements. Fiber laxatives increase the frequency of
bowel movements by one to two per week. Fiber intake
should be increased gradually over seven to ten days,
starting with twice daily administration. The
Institute of Medicine recommends total daily
fiber intake of 38 grams for men and 25 grams for
women under the age of 50, and 30 grams for men
and 21 grams for women over the age of 50.
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 In most patients, the next step is to add an inexpensive
saline laxative such as milk of magnesia. Stimulant
laxatives, lactulose, and polyethylene glycol are
recommended if these interventions fail. Sorbitol and
lactulose have similar efficacy, but their use is limited
because they cause gas.
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 Some experts are recommending polyethylene glycol
(available OTC) as an alternative to saline laxatives
such as milk of magnesia or before stimulants such as
senna or bisacodyl for its benign side-effect profile.
Long term use of milk of magnesia has been
associated with electrolyte imbalances and should be
avoided in patients with renal dysfunction.
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 For chronic constipation, psyllium, polyethylene glycol,
lactulose, or lubiprostone (Amitiza®) are recommended.
Amitiza should be reserved for individuals with chronic
constipation who don’t respond to or tolerate laxatives.
There is not enough evidence to support the use of stool
softeners, stimulant laxatives (e.g., senna, bisacodyl),
milk of magnesia, calcium polycarbophil,
methylcellulose, or bran in chronic constipation. Both
polyethylene glycol and lactulose have sufficient
evidence to support their use in chronic constipation.
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Canadian Paediatric Society, Paediatr Child Health 2011;16(10):661-5
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CONSTIPATION IN INFANTS
In infancy, constipation is mostly functional, but a heightened
vigilance for identifying red flags suggestive of an organic
disorder in this age group is necessary. It is known that
breastfed infants can have greater variability than formula-fed
infants in stool frequency. (Some normal breastfed newborns
may stool with each feeding or may not have a bowel
movement any more often than every seven to 10 days.).
Mineral oil is contraindicated in infants because of
uncoordinated swallowing and the risk of aspiration and
subsequent pneumonitis. Increased intake of fluids and
reducing excess cow’s milk intake may be helpful for
constipation in older infants.
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Recommendations to add brown sugar to formula or
water for infant constipation are anecdotal and not
evidence based, as well as pose a risk of caries
development.
Lactulose and glycerin suppositories may be used. Two
retrospective chart reviews examining the safety of PEG
3350 in infants have been reported. Both showed that at
doses of 0.8 g/kg/day, PEG was well tolerated, effective
and safe in the management of constipation in infants
younger than 18 months of age.
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