CHAPTER 4

OVER-THE-COUNTER AGENTS FOR DIARRHEA

OVER THE COUNTER DRUGS (OTC)

070115200
MSC Suhad Anabousi
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DIARRHEA
 Diarrhea is a gastrointestinal (GI) disturbance characterized by an
abnormal increase in stool:
 Frequency.
 Although the “normal” frequency of bowel movements varies with individual
physiology, more than 3 bowel movements per day is considered abnormal.
 Liquidity
 The water content is increased to 60% to 90%.

 Weight
 Greater than 200 g per 24 hours.

 Volume
 200 mL per 24 hours.
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DIARRHEA
diarrhea results when the intestine is unable to
 In general,
absorb water from the stool, which causes excess water in the
stool.
 Sodium and potassium alkaline salts are excreted along with the
water, leading to a fall in plasma pH (acidosis), which can have
serious metabolic consequences.
 Fluid and electrolyte losses are increased further if vomiting
also occurs.
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DIARRHEA
 Diarrhea may be acute, persistent, or chronic.
 Acute diarrhea:
 Presence of symptoms for fewer than 14 days, generally can be managed with fluid and
electrolyte replacement, dietary interventions, and non-prescription drug treatment.

 Persistent diarrhea:
 Symptoms last 14 days to 4 weeks.

 Chronic diarrhea:
 Lasts more than 4 weeks.

 Chronic and persistent diarrheal illnesses often are secondary to other chronic medical
conditions or treatments and necessitate medical care.
 PATHOPHYSIOLOGY OF DIARRHEA
Diarrhea can be classified based on origin or mechanism.

Classification by origin: Classification by pathophysiologic mechanism:

 Depending on the underlying mechanisms that disrupt

 Viral gastroenteritis normal intestinal function.
 Bacterial gastroenteritis  The common mechanisms of acute diarrhea are osmotic
and secretory, whereas motor commonly underlie
 Protozoal diarrhea chronic diarrheal illnesses.

 Diet-induced diarrhea  Osmotic diarrhea.

 Secretory diarrhea.
5
 Motility-related diarrhea.
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PATHOPHYSIOLOGY OF DIARRHEA
 Classification by origin:

 Viral:
 Rotavirus
 Infects infants.

 It is the most common cause of severe diarrhea disease in infants and young children.

 Can cause severe dehydration and electrolyte disturbances.

 Norovirus
 Infects all ages.

 Source: contaminated water or food.

 Diarrhea associated with viral gastroenteritis is usually self-limiting for 2 to 3 days but
may last up to 2 weeks.
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PATHOPHYSIOLOGY OF DIARRHEA
 Classification by origin:
 Bacterial
 Campylobacter jejuni  Ingestion of contaminated food or water.

 Salmonella  Ingestion of improperly cooked or refrigerated poultry and dairy products.

 Shigella  Ingestion of contaminated vegetables or water.

 Escherichia coli  Ingestion of contaminated food or water.

 Clostridioides difficile  Antibiotic-associated diarrhea leading to pseudomembranous colitis.

 Clostridium perfringens  Ingestion of contaminated food, especially meat and poultry.

 Staphylococcus aureus  Ingestion of improperly cooked or stored food.

 Yersinia enterocolitica  Ingestion of contaminated food.

 Vibrio cholera  Ingestion of contaminated food, including undercooked or raw seafood.

 Bacillus cereus  Ingestion of contaminated food.
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PATHOPHYSIOLOGY OF DIARRHEA

 Classification by origin:
 Bacterial
 Obtaining a thorough history of the patient’s food intake 48–72 hours
before the onset of diarrhea is essential in identifying a possible cause.
 Onset of diarrhea may range between 1 and 72 hrs, depending on the
infecting bacteria.

 Symptoms typically subside over 3 to 5 days.

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PATHOPHYSIOLOGY OF DIARRHEA
 Classification by origin:
 Bacterial
 Bacteria cause diarrhea by:

 Produce toxins that bind to the mucosal cells of the small intestine, causing
hypersecretion of fluid.
 Patients with diarrheal illness caused by toxin-producing pathogens have a watery
diarrhea, with infection primarily involving the small intestine.
 Invade mucosal epithelial cells and produce localized inflammatory changes in the
gut, this overwhelms the reabsorbing capacity of the colon

 If the large intestine is the primary site of infection, invasive organisms produce a dysentery-
like (bloody diarrhea) syndrome characterized by fever, abdominal cramps, tenesmus (straining), and
the frequent passage of small-volume stools that may contain blood and mucus.
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PATHOPHYSIOLOGY OF DIARRHEA

 Classification by origin:

 Protozoal
 Giardia intestinalis  Ingestion of water contaminated with human or animal feces.
 Cryptosporidium spp.
 Entamoeba histolytica.

 Isospora belli  Ingestion of contaminated food or water.

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PATHOPHYSIOLOGY OF DIARRHEA

 Classification by origin:

 Protozoal
 May be described as profuse watery diarrhea, which may be accompanied
by flatulence and/or abdominal pain.

 Due to the extent of fluid loss over an extended duration of time,

individuals with protozoal-induced diarrhea are at risk for dehydration.

 Non-prescription therapies are not available to manage diarrhea

caused by these pathogens, and self management is inappropriate.
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PATHOPHYSIOLOGY OF DIARRHEA
 Classification by origin:

 Diet-induced diarrhea
 Food intolerance can provoke diarrhea and may result from a food allergy or
the ingestion of foods that are excessively fatty or spicy, contain a high amount
of caffeine, have high dietary fibre, or contain many seeds.
 Dietarycarbohydrates (e.g., lactose, sucrose) normally are hydrolyzed to
monosaccharides by the enzyme lactase.
 Ifnot hydrolyzed, these carbohydrates pool in the lumen of the intestine, where they
produce an osmotic imbalance.
 The resulting hyper-osmolarity draws fluid into the intestinal lumen, causing diarrhea.

 The best treatment is prevention by avoiding troublesome foods.

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PATHOPHYSIOLOGY OF DIARRHEA

 Classification by origin:

 Diet-induced diarrhea
 Lactase activity may be reduced by infectious diarrhea; thus,
acute viral diarrhea may cause temporary milk
intolerance in patients of all ages.
short-
 Lactase deficiency resulting from viral gastroenteritis is
lived, but it is particularly problematic during the first few
days of the disease.
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PATHOPHYSIOLOGY OF DIARRHEA
 Classification by pathophysiologic mechanism:

 Osmotic diarrhea.
 Unabsorbed solutes in intestines increase luminal osmotic
load, retarding fluid absorption.
 This may be the result of hyper-magnesemia, undigested lactose
or fructose, or celiac disease.

 Occurs when excess water is pulled into the intestinal tract.

 Osmotic diarrhea ceases when the patient converts to a fasting

state.
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PATHOPHYSIOLOGY OF DIARRHEA

 Classification by pathophysiologic mechanism:

 Secretory diarrhea.
 Impaired fluid absorption and leaking of mucus, blood, and
pus into lumen caused by inflammation of intestinal mucosa.
 Occurs when the intestinal wall is damaged, resulting in an
increased secretion rather than absorption of electrolytes
into the intestinal tract.
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PATHOPHYSIOLOGY OF DIARRHEA
 Classification by pathophysiologic mechanism:
 Motility-related diarrhea.
 This occurs when food moves through the intestines at such an abnormally
rapid transit time (hyper-motility) that less contact time is allowed for
water and nutrient absorption from luminal contents and absorptive
areas of the intestinal wall.
 Those with diabetic neuropathy, gastric/intestinal resection, or a
vagotomy are susceptible to this type of diarrhea.
 Medications that can also cause hypermotility include
parasympathomimetic agents (e.g., metoclopramide, bethanechol), digitalis,
quinidine, and antibiotics.
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CLINICAL PRESENTATION OF DIARRHEA

 Assessment of the individual should include:

 Age.
 Onset and duration of diarrhea.
 Stool characteristics (i.e., frequency, consistency, volume, and presence of blood or pus).

 Recently ingested foods.

 Other symptoms (i.e., abdominal pain, fever, chills).

 Recent international travel destinations.

 Medical history  current medications.

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CLINICAL PRESENTATION OF DIARRHEA

 Stool characteristics give valuable information about the pathophysiology of the

diarrheal illness.
 For example:
 Undigested food particles in the stool suggest disease of the small intestine.
 Black, tarry stools may indicate upper GI bleeding.
 Red stools suggest possible lower bowel or hemorrhoidal bleeding or simply recent ingestion of
red food (e.g., beets) or drug products (e.g., rifampin).
 Passage of many small-volume stools suggests a colonic disorder.
 Yellowish stools may indicate the presence of bilirubin and potentially serious pathology of the
liver.
 A whitish tint to the stool points to a fat malabsorption disease.
 19

CLINICAL PRESENTATION OF DIARRHEA

 Fluid and electrolyte imbalance is the major complication of
diarrheal illness.
 Physical assessment of a patient with symptoms of diarrhea can
provide information useful in assessing the severity of the
diarrhea.
assessment of the patient’s risk for dehydration and the degree
 Therefore,
of dehydration present is key to determining the appropriateness of
self-care and the need for medical referral.
 The specific signs and symptoms of dehydration correlate with the severity
of the diarrhea, as well as the etiology and degree of fluid and electrolyte
losses.
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CLINICAL PRESENTATION OF DIARRHEA

 The provider should ask about the nature and amount of fluid
intake.
 Checking skin turgor and moistness of oral mucous membranes
will help determine the degree of dehydration.

 Vital signs (e.g., pulse, temperature, respiration, blood pressure) are

important indicators of illness severity and should be routinely measured.

 Severity of dehydration can be accurately assessed by evaluating changes

in body.
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CLINICAL PRESENTATION OF DIARRHEA

 Alarm symptoms or atypical symptoms before or during treatment warrant evaluation by
a primary care provider:
 Diarrhea of any severity in infants younger than 6 months of age.

 Moderate diarrhea in children 2 years of age and younger.

 Unusually high fluid output, significant fever, or mental status changes in young
children.
 Pregnant or breastfeeding patients, and patients with HIV.
 Although diarrhea can be a normal physiologic occurrence during pregnancy, it may be a symptom
of GI infection.

 Immunocompromised patients, such as those receiving cancer treatment, organ

transplant recipients
 Blood or mucus in the stools
 High fever ( >38°C).
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CLINICAL PRESENTATION OF DIARRHEA

 Alarm symptoms or atypical symptoms before or during treatment warrant
evaluation by a primary care provider:
 Dehydration or weight loss > 5% of total body weight;

 Signs of worsening dehydration—dry mouth, sunken eyes, crying without tears,

dry skin that is not elastic like normal skin, low blood pressure, rapid pulse, mental
confusion
 Duration of diarrhea >2 days.
 Vomiting.
 Patients with severe abdominal pain or cramping.
 Patients with diabetes, severe cardiovascular or renal diseases, concurrent
respiratory tract infection, or multiple unstable chronic medical conditions, or older
than 60 years of age (with multiple medical problems).
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TREATMENT GOALS

 The goals of self-treatment for diarrhea are:

 To prevent or correct fluid and electrolyte loss and acid–base disturbance.
 To control symptoms.
 To prevent acute morbidity and mortality.
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GENERAL TREATMENT APPROACH

 Initial self-management in both adults and children with mild to moderate,

uncomplicated diarrhea should focus on fluid and electrolyte replacement by
administering commercially available oral rehydration solutions
(ORSs) in adequate doses.
“Non-pharmacologic Therapy” oral
 Simultaneous implementation of

rehydration and specific dietary measures is appropriate for treating mild to

moderate diarrheal illness.

 Symptomatic control also can be achieved by using non-prescription

antidiarrheal drugs, such as loperamide, in carefully selected patients.
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GENERAL TREATMENT APPROACH

 Patients withuncomplicated acute diarrhea who are otherwise healthy usually

improve clinically within 24–48 hours; normal bowel function often is
restored in 24–72 hours without additional treatment.

 If the condition remains the same or worsens after 48 hours of onset,

medical referral is necessary to prevent complications
 26

GENERAL TREATMENT APPROACH

 The patient should be monitored for dehydration by measuring

body weight, vital signs, and mental alertness.
 With effective symptomatic treatment, the patient can expect
reduced stool frequency and return to normal consistency of
stools, as well as a reduction in generalized symptoms such as
lethargy and abdominal discomfort.
appetite will return to
 As the diarrhea resolves, the patient’s
normal and the patient can resume a regular diet.
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NON-PHARMACOLOGIC THERAPY
FLUID AND ELECTROLYTE MANAGEMENT
 Fluid and Electrolyte Management
 Normal dietary intake should be recommended during bouts of diarrhea.

fatty foods, caffeinated beverages, foods rich in

 However,

simple sugars (Sugary foods can cause osmotic diarrhea), and spicy foods
should be avoided.
 The most important recommendation for treating acute diarrhea is to keep
the individual hydrated.

 Give children complex carbohydrate–rich foods, yogurt, lean meats, fruits, and
vegetables.
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NON-PHARMACOLOGIC THERAPY
FLUID AND ELECTROLYTE MANAGEMENT

 Depending on the patient’s fluid and electrolyte status, oral

treatment may be carried out in two phases:
 Rehydration therapy
 Rehydration over 3–4 hours quickly replaces water and electrolyte deficits
to restore normal body composition.

 Maintenance therapy.
 In themaintenance phase, electrolyte solutions are given to maintain
normal body composition until adequate dietary intake is re-established.
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NON-PHARMACOLOGIC THERAPY
FLUID AND ELECTROLYTE MANAGEMENT
 Fluid and electrolyte replacement by oral rehydration therapy (ORT) is
generally regarded as the first line of treatment for acute diarrhoea, for patients
of any age.

 ORT is not intended to stop diarrhoea, but acute diarrhoea is self-limiting and
normally ceases within 24–48 hours. If mild to moderate fluid loss is present, oral
rehydration solution (ORS) that contains water, salt, and sugar can be recommended.
Ingredients Dose
Sodium chloride (table salt) 90 mEq (½ teaspoon)
Potassium chloride (potassium salt) 20 mEq (¼ teaspoon)
Sodium bicarbonate (baking soda) 30 mEq (½ teaspoon)
Glucose (sugar) 20 g (2 teaspoons)
Water Enough to make 1 L of solution
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NON-PHARMACOLOGIC THERAPY
FLUID AND ELECTROLYTE MANAGEMENT
 Fluid and Electrolyte Management

 Patients may prefer to sip one or two teaspoonful's every few minutes rather
than drink large quantities less frequently.
 Recommended doses for patient age and severity of diarrhea:

Guidelines for fluid- and electrolyte-replacement therapy

Dose
Age Group Mild (2–3 stools/day) Moderate (4–5 stools/day)
> 5 years of age 2 L/first 4 hr, 2–4 L/first 4 hr,
then replace ongoing losses then replace ongoing losses
< 5 years of age 50 mL/kg/first 4 hr, 100 mL/kg/4 hr,
then 10 mL/kg or 1/2–1 cup per stool then 10 mL/kg or 1/2–1 cup per stool
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NON-PHARMACOLOGIC THERAPY
FLUID AND ELECTROLYTE MANAGEMENT

 Mechanism of action
 Oral rehydration salts ( ORS) are designed to replace water and electrolytes lost through
diarrhoea and vomiting, but they are not intended to relieve symptoms.
 They contain:

 Sodium and potassium salts to replace these essential ions.

 Citrate and/or bicarbonate to correct acidosis.
 Glucose is also an important ingredient, as it acts as a carrier for the transport of sodium
ions and hence water across the mucosa of the small intestine.
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PHARMACOLOGIC THERAPY

acute, nonspecific diarrhea is self-limiting, non-

 Although in most cases
prescription antidiarrheal products may provide symptom control and will
usually do no harm when used according to label instructions.

 No antidiarrheal drugs have been shown to significantlyimprove

clinical outcomes for acute, nonspecific diarrhea in infants and children 5
years of age and younger.
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PHARMACOLOGIC THERAPY

Adult Dosages
Drug Pediatric Dosages Duration of Use
(maximum daily dosage)
Not recommended for children <6
years except under medical
supervision
4 mg initially, 6–8 years (22–27 kg): 2 mg initially,
Loperamide followed by 2 mg after each loose followed by 1 mg after each loose 48 hours
stool (not to exceed 8 mg/day) stool (not to exceed 4 mg/day)
9–11 years (27–43 kg):2 mg
initially, followed by 1 mg after each
loose stool (not to exceed 6 mg/day)
Not recommended for children <12
Bismuth 525 mg every 30–60 minutes up to
years except under medical 48 hours
subsalicylate 4200 mg/ day (8 doses/day)
supervision
Digestive Taken with each
enzymes With first bite of dairy product Same as adult dosage consumption of
(lactase) dairy product
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PHARMACOLOGIC THERAPY
LOPERAMIDE

 Loperamide:
 Anopioid agonist is a non-prescription antidiarrheal agent that provides
symptomatic relief of acute, nonspecific diarrhea.
 An antiperistaltic agent provides effective control of diarrhea as quickly
as 1 hr after administration.
 When used according to the labelled instructions, loperamide is safe and
effective.
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PHARMACOLOGIC THERAPY
LOPERAMIDE

 Pharmacokinetic
 Loperamide has a high affinity for, and exerts a direct action on, opiate
receptors in the gut wall.
 It also undergoes extensive first-pass metabolism, and so very little reaches
the systemic circulation; it is unlikely to cause any of the side-effects
associated with opiates at the restricted dosage permitted for non-
prescription use.
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PHARMACOLOGIC THERAPY
LOPERAMIDE

 Mechanism of action:
 Loperamide:
 Reduces daily fecal volume,
 Increases viscosity and bulk volume,
 Reduces fluid and electrolyte loss.

 Itreduces peristalsis and increases intestinal transit time by stimulating

peripheral micro-opioid receptors on the intestinal circular muscles to slow
intestinal motility and allow absorption of electrolytes and water.
 38
PHARMACOLOGIC THERAPY
LOPERAMIDE

 Adverse effects
 At usual doses, loperamide has few adverse effects other than occasional
dizziness and constipation.
 Infrequently occurring adverse effects include abdominal pain, abdominal
distention, nausea, vomiting, dry mouth, fatigue, and hypersensitivity
reactions.
 39
PHARMACOLOGIC THERAPY
LOPERAMIDE

 Drug–drug interactions
 Clinically significant drug–drug interactions are reported for loperamide

 (e.g., quinidine, ketoconazole, ritonavir) may result in a 2- to 3-fold increase in

loperamide plasma concentrations.
 40
PHARMACOLOGIC THERAPY
LOPERAMIDE

 Contraindications.
 Loperamide should not be recommended to individuals presenting with

symptoms of acute bacterial diarrhea (e.g., fever, chills, bloody

diarrhea) as expulsion of the toxin is necessary
 41
PHARMACOLOGIC THERAPY
LOPERAMIDE

not effective in treating your diarrhea (if no

 If loperamide is
clinical improvement is observed in 48 hours), check with
your primary care provider or pharmacist about using a
different non-prescription medication.
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PHARMACOLOGIC THERAPY
BISMUTH SUBSALICYLATE

 Bismuth Subsalicylate
 BSS is FDA approved for management of acute diarrhea, in adults and
children 12 years of age and older; it is not recommended for use in young
children.
 Bismuth subsalicylate is claimed to possess adsorbent properties.

 Bismuth preparations havemoderate effectiveness against the prevention

and treatment of traveler’s diarrhea but doses required for relief are large
and must be administered frequently, so these preparations may be
inconvenient
 43
PHARMACOLOGIC THERAPY
BISMUTH SUBSALICYLATE
 Mechanism of action
 The salicylate moiety exerts antisecretory antidiarrheal effects that:
 Reduce:
 Fluid and electrolyte losses,
 The frequency of unformed stools,
 Nausea,
 Vomiting;
 Increase:
 Stool consistency.
 Relieve:
 Abdominal cramping.

 The bismuth moiety exerts direct antimicrobial effects.

 44
PHARMACOLOGIC THERAPY
BISMUTH SUBSALICYLATE

 Adverse effects:
 BSS is relatively benign in recommended doses.

 Themost remarkable adverse effect is darkening of the tongue and

stools (caused by bismuth ion), which is a harmless effect occurring in >
10% of individuals ingesting BSS.

 In excessive doses, BSS may cause ringing in the ears or

neurotoxicity (e.g., tremor, confusion, seizures, hallucinations.
 45
PHARMACOLOGIC THERAPY
BISMUTH SUBSALICYLATE
 Contraindications:
 BSS is not appropriate to recommend to individuals with haematological
diseases (e.g., hypoprothrombinemia, hemophilia), peptic ulcer disease, documented
allergies to salicylates, children < 12 years of age, and those taking
warfarin therapy.
 BSS should not be used in patients taking aspirin or other salicylates because toxic
salicylate levels may be reached, even when labelled dosing directions for each
medication are followed.
 46
PHARMACOLOGIC THERAPY
DIGESTIVE ENZYMES
 Digestive Enzymes

 Is indicated for individuals who have insufficient amounts of lactase in the

small intestine.
 Thus, this agent is not appropriate to treat any cause of diarrhea other than a lactase
deficiency.

 For patients withlactase deficiency who are intolerant of milk products,

lactase enzyme preparations may be taken with milk or other dairy products
to prevent osmotic diarrhea.

 In the body, lactose (a disaccharide present in dairy products) must be broken

down to glucose and galactose to be fully digested. If the lactase enzyme is
unable to break down the lactose, water is drawn into the gastrointestinal
tract and results in diarrhea.
 47

SPECIAL POPULATIONS

 For young children (up to 5 years of age):

 Self-care measures are limited to treating dehydration with ORS;
 Antidiarrheal medications are not recommended.
 48

SPECIAL POPULATIONS
 Use of non-prescription antidiarrheals may be inappropriate during
pregnancy; therefore, pregnant women also should be referred for
medical evaluation before self-treating, especially if signs and
symptoms of persistent diarrhea, weight loss, malnutrition, or fever
or manifestations of volume depletion are present

 BSS-containing products are contraindicated during

pregnancy salicylate component may
because of concerns that the
inhibit platelet function and, in the third trimester, cause
premature closure of the fetal ductus arteriosus.
 Nursing women generally should avoid BSS.
 49
COMPLEMENTARY THERAPIES
PROBIOTICS

 Probiotics

 Convincing evidence suggests that probiotics, are effective in

preventing and treating mild acute, uncomplicated diarrhea, in
previously healthy infants and children, especially rotavirus diarrhea and
antibiotic-associated diarrhea.
 Probiotics is a means by which an exogenous species of bacteria is
introduced into the gut to re-establish normal gut flora.
 50
COMPLEMENTARY THERAPIES
PROBIOTICS

 Probiotics support gut health by several mechanisms:

 They release antimicrobial substances in the intestines.

 Produce acids (e.g., lactic acid) and short-chain fatty acids that lower intestinal pH
and suppress growth of pathogenic bacteria,
 Enhance mucosal barrier integrity and immune responses.
 Compete with pathogenic bacteria for intestinal mucosal binding sites.
 51
COMPLEMENTARY THERAPIES
PROBIOTICS

 Adverse effects:
 Are benign but can include flatulence with initiation (transient effect) and constipation.

 Contraindications:
 Lactobacillus is not appropriate in any individual with immunosuppression or valvular heart
disease due to the risk of bacteremia, those with a milk allergy/ sensitivity because the product is
dairy based or those younger than the age of 3 years.
 52
COMPLEMENTARY THERAPIES
ZINC SUPPLEMENTATION
 Zinc supplementation
 Compelling evidence demonstrates that daily zinc supplementation reduces the
duration, severity, and persistence of acute diarrhea in children younger than 5 years
of age, especially in countries with a high incidence of zinc deficiencies.
 Zinc supplementation may be of no benefit in developed countries, where zinc deficiency
is rare; therefore, its use is not routinely recommended.

 Mechanism of action:
stimulating intestinal water and electrolyte
 Zinc produces antidiarrheal effects by
absorption, and enhancing overall immunity,

 Adverse effects:
 Of note, zinc supplementation is associated with an increased risk for vomiting.