Dr. Omar Rashid Sadeq, MD, PhD.

Associate Prof. of Clinical Pharmacology & Therapeutics

Physiology and Pharmacology Department
. AAUP
Faculty of Medicine,
LECTURE-32 ANTIDIARRHEAL DRUGS AND LAXATIVE AGENTS
1. Identify the therapeutic strategies of antidiarrheal drugs,
main classes and explain their M.O.
2. Understand the major unwanted effects produced by
antidiarrheals.
3. Classify the major classes of medications utilized as
laxatives, their pharmacokinetics and dynamics.
4. Determine clinical indications, contraindications and side
effects of commonly used laxatives.
5. Summarize the major pharmacologic groups used in
inflammatory bowel diseases.
 DIARRHEA
Diarrhea (frequent liquid stool) at least three loose, liquid, or watery gut movements in a day.
Causes of diarrhea include:
foods (spicy, spoiled), bacteria (Escherichia coli, Salmonella) or viruses ,toxins, drug reaction,
laxative abuse, malabsorption syndrome caused by lack of digestive enzymes, stress and
anxiety, bowel tumor, and inflammatory bowel disease such as ulcerative colitis or Crohn’s
disease. Diarrhea can be mild to severe.
Antidiarrheals should not be used for more than 2 days and should not be used if fever is
present.
Because intestinal fluids are rich in water, sodium, potassium, and bicarbonate, diarrhea can
cause minor or severe dehydration and electrolyte imbalances. The loss of bicarbonate places
the patient at risk for developing metabolic acidosis.
Traveler’s Diarrhea: also called acute diarrhea, is usually caused by E. coli. It ordinarily lasts
less than 2 days; however, if it becomes severe, fluoroquinolone antibiotics are usually
prescribed.
 CLINICAL CASE STUDY
A 75-year-old man with terminal metastatic lung cancer had been
hospitalized for 3 months. His renal function had deteriorated, and
laboratory results showed elevated creatinine and BUN. Because of poor
food intake, immobility and requirement for an opioid analgesia, the
patient was severely constipated and required daily laxative therapy.
Which of the following would be a suitable laxative for this patient?
A. Lactulose.
B. Castor oil.
C. Magnesium hydroxide.
D. Sodium phosphate.
E. Mineral oil.
 MANAGEMENT OF DIARRHEA
1. Non-specific therapy:
a) Oral and parenteral rehydration: NaCl, KCl, sodium citrate or glucose dissolved in1
liter of water.
b) Antimotility and antisecretory agents:
i) Opioids:, diphenoxylate and loperamide
ii) α-adrenergic receptor agonist: clonidine
iii) Octreotide.
2. Specific therapy:
a. Antimicrobial agents: macrolides and fluoroquinolones.
b. Antispasmodics: Atropine & oxyphenonium bromide.
c. Adsorbents: Kaolin-pectin and chalk (Ca carbonate) and bismuth subsalicylate.
Probiotic
 ANTIMOTILITY AND ANTISECRETORY AGENTS
1. Codeine: opium alkaloid, reduces GI motility, also has antisecretory effects.
2. Diphenoxylate: structurally related to pethidine, combined with small doses with
atropine, side effects are constipation and paralytic ileus.
3. Loperamide: (the drug of choice for Tx of diarrhea): an opiate analogue and is
more important antidiarrheal agent than morphine: poorly penetrates BBB and has
no abuse potential. Can be used in acute and chronic and traveler's diarrhea.
M.O: Interacts with µ-receptor in the gut, reduces GI motility and increases anal
sphincter tone.
Adverse reactions:
Skin rashes, headache, and paralytic ileus, should not be used in children <4
years of age.
Contraindications: should be avoided in infectious diarrheas and IBD.
 ANTIMOTILITY AND ANTISECRETORY
4. Clonidine: it has antimotility and antisecretory activities,
used in diabetics with autonomic neuropathy.
5. Octreotide: analogue of somatostatin, inhibits 5-HT &
VIP, gastrin, used in refractory diarrhea in patients with
AIDS.
6. Racecadotril: inhibits degradation of enkephalins: is
used for the treatment of acute diarrhea in children and
adults and has better tolerability than loperamide, (less
constipation and flatulence).
Side effects: headache, nausea, vomiting and drowsiness.
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 LAXATIVES
qConstipation (accumulation of hard fecal material in the large intestine, usually fewer than 3 stools per week.
Constipation is a relatively common complaint and a major problem for older adults.
qCauses of constipation: Insufficient water intake and poor dietary habits are contributing factors. Other causes
include (1) fecal impaction, (2) bowel obstruction, (3) chronic laxative use, (4) neurologic disorders (paraplegia), (5)
ignoring the urge to defecate, (6) lack of exercise, and (7) selected drugs, such as anticholinergics, narcotics, and
certain antacids.
qLaxatives and cathartics are used to eliminate fecal matter. Laxatives promote a soft stool, cathartics result in a
soft to watery stool with some cramping, and frequently dosage determines whether a drug acts as a laxative or
cathartic. Purgatives are “harsh” cathartics that cause a watery stool with abdominal cramping.
qThere are four types of laxatives:
(1) Osmotics (saline), (2) Stimulants (contact or irritants), (3) Bulk-forming, (4) Emollients (stool softeners).
qLaxatives should be avoided if there is any question that the patient may have intestinal obstruction; if
abdominal pain is severe; or if symptoms of appendicitis, ulcerative colitis, or diverticulitis are present.
qMost laxatives stimulate peristalsis. Laxative abuse from chronic use is a common problem, especially in older
adults.
qLaxative dependence can become a problem, so patient teaching is an important medical responsibility.
 I. OSMOTIC (SALINE) LAXATIVES
q Osmotics (hyperosmolar laxatives) include salts or saline products, lactulose,
and glycerin. Saline products consist of sodium or magnesium. Hyperosmolar salts
pull water into the colon and increase water in the feces to increase bulk, which
stimulates peristalsis. Saline cathartics cause a semiformed to watery stool
according to low or high doses. Saline cathartics are contraindicated in patients
with heart failure.
q Osmotic laxatives contain electrolyte salts, including (1) Sodium salts (sodium
phosphate or sodium biphosphate) and (2) Magnesium salts (magnesium
hydroxide or magnesium citrate). High doses of salt laxatives are used for bowel
preparation for diagnostic and surgical procedures.
q Lactulose, another saline laxative that is not absorbed, draws water into the
intestines to form a soft stool. It decreases the serum ammonia level and is useful
in liver diseases.
qPatients who have diabetes mellitus should avoid lactulose, because it contains
glucose and fructose.
 II. STIMULANT (CONTACT) LAXATIVES
qStimulant (contact or irritant) laxatives increase peristalsis by irritating sensory nerve endings
in the intestinal mucosa.
qTypes include those containing bisacodyl (Dulcolax), senna and castor oil.
qBisacodyl is the most frequently used and abused laxative and can be purchased OTC.
Bisacodyl and several others of these drugs are used to empty the bowel before diagnostic
tests (barium enema).
q Castor oil is a harsh laxative (purgative) that acts on the small bowel and produces a
watery stool. The action is quick within 2 to 6 hours, so the laxative should not be taken at
bedtime. Castor oil is seldom used to correct constipation. It is used mainly for bowel
preparation.
Adverse Effects
qWith excessive and chronic use of bisacodyl, fluid and electrolyte (especially potassium and
calcium) imbalances are likely to occur. Systemic effects occur infrequently, because absorption
of bisacodyl is minimal. Mild cramping and diarrhea are side effects of bisacodyl.
qCastor oil should not be used in early pregnancy, because it stimulates uterine contraction.
qProlonged use of senna can damage nerves, which may result in loss of intestinal muscular
tone.
 III. BULK-FORMING LAXATIVES
q Psyllium (Prototype drug) Polycarbophil calcium, Polyethylene glycol and Methylcellulose.
qBulk-forming laxatives are natural fibrous substances that promote large, soft stools by
absorbing water into the intestine, increasing fecal bulk and peristalsis. These agents are
nonabsorbable.
qDefecation usually occurs within 8 to 24 hours; however, it may take up to 3 days after drug
therapy is started for the stool to be soft and well formed.
qPowdered bulk-forming laxatives, which sometimes come in flavored and sugar-free forms,
should be mixed in a glass of water or juice, stirred, drunk immediately, and followed by a half
to a full glass of water. Insufficient fluid intake can cause the drug to solidify in the GI tract, which
can result in intestinal obstruction.
qThis group of laxatives does not cause laxative dependence and may be used by patients
with diverticulosis, irritable bowel syndrome, and ileostomy and colostomy. Patients with
hypercalcemia should avoid polycarbophil calcium because of the significant amount of calcium in
the drug.
 IV. EMOLLIENTS (STOOL SOFTENERS)
q Docusate sodium, docusate calcium and docusate sodium with Senna.
q M.O: Emollients are lubricants and stool softeners work by lowering
surface tension and promoting water and fat accumulation in the intestine
and stool. They decrease straining during defecation. Lubricants such as
mineral oil increase water retention in the stool. Mineral oil interfere with
absorption of essential fat-soluble vitamins A, D, E, and K.
q Uses:
q Sodium docusate is recommended as a stool softener for children.
q Frequently prescribed for patients after myocardial infarction or
surgery.
q Side effects: Uncommon, gastric pain, diarrhea, allergic reactions and
rectal bleeding (rare).