a brief description of the topic antidiarrheal pharmacology

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ANTI DIARRHEAL
DRUGS
B Y D R N A I L A R I A S AT A L I
L e c t u r e r
M e d i c a l C o l l e g e
U n i v e r s i t y o f G u j r a t , P a k i s t a n .
n l r i a s a t @ g m a i l . c o m

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General Rule
• 7-8L daily fluids in to GIT tract
• Anti Diarrheal Drugs
1) Anti Motility-
Codeine
Diphenoxylate
Loperamide
2) Drugs that increase viscosity of gut contents-
Kaolin
Chalk
• Diarrhoea is defined as the passage of three or more loose or liquid
stools per day (or more frequent passage than is normal for the
individual). 2

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• Antidiarrheal agents may be used safely in patients with mild to
moderate acute diarrhea.
• These agents should not be
• used in patients with bloody diarrhea,
• high fever, or systemic toxicity because of the risk of worsening
the underlying condition.
• They should be discontinued in patients whose diarrhea is
worsening despite therapy.
• Antidiarrheals are also used to control chronic diarrhea caused by
such conditions as IBS or inflammatory bowel disease (IBD).

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OPIOID AGONISTS
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• By inhibition of presynaptic cholinergic nerves in the submucosal and
myenteric plexuses lead to increased colonic transit time and fecal water
absorption.
• They also decrease mass colonic movements and the gastrocolic reflex.
• Commonly used:
• Loperamide :is a opioid agonist that does not cross the blood-brain barrier
and has no analgesic properties or potential for addiction.
• Administered in doses of 2 mg taken one to four times daily.
• Diphenoxylate: is a prescription opioid agonist
• that has no analgesic properties in standard doses; however, prolonged use
can lead to opioid dependence.
• Commercial preparations commonly contain small amounts of atropine to
discourage overdosage (2.5 mg diphenoxylate with 0.025 mg atropine)

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OPIOID AGONISTS
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• Eluxadoline: is a prescription opioid agonist with high
affinity for the mu receptor
• binds to gut opioid receptors, resulting in slower colonic
transit and increased fecal fluid absorption.
• diarrhea-predominant IBS FDA approved use
• should not be used in patients with a history of pancreatitis,
alcoholism, or known sphincter of Oddi disease.
• Caution is advised in patients with prior cholecystectomy

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COLLOIDAL BISMUTH COMPOUNDS
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• Two bismuth compounds are available: bismuth subsalicylate, a
formulation containing bismuth subsalicylate, and bismuth subcitrate
potassium.
• Bismuth subsalicylate undergoes rapid dissociation within the stomach,
allowing absorption of salicylate.
• 99% of the bismuth appears in the stool.
• Salicylate (like aspirin) is readily absorbed and excreted in the urine.
• M.O.A: precise mechanisms of action of bismuth are unknown
• coats ulcers and erosions, creating a protective layer acid and pepsin.
• also stimulate prostaglandin, mucus, and bicarbonate secretion.

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COLLOIDAL BISMUTH COMPOUNDS
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• Bismuth subsalicylate reduces stool frequency and liquidity in acute
infectious diarrhea, due to salicylate inhibition of intestinal prostaglandin
and chloride secretion.
• Bismuth has direct antimicrobial effects and binds enterotoxins,as for its
benefit in preventing and treating traveler’s diarrhea.
• Bismuth compounds have direct antimicrobial activity against H pylori.
• Clinical Uses: Kaopectate) are widely used by
• patients for the nonspecific treatment of dyspepsia and acute diarrhea.
• Bismuth subsalicylate also is used for the prevention of traveler’s diarrhea
(30 mL or two tablets four times daily).
• Adverse Effects: excellent safety profiles
• harmless blackening of the stool
• High dosages of bismuth subsalicylate may lead to salicylate toxicity.

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BILE SALT-BINDING RESINS
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• The bile salt-binding resins cholestyramine, colestipol, or
colesevelam, may decrease diarrhea caused by excess fecal bile
acids
• Conjugated bile salts are normally absorbed in the terminal ileum.
• Disease of the terminal ileum (eg, Crohn’s disease) or surgical
resection leads to malabsorption of bile salts, which may cause
colonic secretory diarrhea.
• Powder or pill formulations that may be taken one to three times
daily before meals.
• Adverse Effects: bloating, flatulence, constipation, and fecal
impaction.
• Cholestyramine and colestipol bind a number of drugs and reduce
their absorption.

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OCTREOTIDE
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• Somatostatin is a 14-amino-acid peptide that is released in the
gastrointestinal tract and pancreas from paracrine cells, D cells, and enteric
nerves as well as from the hypothalamus
• Somatostatin is a key regulatory peptide that has many physiologic effects:
• 1. It inhibits the secretion of numerous hormones and transmitters,
• including gastrin, cholecystokinin, glucagon, growth
• hormone, insulin, secretin, pancreatic polypeptide, vasoactive
• intestinal peptide, and 5-HT.
• 2. It reduces intestinal fluid secretion and pancreatic secretion.
• 3. It slows gastrointestinal motility and inhibits gallbladder
• contraction.
• 4. It reduces portal and splanchnic blood flow.
• 5. It inhibits secretion of some anterior pituitary hormones

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OCTREOTIDE
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• Somatostatin has short half-life in the circulation (3 minutes) when it is
administered by intravenous injection
• Octreotide is a synthetic octapeptide with actions similar to somatostatin.When
administered intravenously, it has a serum half-life of 1.5 hours
• by subcutaneous injection, resulting in a 6- to 12-hour duration of action.
• A longer-acting formulation is available for once-monthly depot intramuscular
injection.
• Clinical Uses:
• 1. Inhibition of endocrine tumor effects—Two gastrointestinal neuroendocrine
tumors (carcinoid, VIPoma) cause secretory diarrhea and systemic symptoms such
as flushing and wheezing.
• For patients with advanced symptomatic tumors that cannot be completely
removed by surgery, octreotide decreases secretory diarrhea and systemic
symptoms through inhibition of hormonal secretion and may slow tumor
progression.

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OCTREOTIDE
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• 2. Other causes of diarrhea—Octreotide inhibits intestinal secretion and has
dose-related effects on bowel motility.
• In low doses (50 mcg subcutaneously), it stimulates motility, whereas at
higher doses (eg, 100–250 mcg subcutaneously), it inhibits motility.
• Octreotide is effective in higher doses for the treatment of diarrhea due to
vagotomy or dumping syndrome as well as for diarrhea caused by short
bowel syndrome or AIDS.
• Octreotide has been used in low doses (50 mcg subcutaneously) to stimulate
small bowel motility in patients with small bowel bacterial overgrowth or
intestinal pseudo-obstruction secondary to scleroderma.
• 3. Other uses—inhibits pancreatic secretion, octreotide may be of value in
patients with pancreatic fistula.
• It has role of octreotide in the treatment of pituitary tumors (eg,
acromegaly).
• Octreotide is sometimes used in gastrointestinal bleeding.

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OCTREOTIDE
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• Adverse Effects: Impaired pancreatic secretion may cause
steatorrhea, which can
• lead to fat-soluble vitamin deficiency.
• Alterations in gastrointestinal motility cause nausea, abdominal pain,
flatulence, and diarrhea.
• Because of inhibition of gallbladder contractility and alterations in fat
absorption, long-term use of octreotide can cause formation of sludge
or gallstones in over 50% of patients, which rarely results in the
development of acute cholecystitis.
• Because octreotide alters the balance among insulin, glucagon, and
growth hormone, hyperglycemia or, less frequently, hypoglycemia
(usually mild) can occur.
• Prolonged treatment with octreotide may result in hypothyroidism.
• Octreotide also can cause bradycardia.

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