Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 80 Other Gastrointestinal Drugs.
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 80
Other Gastrointestinal Drugs
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
GI Drugs
Antiemetics Antidiarrheals Drugs for irritable bowel syndrome Drugs for inflammatory bowel disease
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Given to suppress nausea and vomiting Emetic response
Complex reflex after activating vomiting center in medulla oblongata
Several types of receptors involved in emetic response Serotonin, glucocorticoids, substance P,
neurokinin1, dopamine, acetylcholine, and histamine
Many antiemetics interact with one or more of the receptors
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Serotonin receptor antagonists Granisetron, dolasetron, palonosetron Ondansetron (Zofran)
• First approved for chemotherapy-induced nausea and vomiting (CINV)
• Blocks type 3 serotonin receptors on afferent vagal nerve• More effective when used with dexamethasone
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Glucocorticoids Unknown mechanism of action (MOA) as
antiemetic Methylprednisolone (Solu-Medrol) Dexamethasone (Decadron) Commonly used to suppress CINV, but this is not
an FDA-approved application Effective alone and in combination with
antiemetics
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Substance P/neurokinin1 antagonists Aprepitant (Emend)
• Blocks neurokinin1-type receptors (for substance P) in the chemoreceptor trigger zone (CTZ)
• Prevents postoperative nausea/vomiting and CINV• Prolonged duration of action (delayed CINV and acute)• Adverse effects• Drug interaction
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Benzodiazepines Lorazepam (Ativan) Used in combination regimens to suppress CINV Three primary benefits
• Sedation• Suppression of anticipatory emesis• Production of anterograde amnesia
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Dopamine antagonists Phenothiazines
• Block dopamine2 receptors in CTZ• Surgery, cancer, chemotherapy, and toxins• Side effects
Extrapyramidal reactions Anticholinergic effects Hypotension and sedation
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Butyrophenones Haloperidol (Haldol) and droperidol (Inapsine)
• Block dopamine2 receptors in CTZ• Postoperative nausea/vomiting, chemotherapy emesis,
radiation therapy, and toxins• Side effects
Similar to phenothiazines May cause prolonged QT and fatal dysrhythmias
Electrocardiographic monitoring needed
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiemetics
Metoclopramide (Reglan) Blocks dopamine receptors in CTZ Postoperative nausea/vomiting, anticancer drug,
opioids, toxins, radiation therapy Cannabinoids
• Dronabinol (Marinol) and nabilone (Cesamet)• Related to marijuana• CINV • MOA with emesis unclear• Potential for abuse and psychotomimetic effects
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Management of Chemotherapy- Induced Nausea and Vomiting
Three types of emesis Anticipatory
• Occurs before drugs are given Acute
• Onset within minutes to a few hours Delayed
• Onset 1 day or longer after drug received
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Management of Chemotherapy-Induced Nausea and Vomiting
Antiemetics are more effective in preventing CINV than suppressing CINV in progress
Give before chemotherapy drugs Monotherapy and combination therapy may
be needed
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs for Motion Sickness
Scopolamine Muscarinic antagonist Side effects
• Dry mouth• Blurred vision• Drowsiness
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs for Motion Sickness
Antihistamines Dimenhydrinate (Dramamine), meclizine (Antivert),
cyclizine (Marezine) Considered anticholinergics—block receptors for
acetylcholine and histamine Side effects
• Sedation (H1-receptor blocking) • Dry mouth, blurred vision, urinary retention, constipation
(muscarinic receptor blocking)
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Diarrhea
Characterized by stools of excessive volume and fluidity and increased frequency of defecation
Symptom of GI disease Causes
Infection, maldigestion, inflammation, functional disorders of the bowel
Complications Dehydration and electrolyte depletion
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Diarrhea
Management Diagnosis and treatment of underlying disease Replacement of lost water and salts Relief of cramping Reducing passage of unformed stools
Two major groups of antidiarrheals Specific antidiarrheal drugs Nonspecific antidiarrheal drugs
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Nonspecific Antidiarrheal Agents
Opioids Most effective antidiarrheal agents Activate opioid receptors in GI tract
• Decrease intestinal motility• Slow intestinal transit• Allow more fluid to be absorbed• Decrease secretion of fluid into small intestine and
increase absorption of fluid and salt Diphenoxylate (Lomotil) and loperamide (Imodium)
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Nonspecific Antidiarrheal Agents
Opioids Diphenoxylate (Lomotil)
• Formulated with atropine to discourage abuse• Opioid used only for diarrhea• High doses can elicit typical morphine-like subjective
responses Loperamide
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Nonspecific Antidiarrheal Agents
Difenoxin Paregoric Opium tincture Bismuth subsalicylate Bulk-forming agents Anticholinergic antispasmodics
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Management of Infectious Diarrhea
General considerations Variety of bacteria and protozoa can be
responsible Infections are usually self-limited Many cases require no treatment Antibiotics should be used only when clearly
indicated Traveler’s diarrhea
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Irritable Bowel Syndrome
IBS: most common disorder of GI tract 20% of Americans affected 3× higher incidence in women than in men
Characterized by cramping abdominal pain (may be severe) that cannot be explained by structural or chemical abnormalities
May occur with diarrhea, constipation, or both Considered IBS when symptoms have been
present for 12 weeks over the past year
22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Irritable Bowel Syndrome
Four groups of drugs historically used American College of Gastroenterology concluded
that most of these agents do not have proof of clinical benefits• Antispasmodics• Bulk-forming agents• Antidiarrheals• Tricyclic antidepressants
Two studies suggest that antibiotics or an acid suppressant may be effective for some patients
23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
IBS-Specific Drugs
Alosetron (Lotronex) Potentially dangerous drug; approved for women
only GI toxicities can cause complicated constipation,
leading to perforation and ischemic colitis Introduced in 2000, withdrawn in less than 10
months, and reintroduced in 2002
24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
IBS-Specific Drugs
Lubriprostone (Amitiza) Approved for constipation-predominant IBS in
women age 18 years and older Tegaserod (Zelnorm)
Short-term therapy of constipation-predominant IBS
25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Inflammatory Bowel Disease
IBD: caused by exaggerated immune response against normal bowel flora
Crohn’s disease Characterized by transmural inflammation Usually affects terminal ileum (can impact all parts
of GI tract) Ulcerative colitis
Inflammation of the mucosa and submucosa of the colon and rectum
May cause rectal bleeding May require hospitalization
26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs for IBD
Not curative: may control disease process Aminosalicylates (sulfasalazine) Glucocorticoids (hydrocortisone) Immunosuppressants (azathioprine) Immunomodulators (infliximab) Antibiotics (metronidazole)
27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Prokinetic Agents
Increase tone and motility of GI tract GERD, CINV, diabetic gastroparesis Metoclopramide (Reglan, Maxolon,
Octamide) Blocks receptors for dopamine and serotonin in
the CTZ Increases upper GI motility and suppresses
emesis Cisapride (Propulsid)
28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Palifermin (Kepivance)
First drug approved for decreasing oral mucositis (OM) Currently indicated only for patients with
hematologic malignancies (can stimulate proliferation of malignant cells of nonhematologic origin)
Synthetic form of human keratinocyte growth factor (KGF)
Stimulates proliferation, differentiation, and migration of epithelial cells
29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Pancreatic Enzymes
Deficiency of enzymes compromises digestion
Pancreatin: hog or beef pancreas Pancrelipase: hog pancreas
Preferred because enzyme activity is far greater than that of pancreatin
Enteric-coated microspheres
30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs Used to Dissolve Gallstones
Chenodiol (chenodeoxycholic acid) Useful for radiolucent stones (not calcium) Increases production of bile acids Most successful in women with low cholesterol
levels Ursodiol (ursodeoxycholic acid)
Does not increase bile acids Reduces the cholesterol content of bile Gradual dissolution of stones
31Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Anorectal Preparations
Symptomatic relief of hemorrhoids and other anorectal disorders Local anesthetics Hydrocortisone Emollients Astringents
Multiple formulations available
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