chapter 80
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Chapter 80. Other Gastrointestinal Drugs. GI Drugs . Antiemetics Antidiarrheals Drugs for irritable bowel syndrome Drugs for inflammatory bowel disease. Antiemetics. Given to suppress nausea and vomiting Emetic response - PowerPoint PPT PresentationTRANSCRIPT
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 80
Other Gastrointestinal Drugs
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2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
GI Drugs Antiemetics Antidiarrheals Drugs for irritable bowel syndrome Drugs for inflammatory bowel disease
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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
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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
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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
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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
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Antiemetics Benzodiazepines
Lorazepam (Ativan) Used in combination regimens to suppress CINV Three primary benefits
• Sedation• Suppression of anticipatory emesis• Production of anterograde amnesia
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Antiemetics Dopamine antagonists
Phenothiazines• Block dopamine2 receptors in CTZ• Surgery, cancer, chemotherapy, and toxins• Side effects
Extrapyramidal reactions Anticholinergic effects Hypotension and sedation
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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
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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
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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
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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
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Drugs for Motion Sickness Scopolamine
Muscarinic antagonist Side effects
• Dry mouth• Blurred vision• Drowsiness
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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)
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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
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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
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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)
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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
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Nonspecific Antidiarrheal Agents Difenoxin Paregoric Opium tincture Bismuth subsalicylate Bulk-forming agents Anticholinergic antispasmodics
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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
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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
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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
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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
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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
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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
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Drugs for IBD Not curative: may control disease process
Aminosalicylates (sulfasalazine) Glucocorticoids (hydrocortisone) Immunosuppressants (azathioprine) Immunomodulators (infliximab) Antibiotics (metronidazole)
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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)
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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
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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
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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
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Anorectal Preparations Symptomatic relief of hemorrhoids and other
anorectal disorders Local anesthetics Hydrocortisone Emollients Astringents
Multiple formulations available