Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 80 Other Gastrointestinal Drugs

2 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. GI Drugs  Antiemetics  Antidiarrheals  Drugs for irritable bowel syndrome  Drugs for inflammatory bowel disease

3 Copyright © 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, neurokinin 1, dopamine, acetylcholine, and histamine  Many antiemetics interact with one or more of the receptors

4 Copyright © 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) First approved for chemotherapy-induced nausea and vomiting (CINV) Blocks type 3 serotonin receptors on afferent vagal nerve Blocks type 3 serotonin receptors on afferent vagal nerve More effective when used with dexamethasone More effective when used with dexamethasone

5 Copyright © 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

6 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antiemetics  Substance P/neurokinin 1 antagonists  Aprepitant (Emend) Blocks neurokinin 1 -type receptors (for substance P) in the chemoreceptor trigger zone (CTZ) Blocks neurokinin 1 -type receptors (for substance P) in the chemoreceptor trigger zone (CTZ) Prevents postoperative nausea/vomiting and CINV Prevents postoperative nausea/vomiting and CINV Prolonged duration of action (delayed CINV and acute) Prolonged duration of action (delayed CINV and acute) Adverse effects Adverse effects Drug interaction Drug interaction

7 Copyright © 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

8 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antiemetics   Dopamine antagonists   Phenothiazines Block dopamine 2 receptors in CTZ Surgery, cancer, chemotherapy, and toxins Side effects   Extrapyramidal reactions   Anticholinergic effects   Hypotension and sedation

9 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antiemetics   Butyrophenones   Haloperidol (Haldol) and droperidol (Inapsine) Block dopamine 2 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

10 Copyright © 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

11 Copyright © 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 Occurs before drugs are given  Acute Onset within minutes to a few hours Onset within minutes to a few hours  Delayed Onset 1 day or longer after drug received Onset 1 day or longer after drug received

12 Copyright © 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

13 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drugs for Motion Sickness  Scopolamine  Muscarinic antagonist  Side effects Dry mouth Dry mouth Blurred vision Blurred vision Drowsiness Drowsiness

14 Copyright © 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 (H 1 -receptor blocking) Sedation (H 1 -receptor blocking) Dry mouth, blurred vision, urinary retention, constipation (muscarinic receptor blocking) Dry mouth, blurred vision, urinary retention, constipation (muscarinic receptor blocking)

15 Copyright © 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

16 Copyright © 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

17 Copyright © 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 Decrease intestinal motility Slow intestinal transit Slow intestinal transit Allow more fluid to be absorbed Allow more fluid to be absorbed Decrease secretion of fluid into small intestine and increase absorption of fluid and salt Decrease secretion of fluid into small intestine and increase absorption of fluid and salt  Diphenoxylate (Lomotil) and loperamide (Imodium)

18 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nonspecific Antidiarrheal Agents  Opioids  Diphenoxylate (Lomotil) Formulated with atropine to discourage abuse Formulated with atropine to discourage abuse Opioid used only for diarrhea Opioid used only for diarrhea High doses can elicit typical morphine-like subjective responses High doses can elicit typical morphine-like subjective responses  Loperamide

19 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nonspecific Antidiarrheal Agents  Difenoxin  Paregoric  Opium tincture  Bismuth subsalicylate  Bulk-forming agents  Anticholinergic antispasmodics

20 Copyright © 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

21 Copyright © 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

22 Copyright © 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 Antispasmodics Bulk-forming agents Bulk-forming agents Antidiarrheals Antidiarrheals Tricyclic antidepressants Tricyclic antidepressants  Two studies suggest that antibiotics or an acid suppressant may be effective for some patients

23 Copyright © 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

24 Copyright © 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

25 Copyright © 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

26 Copyright © 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)

27 Copyright © 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)

28 Copyright © 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

29 Copyright © 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

30 Copyright © 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

31 Copyright © 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