1. Other Gastrointestinal Drugs1

2. GI Drugs Antiemetics Antidiarrheals Drugs for irritable bowel syndrome
Drugs for inflammatory bowel disease 2

3. 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 3

4. 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 4

5. 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 5

6. 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 6

7. Antiemetics Benzodiazepines Lorazepam (Ativan)
Used in combination regimens to suppress CINV
Three primary benefits
Sedation
Suppression of anticipatory emesis
Production of anterograde amnesia 7

8. Antiemetics Dopamine antagonists Phenothiazines
Block dopamine2 receptors in CTZ
Surgery, cancer, chemotherapy, and toxins
Side effects
Extrapyramidal reactions
Anticholinergic effects
Hypotension and sedation 8

9. 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 9

10. 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 10

11. 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 11

12. 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 12

13. Drugs for Motion Sickness
Scopolamine
Muscarinic antagonist
Side effects
Dry mouth
Blurred vision
Drowsiness 13

14. 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) 14

15. 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 15

16. Diarrhea Management Two major groups of antidiarrheals
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 16

17. 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) 17

18. 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 18

19. Nonspecific Antidiarrheal Agents
Difenoxin
Paregoric
Opium tincture
Bismuth subsalicylate
Bulk-forming agents
Anticholinergic antispasmodics 19

20. 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 20

21. 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 21

22. 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 22

23. 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 23

24. IBS-Specific Drugs Lubriprostone (Amitiza) Tegaserod (Zelnorm)
Approved for constipation-predominant IBS in women age 18 years and older
Tegaserod (Zelnorm)
Short-term therapy of constipation-predominant IBS 24

25. 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 25

26. Drugs for IBD Not curative: may control disease process
Aminosalicylates (sulfasalazine)
Glucocorticoids (hydrocortisone)
Immunosuppressants (azathioprine)
Immunomodulators (infliximab)
Antibiotics (metronidazole) 26

27. 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) 27

28. 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 28

29. 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 29

30. 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 30

31. Anorectal Preparations
Symptomatic relief of hemorrhoids and other anorectal disorders
Local anesthetics
Hydrocortisone
Emollients
Astringents
Multiple formulations available 31