1. Other Gastrointestinal Drugs
Chapter 80
Other Gastrointestinal Drugs 1

2. 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 2

3. 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 (these drugs together are first-line for many highly emetogenic chemotherapy regimens) 3

4. 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 4

5. 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)- for DELAYED nausea and vomiting
Adverse effects
Drug interaction 5

6. Antiemetics Benzodiazepines Lorazepam (Ativan)
Used in combination regimens to suppress CINV
Three primary benefits
Sedation
Suppression of anticipatory emesis
Production of anterograde amnesia 6

7. Antiemetics Dopamine antagonists
Phenothiazines (prochlorperazine, promethazine)
Block dopamine2 receptors in CTZ
Surgery, cancer, chemotherapy, and toxins
Side effects
Extrapyramidal reactions
Anticholinergic effects
Hypotension and sedation 7

8. 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 8

9. Antiemetics Metoclopramide (Reglan) Blocks dopamine receptors in CTZ
Postoperative nausea/vomiting, anticancer drug, opioids, toxins, radiation therapy 9

10. Cannabinoids Dronabinol (Marinol) and nabilone (Cesamet)
Related to marijuana
CINV
MOA with emesis unclear
Potential for abuse and psychotomimetic effects (caution in patients with history of psychotic or anxiety disorders

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
Many do not cross the blood-brain barrier like opioids given for pain
Many are not water-soluble and can’t be injected
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