Other Gastrointestinal Drugs Chapter 80 Other Gastrointestinal Drugs 1

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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