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Chapter 80

Other Gastrointestinal Drugs

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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