Chapter 16 Cholinesterase Inhibitors
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Transcript Chapter 16 Cholinesterase Inhibitors
Chapter 80
Other Gastrointestinal Drugs
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
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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 ChemotherapyInduced 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 ChemotherapyInduced 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
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