Download Chapter 16 Cholinesterase Inhibitors

Other Gastrointestinal Drugs
GI Drugs
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Antiemetics
Antidiarrheals
Drugs for irritable bowel syndrome
Drugs for inflammatory bowel disease
Antiemetics
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Given to suppress nausea and vomiting
Emetic response
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Complex reflex after activating vomiting center in
medulla oblongata
Several types of receptors involved in emetic
response
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Serotonin, glucocorticoids, substance P,
neurokinin1, dopamine, acetylcholine, and
histamine
Many antiemetics interact with one or more of the
receptors
Antiemetics
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Serotonin receptor antagonists
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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
Antiemetics
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Glucocorticoids
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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
Antiemetics
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Substance P/neurokinin1 antagonists
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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
Antiemetics
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Benzodiazepines
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Lorazepam (Ativan)
Used in combination regimens to suppress CINV
Three primary benefits
• Sedation
• Suppression of anticipatory emesis
• Production of anterograde amnesia
Antiemetics
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Dopamine antagonists
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Phenothiazines
• Block dopamine2 receptors in CTZ
• Surgery, cancer, chemotherapy, and toxins
• Side effects
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Extrapyramidal reactions
Anticholinergic effects
Hypotension and sedation
Antiemetics
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Butyrophenones
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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
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Metoclopramide (Reglan)
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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
Management of ChemotherapyInduced Nausea and Vomiting
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Three types of emesis
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Anticipatory
• Occurs before drugs are given
 Acute
• Onset within minutes to a few hours
 Delayed
• Onset 1 day or longer after drug received
Management of ChemotherapyInduced Nausea and Vomiting
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Antiemetics are more effective in preventing
CINV than suppressing CINV in progress
Give before chemotherapy drugs
Monotherapy and combination therapy may
be needed
Drugs for Motion Sickness
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Scopolamine
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Muscarinic antagonist
Side effects
• Dry mouth
• Blurred vision
• Drowsiness
Drugs for Motion Sickness
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Antihistamines
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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)
Diarrhea
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Characterized by stools of excessive volume
and fluidity and increased frequency of
defecation
Symptom of GI disease
Causes
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Infection, maldigestion, inflammation, functional
disorders of the bowel
Complications
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Dehydration and electrolyte depletion
Diarrhea
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Management
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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
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Specific antidiarrheal drugs
Nonspecific antidiarrheal drugs
Nonspecific Antidiarrheal Agents
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Opioids
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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
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Diphenoxylate (Lomotil) and loperamide
(Imodium)
Nonspecific Antidiarrheal Agents
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Opioids
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Diphenoxylate (Lomotil)
• Formulated with atropine to discourage abuse
• Opioid used only for diarrhea
• High doses can elicit typical morphine-like subjective
responses
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Loperamide
Nonspecific Antidiarrheal Agents
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Difenoxin
Paregoric
Opium tincture
Bismuth subsalicylate
Bulk-forming agents
Anticholinergic antispasmodics
Management of Infectious Diarrhea
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General considerations
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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
Irritable Bowel Syndrome
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IBS: most common disorder of GI tract
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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
Irritable Bowel Syndrome
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Four groups of drugs historically used
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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
IBS-Specific Drugs
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Alosetron (Lotronex)
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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
IBS-Specific Drugs
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Lubriprostone (Amitiza)
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Approved for constipation-predominant IBS in
women age 18 years and older
Tegaserod (Zelnorm)
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Short-term therapy of constipation-predominant
IBS
Inflammatory Bowel Disease
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IBD: caused by exaggerated immune
response against normal bowel flora
Crohn’s disease
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Characterized by transmural inflammation
Usually affects terminal ileum (can impact all parts
of GI tract)
Ulcerative colitis
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Inflammation of the mucosa and submucosa of the
colon and rectum
May cause rectal bleeding
May require hospitalization
Drugs for IBD
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Not curative: may control disease process
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Aminosalicylates (sulfasalazine)
Glucocorticoids (hydrocortisone)
Immunosuppressants (azathioprine)
Immunomodulators (infliximab)
Antibiotics (metronidazole)
Prokinetic Agents
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Increase tone and motility of GI tract
GERD, CINV, diabetic gastroparesis
Metoclopramide (Reglan, Maxolon,
Octamide)
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Blocks receptors for dopamine and serotonin in
the CTZ
Increases upper GI motility and suppresses
emesis
Cisapride (Propulsid)
Palifermin (Kepivance)
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First drug approved for decreasing oral
mucositis (OM)
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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
Pancreatic Enzymes
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Deficiency of enzymes compromises
digestion
Pancreatin: hog or beef pancreas
Pancrelipase: hog pancreas
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Preferred because enzyme activity is far greater
than that of pancreatin
Enteric-coated microspheres
Drugs Used to Dissolve Gallstones
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Chenodiol (chenodeoxycholic acid)
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Useful for radiolucent stones (not calcium)
Increases production of bile acids
Most successful in women with low cholesterol
levels
Ursodiol (ursodeoxycholic acid)
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Does not increase bile acids
Reduces the cholesterol content of bile
Gradual dissolution of stones
Anorectal Preparations
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Symptomatic relief of hemorrhoids and other
anorectal disorders
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Local anesthetics
Hydrocortisone
Emollients
Astringents
Multiple formulations available