Chapter 66: Other GI Drugs Flashcards
GI drugs
Antiemetics
Antidiarrheals
Drugs for irritable bowel syndrome
Drugs for inflammatory bowel disease
Antiemetics
Given to suppress nausea and vomiting
Emetic response
Complex reflex that occurs after activation of vomiting center in the medulla oblongata
Several types of receptors involved in emetic response:
Serotonin, glucocorticoids, substance P, neurokinin1, dopamine, acetylcholine, histamine
Many antiemetics interact with one or more of the receptors
Antiemetics: Serotonin receptor antagonists
Granisetron, dolasetron, palonosetron
Ondansetron [Zofran]
First approved for chemotherapy-induced nausea and vomiting (CINV)
Also used to prevent nausea and vomiting associated with radiotherapy and anesthesia
Blocks type 3 serotonin receptors on afferent vagal nerve
More effective when used with dexamethasone
Adverse effects: Headache, diarrhea, dizziness, prolonged QT interval, risk of torsades de pointes
Antiemetic: Glucocorticoids
Unknown mechanism of action (MOA) as antiemetic
Methylprednisolone
Dexamethasone
Commonly used to suppress CINV; however, this is not an application approved by the U.S. Food and Drug Administration (FDA)
Effective alone and in combination with antiemetics
Antiemetics: Substance P/neurokinin1 antagonists
Aprepitant
Blocks neurokinin1-type receptors (for substance P) in the chemoreceptor trigger zone (CTZ)
Prevents postoperative nausea/vomiting and CINV
Prolonged duration of action
Adverse effects: Generally well tolerated
Drug interaction: CYP3A4, CYP2D6
Antiemetics: Benzo
Lorazepam [Ativan]
Used in combination regimens to suppress CINV
Three primary benefits:
Sedation
Suppression of anticipatory emesis
Production of anterograde amnesia
Antiemetics: dopamine antagonist, Phenothiazines: Prochlorperazine
Phenothiazines: Prochlorperazine
Block dopamine2 receptors in CTZ (chemo receptor trigger zone)
Surgery, cancer, chemotherapy, and toxins
Most widely used antiemetic in children despite ADR -respiratory depression and local tissue injury. Contraindicated in children under 2y and caution in children older
Side effects
Extrapyramidal reactions
Anticholinergic effects
Hypotension and sedation
Antiemetics: dopamine antagonists, 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 interval and fatal dysrhythmias
Electrocardiogram (ECG) before administration
Antiemetics: dopamine antagonists, Metoclopramide [Reglan]
Blocks dopamine receptors in CTZ
Postoperative nausea/vomiting, anticancer drug, opioids, toxins, radiation therapy
Antiemetics: canabinoids
Dronabinol [Marinol] and nabilone [Cesamet]
Related to marijuana
CINV
MOA with emesis unclear
Potential for abuse and psychotomimetic effects
Management of Chemotherapy- Induced Nausea and Vomiting: 3 times of vomiting
Anticipatory
Occurs before drugs are given
Acute
Onset within minutes to a few hours
Delayed
Onset 1 day or longer after drug administration
Management of Chemotherapy- Induced Nausea and Vomiting
Antiemetics are more effective in preventing CINV than in suppressing CINV in progress
Give before chemotherapy drugs
Monotherapy and combination therapy may be needed
Nausea and Vomiting of Pregnancy
Hyperemesis gravidarum: Dehydration, ketonuria, hypokalemia, and loss of 5% or more of body weight
Nondrug measures
Diet changes, relaxation measures
First-line therapy consists of a two-drug combination: Doxylamine plus vitamin B6
Others: Prochlorperazine, metoclopramide, and ondansetron. methylprednisolone may be tried as a last resort, but only after 10 weeks’ gestation
Drugs for Motion Sickness: scopolamine
Muscarinic antagonist
Side effects
Dry mouth
Blurred vision
Drowsiness
Drugs for Motion Sickness: antihistamines
Dimenhydrinate, meclizine, cyclizine
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
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
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
Opioids
Most effective antidiarrheal agents
Diphenoxylate, difenoxin, loperamide, paregoric, and opium tincture
Activate opioid receptors in GI tract
Reduce 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
Most commonly used: Diphenoxylate [Lomotil] and loperamide [Imodium]
Diphenoxylate [Lomotil]
Formulated with atropine to discourage abuse
Opioid used only for diarrhea
High doses can elicit typical morphine-like subjective responses
Loperamide
Structural analog of meperidine (opioids)
Used to treat diarrhea and to reduce the volume of discharge from ileostomies
Little or no potential for abuse
Nonspecific Antidiarrheal Agents
Difenoxin
Paregoric
Opium tincture
Bismuth subsalicylate
Bulk-forming agents
Anticholinergic antispasmodics
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: Salmonella, Shigella, Campylobacter, or Clostridium infections
Traveler’s diarrhea
Escherichia coli: Usually self-limiting
Ciprofloxacin, norfloxacin
Irritable Bowel Syndrome (IBS)
Most common disorder of GI tract
Affects 20% of Americans
Incidence in women is three times higher 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
IBS tx
Four groups of drugs historically used
American College of Gastroenterology has concluded there is no proof of clinical benefit for most of these agents:
Antispasmodics
Bulk-forming agents
Antidiarrheals
Tricyclic antidepressants
Studies suggest that antibiotics or an acid suppressant may be effective for some patients
Alosetron [Lotronex]
IBS specific drug
Potentially hazardous drug; approved for women only
GI toxicities can cause complicated constipation, leading to perforation and ischemic colitis
Risk management program
Lubiprostone [Amitiza]
Approved for constipation-predominant IBS (IBS-C) in women age 18 years or older
Modest benefits
Tegaserod [Zelnorm]
Short-term therapy of IBS-C and chronic idiopathic constipation (CIC) in women younger than age 55 years who are free of cardiovascular (CV) disease
Inflammatory Bowel Disease (IBD)
Caused by exaggerated immune response to normal bowel flora
Crohn disease
Characterized by transmural inflammation
Usually affects terminal ileum (can affect 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
Drugs for IBD
Not curative; may control disease process
5-Aminosalicylates (sulfasalazine; 5-ASA)
Glucocorticoids (hydrocortisone)
Immunosuppressants (azathioprine)
Immunomodulators (infliximab)
Antibiotics (metronidazole)
5-Aminosalicylates, Sulfasalazine [Azulfidine]
5-ASA reduces inflammation; it also suppresses prostaglandin synthesis and migration of inflammatory cells into affected region
Most effective against acute episodes of mild to moderate ulcerative colitis
Glucocorticoids, Budesonide
Approved for mild to moderate Crohn disease that involves the ileum and ascending colon
Prolonged use of glucocorticoids can cause severe adverse effects, including adrenal suppression, osteoporosis, increased susceptibility to infection, and Cushing’s syndrome
Immunosuppressants: Azathioprine [Imuran] and mercaptopurine [Purinethol]
Induce and maintain remission in both ulcerative colitis and Crohn disease
Onset of effects may be delayed for up to 6 months
Reserved for patients who have not responded to traditional therapy
Adverse effects are pancreatitis and neutropenia
Immunomodulators: Infliximab [Remicade]
Monoclonal antibody designed to neutralize tumor necrosis factor (TNF), a key immunoinflammatory modulator
Moderate to severe Crohn disease and ulcerative colitis
Antibiotics: Metronidazole [Flagyl] and ciprofloxacin [Cipro]
Crohn disease: Can help control symptoms
Ulcerative colitis: Antibiotics largely ineffective
Metronidazole [Flagyl]: Long-term therapy is required; prolonged use of high-dose metronidazole poses risk of peripheral neuropathy
Ciprofloxacin [Cipro]: Highly effective in patients with mild or moderate Crohn disease
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]
Metoclopramide [Reglan]
Suppress emesis and increase upper GI motility
Therapeutic uses
PO: Diabetic gastroparesis and suppression of gastroesophageal reflux
IV: Suppression of postoperative nausea and vomiting, suppression of CINV, facilitation of small bowel intubation, and facilitation of radiologic examination of GI tract
Adverse effects
High-dose therapy: Sedation, diarrhea common
Long-term high-dose therapy: Can cause irreversible tardive dyskinesia (TD)
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
Pancreatic Enzymes
Deficiency of enzymes compromises digestion
Pancrelipase: Pancreatic enzyme for clinical use; mixture of lipases, amylases, and proteases prepared from hog pancreas
Can be sprinkled on food, can be taken as capsules
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 cholesterol content of bile
Gradual dissolution of stones
Anorectal Preparations
Symptomatic relief of hemorrhoids and other anorectal disorders
Local anesthetics
Hydrocortisone
Emollients
Astringents
Multiple formulations available
OTC
