Deja Ch 8 GI Flashcards
What is the main cause of gastroesophageal reflux disease (GERD)?
Decreased lower esophageal sphincter pressure
What complications may arise from GERD?
Strictures; esophagitis; Barrett esophagus (squamocolumnar metaplasia)
What are the drug therapy goals in treating GERD?
To eliminate symptoms; heal esophagitis; prevent the relapse of esophagitis; prevent the development of complications
What types of medications may be useful in the treatment of GERD?
Antacids; H2-receptor antagonists; proton pump inhibitors (PPIs); prokinetic agents (cisapride, metoclopramide, bethanechol); mucosal protectants (sucralfate)
Give the mechanism of action for each of the following drugs or drug classes: Antacids
Weak bases that increase gastric pH through acid-neutralizing ability to form a salt and water
Give the mechanism of action for each of the following drugs or drug classes: H2–receptor antagonists
Competitively antagonize H2 receptors on gastric parietal cells, thereby decreasing acid production
Give the mechanism of action for each of the following drugs or drug classes: PPIs
Inhibit gastric acid secretion via inhibiting gastric parietal cell H+/K+-ATPase. Restoration of acid secretion requires resynthesis of the H+/K+-ATPase (proton pump).
Give the mechanism of action for each of the following drugs or drug classes: Cisapride
Increases lower esophageal sphincter pressure; accelerate gastric emptying time; increases amplitude of esophageal contractions; 5-HT4 agonist; 5-HT3antagonist
Give the mechanism of action for each of the following drugs or drug classes: Metoclopramide
Dopamine (D2) receptor antagonist; increases lower esophageal sphincter pressure; accelerates gastric emptying time
Give the mechanism of action for each of the following drugs or drug classes: Sucralfate
When exposed to acid, complexes with positively charged proteins to form a viscous coat, thereby protecting gastric lining from gastric acid secretions
What are the adverse effects caused by metoclopramide?
Anxiety; insomnia; extrapyramidal symptoms; increased prolactin levels
What are the adverse effects caused by sucralfate?
Constipation; nausea; abdominal discomfort
What are the possible adverse effects of antacids?
Belching (sodium bicarbonate and calcium carbonate); diarrhea (magnesium salts); constipation (calcium or aluminum salts); acid-base disturbances; bone damage via binding phosphate in the gut (aluminum salts); worsening of hypertension and congestive heart failure (CHF) (sodium salts); decreased absorption of medications via pH alteration or formation of insoluble complexes (tetracycline, fluoroquinolones, isoniazid [INH], ferrous sulfate, ketoconazole, PPIs)
Which antacid(s) can produce a metabolic alkalosis?
Sodium bicarbonate; calcium carbonate
What causes the milk-alkali syndrome?
Ingestion of excessive amounts of calcium and absorbable alkali such as sodium bicarbonate or calcium carbonate
What is a potential complication after discontinuing chronic antacid use?
Acid rebound
List the names of the H2-receptor antagonists:
Cimetidine; famotidine; ranitidine; nizatidine
Which H2-receptor antagonist inhibits hepatic cytochrome P-450 metabolizing enzymes?
Cimetidine
Name at least five drugs showing potential drug interactions with cimetidine:
- Warfarin 2. Diazepam 3. Phenytoin 4. Metronidazole 5. Propranolol 6. Lidocaine 7. Calcium channel blockers (CCBs) 8. Theophylline 9. Certain tricyclic antidepressants (TCAs); chlordiazepoxide
Which H2-receptor antagonist can cause gynecomastia?
Cimetidine (prolactin-stimulating activity)
Which H2-receptor antagonist has antiandrogenic activity?
Cimetidine
List the names of the PPIs:
Omeprazole; esomeprazole; lansoprazole; rabeprazole; pantoprazole
What are the common side effects of PPIs?
Headache; dizziness; nausea; diarrhea; constipation. Prolonged use can lead to bacterial overgrowth in the GI tract. Note also that a recent analysis revealed that people (age > 50) taking high doses of PPIs for more than a year were 2.6 times as likely to break a hip as were people not taking PPIs. Histamine H2-receptor inhibitors also increased fracture risk, but not to the extent as did PPIs.
What is the most serious side effect of cisapride?
Prolongation of the QT interval
Cisapride should be avoided in which type of patients?
Patients with prolonged QT intervals; patients taking medications that inhibit cytochrome P-ISO 3A4 (fluconazole, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir)
What arrhythmia can be caused by prolongation of the QT interval?
Torsades de pointes (a polymorphic ventricular tachycardia)
Which drugs increase cisapride blood levels by inhibiting the cytochrome P-450 3A4 enzymes that metabolize cisapride? (Please mention at least four drugs).
- Erythromycin 2. Clarithromycin 3. Itraconazole 4. Fluconazole 5. Ketoconazole 6. Indinavir 7. Ritonavir 8. Class 1A antiarrhythmics 9. Class III antiarrhythmics 10. Certain TCAs 11. Certain antipsychotics
What three mediators can stimulate acid secretion from parietal cells?
- Acetylcholine 2. Histamine (via H2 receptor) 3. Gastrin
Name three causes of peptic ulcer disease (PUD):
- Helicobacter pylori infection (primary cause) 2. Nonsteroidal anti-inflammatory drugs (NSAIDs) 3. Extreme physiologic stress (ie, patients in the ICU setting being ventilated, burn patients)
What type of patients do acute peptic ulcers occur in?
Hospitalized patients who are critically ill (stress ulcers)
What is the name of the syndrome that is characterized by hypersecretion of gastric acid secondary to a gastrin-secreting tumor?
Zollinger-Ellison syndrome
Which are the drug therapy goals in treating PUD?
Control H. pylori infection; alleviate symptoms; promote healing; prevent recurrences; prevent complications (eg, hemorrhage)
What types of medications are useful for the treatment of PUD?
Antimicrobial agents; H2-receptor antagonists; PPIs; prostaglandins; antimuscarinic agents; antacids; mucosal protective agents; bismuth salts
How might H. pylori play a role in peptic ulcer development?
Direct mucosal damage; alterations in inflammatory response; induced hypergastrinemia
Meals worsen the pain associated with what type of ulcer?
Gastric ulcer
Meals relieve the pain associated with what type of ulcer?
Duodenal ulcer
What treatment options are available to eradicate H. pylori?
Triple therapy with a PPI added to two antimicrobial agents such as metronidazole, amoxicillin, tetracycline, or clarithromycin; four-drug regimens consisting of triple therapy plus bismuth subsalicylate; (must use triple or quadruple antibiotic therapy to eradicate H. pylori)
Why should you not give bismuth subsalicylate to children?
May be associated with Reye syndrome (contains salicylates)
What is Reye syndrome?
Acute onset encephalopathy and fatty liver formation. Symptoms begin with vomiting, lethargy, and confusion progressing to stupor, respiratory distress, coma, and seizures. Its cause is unknown, but has been found to be associated with aspirin use in young children. Therefore, aspirin administration is to be avoided in pediatric patients.
How do prostaglandins help treat PUD?
Prostaglandins such as PGE2 and PGI2inhibit gastric acid secretion and stimulate secretion of bicarbonate and mucus (cytoprotective activity); used to treat NSAID-induced peptic ulcers
Which prostaglandin analog is commonly used as a cytoprotective agent for the treatment of PUD?
Misoprostol (synthetic PGE1 analog)
Why should misoprostol not be given to a preterm pregnant woman?
Induction of premature uterine contractions (abortifacient properties)
What are the two forms of inflammatory bowel disease (IBD)?
- Crohn disease 2. Ulcerative colitis (UC)
Does treatment of IBD cure or control the disease process?
Control
What types of medications are used to treat IBD?
Corticosteroids; aminosalicylates; immunosuppressives; monoclonal antibodies
Sulfasalazine is cleaved by gut bacteria in the colon to produce what two compounds?
- Sulfapyridine (sulfonamide antibiotic) 2. Mesalamine (5-aminosalicylic acid, 5-ASA)
What is the active component of sulfasalazine for IBD?
Mesalamine or 5-ASA; 5-ASA is the metabolite active against IBD, while sulfapyridine is the metabolite active against rheumatoid arthritis. Formulation into sulfasalazine is necessary to prevent rapid proximal gut absorption so that sufficient 5-ASA is delivered to the distal gut to effectively treat IBD.
How does mesalamine work in the treatment of IBD?
Anti-inflammatory effects; immunomodulating effects
What type of vitamin supplementation should patients receive while on sulfasalazine?
Folic acid since sulfasalazine may interfere with absorption of folic acid in the gut, leading to megaloblastic anemia
What types of immunosuppressives are used to treat IBD?
Cyclosporine A; methotrexate; azathioprine; 6-mercaptopurine
What is the name of the monoclonal antibody indicated for the treatment of Crohn disease?
Infliximab
What is infliximab’s mechanism of action?
Monoclonal antibody that binds to soluble and bound forms of tumor necrosis factor-alpha (TNF-_)
True or False? Once remission has been achieved with ulcerative colitis, corticosteroids are used as maintenance therapy.
False. Corticosteroids should not be used to maintain disease remission due to their high systemic toxicity. Aminosalicylates or immunosuppressive agents are used for maintenance therapy for UC.
Name a major chemosensory area for emesis:
Chemoreceptor trigger zone (CTZ)
Where is the Chemoreceptor trigger zone (CTZ) found?
Area postrema of the fourth ventricle of the brain
Give examples of drug classes that are effective in the treatment of nausea and vomiting:
Antihistamine-anticholinergics; benzodiazepines; butyrophenones; cannabinoids; corticosteroids; phenothiazines; substituted benzamides; 5-HT3-receptor antagonists; neurokinin receptor antagonists
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Antihistamine-anticholinergics
Diphenhydramine; hydroxyzine; meclizine; cyclizine; promethazine; pyrilamine; scopolamine; trimethobenzamide
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Benzodiazepines
Alprazolam; diazepam; lorazepam
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Butyrophenones
Haloperidol; droperidol; domperidone
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Cannabinoids
Dronabinol; nabilone
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Corticosteroids
Dexamethasone; methylprednisolone
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Phenothiazines
Prochlorperazine; chlorpromazine; perphenazine
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Substituted benzamides
Metoclopramide
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: 5-HT3–receptor antagonists
Ondansetron; dolasetron; granisetron
Give examples of specific drugs in each of the following drug classes used in the treatment of nausea and vomiting: Neurokinin receptor antagonists
Aprepitant (oral); fosaprepitant (IV formulation converted to aprepitant)
Do synthetic cannabinoids have psychotropic activity?
No
How does metoclopramide work as an antiemetic?
Blocks dopamine receptors centrally in the CTZ
What is intractable emesis leading to dehydration and hypotension during pregnancy called?
Hyperemesis gravidarum
What are the drugs of choice for treating emesis during pregnancy?
Meclizine; cyclizine; promethazine
What antihistamine is often used to treat motion sickness?
Meclizine
What anticholinergic is often used to treat motion sickness?
Scopolamine
How is scopolamine normally administered?
As a transdermal patch to prevent systemic anticholinergic effects
What medication is often used in combination regimens to enhance antiemetic activity?
Dexamethasone
What are the side effects of cannabinoids?
Anxiety; memory loss; confusion; motor incoordination; hallucinations; euphoria; relaxation; hunger; gynecomastia
What are the side effects of the phenothiazine antiemetics?
Extrapyramidal symptoms; sedation; hypotension
Why doesn’t ondansetron cause extrapyramidal side effects?
Blocks 5-HT3 instead of dopamine receptors in the CTZ
What chemotherapy agent has one of the highest emetogenic potentials?
Cisplatin
What over-the-counter (OTC) medication can be given in combination with metoclopramide to reduce its extrapyramidal side effects?
Diphenhydramine can be used for its anticholinergic properties. EPS symptoms with metoclopramide use are due to central dopamine receptor blockade, and tardive dyskinesia, if it develops, may be irreversible. Therefore, metoclopramide should only be used for short-term therapy if possible.
What macrolide antibiotic also has prokinetic properties for the GI tract?
Erythromycin, though tolerance to this effect develops rapidly, limiting its usefulness
Name three classes of drugs that are effective in the treatment of diarrhea:
- Adsorbents 2. Antimotility agents 3. Antisecretory agents
Define adsorbent:
A substance offering a suitable active surface, upon which other substances may adhere to
Give examples of specific drugs in each of the following drug classes used in the treatment of diarrhea: Adsorbents
Kaolin; pectin; polycarbophil; attapulgite
Give examples of specific drugs in each of the following drug classes used in the treatment of diarrhea: Antimotility agents
Diphenoxylate; loperamide; morphine
Give examples of specific drugs in each of the following drug classes used in the treatment of diarrhea: Antisecretory agents
Bismuth subsalicylate
Give the antidiarrheal mechanism of action for each of the following drug classes: Adsorbents
Adsorbs (adheres to) drugs, nutrients, toxins, and digestive juices
Give the antidiarrheal mechanism of action for each of the following drug classes: Antimotility agents
Decrease peristalsis by activating presynaptic opioid receptors in the enteric nervous system
Give the antidiarrheal mechanism of action for each of the following drug classes: Antisecretory agents
Decrease fluid secretion in the bowel
What adsorbent can absorb 60 times its weight in water and treat both diarrhea and constipation?
Polycarbophil
What are the potential side effects of bismuth subsalicylate?
Salicylism (tinnitus, nausea, vomiting); darkening of tongue; darkening of stools; induce gout attacks in susceptible patients
What antidiarrheal can decrease tetracycline absorption if given concomitantly?
Bismuth subsalicylate
What antidiarrheal is often formulated in combination with atropine?
Diphenoxylate
Which class of antidiarrheals can cause paralytic ileus?
Antimotility agents
What medication is often used to treat flushing and diarrhea seen in carcinoid syndrome and vasoactive intestinal peptide secreting tumors (VIPomas)?
Octreotide
What is octreotide’s mechanism of action?
Synthetic analog of somatostatin which blocks release of serotonin and other vasoactive peptides; direct inhibitory effects on intestinal secretion; direct stimulatory effects on intestinal absorption
What are the non-antidiarrheal uses of octreotide?
Esophageal varices; acromegaly
What medication can be used in conjunction with antibiotics to bulk stools and absorb Clostridium difficile toxins A and B in C. difficile colitis?
Cholestyramine, a nonabsorbable binding agent
What types of medications cause constipation?
Opioid analgesics; anticholinergics; calcium-containing antacids; aluminum-containing antacids; calcium channel blockers; clonidine; iron; sodium polystyrene sulfonate
Give examples of drug classes that are effective in the treatment of constipation:
Bulk forming agents; irritants and stimulants; stool softeners
Give examples of specific drugs in each of the following drug classes used in the treatment of constipation: Bulk forming agents
Methylcellulose; psyllium; bran; magnesium-containing salts; polyethylene glycol
Give examples of specific drugs in each of the following drug classes used in the treatment of constipation: Osmotic laxatives
Lactulose; magnesium hydroxide (milk of magnesia); sorbitol; magnesium citrate; sodium phosphate; polyethylene glycol
Give examples of specific drugs in each of the following drug classes used in the treatment of constipation: Irritants and stimulants
Cascara; senna; aloe; bisacodyl
Give examples of specific drugs in each of the following drug classes used in the treatment of constipation: Stool softeners
Mineral oil; docusate (oral or enema, trade name: Colace); glycerin suppository
Give examples of specific drugs in each of the following drug classes used in the treatment of constipation: Cl_ channel activators
Lubiprostone (Amitiza)
Give the mechanism of action for each of the following drug classes: Bulk-forming agents
Form gels in large intestine which causes water retention and intestinal distention, thereby increasing peristaltic activity
Give the mechanism of action for each of the following drug classes: Osmotic laxatives
Nonabsorbable compounds which draw fluid into the colon to maintain osmotic neutrality
Give the mechanism of action for each of the following drug classes: Irritants and stimulants
Irritate gut lining which subsequently increases peristalsis
Give the mechanism of action for each of the following drug classes: Stool softeners
Surfactants that become emulsified with stool, thereby softening feces
Give the mechanism of action for each of the following drug classes: Cl channel activators
Activate CIC-2 Cl_ channels in the apical membrane of intestinal cells increasing fluid and intestinal motility without altering serum Na+ or K+ levels. The effects are localized to the GI tract, increase fluid secretion into the intestinal lumen, and accelerate fecal transit.
What are the potential side effects of bisacodyl?
Abdominal cramping; atonic colon
