Drugs for GI disorders Flashcards
True/False? The human immune system accounts for the gut microbiome
True/False? The human immune system accounts for the gut microbiome
True/False? Modern antibiotics do not disrupt the “helpful” bacteria in our microbiome
True/False? Modern antibiotics do not disrupt the “helpful” bacteria in our microbiome
What drugs treat Peptic Ulcer disease?
PPIs, H2 Receptor antagonists, sucralfate, misoprostol, microbial agents to eradicate Helicobacter pylori
What drugs treat Gasteresophageal reflux disease?
PPIs, H2, receptor antagonists, antacids, metoclopramide
What class of drugs treat delayed gastric emptying?
Promotility agents
What class of drugs treat Constipation?
Laxatives
What class of drugs treat Diarrhea?
Antidiarrheals (duh)
What drugs treat irritable bowel disease?
Aminosalicylates, TNF-alpha antibodies, immunosuppressants, corticosteroids
What is the primary symptom of Peptic Ulcer Disease?
Excess acid production or decreased barrier function, which can overwhelm defense mechanisms and allow ulcers to form in varous areas of GIT
Where does PUD affect?
Upper GIT (stomach, duodenum, lower esophagus)
Wherever the mucosal epithelium can be exposed to acid and pepsin
What are the contributing factors of PUD?
Helicobacter pylori infection
Nonsteroidal antiinflammatory drugs (NSIDS)
Stress, (esp. in patients with chronic illness)
What is the first line treatment for PUD? What happens if the patient has H. pylori infections?
Proton pump inhibitors (PPIs)
Patients with H. pylori infections require antimicrobial agents to prevent relapse
What is gastroesophageal reflux disease (GERD)?
Dysfunctional relaxation of the lower esophageal sphincter that allows the acidic gastric contents to reflux into the esophagus
What can GERD lead to?
Inflammation, ulcerations, bleeding, possibly Barrett esophagus
How is GERD treated commonly?
PPIs, H2 histamine receptor antagonists, DA antagonists (increase the tone of the lower esophageal sphincter)
True/False? Since COX-1 inhibitors can lead to gastric ulcers, COX-2 inhibitors (such as celecoxib) are prescribed as they are safer
True/False? Since COX-1 inhibitors can lead to gastric ulcers, COX-2 inhibitors (such as celecoxib) are prescribed as they are safer
They carry a lower risk of ulcer formation than nonselective NSAIDS but they appear to be associated with an increase in heart attack/stroke
What is Omeprazole and what does it do?
Proton pump inhibitor, inhibits the parietal cell H+K+-ATPase preventing the pump from functioning
What is the advantage of Omeprazole (and any other PPI)?
Nonspecificity - will reduce acid secretion independently of how secretion is stimulated
Why does Omeprazole accumulate in parietal cells?
Because of its pKa
Parietal cells are acidic
True/False? Omeprazole is a prodrug that is converted to its active form by an enzyme in the parietal cell
True/False? Omeprazole is a prodrug that is converted to its active form by an enzyme in the parietal cell
It is converted by acid
Does Omeprazole bind to enzymes temporarily?
No, covalently and irreversibly modifies the enzyme
Which is superior for NSAID-associated damage prevention, PPIs or H2 receptor agonists?
PPIs
What is Esomeprazole?
S enantiomer of Omeprazole, much more effective
Higher bioavailability because of lower first-pass metabolism than R isomer
What effects do prostaglandins exert to the GI system?
Cytoprotection and decreased acid secretion (among others)
Can Prostaglanin analogs such as misoprostol be used to prevent NSAID-induced damage?
Yes but not used first-line
What are antacids what do they do?
Inorganic bases that neutrolize hydrochloric acid
What are the effects of Magnesium and Aluminum on digestion, respectively?
Magnesium: Laxative effect
Aluminum: constipating effect
What is Sucralfate?
Protective agent
Aluminum salt of sucrose octasulfate
What does sucralfate do?
Binds electrostatically to positively charged tissue proteins and mucin within the ulcer crater to form a viscous barrier
prevents further damage from acid/pepsin
also binds bile salts/stimulates production of mucosal prostaglandins
Does Sucralfate affect gastric acid secretion?
no
When is Sucralfate used?
As an alternative to PPIs or H2 antagonists to promote healing of ulcers
What do dopamine receptor antagonists such as metoclopramide do?
Promote motility by affecting different GI receptors
Increases tone of Lower esophageal sphincter (GERD)
Increases force of gastric contractions
Antiemetic agent
What is the primary symptom of constipation?
Abnormally difficult passage of hard/infrequent stools
What are some of the causes of constipation?
Diet
Pregnancy
drugs (opioids, Al-containing antacids, Iron)
GI, metabolic, or neurological disorders
What is the ideal treatment of constipation?
What medication can help if this ideal treatment is insufficient?
Dietary and lifestyle change (inc. fluid/fibre intake, physical exercise)
Often a laxative is necessary
What are the 6 types of laxatives?
- Bulk-forming laxatives
- Emollients
- Lubricants
- Saline laxatives
- Hyperosmolar agents
- Stimulant laxatives
What are the characteristics of bulk-forming laxatives?
Nonabsorbable cellulose-like materials that remove dietary fibre
They hydrate in the presence of water and swell into a pliable soft mass that activates the defecation reflex (reduces intestinal transit time)
Can have a paradoxical antidiarrheal effect resulting from their ability to bind excess water
What are the characteristics of emollients?
Ionic detergents that soften feces and permit easier defecation by lowering the surface tension and permitting water to interact more effectively with the solid stool
The most commonly used agent in this category is docusate sodium
What are the characteristics of Lubricants?
Oral nonabsorbable laxatives that act by lubricating the stool to facilitate passage.
- They may also act on the colonic epithelium to reduce water passage*
- eg mineral oil*
What are the characteristics of Saline Laxatives?
inorganic salts with poorly absorbed cations such as magnesium, or anions such as sulfate or phosphate
Draw water into the intestine by osmotic means, resulting in increased GI propulsion/evacuation
Because of appreciable amounts of Mg may be absorbed, these should be avoided in patients wihth renal insufficiency
What are the characteristics of Hyperosmolar agents?
Hyperosmolar agents increase intestinal content osmolarity, leading to accumulation of fluid in the colon
Abdominal bloating and flatulence are common side effects as lactulose and sorbitol are poorly absorbed and undergo bacterial fermentation into organic acids and CO2
What is the most common hyperosmolar laxative?
Polyethylene Glycol (PEG)
poorly absorbed by gut but not metabolised by colonic bacteria
What are the characteristics of stimulant laxatives?
Anthraquinones are converted by colonic bacteria to their active form
Act on the intestinal epithelium to increase fluid accumulation and contraction
What causes Trafellers’ Diarrhea?
Enterotoxgenic E. coli (ETEC)
How does misoprostol treat severe constipation?
By binding to prostanoid receptors 4 on epithelial cells, which triggers a GPCR (increases cAMP)
How does Linaclotide function?
Mimics the action of endogenous guanylin and uroguanylin, bot guanylate cyclase type C (GC-C) receptor ligand
Increases the flow of electrolytes and water int o the lumen of the GI tract
cGMP into the serosa leads to a reduction in visceral hyperalgesia
Used to treat irritable bowel syndrome with constipation and chronic constipation with no known cause
How do opioid antagonists function?
Act on enteric neurons to decrease secretion and promote fluid reabsorption from the lumen
Decrease motility resulting in slowed transit through GI tract, allowing greater time for fluid absorption (drier fecal mass)
Can be used as analgesics which would cause constipation
Used to prevent Opioid induced constipation
True/False? Opioid Antagonists cross the blood brain barrier
True/False? Opioid Antagonists cross the blood brain barrier
What is Loperamie and how does it function?
Opioid agonist
Specific antidiarrheal agent that does not cross BBB
Antisecretory effect on GIT mediated via mu-opioid receptors
At high doses, decreases motility via mu opioid receptor in myenteric plexa of bowel
Should you use Loperamide in the symptomatic treatment of diarrhea caused by enteric organisms such as Shigella and enterohemorragic E. coli or for C. difficile infection?
NO
Can be made worse
What are the two main manifestations of Inflammatory bowel disease?
Ulcerative colitis and Crohn’s disease?
What does the current treatment of IBD consist of?
Sulfasalazine and Mesalazine
What is Mesalamine/Mesalazine? How do they work?
What is Sulfasalazine? How does that work?
Unconjugated 5-aminosalicylates (5-ACA)
Rapidly absorbed in jejunum (only 20% reach terminal ileum and colon)
Sulfasalazine is a prodrug that gets converted into mesalazine and sulfapyridine by gut bacteria
Prevents first pass so more drug gets into colon
How can glucocorticoids help treat IBD?
Illeal-release budesonide in CD and colonic-release budesonide MMX in UC are effective induciton agents
Second generation coritcosteroids have a better safety and tolerability profile
Long term corticosteroid use is not recommended
