9.1 - Gastrointestinal Drugs Flashcards
What is an ulcer?
Defined as a rea of erosion passing through the lining of the GI wall
What causes stomach ulcers?
An imbalance between:
Aggressive factors
–> Acid, pepsin (digestive enzyme), bile (irritant), H. Pylori, NSAIDs
and Protective Factors
–> Mucus (protective layer), Pgs, bicarb (buffer), circulation
What is the stomach’s last line of defense against stomach acid?
Sufficient gastric circulation allows epithelial cells to dump acid rather than being damaged by it - this is why chronic stress can predispose someone to stomach ulcers (because blood is shunted from the GI tract)
What fraction of duodenal ulcers are caused by H. Pylori vs NSAIDs?
H. Pylori - 92%
NSAIDS - 5%
What fraction of gastric ulcers is caused by H. Pylori vs NSAIDs?
H. Pylori - 70%
NSAIDs - 25%
What are the two ways NSAIDs cause gastric damage?
Topical
–> gastric epithelial cells are damaged by absorbing an acidic drug (ASA)
Systemic
–> NSAIDs reduce synthesis of Pgs that are protective to gastric mucosa. Less of these protective PGs means less mucus, bicarb, and gastric circulation; as well as an increase in HCl secretion
Increased risks of NSAID related ulcers include:
Pts with a history of ulcer complications, who use multiple NSAIDs and/or high doses, who are on an anticoagulant, or who are 60+ years old.
In what two ways do antacids like magnesium hydroxide, aluminum hydroxide, and calcium carbonate help treat peptic ulcers?
By increasing pH (less acidic environment)
More alkaline environment means reduced activity of pepsin
What adverse effects do all antacids share?
They may reduce the absorption of certain drugs, such as digoxin, tetracycline, or ciprofloxacin
What are the five kinds of drugs used to treat peptic ulcers?
- Antacids
- Mucosal defenses
- H2 Antagonists
- PPIs
- Antibacterial drugs
What two drugs form a protective barrier over gastric mucosa?
Sucralfate and Bismuth Subsalicylate
What is an adverse effect of sucralfate?
Constipation
On top of forming a protective barrier over gastric mucosa, what does bismuth subsalicylate do for ulcers?
It also have bacteriostatic, antisecretory, and anti-inflammatory activities
What are the adverse effects of bismuth subsalicylate?
Can cause black tongue and feces
What kind of drug is misoprostol? What is its mechanism of action?
A PGE1 analogue
–> Synthetic PG stimulates submucosa blood flow, and increased production of bicarb and mucus
–> Also attenuates histamine-induced gastric acid secretion
What are the adverse effects of misoprostol?
Diarrhea and cramps (including contraction of the uterus - not given to pregnant women)
Used off label for cervical ripening or induction of labour.
What pump maintains the stomach’s acidity?
A hydrogen-potassium ATPase
Which things stimulate the ATPase that maintains gastric acidity?
Ach, Histamine (2 receptors), gastrin
Prostaglandins (PGE1) inhibits a secondary messenger after H2 stimulation.
What kinds of drugs are cimetidine, ranitidine, famotidine, and nizatidine?
H2 Receptor Antagonists
–> Decrease secretion of gastric acid by parietal cells, especially at night
What adverse effects are seen specifically with cimetidine?
–> Inhibits hepatic metabolism
–> Anti-androgenic effects (gynecomastia, erectile dysfunction, reduced libido, menstrual irregularities)
What is an adverse effect of all H2 receptor antagonists?
Rebound acidity after discontinuation of chronic use (4+ weeks)
What kinds of drugs are esomeprazole, omeprazole, pantoprazole, rabeprazole, dexlansoprazole and lansoprazole?
PPIs
–> Inhibit hydrogen-potassium ATPase
What are the adverse effects of PPIs?
Well tolerated overall, however:
–> Headache and diarrhea
–> Can decrease absorption of Vit B12 and Iron
–> Long term, they increase the risk of osteoporosis or related fractural, as well as C. Diff or other GI infections
What are the two antibiotic regimens to treat H. Pylori? How long are these regimens? What are their eradication rates?
Triple therapy without bismuth and quadruple therapy with bismuth
Have a duration of 7-14 days (most are 2 weeks)
Eradication rate of 85-95%
What is the triple therapy without bismuth for H. pylori?
PPI (lanzoprazole)
+ Amoxicillin
+ Clarithromycin
+ Metrnidazole
What is the quadruple therapy with bismuth for H. Pylori?
PPI
+ Tetracycline
+ Bismuth subsalicylate
+ Metronidazole
What kinds of drugs are bisacodyl and sennosides? What is their mechanism of action?
Stimulant
–> Stimulates peristalsis and increase water and electrolytes in colon
What kinds of drugs are psyllium and inulin? Mechanism of action?
Bulk-forming laxatives
–> Stimulate water retention within the stool (like dietary fiber)
What kind of medication is docusate? Mechanism of action?
Surfactant
–> Alters stool consistency and facilitates penetration of water into feces
What kinds of medication are lactulose, polyethylene glycol, and magnesium hydroxide? Mechanism of action?
Osmotic Laxatives
–> Poorly absorbed molecules that draw water into intestine
What kind of laxative is mineral oil?
Lubrifaction
–> Can decrease absorption of fat soluble vitamins (A, D, E, K) and oral contraceptives
What kind of drugs are methylnaltrexone and naloxegol? Mechanism of action?
Anti-Opioid
–> May be used to treat refractory opioid-induced constipation
In addition to loperamide, what drugs can act as antidiarrheal agents?
Anticholinergic drugs, verapamil, Aluminum salts, combination of diphenoxylate and atropine.
