9.1 - Gastrointestinal Drugs

Question 1

What is an ulcer?

Answer 1

Defined as a rea of erosion passing through the lining of the GI wall

Question 2

What causes stomach ulcers?

Answer 2

An imbalance between:

Aggressive factors
–> Acid, pepsin (digestive enzyme), bile (irritant), H. Pylori, NSAIDs

and Protective Factors
–> Mucus (protective layer), Pgs, bicarb (buffer), circulation

Question 3

What is the stomach’s last line of defense against stomach acid?

Answer 3

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)

Question 4

What fraction of duodenal ulcers are caused by H. Pylori vs NSAIDs?

Answer 4

H. Pylori - 92%
NSAIDS - 5%

Question 5

What fraction of gastric ulcers is caused by H. Pylori vs NSAIDs?

Answer 5

H. Pylori - 70%
NSAIDs - 25%

Question 6

What are the two ways NSAIDs cause gastric damage?

Answer 6

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

Question 7

Increased risks of NSAID related ulcers include:

Answer 7

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.

Question 8

In what two ways do antacids like magnesium hydroxide, aluminum hydroxide, and calcium carbonate help treat peptic ulcers?

Answer 8

By increasing pH (less acidic environment)
More alkaline environment means reduced activity of pepsin

Question 9

What adverse effects do all antacids share?

Answer 9

They may reduce the absorption of certain drugs, such as digoxin, tetracycline, or ciprofloxacin

Question 10

What are the five kinds of drugs used to treat peptic ulcers?

Answer 10

1. Antacids
2. Mucosal defenses
3. H2 Antagonists
4. PPIs
5. Antibacterial drugs

Question 11

What two drugs form a protective barrier over gastric mucosa?

Answer 11

Sucralfate and Bismuth Subsalicylate

Question 12

What is an adverse effect of sucralfate?

Answer 12

Constipation

Question 13

On top of forming a protective barrier over gastric mucosa, what does bismuth subsalicylate do for ulcers?

Answer 13

It also have bacteriostatic, antisecretory, and anti-inflammatory activities

Question 14

What are the adverse effects of bismuth subsalicylate?

Answer 14

Can cause black tongue and feces

Question 15

What kind of drug is misoprostol? What is its mechanism of action?

Answer 15

A PGE1 analogue
–> Synthetic PG stimulates submucosa blood flow, and increased production of bicarb and mucus
–> Also attenuates histamine-induced gastric acid secretion

Question 16

What are the adverse effects of misoprostol?

Answer 16

Diarrhea and cramps (including contraction of the uterus - not given to pregnant women)

Used off label for cervical ripening or induction of labour.

Question 17

What pump maintains the stomach’s acidity?

Answer 17

A hydrogen-potassium ATPase

Question 18

Which things stimulate the ATPase that maintains gastric acidity?

Answer 18

Ach, Histamine (2 receptors), gastrin

Prostaglandins (PGE1) inhibits a secondary messenger after H2 stimulation.

Question 19

What kinds of drugs are cimetidine, ranitidine, famotidine, and nizatidine?

Answer 19

H2 Receptor Antagonists
–> Decrease secretion of gastric acid by parietal cells, especially at night

Question 20

What adverse effects are seen specifically with cimetidine?

Answer 20

–> Inhibits hepatic metabolism
–> Anti-androgenic effects (gynecomastia, erectile dysfunction, reduced libido, menstrual irregularities)

Question 21

What is an adverse effect of all H2 receptor antagonists?

Answer 21

Rebound acidity after discontinuation of chronic use (4+ weeks)

Question 22

What kinds of drugs are esomeprazole, omeprazole, pantoprazole, rabeprazole, dexlansoprazole and lansoprazole?

Answer 22

PPIs
–> Inhibit hydrogen-potassium ATPase

Question 23

What are the adverse effects of PPIs?

Answer 23

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

Question 24

What are the two antibiotic regimens to treat H. Pylori? How long are these regimens? What are their eradication rates?

Answer 24

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%

Question 25

What is the triple therapy without bismuth for H. pylori?

Answer 25

PPI (lanzoprazole)
+ Amoxicillin
+ Clarithromycin
+ Metrnidazole

Question 26

What is the quadruple therapy with bismuth for H. Pylori?

Answer 26

PPI
+ Tetracycline
+ Bismuth subsalicylate
+ Metronidazole

Question 27

What kinds of drugs are bisacodyl and sennosides? What is their mechanism of action?

Answer 27

Stimulant
–> Stimulates peristalsis and increase water and electrolytes in colon

Question 28

What kinds of drugs are psyllium and inulin? Mechanism of action?

Answer 28

Bulk-forming laxatives
–> Stimulate water retention within the stool (like dietary fiber)

Question 29

What kind of medication is docusate? Mechanism of action?

Answer 29

Surfactant
–> Alters stool consistency and facilitates penetration of water into feces

Question 30

What kinds of medication are lactulose, polyethylene glycol, and magnesium hydroxide? Mechanism of action?

Answer 30

Osmotic Laxatives
–> Poorly absorbed molecules that draw water into intestine

Question 31

What kind of laxative is mineral oil?

Answer 31

Lubrifaction
–> Can decrease absorption of fat soluble vitamins (A, D, E, K) and oral contraceptives

Question 32

What kind of drugs are methylnaltrexone and naloxegol? Mechanism of action?

Answer 32

Anti-Opioid
–> May be used to treat refractory opioid-induced constipation

Question 33

In addition to loperamide, what drugs can act as antidiarrheal agents?

Answer 33

Anticholinergic drugs, verapamil, Aluminum salts, combination of diphenoxylate and atropine.