Pharmacology

Question 1

What is the MOA of the histamine-2 receptor antagonists?

Answer 1

• Competitive inhibition of gastric acid secretion by blocking the histamine receptor on the gastric parietal cell
• Famotidine is the most potent, has the longest duration of action
  
  • Excreted unchanged in the urine
• Cimetidine, ranitidine least potent
  
  • Hepatic metabolism
  • Ranitidine may have some gastric prokinetic activity (although one study failed to find ranitidine effective in preventing reflux in anesthetized dogs)

Question 2

What is the MOA of the PPIs?

Answer 2

• Irreversible binding of HK ATPase on the luminal side of the parietal cell; stops secretion of hydrogen into the gastric lumen
• Omeprazole is a prodrug–undergoes first-pass hepatic metabolism, selectively sequestered in acidic environment of the parietal cells and transfomred to the active drug
• Shown to be more effective than H2RAs
• Suppression of gastric acid secretion continues for a few days after cessation of PPI therapy because of irreversible inhibitionof the proton pump enzyme

Question 3

What is the MOA of sucralfate?

Answer 3

• Octasulfate of sucrose combined with AlOH; functions by becoming viscous, binding tightly to epithelial cells in the acidic environment of the stomach, especially to the base of erosions and ulcers
• Serves as a physical barrier and protects the ulcer from pepsin and bile acids; stimulates local production of prostaglandins and binding to epidermal growth factor, favoring mucosal repair

Question 4

What is the MOA of misoprostol?

Answer 4

• PGE1 analog; stimulates secretion of mucus and bicarbonate and increases gastric mucosal blood flow
• Acts directly on parietal cells to inhibit nocturnal acid secretion and secrestions in response to food, pentagastrin and histamine

Question 5

What is the MOA of maropitant?

Answer 5

• NK-1 receptor antagonist that blocks the actions of substance P in the CNS and peripheral NK-1 receptors in the GI tract
• NK-1 receptor antagonists may also reduce visceral pain and reduce the MAC of sevo if given IV during anesthesia

Question 6

What is the MOA of dolasetron/ondansetron?

Answer 6

• Competitive blockade of 5HT3 receptors peripherally and centrally (in the CRTZ and medullary vomiting center)

Question 7

What is the MOA of cisapride?

Answer 7

• Serotonin agonist/serotonergic drug
• Unlike metoclopramide, does not cross the BBB or have antidopaminergic effects
• Enhances gastric emptying while increasing gastroesophageal sphincter pressure
  
  • Does not have any effect on esophageal motility as the esophagus is striated muscle!
• May also increase SI motility

Question 8

What is the MOA of metoclopramide?

Answer 8

• Central dopaminergic antagonist and peripheral serotonin antagonist
• Increases lower esophageal sphincter tone and stimulates gastric contractions while relaxing the pylorus and duodenum
• Readily crosses the BBB where antagonism at the CRTZ produces an antiemetic effect

Question 9

What is the MOA of erythromycin as a prokinetic medication?

Answer 9

• Stimulates motilin receptors
• Increases lower esophageal sphincter pressure as well as small and large bowel peristalsis
• Concern that tolerance will develop with sustained use of the drug