PUD pharmacology Flashcards
What does mucus secretion require?
prostaglandin E2
which has high [H+] and which has low [H+]?
- empty stomach
- full stomach
empty stomach: high [H+]
full stomach: low [H+}
What stimulates D cells to secrete somatostatin?
What stimulates G cells to secrete gastrin?
H+ —> D cells –> somatostatin
Food —> G cells –> Gastrin
What are the mucosal epithelial cells protected by?
What is important to note about the rest of the intestinal tract mucosal barrier?
Gastric mucosal epitheilial cells are protected by a hydrophobic layer of mucus
The mucosal barrier of the rest of the intestinal tract is hydrophili
What are the two mechanisms by which NSAIDs produce gastric ulcers?
- Directly disrupt thehydrophobic part of phospholipid mucosal barrier barrier and reduce the effectiveness of barrier (can be avoided using pills that are coated) –>allow proton diffusion through barrier
- After absorption, NSAIDs inhibit mucus secretion and reduce the mucus barrier thickness (by inhibiting prostaglandin secretion via COX1)
In addition to NSAIDs, what other drug decreases mucus secretion?
What agent can be used to maximize mucosal protection? What is the side effect?
-Glucocorticoids also decrease mucus secretion
Long-acting prostaglandin analog (Lubiprostone)
Side effect: secretory diarrhea, because PGs also increase electrolyte and fluid secretion in the GI tract
Agents used to treat peptic ulcer disease (5)
- Agents to protect the mucosa
- Antacids
- H2 blockers
- PPIs
- Combination therapy for H. pylori ulcers
Sucralfate
“band-aid” over ulcer
- forms viscous solution that coats the stomach and ulcer
- selectively binds to ulcerate mucosa
- acts to protect and facilitates healing
- decreases acid secretion
- not absorbed, so minimal side effects
- must be taken several times/day on empty stomach, administered as a slurry, so not that pleasant, not prescribed often
Anatacids:
- MOA
- side effects
- Act as buffer
- Side effects vary with type (carbonates, magnesium hydroxide, aluminum hydroxide)
- carbonates cause gas and belching, alkalosis
- Mg causes diarrhea, Al causes constpiation
- may interefere with drug absoprtion
- Mg and Al are cleared by the kidney, should not be used in patients with comprimsed renal function
-tidine drugs
H2 blockers (competitive antagonists)
i.e. cimetidine
Where are H2 blockers metabolized? Where are they secreted?
Relatively what is half life
Side effects?
- Metabolized by liver, excreted by glomerula filtration and renal secretion
- relatively SHORT t/2
- alter metabolism of other drugs that use p450, relatively few side effects
what are H2 blockers better for inhibiting?
better for inhibition of _basal (nocturnal) acid secretion _
PPIs are lipo philic/phobic
lipophilic pro-drugs
Side effects of PPIs (3)
- may reduce Ca absorption (hip fractures)
- increase risk of gastric and intestinal infections due to lack of gastric acidifications
- drug interactions:
- decreased acidity interferes with absorption of some drugs
- metabolized by liver p450 enzymes, may prolong t/2 of other agents metabolized by same enzymes
Quadruple therapy for H. pylori infection
- PPI
- Bismuth subsalicylate (sticks and coats ulcers, promotes healing, bactericidal)
- Metronidazole
- Tetracycline
Triple therapy for H. pylori infections
- H2 blocker or PPI
- Metronidazole
- Clarithromycin or Tetracycline
note: for triple and quadruple therapy, several variations are available.
Which two drugs might also inhibit the secretion of instrinsic factor?
H2 receptor blockers and PPIs
Best therapy option to give patient taking daily aspirin to prevent gastritis development
Lubiprostone: rebuilds the hydrophobic mucus layer which will be deficient since NSAIDs inhibit prostaglandin production
An elderly pateitn is currently in rehab facilitation because she recently cracker her pelvis after a fall. She has GERD and is taking a daily PPI. She also takes metformin (T2DM) and ACE-I. Which of the following potential side effects of the PPI should be taken into consideration?
a) diarrhea secondary to decreased Mg absorption
b) metabolic alkalosis because PPIs also inhibit the H/K ATPase in the renal collecting ducts
c) increased half life of metformin
d) increased incidence of A fib
e) increased incidence of diarrhea due to C. diff infection
a) diarrhea secondary to decreased Mg absorption
* PPIs might interfere with Mg absoprtion, because Mg dissociated from its anion at acid pH. However, the normal intake of Mg is not large enough to result in diarrhea, even if none of it is absorbed
b) metabolic alkalosis because PPIs also inhibit the H/K ATPase in the renal collecting ducts
* *PPIs do not cause metabolic alkalosis *
c) increased half life of metformin
d) increased incidence of A fib
* PPIs do not interfere with K+ metabolism are aren’t known to increase A fib incidence
e) increased incidence of diarrhea due to C. diff infection
- PPIs prevent gastric acidification, so orally ingest microorganisms (like C. Diff) can survive down to stomach.
