GI Ulcer

Question 0

Regulation of gastric acid secretion from parietal cells:

1) Neural stimulation via the vagus nerve secretes _____.
2) Endocrine stimulation via ________ released antral G cells.
3) Paracrine stimulation by local release of _________ from enterochromaffin-like cells.

Answer 0

1) Ach
2) Gastrin
3) histamine

Question 1

Whats do NSAIDS interfere with in PUD

Answer 1

-interfere with biosynthesis of prostglandins (PGE2 and PGI2) by inhibition of COX-1; luminal presence of the drug plays a minor role.

Question 2

5 protective factors in PUD.

Answer 2

1) Secretion of a thick mucus layer hat forms barrier against acid and pepsin.
2) Secretion of bicarbonate by superficial epithelial cells.
3) Blood flow maintains mucosal integrity.
4) Prostaglandin secretion stimulated by low pH- attenuates acid production, stimulates secretion of mucus and bicarbonate, promotes vasodilation and inhibits the histamine evoked cAMP-dependent pathway.
5) Rapid turnover of GI epithelia.

Question 3

4 aggressive factors in PUD.

Answer 3

1) H. pylori
2) NSAIDS
3) Gastric acid
4) Pepsin

Question 4

If PUD caused by NSAID, what is therapeutic guidelines?

Answer 4

-Stop NSAID or switch to more COX-2 selective agent. Heal with anti ulcer meds.

Question 5

If PUD from H. pylori, what is the therapeutic guidelines?

Answer 5

Eradication method:

• PPI based 3 drug regimen- PPI, clarithromycin, amoxicillin or metronidazole for 14 days
• Bismuth-based 4 drug regimen- bismuth subsalicylate, metronidazole, tetracycine plus PPI for 10-14 days

Question 6

What is stage 1 PUD and how would you treat?

Answer 6

<2-3 per week.

-Diet modification, antacids, H2-receptor blocker

Question 7

What is stage 2 PUD and how would you treat?

Answer 7

> 2-3times/ week with or w/o esophagitis.

-PPI

Question 8

What is stage III PUD and how would you treat?

Answer 8

Chronic unrelenting heartburn with esophageal complications.

-PPI 1-2x per day.

Question 9

How do you treat PUD in pregnancy?

Answer 9

-Anacids or sucrafate for most cases; H2 blockers (ranitidine) and PPI (iansoprazole) can be used if symptoms are intractable.

Question 10

1) What antibiotic is used in PUD and a preferred component due to low resistance/toxicity?
2) What antibiotic has shown increase resistance in PUD?
3) Alternative for patients allergic to penicillins.
4) Used in bismuth-based quadruple therapy.

Answer 10

1) Amoxicillin.
2) Clarithromycin
3) Metronidazole
4) Tetracycline

Question 11

What is a colloidal suspension in MgAI silicate clay and undergoes rapid dissociation in the stomach?

Answer 11

Bismuth subsalicylate (pepto-bismal)- Salicylate is absorbed whereas bismuth is excreted in feces.

Question 12

Name the prototype antacid

Answer 12

Magnesium hydroxide-aluminum hydroxide

Question 13

Name a histamine H2-receptor antagonists and what is the MOA?

Answer 13

Cimetidine- blocks acid secretion from parietal cells that is stimulated by histamine; indirectly decreases gastrin- and ACh-induced acid secretion.

Question 14

List a proton pump inhibitor and describe the MOA:

Answer 14

Omeprazole- prodrug that irreversibly inhibits H+, K+-ATPase (proton pump)

Question 15

T/F: Bismuth subsalicylate:

1) Bismuth part has antibacterial activity against H. pylori (cell wall disruption); and can also bind E.coli entero toxins.
2) Forms a barrier that protects ulcers from further damage.
3) Bismuth part has anti-secretory and anti-inflammatory activities.

Answer 15

1) True
2) True
3) False: the salicylate part has this action

Question 16

Therapeutic uses of bismuth subsalicylate includes:

Answer 16

1) PUD
2) Diarrhea- reduces stool frequency and liquidity in non-specific and acute infection (travelers diarrhea) due to salicylate inhibition of intestinal prostaglandin and chloride secretion.
3) Nausea and cramping…yay Pepto-Bismol

Question 17

Adverse effects of bismuth subsalicylate includes:

Answer 17

1) Harmless black discoloration of stool and tongue
2) Salicylum- can cause tinnitus
3) Reye’s syndrome

Question 18

MOA of antacids (mag hydroxide-aluminum hydroxide)

Answer 18

Alkaline compounds that neutralize gastric acid and thus raise stomach pH; potency expressed in acid-neutralizing capacity (ANC) units.
-Most elevate to pH around 5

Question 19

T/F: Magnesium hydroxide-aluminum hydroxide:

1) Rapid onset with 1-2 hour duration.
2) Al3+ can cause diarrhea (laxative effect) due to stimulation of peristaltic activity.
3) Mg 2+ causes smooth muscle relaxation to counter this effect.
4) Unlike carbonate-based antacids, these ions are not well absorbed systemically(do not increase metabolic acidosis) and do not generate CO2( no belching).
5) Still commonly used for relief of mild symptoms of dyspepsia and GERD.
6) Does not interfere with absorption of other drugs.

Answer 19

1) True
2) False- action of Mg 2+
3) False- action of Al 3+
4) True
5) True
6) False- can interfere- take 2 hr before or after other meds.

Question 20

T/F: Cimitidine:

1) Competitive inhibitors of H2 receptors on apical membranes of parietal cells; high selective and do not stimulate H1 or H3 receptors.
2) In the presence of H2-receptor blockade, the response to direct stimulation of parietal cells with gastrin and Ach diminished.
3) Increases total acid secretion by about 70% over 24 hours; most effective in increasing basal (and thus nocturnal) acid secretion.
4) Slower onset than antacids but have a longer duration (6-10hrs); can be taken prophylactically.
5) Tolerance can develop rapidly

Answer 20

1) False- basolateral membranes
2) True
3) False- Suppresses instead of increases
4) True
5) True

Question 21

Cimitidine is therapeutically used for PUD for SHORT/LONG-term therapy. It is used for GERD and best for ___________ use, modest postprandial. Also used in aspiration ___________- anesthesia suppresses the glottal reflex, permitting potentially fatal aspiration of gastric acid to the lungs.

Answer 21

Short term, nocturnal, pneumonitis.

Question 22

Adverse reactions of cimitidine include:

Answer 22

• Remarkebly well tolerated.
  1) Endocrine effects- blocks androgen receptors, causing loss of libido, impotence and gynecomastia.
  2) CNS effects
  3) Pneumonia
  4) Drug interactions- inhibits multiple CYP isoforms

Question 23

What is this: Activation occurs within parietal cells in the acidic secretary canaliculi; H+-catalyzed formation of a sulfenamide intermediate that is reactive towards Cys-SH groups on the H+, K+-ATPase. Taken 30 min before meals to stimulate acid formation within parietal cells.

Answer 23

Omeprazole- only active pumps are blocked; only 10% of pumps are active in fasting state.

Question 24

Omeprazole (PPIs) are substrates of CYP _____ and ________; Asian variant of ______ correlates with slow metabolism and potential toxicity. Dose reduction necessary in patients with _______ disease.

Answer 24

2C19, 3A4, 2C19, hepatic

Question 25

Therapeutic uses of PPIs (Omeprazole) include PUD, GERD, and what else?

Answer 25

-Zollinger-Ellison syndrome (hypersecretion of acid due to increased production of gastrin) and NSAID-associated ulcers.

Question 26

Adverse reactions of omeprazole include:

Answer 26

• Nausea, abdominal pain, constipation/diarrhea and flatulance most common.
• Drug interactions with warfarin, diazepam, cyclosporine.
• Pneumonia; stomach infections
• Bone fractures from decreased calcium absorption with long term use.
• Rebound hypersecretion of gastric acid upon discontinuation.

Question 27

List a mucosal protective agent and describe structure

Answer 27

Sucralfate- Complex compound composed of sulfated sucrose and aluminum hydroxide.

Question 28

MOA of sucralfate

Answer 28

• Forms a gel at pH<4; selectively binds necrotic tissue forming a barrier to acid and pepsin (6 hr duration).
• Orally administered and not absorbed.
• No acid neutralizing activity and does not reduce acid secretion.
• Taken on empty stomach.

Question 29

What is used for duodenal and stress ulcers. The advantage is that stomach pH is not increased so the risk of nosocomial pneumonia in critically ill patients is significantly lower.

Answer 29

Sucralfate

Question 30

Adverse reactions of sucralfate include:

Answer 30

• Constipation

- Reduced absorption of other drugs

Question 31

What is a prostaglandin (PGE1) analog

Answer 31

Misoprostol

Question 32

MOA of misoprostol

Answer 32

Substitutes for PGs when their synthesis has been inhibited by NSAIDS; reduces acid secretion from parietal cells, promotes bicarbonate and mucus secretion from epithelial cells and maintains submucosal blood flow.

Question 33

What is used for prevention of gastric ulcers in patients undergoing long-term therapy with NSAIDS (MUST BE GIVEN QID). In combination with mifepristone (RU-489) to induce abortion (so contraindicated in pregnancy!!!!)

Answer 33

Misoprostol

Question 34

Adverse effects of misoprostol

Answer 34

-Dose dependent diarrhea and abdominal pain