21 – Gastric Ulcers

Question 1

Humans vs. animals with gastric ulcers: ‘what causes them’

Answer 1

• Humans: bacterial component
• Animals: no found bacterial component yet

Question 2

How is the gastric mucosa usually protected?

Answer 2

• Mucous layer coating cells
  o Mucosal cell membrane NOT permeable to HCl
  o Bicarb in mucous (can neutralize acid if it sneaks by)
• Tight junctions between cells: no HCl passage
• Rapid turnover of mucosal cells
• Pepsinogen is inactive when secreted
• *need blood flow for mucous, bicarb and turnover of cells!

Question 3

What happens when you eat and vagal nerve stimulation?

Answer 3

• Basolateral receptor activation will INCREASE translocation of H/K ATPase pumps into apical membrane
• *negative feedback loop when pH is too low

Question 4

When there are ulcers, what do you want to do?

Answer 4

• Reduce the amount of acid!
  o INHIBIT PROTON PUMPS
• May allow for some bacterial infections due to less protection

Question 5

Proton pump inhibitors

Answer 5

• Blocks the H/K ATPase pump
  o Now H can not go into the lumen
  o Cl- does NOT then go either
• *significant reduction in acid production

Question 6

Race horses and ulcers

Answer 6

• Stressed and odd diets=more common
• *ulcers in NON-GLANDULAR PORTION

Question 7

Omeprazole (Gastrogard)

Answer 7

• Short half life in blood, but long effect at site of action (irreversible inhibition)
• 4mg/kg: ulcer treatment
• 1mg/kg: ulcer prevention

Question 8

What do you need to watch out for with Omeprazole (Gastrogard)?

Answer 8

• GI ulcer relapse when off therpay
• Chronic gastric acid reduction leads to HYPERGASRINEMIA (increase Gastrin production to try and get the pH to go down)
  o Mucosal cell hyperplasia (cancer? No evidence)
  o Rugal hypertrophy
  o Carcinoids
• CYP-enzyme inhibitor (watch for drug interactions!)

Question 9

Omeprazole vs. famotidine in sled dogs

Answer 9

• Applicable to normal pets?
• When used omeprazole to decrease ulcers (for a dog that ran 300 miles)

Question 10

Ulcers in dogs and cats: what is the thing to use?

Answer 10

• Using a proton pump inhibitor is the way to go
• *should be tapered in pets AFTER PROLONGED USE of >3-4 weeks

Question 11

Equine Drug Compounding: Gastrogard vs. compounded suspension for Omeprazole

Answer 11

• Bioavailability in compound=LOWER
• Severity of ulcers actually decreased with Gastrogard
• *proton pump inhibitors need to go into SI then into blood and then blood takes them to vascular side of stomach
  o BLOOD LEVELS MATTER!
  o Omeprazole is very sensitive to acid=needs to be gastro-protective to make it to the small intestine
• When buy compounded=pure Omeprazole=lots broken down in stomach=wont work
• *need to use the trademarked product

Question 12

Omeprazole: what is the effect on the CSF?

Answer 12

• Pump bicarb into brain to make CSF
• *one paper in rabbits showed that it may decrease CSF production

Question 13

H2-receptor antagonists

Answer 13

• Block parietal cell HCl secretion through H2 receptor inhibition
• *limited evidence of efficacy in dogs/cats (only 1 ‘paper’)
• *recommended PPI be used instead

Question 14

H2-receptor antagonists examples

Answer 14

• Cimetidine (Tagamet)
• Ranitidine (Zantac)
• Famotidine (Pepsid AC)
• *MASSIVE IN HUMANS

Question 15

PK of H2 blockers

Answer 15

• Orally absorbed, but low bioavailability in horses and ruminants
• Short half-life
• CYP inhibition: DECREASE metabolism of other drugs (Cimetidine is notorious!)

Question 16

‘acid rebound’

Answer 16

• Increase in parietal cell mass may occur with chronic use of H2 blockers OR proton pump inhibitors
• Increased serum gastrin and/or upregulation of H2 receptors
• Parietal cells more sensitive to histamine

Question 17

Antacids

Answer 17

• AIOH, MgO, MgOH, CaCO3
  o Maalox, tums, rolaids, etc
• *neutralize stomach acid to form water and neutral salt
• Usually not absorbed systemically

Question 18

Pros of antacids

Answer 18

• Helpful for low grade problems
  o But animals can’t tell us it is ‘minor’
• Do NOT change acid production
  o If anything they may increase more acid

Question 19

Sucralfate

Answer 19

• Dissociates in gastric acid to for SUCROSE OCTASULFATE and AIOH
  o Sucrose octasulfate ‘coats’ the ulcer
  o Increases mucosal PGE synthesis
  o Fewer adverse drug reactions in normal patients
• Hard to demonstrate benefits, may interfere with absorption of other drugs

Question 20

Misoprostol

Answer 20

• Synthetic PGE analogue
• Stimulates bicarbonate and mucus secretion
• Increases mucosal blood flow
• Decreases vascular permeability
• Increases cellular proliferation
• *used to create a medically induced abortion

Question 21

When might misoprostol be useful?

Answer 21

• Preventative for NSAID-induced ulcers in dogs
• Doesn’t prevent methylprednisolone-induced GI
• *better PREVENTATIVE than treatment
• Fewer adverse effects
• *NOT REALLY SURE

Question 22

Bacteria that causes ulcers in domestic species?

Answer 22

• NONE found
• *imbalance between acid production and protection mechanisms