Ulcers Flashcards
GI ulcers
-painful
-hemorrhage
-Most severe: may erode through gastric wall, emptying contents into periteneum
**common in race horses
Gastric mucosa protection
- mucous layer coating cells
-High level of bicarb secretions
2.Tight junctions between cells: no HCl passage in mucosal cell membranes - Rapid turnover of mucosa cells
-need blood flow to stomach wall to bring everything needed for all to function - Pepsinogen is inactive when secreted
Negative feedback loop for stomach acid
1.When pH starts to rise, gastrin is released, stimulating parietal cells causing production of acid
2.Ach from vagas nerve will also stimulate acid production
- Local feedback where histamine activates and causes acid release
**pH too low, somatostatin which will feedback and cause an increased
How to prevent acid production?
Use proton pump inhibitors
-blocks membrane pump (H/K pump) and results in less Ca entering
Proton pump inhibitors
-Often end in azole (but don’t confuse with antifungal azole drugs)
-oral, injectable, paste
Omeprazole (Gastrogard)
-short half life, but long effect
-irreversible inhibition
-Can be used at 4mg/kg for ulcer treatment AND 1mg/kg to prevent ulcers
-expensive… especially in horses
Side effects of Omeprazole
-GI ulcer relapse when off therapy
-Chronic gastric acid reduction leads to hypergastrinemia
*may lead to mucosal cell hyperplasia, rugal hypertrophy and carcinoids
-CYP enzyme inhibitor= WATCH OUT for drug interactions
Gastric ulcers in cats and dogs
-Use proton pump inhibitors twice daily for treating acid-related gastric ulcers
**important to taper after prolonged use for more than 3-4 weeks… due to hypergastrinemia potential
Equine Drug compounding
-Bioavailability of compounded products were low and saw that Trademark Gastrogard is better
**Gastrogard better because proton pump inhibitors don’t work in stomach, need to be absorbed into the blood level. Omeprazole is sensitive to acid so will be gastric protected. Compounded omeprazole does not have the gastric protection!
Omeprazole and CSF effect
Some evidence that there is a decrease in CSF production
in dogs and rabbits study
H2-receptor antagonists
decreases acid production by blocking H2 receptors in parietal cells
-end in “tidine”
>Cimetidine, Ranitidine, Famotidine
-used in humans, but not great evidence for animals
Cimetidine
-affects liver enzymes (CYP inhibition) and impacts other drugs metabolism
Famotidine
-pepsid
-given with food or antacids
-not prokinetic
Low grade irritation/gastric irritation
Few studies
-star gazing dog
-endoscopy saw gastroesophageal sphincter issue
-gave famotidine and omeprazole
-clinical signs resolved
Acid rebound
-increase in parietal cell mass may occur with chronic use of H2 blockers or proton pump inhibitors which would then increase serum gastrin and upregulate H2 receptors
-parietal cells more sensitive to histamine
Antacids
-neutralize stomach acid to form water and a neutral salt
-low grade issues
-not commonly used in animals
-not absorbed, work directly in stomach
Sucralfate
-dissociated in gastric acid to form sucrose octasulfate and AlOH
-will coat ulcer and increase mucosal PGE synthesis (reducing acid production)
Misoprostol
-prostaglandin E analogue
-suppresses acid production/stimulates bicarbonate, increases blood flow and mucous production, decreases vascular permeability
-will cause womens abortion
Why use misoprostol?
-preventative for NSAID-induced ulcers in dogs
-doesn;t prevent methylprednisolone induced GI hemorrhage
**better preventative than treatment
Helicobacter
-found to cause ulcers in humans… but no evidence that it is present in companion animals
