Lecture 17/18 - GI medications Flashcards
What is responsible for protecting the stomach from acidic conditions?
Bicarbonate + Mucous
When do ulcers occur, most basic mechanism?
Acid > Protective layer
What can cause ulcers?
Drugs = NSAIDs + Corticosteroids H.pylori Mast cell tumors GI diseases Long interavals of no food in horses
What is the most basic mechaism by which ulcers are healed?
decrease acid
What are common signs of ulcers in dogs?
Vomiting +/- blood
Weight loss + Anaemia
Black tarry stool
What are common signs of ulcers in cats?
Vomiting +/- blood
Anemia + Weight loss + loss of appetite
Abdominal pain
Tarry stool
What is EGUS?
Equine gastric ulcer syndrome
What type of horse is most prone to ulcerations?
Racing horses (~60%)
What is the most basic mechanism by which horses get ulcers?
Always producing acid, so must be able to eat at all times to prevent erosion of stomach lining
What are signs that a horse may have a stomach ulceration?
Poor appetite + Lethargy + Weight loss + Poor performance + Attitude
What are the two parts of a horses stomach?
Non-glandular + Glandular
What is ESGUS?
Non-glandular
What is EGGUS?
Glandular
What portion of the stomach is most prone to ulcerations?
Non-glandular
What is an important mechanism by which H+ is taken into the parietal cell?
Histamine from ECL cell stimulates H2
What is the important protective portion of the molecular cascade of parietal cells?
PGE2 + PGI2 –> stimulates EP3
What does EP3 do? (two different cells)
Superficial epi cell = mucous + bicarb
Parietal cell = prevents H+ secretion
What inhibits PG’s?
NSAIDs
What do antacids block?
H+ directly
What do proton pump inhibitors inhibit?
H/K ATPase
What is the pH at the mucous layer?
7
What is the pH in the gastric lumen?
2
What does Mg do in the stomach?
Binds H+
Not absorbed
Also acts as a laxative
What does Al do in the stomach?
Binds H+
Not absorbed
Causes constipation
Combine with Mg
What two transmitters increase acid production?
M1/M3 = ACh H2 = Histamine
What are the three elements used in antacids?
Aluminum + Magnesium + Calcium
What is the product of antacids with H+?
Water + Neutral salt
When should antacids not be used? Why?
Renal failure
Mg will accumulate = CNS toxicity
What side effect do you see with Calcium as an antacid?
Creates CO2 = Burping
When should antacids be used, what types of Gi disorders?
Acidity in mild gastric disease
Don’t work with ulcerations
When is Mg used to cause diarrhea in cattle, goats, and sheep?
Grain overload
What type of receptor are H2’s linked with?
Gs = inc. cAMP
What are the four H2 antagonists?
Cimetidine
Ranitidine
Famotidine
Nizatidine
What is the result of H2 antagonists?
Reduction in Gastric acid + Pepsin secretion
How should H2 antagonists be handled in renal patients?
50% the dose
What should you watch out for with cimetidine?
Many drug interactions due to CYPs inhibition
What can occur with ranitidine?
Increase motility through M stimulation + decrease in acid
When is ranitidine recommended?
Feline megacolon
When are H2 blockers benefical?
Gastric + Duodenal ulcerations
Gastric erosions
Esophageal reflux disease
Gastritis
What H2 blocker is used in horses for ESGUS?
Ranitidine
Why are H2 blockers used in severe allergic reactions?
Decrease vasodilation effect of histamine on BV
How do proton pump inhibitors work?
Irreversible blockade of acid formation
How long does it take proton pump inhibitors to work?
2 to 5 days
Why do proton pump inhibitors have to be taken continuously?
Body will continue replacing H/K ATPase pumps
How should proton pump inhibitors be given?
Empty stomach for best absorption
Eat 30 min later
Where are proton pump inhibitors absorbed in the GI tract?
Intestine
What are the three proton pump inhibitors?
Omeprazole
Esomeprazole
Pantoprazole
When is a good time to use proton pump inhibitors in dogs?
Long-lasting acid suppression needed
Reduces risks of ulcers in dogs taking NSAIDs
What can proton pump inhibitors treat in horses?
EGGUS + ESGUS
What needs to be given with PPI in EGGUS?
Cytoprotectives
What is important to tell the client when giving them PPI’s?
DO NOT CRUSH UP, need to be protected from stomach acid
What are the most effective drugs in healing ulcers?
PPI’s
What are possible adverse reactions to PPI’s?
Bacterial overgrowth
Aspiration pneumonia
Long-term increase in gastrin
Gastric cancer
What does omeprazole inhibit? Do you need to worry about this?
P450’s. No, doesnt inhibit enough of it
How do cytoprotective agents work?
Create physical barrier between gastric epi + gastric lumen
How does bismuth work?
Bind to ulcer bed = protective coating
Increases PG’s = increased Bicard + decrease pepsin
What is important to remember about bismuth?
Toxic to cats and probably dogs due to salicylate
What are the side effects of sucralfate?
Constipation + Stomach upset
Why does sucralfate cause constipation?
Aluminum
When is sucralfate used in horses?
EGGUS
What is used with sucralfate in EGGUS?
omeprazole
What is misoprostol?
Synthetic PG’s E1 analogue
When is misoprostol used?
NSAID use in older dogs
What side effects can occur with misoprostol?
Diarrhea + Abdominal cramps
Increase nephrotoxicity of other drugs
What does erythromycin stimulate?
Motilin
What does cisapride stimulate?
Serotonin
What are the two prokinetic D2 antagonists?
Metoclopramide + Doperiodone
What do the prokinetic, D2 antagonists do?
Increase ACh release via D2 blockage
Reduce gastroesophageal reflux via increase sphincter tone
What prokinetic drug is used in cats and dogs?
Metoclopramide
What side effect can occur with metoclopramide? Why?
Can get into CNS
Excitement in horses + Anxiety + Involuntary movements
Increase potlactin
When is metoclopramide used in dogs?
Vomiting disorders
Delayed gastric emptying (post-operative)
Decrease gastroesophageal reflux
What is important to know about metoclopramide?
NOT APPROVED IN FOOD ANIMALS
What is domperidone used for?
Increase prolactin secretion
Treat fescue toxicity + agalactia in mares
Vomiting + Reflux
When is bethanechol used in dogs? Why?
Dogs have striated muscle in esophagus
Increases contraction
Treatment of megasesophagus
Cattle = cecal dilatation
When is erythromycin used?
Diabetic gastroparesis in dogs
What does Serotonin increase cause?
Increase ACh = increase motility SM
When is ipecac used?
After ingestion of toxins or drug overdose
How does apomorphine work?
Stimulates D2 in CTZ
When should you NEVER induce vomiting?
If animal has swallowed strong acid or alkali compound
What is really good at making cats vomit?
Xylazine
What is a neurokinin antagonist in vet medicine?
Maropitant
What does a neurokinin antagonist do?
Inhibit Substance P on NK1 receptor
What are neurokinin antagonoist used for?
Acute vomiting
Motion sickneess
Chemotherapy