Therapeutics for GI Diseases- SA

Question 1

describe gastric ulceration and erosion

Answer 1

1. gastric ulcers consist of full thickness loss of the gastric mucosa
2. gastric erosions are characterizes by partial loss of mucosa, with preservation of the muscularis mucosa
3. clinical signs
   -coffee ground vomitus
   -melena
4. GUE can be due to:
   -primary GI disease: FB, neoplasia, SEVERE inflammation
   -secondary GI disease: NSAIDs, liver disease, uremia

Question 2

describe the main indications for antiulcer medications

Answer 2

1. treatment of CONFIRMED gastric ulceration
   -diseases causing true GUE
   -NSAID toxicity (COX1 inhibition)
2. management of diseases where gastric ulceration is a risk
   -renal disease
   -liver failure
3. prevention of secondary esophagitis in severe vomiting
   -or where reflux is a concern (ex. post BOAS surgery)
4. they are NOT anti-emetics and are not needed for every case of vomiting
   -gastritis does NOT = gastric ulceration

Question 3

describe H2 antagonists (4)

Answer 3

1. cimetidine/zitac (only vet product), ranitidine/zantac, famotidine/pepcid

-FILL IN MOA

2. admin: IV bolus, IV infusion, PO
   -if give IV remember that continuous use can lead to pharmacological intolerance (so only IV for a short period of time)
3. DOA:
   -cimetidine: every 6-8 hours, only suppresses acid production for 3-5 hours
   -ranitidine: every 8-12 hours
   -famotidine: every 12-24 hours (not vet labeled but used more commonly bc longer DOA)
4. ranitide also has prokinetic effect in upper GI and to a lesser extent lower GI, but potentially carcinogenic so no longer labeled for humans

Question 4

describe sucralfate

Answer 4

1. nonspecific drug, provides protection to lining of stomach (ulcer bandaid)
2. indicated for symptomatic treatment of gastric ulceration from a variety of causes
   -in humans is as effective as antacids or H2 receptor antagonists in healing ulcuers
3. can bind to other medications, potentially affecting their absorption
   -should be given at least 2 hours before a mea and 30 min before antacids to prevent binding
4. for ulcers or severe esophagitis, give every 6 hours

Question 5

describe proton pump inhibitors

Answer 5

1. omeprazole, pantoprazole, esomeprazole, and lansoprazole
2. target final common pathway of gastric acid production
3. irreversible inhibition of the H+/K+/ATPase in parietal cells
4. maximum inhibitory effect 2-4 days after initiation of therapy
   -inhibit existing and newly produced so need multi day dosing for max effect
5. twice daily dosing needed for consistent acid suppression
6. greater efficacy than H2 antagonists in healing ulcers in humans
   -limited evidence in CLINICAL canine and feline cases

Question 6

describe use of proton pump inhibitors

Answer 6

1. used increasingly commonly but off label since no vet registered product
2. most effective if admin just before a meal (every 12 hours)
3. efficacy is reduced if admin with H2 receptor antagonists
4. dose needs to be tapered if admin for longer than 3-4 weeks to avoid rebound hyperacidity
5. there is NO evidence to support the prophylactic use of gastroprotectant therapy in dogs and cats with nonerosive gastritis (ex. due to dietary indiscretion)
   -gastritis does NOT = gastric ulceration!!

Question 7

describe anti-emetic therapy

Answer 7

1. vomiting frequently occurs secondary to primary or secondary GI disease
   -anti-emetic therapy should ONLY be considered as symptomatic therapy
   -still need to determine and resolve the underlying disease process!!
2. main classes:
   -NK1 antagonists (neurokinin): maropitant
   -5HT3 antagonists (serotonin): ondansetron
   -D2 antagonists (dopamine): metaclopramide

Question 8

describe maropitant

Answer 8

1. selective antagonist of substance P at the NK1 receptor
2. inhibits the final common pathway involved in activating the vomiting reflex in the CNS
3. effective against emesis produced by BOTH peripheral and central stimuli
4. oral dose is higher than injectable dose due to significant first pass metabolism in the liver when given orally
5. effective antiemetic for dogs:
   -acute gastroenteritis
   -cytotoxic-induced vomiting
   -motion sickness (higher dose required)
   -use symptomatically, NOT therapeutically
   -if vomiting persists, investigate rather than repeating treatment
   -do NOT use if GI obstruction is suspected: can go wrong very rapidly

6, LESS effective as anti-nausea drug than ondansetron!!!!!

Question 9

describe ondansetron

Answer 9

1. 5HTs (serotonin) antagonist; blocks serotonin receptors in the GIT and CNS
2. to control cytotoxic drug induced emesis and persistent vomiting (ex. pancreatitis)
3. more effective for GI-mediated nausea than maropitant!

Question 10

describe metaclopramide

Answer 10

1. antagonizes:
   -D2 dopaminergic receptors
   -5HT3 serotonergic receptors
2. also has a peripheral pro-cholinergic effect (prokinetic)
3. LESS effective in CATS than dogs
4. main indications:
   -emesis-inducing disorders which involve central or peripheral activation of vomiting
   -GE reflux, decreased gastric emptying
   -NOT very effective against nausea!!
5. if suspect GI obstruction with a FB DO NOT USE (prokinetic effect would be so so bad with FB)

Question 11

describe drugs inducing vomiting

Answer 11

1. emergency induction of vomiting: ex. toxic ingestion
2. dogs: apomorphine:
   -dopamine agonist
   -rapid onset (within minutes)
   -NOT rec in cats (poor efficacy)
3. cats: dexmedetomidine
   -alpha-2 adrenergic agonist
   -rapid onset (within minutes)
   -reversible with atipamazole (alpha 2 antagonist)
   -NOT rec in dogs (poor efficacy)

Question 12

describe motility modifying drugs

Answer 12

1. when:
   -delayed gastric emptying, ileus
   -rabbit: decreased GI motility
   -cat: megacolon
2. what:
   -cisapride: 5HT4 (also works on serotonin system) receptor agonist; upper and lower GI
   –more effective on LES tone for GI reflux and gastric motility than metoclopramide

-ranitidine: acetylcholinesterase (stimulates cholinergic system); upper GI > lower GI

-metoclopramide: D2 receptor antagonist; upper GI

Question 13

describe hepatic support drugs for liver disease support

Answer 13

1. SAMe + silybin: provides antoxidant support and promotes hepatocellular regeneration
2. milk thistle: provides antioxidant support, promotes hepatocyte regeneration, and stabilizes cell membranes
3. ursodiol: reduces hepatic cholesterol absorption, promotes bile flow, has anti-inflammatory and cytoprotectant effects

Question 14

describe hepatic support drugs for hepatic encephalopathy

Answer 14

1. lactulose: increases colonic water content, reducing pH of colon and ammonia absorption (NH3 > NH4+)
2. neomycin: reduces intestinal ammonia-producing bacteria
   -not used much anymore due to toxicity

Question 15

describe probiotics

Answer 15

1. evidence of activity at cellular level in gut
2. clinical efficacy has been shown in humans
3. as of yet, little confirmed clinical efficacy in pets
   -not all products are the same!
   -but half of the pets in the US are receiving these (don’t harm at least, unsure of efficacy)

Question 16

describe prednisolone as used for intestinal bowel disease

Answer 16

1. corticosteroid used at immunosuppressive doses
2. first line treatment for IBD in dogs and cats, particularly in cases of lymphoplasmacytic enteritis, where it helps control immune-mediated inflammation
3. longer term use may cause PU/PD, immunosuppression, GI ulceration, and diabetes (esp in cats)
4. careful dose tapering is required to prevent adrenal insufficiency

Question 17

describe cyclosporine as used for intestinal bowel disease

Answer 17

1. calcineurin inhibitor that suppresses T cell activation, without significant impact of glucocorticoid pathways, making it a useful alternative to corticosteroids
2. good for refractory or steroid-resistant IBD, esp in severe lymphocytic-plasmacytic enteritis or granulomatous enteritis
3. common adverse effects include nephrotoxicity, vomiting, diarrhea, gingival hyperplasia (esp in cats), and secondary infections due to immunosuppression
4. careful monitoring of blood levels and potential drug interactions is recommended