1. Chapter 11 Gastrointestinal Drugs Dr. Dipa Brahmbhatt VMD MpH dbrahmbhatt@vettechinstitute.edu

2. Emetics Emetics (don’t use in unconcious/seizuring/compromised animal) – Drugs that induce vomiting – Used in the treatment of poisoning and drug overdose – Vomiting should not be induced if caustic substances have been ingested (Ammonia, lye, bleach) Always check with poison control prior to inducing vomiting – Can be centrally acting (working on the CRTZ) or peripherally acting (working on receptors locally)

3. Emetics Centrally acting Apomorphine (Apokyn) – Choice for Dogs – Stimulates dopamine receptors in CRTZ – Morphine derived emetic – Peripherally: SQ/IM: vomit in 5-10 minutes – Subconjunctivally: Conjunctiva sac: vomit in 10 – 20 minutes – SE: Protracted vomiting, CNS depression and restlessness Xylazine – Choice for cats – SE: bradycardia, decreased respiratory rate

4. Inducing Emesis Apomorphine Xylazine

5. Emetics Peripherally acting Ipecac syrup – 2 alkaloids: emetine & cephaeline Irritate gastric mucosa and stimulate CRTZ – Stomach and SI evacuated: 10-30 mins – SE: Higher doses cause CV problems Home remedies – Hydrogen peroxide – Salt and water/ mustard and water/ salt followed by water – Less reliable than other emetics

6. Emetics Activated charcoal is given if emesis is contraindicated It absorbs many chemicals and drugs in the upper GI tract Liquid/ Powder form (reconstituted with water) SE: Constipation, diarrhea and blackening of feces Superchan, Vet Powder, Vet Liquid, Toxiban (activated charcoal and kaolin)

7. Ulcers Ulcer: erosions of mucosa – Causes: metabolic disease, drug therapy & stress – C.S.: Anorexia, melena, abdominal pain, and hematemesis – Protected by Mucus which protects mucosa from gastric secretions Sphincter muscles: cardiac and pyloric prevent reflux of acid to esophagus and duodenum

8. ↑ release of HCL from parietal cells - stomach

9. Activated by Histamine Gastrin Acetylcholine

10. Antacid Systemic: sodium bicarbonate, calcium carbonate Nonsystemic: magnesium hydroxide, aluminum/magnesium hydroxide, aluminum hydroxide Cimetidine (Tagament®) Ranitidine (Zantac®) Famotidine (Pepcid®) Sucralfate Misoprostol Omeprazole Lansoprazole

11. Antiulcer Drugs Antiulcer drugs – Help prevent the formation of ulcers – Categories include Antacids Histamine-2 receptor antagonists Mucosal protective drugs Prostaglandin analogs Proton pump inhibitors

12. Antiulcer Drugs Antacids Promote ulcer healing by neutralizing HCl and reducing pepsin activity Rapid onset and short duration of action Interact with other drugs – By adsorption or binding the other drugs – By increasing stomach pH (decrease of absorption of certain drugs) – By increasing urinary pH (inhibit elimination of weak bases)

13. Antiulcer Drugs Antacids May be systemic or nonsystemic Examples: – Systemic (in blood): sodium bicarbonate, calcium carbonate – Nonsystemic (in GI): » Magnesium hydroxide: milk of magnesia, given to cows to treat rumen acidosis (increases rumen pH) » Aluminum/magnesium hydroxide, aluminum hydroxide: Mylanta used in foals and dogs in adjunct treatment for ulcer » Aluminium hydroxide: Amphojel lowers phospahte levels

14. Antiulcer Drugs Histamine-2 receptor antagonists Prevent acid reflux by competitively blocking the H 2 receptors of the parietal cells in the stomach, thus reducing gastric acid secretion SE: rare, diarrhea and inhibition of liver enzymes Examples: – Cimetidine (Tagament®) – Ranitidine (Zantac®) – Famotidine (Pepcid®) Most potent Fewer SE than zantac Less bioavailable More potent than tagamet Longer duration of action Than tagamet

15. Antiulcer Drugs Mucosal protective drugs  Combine with protein to form an adherent substance that covers the ulcer and protects it from stomach acid and pepsin  An example is sucralfate  SE: Constipation  Don’t give with H 2 receptor antagonist Mucosal protective drugs  Combine with protein to form an adherent substance that covers the ulcer and protects it from stomach acid and pepsin  An example is sucralfate  SE: Constipation  Don’t give with H 2 receptor antagonist

16. Antiulcer Drugs Prostaglandin analogs Suppress gastric secretions and increase mucus production in the GI tract An example is misoprostol, which is usually given to animals taking NSAIDs Pregnant women need to be careful while handling SE: GI: diarrhea, vomiting, abdominal pain Proton pump inhibitors Bind irreversibly to the H + -K + -ATPase enzyme on the surface of parietal cells of the stomach; this inhibits hydrogen ion transport into the stomach so that it cannot secrete HCl Examples: – Omeprazole (gastroguard) – Lansoprazole

17. Antiulcer Drugs Omeprazole – Horses and foals > 4 wks of age – Heal gastric ulcer and prevent re-occurrence Causes: feeding problems (less hay) Intensive training Development/growth Lansoprazole (Prevacid) – Used to tx. Gastroesophageal reflux and ulcers – Extra lable

18. BLOAT Foamy/pasture/legume Rumen is distended Asphyxiate the animals

19. Antifoaming Agents – Reduce or prevent the formation of foam – Used in ruminants, whose rumens are subject to acute frothy bloat – Make this foam less stable, breaking it up to promote gas release through belching – Administered as solutions by stomach tube directly into the forestomach – Examples include poloxalene and polymerized methyl silicone

20. Motility Enhancing Prokinetic agents – Increase the motility of parts of the GI tract to enhance movement of material through it – Types of prokinetic agents are: parasympathomimetics dopaminergic antagonists serotonergic agents

21. Prokinetic Agents Parasympathomimetic agents include – Acetylcholinesterase inhibitors, which compete with ACh for acetylcholinesterase, resulting in increased intestinal tone and salivation An example is neostigmine Tx of rumen atony and to diagnose myasthenia gravis in dogs SE: Vomiting diarrhea and increased salivation – Cholinergics, which make a precursor to acetylcholine An example is dexpanthenol

22. Prokinetic Agents Dopaminergic agents stimulate gastroesophageal sphincter, stomach, and intestinal motility by sensitizing tissues to the action of the neurotransmitter ACh Examples include metoclopramide and domeridone Don’t use reglan with antichlinergic drugs Serotonergic agents stimulate motility of the gastroesophageal sphincter, stomach, small intestine, and colon An example is cisapride

23. Enzyme Supplements – Pancreatic enzymes must be supplemented in the diet when the pancreas is not functioning properly (as in pancreatic exocrine insufficiency) – Pancrealipase contains primarily lipase, but also contains amylase and protease – Can be irritating to the skin on contact and to nasal passages upon inhalation

24. Appetite-Stimulating Drugs Serotonin antagonist antihistamines – Promote appetite by inhibition at the serotoninergic receptors which control satiety – Side effects include sedation and dry mouth Benzodiazepines – Effective appetite stimulants in cats but not dogs – Side effects include sedation and ataxia Tetracyclic antidepressants – Stimulate appetite by antagonizing alpha2-receptors – Side effects include sedation, vocalization

25. Appetite Stimulating Drugs Glucocorticoids – Stimulate steroid-induced euphoria which stimulates appetite – Side effects include polydipsia, polyuria, dull haircoat, weight gain, and behavioral changes Anabolic steroids – Stimulate hematopoiesis, appetite, and weight gain – Side effects include hepatotoxicity, masculinization, and early closure of growth plate in young animals

26. Appetite Stimulating Drugs Progestins – Used to stimulate appetite and promote weight gain in anorectic cats and dogs – Side effects include behavioral changes, endometritis, and mammary enlargement

27. Appetite Suppression Dirlotapide (Slentrol®) – Drug for management of obesity in dogs – Side effects include vomiting, diarrhea, lethargy, and anorexia

28. Dental prophylaxis