1. Chapter 11 Gastrointestinal Drugs

2. Autonomic Nervous System
Sympathetic = “Fight or Flight”
Parasympathetic =
EAT TURKEY & SLEEP IT OFF
Autonomic Nervous System

3. Control Mechanisms of the GI Tract
One control mechanism of the GI tract is the autonomic nervous system (parasympathetic and sympathetic branches)
Parasympathetic stimulation increases intestinal motility, increases GI secretions, and relaxes sphincters
Cholinergic drugs simulate these actions
Anticholinergic drugs inhibit these actions
Sympathetic stimulation decreases intestinal motility, decreases GI secretions, and inhibits the action of sphincters
Sympathetic nerves simulate these actions

4. Gastrointestinal Disorders
Among the most common complains in veterinary medicine
Underlying causes include:
Infectious sources, dietary excess, adverse drug effects, systemic disease
These disorders result in clinical signs such as:
Diarrhea, constipation, vomiting, bloat, ulcer development, (generally associated with pain)

5. Drugs Affecting the GI Tract
Antisialogues
Drugs that decrease salivary flow
Used to limit the flow of excess saliva, which often occurs secondary to anesthetic drug use
Examples include anticholinergics such as glycopyrrolate and atropine
These drugs can also affect peristalsis because they are also used to treat vomiting, diarrhea, and excess gastric secretion

6. Glycopyrrolate (Robinul) and Atropine

7. Antidiarrheals
Antidiarrheals are drugs that decrease peristalsis, thereby allowing fluid absorption from the intestinal contents
Examples:
Anticholinergics
Protectants/adsorbents
Opiate-related agents
Probiotics
Metronidazole

8. Antidiarrheals Anticholinergics are used to treat tenemus and vomiting
Examples:
Atropine
Aminopentamide
Isopropamide
Propantheline
Methscopolamine
Side effects include dry mucous membranes, urine retention, tachycardia, and constipation

9. Antidiarrheals Protectants & Adsorbents
Protectants coat inflamed intestinal mucosa with a protective layer
Adsorbents bind bacteria and/or digestive enzymes and/or toxins to protect intestinal mucosa from damaging effects
Examples:
Bismuth subsalicylate (bismuth + aspirin-like product)
Kaolin/pectin
Activated charcoal
Side effects include constipation

10. Antidiarrheals Opiate-related agents
Narcotic analgesics control diarrhea by decreasing both intestinal secretions and the flow of feces and increasing segmental contractions
Examples:
Diphenoxylate
Loperamide
Paregoric
Side effects include CNS depression, ileus, urine retention, bloat, and constipation

11. Antidiarrheals Probiotics
Probiotics seed the GI tract with beneficial bacteria; use is based on the theory that some forms of diarrhea are caused by disruption of the normal bacterial flora of the GI tract
Must be refrigerated to maintain the viability of the bacteria
Examples:
Plain yogurt with active cultures
Variety of trade-name products

12. Probiotics

14. Antidiarrheals Metronidazole
A theory regarding the development of diarrhea is that anaerobic bacteria may increase due to disruption of normal GI flora
One way to treat this is to use an antibiotic effective against anaerobic bacteria
Metronidazole is an example of an antibiotic used to treat diarrhea

15. Metronidazole

16. Laxatives
A laxative loosens the bowel contents and encourages evacuation of stool
Laxatives help animals evacuate without excessive straining; treat chronic constipation from nondietary causes and movable intestinal blockages; and evacuate the GI tract before surgery, radiography, or diagnostic procedures
Cathartics are harsher laxatives; purgatives are harsh cathartics

17. Laxatives Types of Laxatives include: Osmotic Stimulant Bulk-forming
Emolliments

18. Laxatives
Osmotic
Pull water into the colon and increase water content in the feces, thereby increasing bulk and stimulating peristalsis
Are salts or saline product that may cause electrolyte imbalances if absorbed systemically
Examples include: lactulose, sodium phosphate with sodium biphosphate, magnesium sulfate, magnesium hydroxide

19. Laxatives
Stimulant
Increase peristalsis by chemically irritating sensory nerve endings in the intestinal mucosa
Many are absorbed systemically and cause a variety of side effects
Examples include bisacodyl, phenolphthalein, and castor oil

20. Laxatives Bulk-forming
Substances that absorb water into the intestine, increase fecal bulk, and stimulate peristalsis, resulting in large, soft stool production (which tends to look normal)
Are not systemically absorbed, so side effects are rare
Examples include psyllium hydrophilic mucilloid, polycarbophil,and bran

21. Laxatives
Emollients
Can be stool softeners (reduce stool surface tension and reduce water absorption through the colon), lubricants (facilitate the passage of fecal material, increasing water retention in stool), or fecal wetting agents (detergent-like drugs that permit easier penetration and mixing of fats and fluid with the fecal mass)
Examples include docusate sodium, docusate calcium, docusate potassium, and petroleum products

23. Antiemetics Antiemetics
Drugs that control vomiting that help alleviate discomfort and help control electrolyte balance
Most are given parenterally, as the patient may vomit the medication before it can be absorbed through the GI tract
Examples:
Phenothiazine derivatives
Antihistamines
Anticholinergics
Procainamide derivatives
Serotonin receptor antagonists

24. Antiemetics Vomiting has many causes including:
Viral and bacterial infections, dietary indiscretion, food intolerance, surgery, pain, or other drugs
The vomiting center of the brain have many inputs that tell it to activate including:
Equilibrium changes in the ear, responses due to pain or fear, intracranial pressure changes, vagus nerve stimulation in the GI tract, and activity in the chemoreceptor trigger zone

25. Antiemetics Phenothiazine derivatives
Inhibit dopamine in the chemoreceptor trigger zone, thus decreasing the stimulation to vomit
Side effects include hypotension and sedation
Examples:
Acepromazine
Chlorpromazine
Prochlorperazine
Perphenazine

26. Antiemetics Antihistamines
Controls vomiting when the vomiting is due to motion sickness, vaccine reactions, or inner ear problems
Work by blocking input from the vestibular system to the CRTZ
A side effect is sedation
Examples:
Trimethobenzamide
Dimenhydrinate
Diphenhydramine

27. Antiemetics Anticholinergics
Block acetylcholine peripherally, which decreases intestinal motility and secretions
May decrease gastric emptying (which may increase the tendency to vomit)
Side effects include dry mouth, constipation, urinary retention, and tachycardia
Examples:
Aminopentamide
Atropine
Propantheline

28. Antiemetics Procainamide derivatives
Work centrally by blocking the CRTZ and peripherally by speeding gastric emptying, strengthening cardiac sphincter tone, and increasing the force of gastric contractions
Should not be used in animals with GI obstructions, GI perforation, or GI hemorrhage
An example used in veterinary medicine is metoclopramide

29. Antiemetics Serotonin receptor antagonists
Work selectively on 5-HT3 receptors, which are located peripherally and centrally
Work on the theory that some chemicals cause vomiting because they increase serotonin release from small intestinal cells
Examples:
Ondansetron
Dolasetron

30. Maropitant (Cerenia®)

31. Antiemetics Neurokinin receptor antagonists
Work on NK1 receptors located in the center of the brain
Work by inhibiting substance P, the key neurotransmitter involved in vomiting
Maropitant citrate (Cerenia®)
Used to prevent acute vomiting and motion sickness
Side effects include:
Pain at the injection site, hypersalivation, and diarrhea

32. Emetics Emetics Drugs that induce vomiting
Used in the treatment of poisoning and drug overdose
Vomiting should not be induced if caustic substances have been ingested
Always check with poison control prior to inducing vomiting
Activated charcoal is given if emesis is contraindicated (it absorbs many chemicals and drugs in the upper GI tract)

33. Emetics
Can be centrally acting (working on the CRTZ) or peripherally acting (working on receptors locally)
Centrally acting
Apomorphine
Xylazine
Peripherally acting
Ipecac syrup
Home remedies

34. Inducing Emesis
Apomorphine
Xylazine

35. 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

36. Antiulcer Drugs Antacids
Promote ulcer healing by neutralizing HCl and reducing pepsin activity
Interact with other drugs
By adsorption or binding the other drugs
By increasing stomach pH
By increasing urinary pH
May be systemic or nonsystemic
Examples:
Systemic: sodium bicarbonate, calcium carbonate
Nonsystemic: magnesium hydroxide, aluminum/magnesium hydroxide, aluminum hydroxide

37. Antiulcer Drugs Histamine-2 receptor antagonists
Prevent acid reflux by competitively blocking the H2 receptors of the parietal cells in the stomach, thus reducing gastric acid secretion
Examples:
Cimetidine (Tagament®)
Ranitidine (Zantac®)
Famotidine (Pepcid®)

38. 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

39. Antiulcer Drugs Prostaglandin analogs Proton pump inhibitors
Suppress gastric secretions and increase mucus production in the GI tract
An example is misoprostol, which is usually given to animals taking NSAIDs
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
Lansoprazole

41. 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

42. 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

43. Prokinetic Agents Parasympathomimetic agents include
Acetylcholinesterase inhibitors, which compete with ACh for acetylcholinesterase, resulting in increased intestinal tone and salivation
An example is neostigmine
Cholinergics, which make a precursor to acetylcholine
An example is dexpanthenol

44. 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
Serotonergic agents stimulate motility of the gastroesophageal sphincter, stomach, small intestine, and colon
An example is cisapride

45. 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

46. 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

47. 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

48. 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

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