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11. gastrointestinal drugs

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  • 1. Chapter 11 Gastrointestinal Drugs Copyright © 2011 Delmar, Cengage Learning
  • 2. Basic Anatomy and Physiology
    • The term gastrointestinal (GI) tract describes a long, muscular tube that begins at the mouth and ends at the anus.
    • Structures:
      • Oral cavity
      • Esophagus
      • Stomach
      • Small intestine
      • Large intestine
    • Structures vary from monogastric animals with simple stomachs to ruminant animals with multichambered forestomachs
    Copyright © 2011 Delmar, Cengage Learning
  • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 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, or pain
    Copyright © 2011 Delmar, Cengage Learning
  • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 6. Drugs Affecting the GI Tract
    • Antidiarrheals
      • Drugs that decrease peristalsis, thereby allowing fluid absorption from the intestinal contents
      • Examples:
        • Anticholinergics
        • Protectants/adsorbents
        • Opiate-related agents
        • Probiotics
        • Metronidazole
    Copyright © 2011 Delmar, Cengage Learning
  • 7. Drugs Affecting the GI Tract
    • Antidiarrheals (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 8. Drugs Affecting the GI Tract
    • Antidiarrheals (cont.)
      • Protectants/adsorbents coat inflamed intestinal mucosa with a protective layer (protectants) or bind bacteria and/or digestive enzymes and/or toxins to protect intestinal mucosa from damaging effects (adsorbents)
      • Examples:
        • Bismuth subsalicylate (bismuth + aspirin-like product)
        • Kaolin/pectin
        • Activated charcoal
      • Side effects include constipation
    Copyright © 2011 Delmar, Cengage Learning
  • 9. Drugs Affecting the GI Tract
    • Antidiarrheals (cont.)
      • Opiate-related agents 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
    Copyright © 2011 Delmar, Cengage Learning
  • 10. Drugs Affecting the GI Tract
    • Antidiarrheals (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 11. Drugs Affecting the GI Tract
    • Antidiarrheals (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 12. Drugs Affecting the GI Tract
    • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 13. Drugs Affecting the GI Tract
    • Types of 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
    Copyright © 2011 Delmar, Cengage Learning
  • 14. Drugs Affecting the GI Tract
    • Types of Laxatives (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 15. Drugs Affecting the GI Tract
    • Types of Laxatives (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 16. Drugs Affecting the GI Tract
    • Types of Laxatives (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 17. Drugs Affecting the GI Tract
    • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 18. Drugs Affecting the GI Tract
    • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 19. Drugs Affecting the GI Tract
    • Antiemetics (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 20. Drugs Affecting the GI Tract
    • Antiemetics (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 21. Drugs Affecting the GI Tract
    • Antiemetics (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 22. Drugs Affecting the GI Tract
    • Antiemetics (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 23. Drugs Affecting the GI Tract
    • Antiemetics (cont.)
      • Serotonin receptor antagonists
        • Work selectively on 5-HT 3 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
    Copyright © 2011 Delmar, Cengage Learning
  • 24. Drugs Affecting the GI Tract
    • 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
      • Used to prevent acute vomiting and motion sickness
      • Side effects include:
        • Pain at the injection site, pre-travel vomiting and hypersalivation, and diarrhea
    Copyright © 2011 Delmar, Cengage Learning
  • 25. Drugs Affecting the GI Tract
    • 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)
    Copyright © 2011 Delmar, Cengage Learning
  • 26. Drugs Affecting the GI Tract
    • Emetics (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 27. Drugs Affecting the GI Tract
    • Antiulcer drugs
      • Help prevent the formation of ulcers
      • Categories include
        • Antacids
        • Histamine-2 receptor antagonists
        • Mucosal protective drugs
        • Prostaglandin analogs
        • Proton pump inhibitors
    Copyright © 2011 Delmar, Cengage Learning
  • 28. Drugs Affecting the GI Tract
    • Antiulcer drugs (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 29. Drugs Affecting the GI Tract
    • Antiulcer drugs (cont.)
      • 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
        • Examples:
          • Cimetidine
          • Ranitidine
          • Famotidine
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 30. Drugs Affecting the GI Tract
    • Antiulcer drugs (cont.)
      • 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
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 31. Drugs Affecting the GI Tract
    • Antifoaming drugs
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 32. Drugs Affecting the GI Tract
    • 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, and serotonergic 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
    Copyright © 2011 Delmar, Cengage Learning
  • 33. Drugs Affecting the GI Tract
    • Prokinetic agents (cont.)
      • 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
    Copyright © 2011 Delmar, Cengage Learning
  • 34. Drugs Affecting the GI Tract
    • 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
        • • Refer to Table 11-1 in your textbook
    Copyright © 2011 Delmar, Cengage Learning
  • 35. Drugs Affecting the GI Tract Appetite Altering 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
    Copyright © 2011 Delmar, Cengage Learning
  • 36. Drugs Affecting the GI Tract Appetite Altering 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
    Copyright © 2011 Delmar, Cengage Learning
  • 37. Drugs Affecting the GI Tract Appetite Altering Drugs
    • Progestins
      • Used to stimulate appetite and promote weight gain in anorectic cats and dogs
      • Side effects include behavioral changes, endometritis, and mammary enlargement
    • Dirlotapide
      • Drug for management of obesity in dogs
      • Side effects include vomiting, diarrhea, lethargy, and anorexia
    Copyright © 2011 Delmar, Cengage Learning
  • 38. Dental Prophylaxis and Treatment
    • Refer to Table 11-1 in your textbook
    Copyright © 2011 Delmar, Cengage Learning

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