Unit XIV & XV: Gastrointestinal System Drugs & Nutrients

1. Unit XIV & XV: Gastrointestinal System Drugs & Nutrients Clinical Pharmacology Lourdes College Amy Spangler RN MS CPNP

2. Effects of Drugs on the Digestive System • Drugs may be administered to relieve symptoms and disorders of the digestive system • Drugs may also cause symptoms to digestive system • Drugs used in digestive disorders primarily alter GI secretion, absorption, or motility

3. Drugs Used for Peptic Ulcer (PUD) and Acid Reflux Disorders (GERD)

4. Drugs for Peptic Ulcer Disease • Peptic ulcer disease • Upper GI disorders • Degrees of erosion of the gut wall • Cause • Imbalance between mucosal and aggressive factors

5. Figure 76-1 The relationship of mucosal defenses and aggressive factors to health and peptic ulcer disease.

6. Classes of Antiulcer Drugs • Antibiotics • Antisecretory agents • Mucosal protectants • Antisecretory agents that enhance mucosal defenses • Antacids

7. Figure 76-2 A model of the regulation of gastric acid secretion showing the actions of antisecretory drugs and antacids.

8. H. pylori

9. Helicobacter pylori • Test: breath test or serum • Treatment (two antibiotics are prescribed.) • Bismuth compounds • Ranitidine bismuth citrate (Tritec) • Bismuth subsalicylate (Pepto)* • Clarithromycin • Amoxicillin • Tetracycline • Metronidazole • H2 RA and PPI

10. Histamine-2 Receptor Antagonists (H2RAs) • Histamine causes strong stimulation of gastric acid secretion (PNS – Vagus Nerve) • H2RAs inhibit both basal secretion of gastric acid and secretion stimulated by histamine, acetylcholine, and gastrin • Decrease amount, acidity, and pepsin content of gastric juices

11. Histamine2-Receptor Antagonists • Cimetidine [Tagamet] • Ranitidine [Zantac] • Ranitidine bismuth citrate [Tritec] • Famotidine [Pepcid] • Nizatidine [Axid]

12. H2 antagonists • May decrease absorption of other drugs which require acidic environment • Cimetidine: inhibits liver cytochrome P-450 of some drugs • Warfarin, theophylline, phenytoin • Dosages should be reduced • Alcohol metabolism is also inhibited.

13. Proton Pump Inhibitors (PPIs) • Strong inhibitors of gastric acid secretion • Bind irreversibly to the gastrin proton pump to prevent release of gastric acid from parietal cells – blocks final step • Suppresses gastric acid secretion in response to all primary stimuli, histamine, gastrin, and acetylcholine • example: Omeprazole (Prilosec) • Also; esomeprazole (Nexium), lansoprazole (Prevacid) • Biotransformed in liver • Prilosec and Nexium inhibit metabolism of anticoagulants, diazepam and phenytoin (may increase blood levels)

14. Sucralfate • Used to prevent and treat peptic ulcer disease • Does not neutralize acid or decrease secretion • Acts locally on gastric and duodenal mucosa • Low incidence of adverse effects • Give alone 30 to 60 min before meals • Give 2 hours before or after drugs as it may prevent other drugs absorption

15. Prostaglandin • Prostaglandin E inhibits gastric acid secretion and increases mucus and bicarbonate secretion, mucosal blood flow, and perhaps mucosal repair • PT: Misoprostol (Cytotec) • Blocks secretion of excess acid and protects stomach mucosa in those with use of chronic NSAIDS • Use in duodenal and peptic ulcers caused by NSAID • Added to an NSAID to decrease negative GI effect: Arthrotec (diclofenac and misoprostol) • Contraindicated in pregnancy, induces abortion

16. Antacids • Alkaline substances that neutralize acids • Inhibits conversion of pepsinogen to pepsin by raising pH • Aluminum compounds have low neutralizing capacity and slow onset • Magnesium-based have high neutralizing capacity and rapid onset • Example: Maalox (aluminum hydroxide and magnesium hydroxide) • Calcium compounds have rapid onset but may cause “acid rebound”, caldcium carbonate (Tums) – best as Ca++ supp. • Mixtures may be used, as well as addition of other ingredients • Al & Ca: constipation, Mg++: loose stools

17. Antacids…interactions • May chelate and make insoluble • May decrease absorption of some drugs • If drug needs strong acid environment • Enteric coatings

18. http://hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease4&organ=5&disease=16&lang_id=1http://hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease4&organ=5&disease=16&lang_id=1 John’s Hopkins University Digestive Disease Library- Stomach and Duodenum Peptic Ulcer Disease

19. Laxatives and Cathartics

20. Laxatives • Used to ease or stimulate defecation • Soften the stool • Increase stool volume • Hasten fecal passage through the intestine • Facilitate evacuation from the rectum

21. Indications for Laxative Use • Constipation is determined by stool consistency and frequency of defecation. • Indications: • Diagnosis • Treatment/procedure preparation • Constipation • Poisoning

22. Classification of Laxatives • Bulk-forming laxatives • Psyllium [Metamucil] • Stimulant laxatives • Bisacodyl [Dulcolax] • Osmotic laxatives • Milk of magnesia (MOM) • Surfactant laxatives (stool softeners) • Docusate sodium [Colace]

23. Laxatives • Bulk-forming laxatives are substances that are largely unabsorbed from intestine adding bulk to fecal mass to stimulate peristalsis. Pull water into intestinal lumen • Psyllium (Metamucil) • Methylcellulose (Citrucel) • Polycarbophil (Fiberall, Fibercon)

24. Laxatives • Osmotic laxatives increase osmotic pressure in intestinal lumen and cause water to be retained. Distension of bowel promotes peristalsis. • Magnisium Citrate (Milk of Magnesia) • Fleets enema • Lactulose pulls water into intestinal lumen • Used to treat constipation and hepatic encephalopathy d/t increased BUN, cramping is main SE. • Polyethelene glycol (GoLytely, MiraLax) evacuant, bowel prep for surgery or treatment for chronic constipation (dose dependent/formulation).

25. Laxatives, cont. • Stimulant cathartics are strongest and most abused laxative. Act on the intestinal wall of the small bowel and colon to increase the amounts of fluids and electrolytes within the intestinal lumen. PO or suppository • Bisacodyl (Dulcolax), senna (Senokot)

26. Laxatives, cont. • Lubricant laxative lubricates fecal mass and slows colonic absorption of water from fecal mass. • Mineral Oil – enema or PO

27. Laxatives, misc. • Miscellaneous laxatives – Other uses • Sorbitol pulls water into intestinal lumen. Given with Kayexalate to aid in expulsion of potassium and in Activated Charcoal to help promote elimination of toxins.

28. Stool Softeners • stool softeners (surfactant laxatives) decrease the surface tension of fecal mass to allow water to penetrate stool (softer poopy). • Ducosate sodium (Colace, correctol)

29. Dietary and Herbal Supplements • Many plant-based supplements such as cascara, psyllium, senna are stimulant laxatives and should only be used short term for the same reason as the prescriptive or OTC forms. • castor oil obsolete, can cause toxicity and should not be used. • Aloe is not recommended due to strong stimulant effect

30. Antidiarrheals

31. Antidiarrheal Agents • Opioids • Diphenoxylate [Lomotil] • Activate opioid receptors in the GI tract, decrease intestinal motility, slow intestinal transmit, more time for fluids and electrolytes to be absorbed • Camphorated tincture of opium (Paregoric) • Loperamide (Immodium, Kaopectate)

32. Antidiarrheal drugs • Bismuth salts (Pepto-Bismol) • have antibacterial and antiviral activity. ASA component may decrease inflammation Polycarbophil (FiberCon) and psyllium (Metamucil) decrease fluidity of stools • Specific therapy dependent on cause and may include • Antibacterial – Metroniazole/ Cipro • Enzymatic – if low level of GI enzymes • bile salt-binding - Questran • Short gut syndromes: hycosyamine (anaspaz)

33. Nonspecific therapy is adequate fluid and electrolyte replacement • Do not use antidiarrheals with simple gastroenteritis or abdominal pain (unknown diagnosis)

34. Antiemetics

37. Treatment is based on cause! • Opioid acting directly on CTZ? • Chemotherapy? • Anxiety? • NSAIDs causing irritation of gastric mucosa? • Motion sickness? • Increased intracranial pressure? • GI obstruction?

38. Serotonin Receptor Antagonists • Blocks serotonin: the major neurotransmitter for emesis • 5-HT3 located in CTZ, vagal nerve terminals in stomach and small intestine. When these are blocked: prevents initiation of signal for nausea and vomiting.

39. Antiemetics • Ondansetron [Zofran] • Blocks type 3 serotonin receptors on afferent vagal nerve • More effective when used with dexamethasone • Used to prevent or treat moderate to acute severe nausea and vomiting associated with cancer chemotherapy, radiation, and postoperatively • IV, PO • Antagonize receptors and prevent activation by emetogenic anticancer drugs

40. Dopamine Receptor AntagonistsPhenothiazines • Used for Acute Psychosis too (Thorazine) • CNS depressants • Block dopamine from receptor sites in brain and CTZ • Effective in preventing or treating nausea and vomiting induced by drugs, radiation, surgery and most other stimuli • Ineffective in motion sickness • Cause sedation • Prochlorperazine (Compazine) and • trimethobenzamide (Tigan) • Promethazine (Phenergan) also competitive at the H1 receptor w/ histamine

41. Cannibinoids • Dronabinol (Marinol) is a cannabinoid used in management of nausea and vomiting associated with anticancer drugs and unrelieved by other drugs • Side effects include psychiatric symptoms, high abuse potential, and withdrawal syndrome • Schedule II narcotic • Decreased use since ondestron emerged

42. Drugs for Motion Sickness

43. Muscarinic Receptor Antagonists • Scopalamine (Transderm –Scop) • anticholinergic drug • Reversible inhibitor of the actions of acetylcholine at muscarinic recepetors. Prevents actions of acetylcholine in vestibular system. • Effective in relieving motion sickness. Available in transdermal patch (decreased SE)

44. Histamine Receptor Antagonists (Antihistamines) • All antihistamines used in nausea work by anticholinergic activity: H1 receptor blocking agents relieve nausea and vomiting by blocking action of acetylcholine in brain. • May be effective in treating motion sickness • Not all antihistamines are effective as antiemetics • Meclizine (Antivert) • PT: Dimenhydrinate (Dramamine)

45. Benzodiazepine Antianxiety Drugs • Often used in multi-drug regimens to prevent nausea and vomiting associated with cancer chemotherapy • Produce relaxation and inhibit cerebral cortex input to vomiting center • Lorazepam (Ativan) commonly used

46. Other antiemetics • Metoclopramide (Reglan) is a prokinetic agent that increases GI motility and rate of gastric emptying by increasing release of acetylcholine in GI tract. Blocks dopaminegic (D2) receptors at the CTZ and blocks at sertogonergic (HT3) receptors. Antagonizes dopamine. Contraindicated in Parkinson’s disease • Phosphorated carbohydrate solution (Emetrol) is a hyperosmolar solution with phosphoric acid. Reduces smooth muscle contraction in GI tract (OTC)

47. Irritable Bowel Syndrome • Antispasmodics (hyosyamine, dicyclomine) • Bulk forming agents (Psyllium)* • Antidiarrheals (loperamide)* • TCA’s • Antbiotics and acid supresssants • Alosetron (Lotronex) • Tegaserod (Zelnorm)

48. Drugs for Inflammatory Bowel Disease (IBD) • Crohn’s disease and ulcerative colitis • see Table 78-5 • 5-aminosalicylates (Sulfasalazine) • Glucocorticoids (dexamethasone) • Immunomodulators (azathioprine (Imuran), mercaptopurine)

49. Vitamins

50. Intake of Vitamins • Recommended Dietary Allowances (RDAs) for vitamins are set by the Food and Nutrition Board of the Nation Academy of Sciences and represent the average daily dietary intake sufficient to meet the nutrient requirements of nearly all (97%-98%) healthy individuals in a particular life stage or gender.