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Nursing 3703 Pharmacology Digestive System Drugs

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  1. Nursing 3703PharmacologyDigestive System Drugs By Linda Self APN, MSN, CCRN

  2. Effects of Drugs on the Digestive System • Digestive system and drug therapy have a reciprocal relationship • Some medications cause GI symptoms (e.g. EES); conversely, some GI disorders alter the absorption and metabolism of drugs (liver failure) • Drugs affecting the GI tract include: laxatives, antidiarrheals, antiemetics, drugs used in acid-peptic disorders . Others include cholinergics (Aricept) anticholinergics (atropine), corticosteroids and anti-infectives.

  3. Review physiology of the digestive system Organs and some associated disorders • Oral cavity-stomatitis • Esophagus-GERD • Stomach—peptic ulcers, gastritis • Small intestine—malabsorption, Inflammatory bowel • Large intestine—diarrhea, constipation • Pancreas—pancreatitis, Diabetes, ARDS • Gallbladder—cholestasis,cholelithiasis, cholecystitis • Liver—hepatitis, cirrhosis

  4. Cell protective mechanisms in stomach • Secretion of mucus and bicarbonate • Dilution of gastric acid by food and secretions • Prevention of diffusion of HCL from the stomach lumen back into the gastric mucosal lining • Presence of prostaglandin E • Alkalinization of gastric secretions by pancreatic juices and bile

  5. Cell Destructive Effects in Stomach • Gastric acid, secreted by parietal cells • Paretal cells contain receptrors for acetylcholine, gastrin and histamine, all of which stimulate gastric acid production • Acetylcholine is released by vagus nerve endings in response to stimuli, such as thinking about food

  6. Cell destructive effects cont. • Gastrin is a hormone released by the stomach and duodenum in response to food ingestion. Affects parietal cells which in turn causes gastric acid to be released in stomach. • Histamine is released from cells in the gastric mucosa and diffuses into nearby parietal cells • Pepsin is a proteolytic enzyme that helps digest protein foods and also can digest the stomach wall

  7. Cell destructive effects H. pylori is a gram negative bacterium found in the gastric mucosa of most clients with chronic gastritis • In 75% of those with gastric ulcers and in 90% of clients with duodenal ulcers • Spread by oral fecal route or by iatrogenic spread • Thought to affect mucosal function

  8. Peptic Ulcer Disease Gastric Ulcers • Associated with stress, NSAIDs or H. pylori • Manifested by painless bleeding • Take longer to heal than duodenal ulcers • When associated w/stress, can occur at any age • With H. pylori and NSAIDs generally are in 6th or 7th decade • chronic

  9. PUD cont. Duodenal Ulcers • Can occur at any age • Occur equally in men and women • Manifested by abdominal pain • Associated with cigarette smoking • Also associated with NSAIDs and H. pylori

  10. Peptic Ulcer and Acid Reflux Disorders • Characterized by ulcer formation in the esophagus, stomach or duodenum • Occurs in areas that are exposed to gastric acid and pepsin • Gastric and duodenal ulcers are more common than esophageal ulcers • Parietal cells contain receptors for acetylcholine—implication of which is stimulation by/of vagus

  11. Upper GI Disorders • Gastritis—acute or chronic inflammatory reaction of gastric mucosa. Usually will see peptic ulcers with gastritis • Non-steroidal anti-inflammatory Drug Gastropathy • Occurs with damage to mucosa by ASA or other NSAIDs Chronic ingestion causes irritation of the gastric mucosa, inhibits the synthesis of prostaglandins (which protect mucosal lining) and increasess the synthesis of leukotrienes and other substances that can cause mucosal damage

  12. Selected Upper Gastrointestinal Disorders • Review p. 853 in text • Include Gastritis • Nonsteroidal anti-Inflammatory Drug Gastropathy • Stress Ulcers • Zollinger-Ellison Syndrome-rare; excessive secretion of gastric acid and a high incidence of ulcers. Caused by gastrin-secreting tumors in pancreas, stomach or duodenum. Often malignant.

  13. Gastroesophageal Reflux Disease • Most common disorder of the esophagus • Characterized by regurgitation of gastric contents into the esophagus • Occurs most often after a meal • Worse when recumbent • Caused by incompetent lower esophageal sphincter • Foods that cause relaxation include: etoh, caffeine, fats, chocolate, cigarrette smoking, gastric distention and medications (beta adrenergic blockers, calcium channel blockers, nitrates)

  14. GERD cont. • Occurs in men, women, and children • Common during pregnancy • More common after 40 years of age

  15. Classifications and Individual Drugs • Antacids—alkaline substances that neutralize acids. Raising the pH to approximately 3.5 neutralizes more than 90% of gastric acid and inhibits conversion of pepsinogen to pepsin. Commonly used antacids are aluminum, magnesium, and calcium compounds.

  16. Antacids • Antacids vary in onset of active and dosage needed for neutralization • Aluminum compounds require large doses for effectiveness. They can cause constipation, hypophosphatemia and osteomalacia. • Magnesium based antacids have more rapid onset than Al++ but can cause diarrhea and hypermagnesemia • Calcium compounds can cause hypercalcemia and hypersecretion of gastric acid==“rebound”

  17. Antacids • May be in combinations such as aluminum and magnesium hydroxide • Decreases the diarrhea and constipation • Most antacids are pregnancy category C • Antacids may be used in children • Antacides with magnesium are contraindicated because hypermagnesemia may result • Additives such as simethicone may be added • pills are as effective as liquids

  18. Use in Older Adults • Smaller doses as they secrete less acid • May have some renal compromise • Older adults often take large doses of NSAIDs • H2 receptor antagonists sometimes cause more side effects • Sucralfate is well tolerated • PPIs are drugs of choice in this population

  19. Helicobacterpylori • Requires combination of two antimicrobials and a PPI or an H2RA • Use amoxicillin, clarithromycin, metronidazole or tetracycline for antibiotic portion • More than antimicrobial is indicated to prevent resistance • Bismuth compound is added for its antibacterial effects as well as increasing the HCO3- and mucous contents of the stomach • Adding an H2RA or PPI decreases S/S and hastens healing

  20. Histamine 2 Receptor Antagonists • Histamine release causes contraction of smooth muscle in bronchi, GI tract, increases permeability of capillaries,stimulation of sensory nerve endings and strong stimulation of gastric acid secretion • Vagal stimulation causes release of histamine from cells in stomach, acts on receptors in parietal cells>>>>increases HCL production. • Called H2 receptors

  21. Histamine 2 Receptor Antagonists • Traditional antihistamines or H1 receptor antagonists generally reduce the effects of histamine in the body but do not block histamine effects on gastric acid production. • Replaced as first choice drugs by the PPIs • Prototype is cimetidine • Generally are pregnancy category B • May have multiple drug interactions and SE • Available OTC and by Rx

  22. H2RA • Reduce dosage in pregnancy • Cimetidine affects the cytochrome p450 drug metabolizing system in the liver; may cause confusion and antiadrogenic effects (gynecomastia) • Ranitidine more powerful • Use for up to 8 weeks • May be used long term but with variable dosing • Antacids may be given concurrently to relieve pain

  23. Proton Pump inhibitors • Strong inhibitors of gastric acid secretion • Bind irreversibly to the gastric proton pump to prevent the release of gastric acid from parietal cells • Suppresses acid secretion in response to all primary stimuli including histamine, gastric, and acetylcholine • Are the drugs of first choice in erosive esophagitis, erosive gastritis and Zollinger-Ellison

  24. PPIs • More effective than H2RA • Faster symptom relief and faster healing • Used in prevention of esophagitis • Tx H. pylori associated ulcers • Side effects are nausea, diarrhea and HA • Long term effects??? Implications??

  25. Prostaglandin • Naturally occurring prostaglandin E is produced by mucosal cells of the stomach and duodenum. It inhibits gastric acid secretion and increases mucous and bicarbonate, mucosal blood flow and mucosal repair. With inhibition of Prostaglandin E, erosion and ulceration of the gastric mucosa may occur. • Implications

  26. Cytotec (misoprostol) • Synthetic form of prostaglandin E • Indicated for clients at high risk for GI ulceration and bleeding and in those who take NSAIDs • Contraindicated in women of childbearing age and during pregnancy (see text p. 862) • May induce abortion • Side effects include diarrhea and abdominal cramping

  27. Sucralfate • Preparation of sulfated sucrose and aluminum hydroxide that binds to normal and ulcerated mucosa • Mechanism of action is unclear • Thought to possible bind to the ulcer and form a protective barrier between the mucosa and gastric acid, pepsin and bile salts; and stimulating prostaglandin synthesis • Effective in healing duodenal ulcers and in prevention of recurrence

  28. Sucralfate • Side effects include constipation and dry mouth • Must be given Bid • Cannot be given with an antacid, H2RA or PPI • May bind other drugs and prevent their absorption • Give 2 hours before or after other drugs

  29. Effects of Acid Suppressant Drugs on Nutrients • Dietary folate, iron and Vitamin B12 are better absorbed from an acidic environment • Less acidic environment can cause deficiencies of these nutrients • Sucralfate interferes with the absorption of the fat soluble vitamins • Magnesium containing antacids interfere with absorption of Vitamin A

  30. Nursing Actions • Review administration on p. 865-867

  31. Antiemetics • Used to prevent or treat nausea and vomiting • Vomiting is the expulsion of stomach contents through the mouth • Vomiting can occur w/o nausea

  32. Origin of vomiting • Vomiting center is located in medulla oblongata • Stimuli are relayed to the vomiting center from the periphery (gastric mucosa, peritoneum, intestines, joints(?)) and centrally (from the cerebral cortex; vestibular apparatus and from neurons in the fourth ventricle==chemoreceptor trigger zone) sites

  33. The vomiting center, chemoreceptor trigger zone and GI tract contain benzodiazepine, cholinergic, dopamine, histamine, opiate and serotonin receptors that are stimulated by emetogenic drugs and toxins • For example: chemotherapy may stimulate the CTZ which then signals the vomiting center • Motion sickness—changes in body motion>>stimulate receptors in inner ear>>transmitted to the CTZ and the vomiting center

  34. Triggering the vomiting center • Efferent impulses cause glottic closure • Contraction of abdominal muscles and diaphragm • Relaxation of the GE sphincter • Reverse peristalsis • Projection or expulsion

  35. Causes of nausea and vomiting • Pain • Emotional disturbances • Radiation therapy • Motion sickness • Drug therapy: especially with alcohol, ASA, digoxin, anticancer drugs, antimicrobials, estrogen preparations and Opioids

  36. Causes of Nausea and Vomiting • GI disorders such as inflammation of the GI tract, liver, gallbladder, pancreas, impaired GI motility and muscle tone (gastroparesis) and ingestion of food that is irritating to the mucosa • Cardiovascular, infectious, neurologic or metabolic disorders

  37. Antiemetic Drugs • Most have anticholinergic, antidopaminergic, antihistaminic or antiserotonergic effects • Generally are more effective in prophylaxis than treatment • Most act on the vomiting center, the chemoreceptor trigger zone, the cerebral cortex, vestibular apparatus or any of the above

  38. Antiemetic Drugs Phenothiazines—CNS depressants used in psychoses • Block dopamine from receptor sites in the brain • Act on CTZ and the vomiting center • Not all phenothiazines are anti-emetics • Cause drowsiness • Prochlorperazine (Compazine) and promethazine (Phenergan) are examples • Some are pregnancy category B, others C, should check 1st

  39. Side effects continued • Extrapyramidal symptoms which include: Dyskinesias (rhythmic movements), dystonias (rhythmic jerks) and akathesia (inability to sit still) related to dopamine receptor blockade

  40. Antihistamines • Prevent histamine from exerting its widespread effects on the body • Classic antihistamines or H1 receptor blocking agents are thought to block the action of acetylcholine in the brain (anticholinergic) • Indicated in Motion sickness • Examples are Dramamine, hydroxyzine (Vistaril), meclizine (Antivert)

  41. Corticosteroids • May affect prostaglandin activity in the cerebral cortex • Dexamethasone and methyprednisolone are commonly used in the management of chemotherapy induced emesis, usually in combination with other anti-emetics

  42. Benzodiazepine antianxiety drugs • Not classic anti-emetics but often used in multidrug regimens to prevent nausea and vomiting associated with cancer chemotherapy • Inhibit cerebral cortex input to the vomiting center • May give to those with anticipatory nausea before chemotherapy • Example is Ativan (lorazepam)

  43. 5 Hydroxytryptamine (5-HT3 or Serotonin)Receptor Antagonists • Ondansetron, granisetron and dolasetron are used to prevent or treat moderate to severe nausea and vomiting r/t cancer chemotherapy, radiation therapy and postoperatively • Some anticancer drugs seem to affect a subset of 5-HT3 recptors in the CTZ and the GI tract • These drugs antagonize receptors both peripherally (GI) and in the CTZ to prevent activation

  44. 5-HT3 receptor antagonists cont. • Can be given IV or orally • Side effects are mild to moderate and include: diarrhea, headache, dizziness, constipation, muscle aches and transient liver enzymes elevation • Ondansetron (Zofran) is the prototype • Metabolized by the liver

  45. Miscellaneous Antiemetics • Dronabinol (Marinol) is a cannabinoid used in the management of nausea and vomiting associated with anticancer drugs and unrelieved by other drugs. • Schedule III under federal narcotic laws • Withdrawal S/S may occur • Sleep disturbances

  46. Reglan • Prokinetic that increases GI motility and the rate of gastric emptying by increasing the release of acetylcholine from nerve edings in the GI tract • Can cause decreased n/v associated with gastroparesis • Has central antiemetic effects, antagonizes the action of dopamine • Can be given IV, PO or IM

  47. Reglan continued • Side effects include sedation, restlessness, and extrapyramidal reactions • May increase the effects of alcohol and cyclosporine and decrease the effects of cimetidine and digoxin (decrease time for passage)

  48. Emetrol • Phosphorated carbohydrate solution • Hyperosmolar solution with phosphoric acid • OTC • Felt to work by reducing smooth muscle contraction in the GI tract

  49. Scopolamine • Anticholinergic drug • Transdermal patch • Excellent for motion sickness

  50. Contraindications • When can delay or prevent diagnosis • When s/s of toxicity may be masked • Reglan is relatively contraindicated in Parkinson’s disease because it further dples dopamine