Drugs Affecting the digestive system

1. Drugs Affecting the digestive system Chapters 56, 59, 62 By Sandy Kaminski

2. Chapter 56:Physiology of the Digestive System The organs of the digestive system • Oral cavity • Esophagus • Stomach • Small intestine • Large intestine • Pancreas • Gallbladder • Liver

3. The Main Function of the GI System • To provide the body with fluids, nutrients, and electrolytes in forms that can be used at the cellular level. • The system also disposes of waste products that result from the digestive process. • Saliva • Gastric Juices • mucus • digestive enzymes • hydrochloric acid • Electrolytes • Pancreatic juices • amylase • lipase • trypsin and chymotrypsin • Bile

4. Effects of Drugs on the Digestive System • To relieve symptoms and disorders of the digestive system • To alter the digestive system secretion, absorption, or motility • Drugs used may also cause digestive symptoms • ie, nausea, vomiting, constipation, diarrhea, abdominal pain

5. Questions: The major digestive enzyme in gastric juice is pancreatase. The parasympathetic nervous system increases motility and secretions. Blood flow increases during digestion, absorption, and parasympathetic stimulation • F. The major digestive enzyme in gastric juice is pepsin, a proteolytic enzyme. • T • T

6. Questions • The sympathetic nervous system (fight or flight) increase gastric motility and secretions. • The GI secretions can break down medications so they can be absorbed or they may destroy the medications. • F • T

7. Chapter 59:Drugs Used for Peptic Ulcer (PUD) and Acid Reflux Disorders (GERD)

8. Peptic Ulcer Disease (PUD) • Attributed to an imbalance between cell-destructive and cell-protective effects • Such as • gastric acid • Pepsin • H. pylori infection • NSAIDs • Stress • Cigarette smoking

9. PUD • Gastric Acid • secreted by parietal cells in the mucosa of the stomach antrum, near the pylorus • Dissolve food • Act as a bactericide • Convert pepsinogen to pepsin • Pepsin • A proteolytic enzyme that helps digest protein but can also digest the stomach wall • Proton-pump system catalyzes the production of gastric acid and acts as a gastric acid (proton) pump to move gastric acid from parietal cells in the mucosal lining of the stomach into the stomach lumen.

10. PUD • Helicobacter pylori (H. pylori) • Bacterium found in GI tract of 75% in those with gastric ulcers and more than 90% in those with duodenal ulcers • It colonizes the mucus-secreting epithelial cells of the stomach mucosa and is thought to produce gastritis and ulceration by impairing mucosal function. • Antibiotics are used to eradicate H. pylori • amoxicillin, clarithromycin, metronidazole, tetracycline • Cell-protective effects • secretion of mucus and bicarbonate • dilution of gastric acid by food and secretions • prevention of diffusion of hydrochloric acid from the stomach lumen back into the gastric mucosal lining • the presence of prostaglandin E • alkalinization of gastric secretions by pancreatic juices and bile

11. Gastroesophageal Reflux Disease (GERD) • Most common disorder of the esophagus • Regurgitation of gastric contents (gastric acid and pepsin) into esophagus • Main cause is incompetent lower esophageal sphincter (LES) • Main symptoms – heartburn and pain on swallowing

12. Risk factors that contribute to impaired contraction of the LES include • foods (eg, fats, chocolate) • fluids (eg, alcohol, caffeinated beverages) • medications (eg, estrogens, progesterone, beta-agonists, anti-cholinergics, calcium channel blockers, narcotics, nitrates) • gastric distension • cigarette smoking • recumbent posture • Obesity • Pregnancy

13. What can PUD and GERD lead to? • PUD • Bleeding • Perforation • Obstructions • GERD • Barrett’s esophagus • Tissue lining changes and resembles that of instestine • 30 to 125 times more likely to develop esophageal cancer • Esophageal cancer • Laryngeal cancer • Erosive esophagitis • Esophageal strictures

14. Antacids • Alkaline substances that neutralize acids • Raising the pH to approximately 3.5 neutralizes more than 90% of gastric acid and iinhibits conversion of pepsinogen to pepsin • Commonly used antacids are aluminum, magnesium, and calcium compounds • Used to treat PUD, GERD, esophagitis, heartburn, gastritis, GI bleeding, stress ulcers

15. Antacids: Drug Interactions • Most often they decrease the absorption of other medications by the process of chelation • Chelation • Chemical binding, or inactivation, of another drug • Produces insoluble complexes • Result: reduced drug absorption • also affect the absorption of some nutrients. • Dietary folate, Fe, Ca, and Vit B12 are better absorbed in acidic environment and therefore deficiencies may occur.

16. Antacids: Nursing Implications • Assess for allergies • Preexisting conditions that may restrict the use of antacids include • Electrolyte imbalances • Renal disease • DM • Pregnancy • GI obstruction • HF

17. Histamine2 Receptor Antagonists (H2RAs) • Histamine causes strong stimulation of gastric acid secretion • 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 • Cimetidine, ranitidine (Zantac), famotidine are available H2RAs

18. H2 Antagonists: Nursing Implications • Assess for allergies and impaired renal or liver function • Dose must be reduced in renal impairment • Use with caution in clients who are confused, disoriented, or elderly • Take 1 hour before or after antacids • Available in both OTC and Rx preparations • For intravenous doses • follow administration guidelines

19. 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 thereby blocking final step of acid production • Suppress gastric acid secretion from parietal cells in response to all primary stimuli (histamine, gastrin, and acetylcholine) • Available preparations: • Omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole

20. Proton Pump Inhibitors: Nursing Implications • Assess for allergies and history of liver disease • Pantoprazole is available for parenteral administration, and can be used for clients who are unable to take oral medications • Safe for short-term therapy • Use cautiously in those with severe liver impairment • Lansoprazole and rabeprazole

21. Helicobacter Pylori Agents • Recommended treatment includes • Two or three antimicrobials • Amoxicillin, clarithromycin, metronidazole, tetracycline • Single agent not used b/c of concern about emergence of drug-resistant H. pylori • PPI or H2RA • PPI = proton-pump inhibitor • H2RA = Histamine 2 Receptor Antagonists • Accelerates symptom relief and healing of the ulcer

22. Questions: • Risk factors for PUD include stress, NSAID ingestion, Helicobacter pylori infection, and cigarette smoking. • Prostaglandin E and mucus are cell-protecting effects that protect the wall from injury. • GERD is thought to be the result of an incompetent upper esophageal sphincter. • T • T • F - lower esophageal sphincter

23. Chapter 62:Anti-Emetics

24. Definitions • Nausea: unpleasant sensation of abd discomfort accompanied by a desire to vomit. May occur without vomiting. • Vomiting: expulsion of stomach contents through the mouth, May occur without prior nausea. • Occurs when the vomiting centre (VC) or chemoreceptor trigger zone (CTZ) are stimulated

25. Causes of N/V in hospital • Gastrointestinal disorders • including infection or inflammation in the GI tract, liver, gall-bladder, or pancreas • impaired GI motility and muscle tone (eg, gastroparesis) • overeating or ingestion of foods or fluids that irritate the GI mucosa • Cardiovascular, infectious, neurologic, or metabolic disorders • Drug therapy • Pain and other noxious stimuli • Emotional disturbances; physical or mental stress • Radiation therapy • Motion sickness • Post-operative status

26. Mechanism of Action of Anti-Emetics • blocking one of the vomiting pathways, thus blocking the stimulus that induces vomiting • several different therapeutic classifications • anti-cholinergic • anti-dopaminergic • anti-histaminic • anti- serotonergic effects • more effective in prophylaxis than treatment • Eg. Administering Morphine IV with Gravol IV • Eg. Taking anti-motion meds 30 minutes prior to getting on the boat!!

28. CTZ – Chemoreceptor Trigger Zone

29. Classifications of Anti-emetics – all lumped into anti-cholinergics / anti-dopminergics/ anti-histaminic/anti-serononergic 1. Phenothiazines • Block dopamine from receptor sites in brain and CTZ • (chemoreceptor trigger zone) • chlorpromazine (Largactil) is the prototype • prochlorperazine (Stemetil) • CNS depressant – therefore causes sedation • Effective for n/v induced by drugs and radiation therapy • Not effective for motion sickness 2. Anti-histamines • block action of acetylcholine in brain (anti-cholinergic effects) • Dimenhydrinate (Gravol) and meclizine (Bonamine) • effective in treating motion sickness

30. Classifications of Anti-emetics – all lumped into anti-cholinergics / anti-dopminergics / anti-histaminic / anti-serononergic 3. Corticosteriods • Block prostaglandin activity in the cerebral cortex • Dexamethasone (Decadron) • Commonly used in the management of chemotherapy-induced emesis and intra-operatively • Causes euphoria, insomnia 4. Benzodiazapines • Produce relaxation and inhibit cerebral cortex input to vomiting center • lorazepam(Ativan) • Anticipatory chemotherapy induced n/v

31. Classifications of Anti-emetics – all lumped into anti-cholinergics / anti-dopminergics/ anti-histaminic/anti-serononergic 5. Prokinetic Agents • Increase the release of Ach from the GI tract • metoclopramide (Maxeran) • Increases GI motility • Used in gastroparesis (gastric retention of foods) • May increase the effects of alcohol 6. 5-Hydroxytryptamine 3 (5-HT3 or Serotonin Receptor Antagonists) • Antagonize serotonin receptors • ondansetron (Zofran) • Moderate to severe n/v (cancer therapy, post-op) • May cause diarrhea, headache, muscle aches, elevated liver enzymes

32. What’s important for me to know about anti-emetics? • Drug selection, dose and route depend on the cause of the nausea/vomiting • Most adverse affects are sedation, drowsiness, dry mouth, diarrhea or constipation, and headache • Multi-drug regimens may be used to treat n/v • Use in special populations should be considered • Eg. Older adults – increased sedative effects • Eg. Scopolamine not recommended in pediatric population • Eg. Metoclopramide doses should be reduced in renal failure patients

33. What’s important for me to know about anti-emetics? • Antiemetics have anticholinergic, antidopaminergic, antihistaminic, or antiserotonergic effects. Most exert an effect on the vomiting center, CTZ, cerebral cortex, vestibular apparatus, or a combination of these areas • Pretreatment is usually most effective • 5-HT3receptor antagonists like ondansetron are usually considered the most effective antiemetics.

34. Question – T or F • The benzodiazapine antianxiety drugs are used as anti-emetics in multidrug regimens to prevent nausea and vomiting associated with chemotherapy. True!