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Nursing 3703 Pharmacology Digestive System Drugs

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1 Nursing 3703 Pharmacology Digestive 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 Helicobacter pylori 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

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

51 Management Considerations
5-HT3 antagonists 1st choice in chemotherapy induced or postoperative N/V Drugs with anticholinergic and antihistaminic properties are preferred for motion sickness If ambulatory, opt for drug that causes less sedation Phenergan is used for its antihistaminic, antiemetic and sedative effects

52 Management Considerations cont.
Phenothiazines can have serious side effects Reglan may be preferred for non-obstructive gastric retention

53 Herbals Efficacy still debatable

54 Chemotherapy-induced Nausea and Vomiting
Chemo may be given during sleeping hours Decrease food intake few hours before Tx Antiemetics should be given before the emetogenic Tx and may be given for 2-3 days 5-HT2 receptor antagonists are drugs of choice for this indication Reglan is valid option but may need to give diphenhydramine to prevent the EPS Sometimes combo of steroid and 5-HT3 RA useful

55 Laxatives and Cathartics
When stomach and duodenum are distended with food, gastrocolic and duodenocolic reflexes are initiated The cerebral cortex controls the defecation reflex so that defecation can occur at acceptable times and places In people who inhibit the defecation reflex or fail to respond to the urge to defecate, constipation develops

56 Laxatives are chemical substances that act to facilitate passage of bowel contents
Cathartics—a purgative action of the bowels, action is stronger and generally produces elimination of liquid stools

57 Indications for Use Reduce cholesterol Obtain stool sample
Accelerate excretion of parasites after anthelminthics started Accelerate elimination of potentially toxic substances (Kayexalate) Pre-op Prevent straining at stool w/CAD, hemorrhoids Relieve constipation in pregnancy, in the elderly; in children with megacolon, and in those w/decreased motility

58 Laxatives and cathatics should not be used in the presence of undiagnosed abdominal pain
Could cause an inflamed organ to rupture Oral agents are contraindicated in intestinal obstruction and fecal impaction

59 Laxatives Bulk-forming laxatives—Citrucel, Metamucil
Surfactant Laxatives—mainly prevent straining. They allow water to penetrate stool and act as detergent to facilitate admixing of fat and water in the stool. Colace (docusate) or Surfak. Saline—magnesium citrate. Nulytely.Increase osmotic pressure in intestinal lumen.Not safe for frequent use. Affect fluids and lytes.

60 Cathartics Stimulant type are the strongest and most abused
Cascara,bisacodyl, castor oil and senna products Mineral oil is a lubricant laxative. It slows colonic absorption of water.

61 Other Lactulose—a disaccharide that is not absorbed from the GI tract. Pulls water into intestinal lumen. Used to treat constipation and hepatic encephalopathy. Lactulose reduces production of ammonia in the intestine. Can affect lyte and water balance. Sorbitol—monosaccharide that puls water into the intestinal lumen and has laxative effects. It is given with Kayexalate (potassium removing resin to treat hyperkalemia).

62 Laxative Abuse Public health problem in elderly
Use in patients with cancer What is normal? What are some measures to prevent constipation?

63 Safety in Use Saline cathartics must be used cautiously in the renally impaired Lactulose may be indicated in those with hepatic encephalopathy Seen frequently in form of enemas in hyperkalemia in hospital

64 Antidiarrheals Diarrhea is a symptom of numerous conditions that increase bowel motility; cause secretion or retention of fluids in the intestinal lumen and cause inflammation or irritation of the GI tract. End result: bowel contents are rapidly propelled and absorption of fluids and electrolytes is limite.d

65 Causes of Diarrhea Abuse of laxatives
Intestinal infections—E. Coli 0157:H7 (can result in a hemolytic uremic syndrome), Traveller’s diarrhea (E. coli), Campylobacter jejuni, Salmonella, Shigella, rotatvirus Inflammatory bowel diseases Drug therapy—pseudomembranous colitis—Clostridium difficile (anaerobic, spore forming rods)

66 Antidiarrheals Opiate related drugs Paregoric
Defenoxin with atropine—Motofen Diphenoxylate with atropine--Lomotil

67 Antibacterials Azithromycin for Traveller’s diarrhea
Cipro—E.coli, Camylobacter, Shigella EES—amebiasis Flagyl—Clostridium difficile Bactrim-Traveller’s diarrhea Vancomycin—Clostridium difficile, even in form of enemas

68 Miscellaneous Questran—Crohns’. Binds and inactivates bile salts in the intestine. Octreotide—diarrhea associated with HIV, carcinoid tumors, cancer therapies or intractable diarrhea caused by other drugs. Pancreatin—pancreatic enzymes used for replacement in patients w/deficiency of pancreatic enzymes

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