1. Nursing 3703 Pharmacology Digestive System Drugs
By Linda Self

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 (e.g. liver failure)

3. Effects of drugs on the digestive system
Drugs affecting the GI tract include: laxatives, antidiarrheals, antiemetics, and drugs used in acid/peptic ulcer disorders. Others include cholinergics (Aricept), anticholinergics (atropine), corticosteroids and anti-infectives.

4. Cell protective mechanisms in the stomach
Secretion of mucous 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
Parietal cells contain receptors for acetylcholine, gastrin and histamine. All of which stimulate gastric acid production
Acetylcholine is released by vagus nerve endings in response to stimuli. For example, seeing or smelling certain foods or even 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 trun 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 cont.
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 patients 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
Tend to be chronic

9. PUD cont. Duodenal ulcers Can occur nearly 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 the vagus

11. Other Upper GI Disorders
Gastritis—acute or chronic inflammatory reaction of gastric mucosa
Often will see peptic ulcers with gastritis
NSAID gastropathy:
Chronic ingestion causes irritation of the gastric mucosa, inhibits the synthesis of prostaglandins (which protect mucosal lining) and increases synthesis of substances that can cause mucosal damage (leukotrienes)

12. Gastroesophageal Reflux Disease (GERD)
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

13. GERD
Foods that cause relaxation of the lower esophageal sphincter include: etoh, caffeine, fats, chocolate, cigarette smoking, gastric distention and certain medications (beta blockers, calcium channel blockers and nitrates)

14. GERD Occurs in men, women and children Common during pregnancy
Traditionally more common in persons over 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 Vary in onset of action 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

17. Antacids
Calcium compounds can cause hypercalcemia and hypersecretion of gastric acid==‘rebound’
May be in combinations such as aluminum and magnesium hydroxide
Decreases the diarrhea and constipation

18. Antacids Most are pregnancy category C May be used in children
Antacids with magnesium are contraindicated in renal failure because hypermagnesemia may result
May contain additives such as simethicone
Pills are as effective as liquids

19. Antacids Some examples are: Amphogel (Al++) Maalox (Mg++ and Al++)
Mylanta (Mg++, Al++ and simethicone)

20. Use of antacids in older adults
Need smaller dosages as they secrete less acid
May have some pre-existing renal compromise
Older adults often take large amounts of NSAIDs
H2 receptor antagonists sometimes cause more side effects
Sucralfate is well tolerated PPIs are drugs of choice in this population

21. Helicobacter pylori Increasingly common
Requires combination of two antimicrobials and a PPI or H2 receptor antagonist
Use amoxicillin, clarithromycin, metronidazole or tetracycline for antibiotic action
More than one antimicrobial is indicated to prevent resistance

22. H. pylori
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

23. Histamine 2 Receptor Antagonists (H2RAs)
Histamine release causes contraction of smooth muscle in bronchi, GI tract, increases permeability of capillaries, stimulates sensory nerve endings and causes 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.

24. 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
Have been replaced as first choice drugs by the PPIs
Prototype is cimetidine
Generally are pregnancy category B

25. H2RA Often have multple drug interactions and SE
Available OTC and by prescription
Reduce dosage in pregnancy
Ranitidine is more powerful than cimetidine
May use for up to 8 weeks
Examples are: cimetidine, ranitidine, famotidine and nizatidine.

26. H2RA
Cimetidine affects the cytochrome p450 drug metabolizing system in the liver; may cause confusion and antiandrogenic effects (gynecomastia)

27. Proton Pump Inhibitors (PPIs)
Very 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, gastrin and acetylcholine.
Are the drugs of first choice in erosive esophagitis, erosive gastritis and in Zollinger-Ellison (gastrin secreting tumors)

28. PPIs More effective than H2RAs
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……..hypocalcemia, vitamin deficiencies, others

29. Examples of PPIs Nexium (esmeprazole) Prevacid (lansoprazole
Prilosec (omeprazole)
Protonix (pantoprazole)
Aciphex (rabeprazole)

30. 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 ulcerations can occur.

31. Cytotec (misoprostol)
Synthetic form of prostaglandin E
Indicated for clients at high risk for GI ulceration and bleeding and in those who take NSAIDs frequently
Contraindicated in women of childbearing potential (unless effective birth control methods are being used) and during pregnancy as it can cause abortion.

32. Cytotec May induce abortion
Side effects include diarrhea and abdominal cramping

33. Sucralfate (carafate)
Preparation of sulfated sucrose and aluminum hydroxide that binds to normal and ulcerated mucosa
Mechanism of action is unclear
Thought to possibly bind to the ulcer and form a protective barrier between the mucosa and gastric acid, pepsin and bile salts; and stimulates prostaglandin synthesis
Effective in treating duodenal ulcers and in preventing recurrences

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

35. 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 defiencies of these nutrients
Sucralfate interferes with the absorption of the fat soluble vitamins
Magnesium containing antacids interfere with absorption of Vitamin A

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

37. 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 (cerebral cortex, vestibular apparatus in the ear and from the chemoreceptor trigger zone in the 4th ventricle).

38. Vomiting center, chemoreceptor trigger zone and the GI tract contain benzodiazepine, cholinergic, dopaminic, histaminic, 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 triggers receptors in inner ear>>CTZ and the vomiting center

39. Triggering the vomiting center
Sequence goes as follows:
Efferent impulses cause glottic closure
Contraction of abdominal muscles and diaphragm
Relaxation of the GI sphincter
Reverse peristalsis
Projection or expulsion

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

41. 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 as well

42. 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, the vestibular apparatus or a combination of.

43. Phenothiazines Are CNS depressants used in psychoses
Block dopamine from receptors sites in the brain
Act on the CTZ and the vomiting center
Not all phenothiazines are anti-emetics
Compazine (prochlorperazine) and Phenergan (promethazine) are examples of phenothiazines
Compazine and phenergan are Cat. C.

44. Phenothiazines—side effects
Can cause extrapyramidal symptoms (EPS) which include: dyskinesias (rhythmic movements), dystonias (rhythmic jerks), and akathesia (inability to sit still) related to dopamine receptor blockade

45. Antihistamines as antiemetics
Prevent histamine from exerting its widespread effects on the body
Classic antihistamines or H1 receptor blocking agents are though to block the action of acetylcholine in the brain (anticholinergic)
Indicated in motion sickness
Examples are: Dramamine, Vistaril (hydroxyzine), Antivert (meclizine)

46. Corticosteroids
May affect prostaglandin activity in the cerebral cortex
Dexamethasone and methylprednisolone are commonly used in the management of chemotherapy-induced emesis; usually in combination with other antiemetics

47. Benzodiazepine antianxiety drugs
Not classic anti-emetics but often are used in multi-drug 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)

48. 5 Hydroxytryptamine (5-HT3 or Serotonin) Receptor Antagonists
Zofran (ondansetron)
Kytril (granisetron)
Anzemet (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 receptors in the CTZ and the GI tract

49. 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
Zofran (ondansetron) is the prototype
Are metabolized by the liver

50. Miscellaneous antiemetics
Marinol (dronabinol) 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
Can cause sleep disturbances

51. Reglan (metoclopramide)
Prokinetic that increases GI motility and the rate of gastric emptying by increasing the release of acetylcholine from nerve endings 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

52. Reglan cont.
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)

53. Emetrol Also known as phosphorated carbohydrate solution
Is a hyperosmolar solution with phosphoric acid
Is OTC
If felt to work by reducing smooth muscle contraction in the GI tract

54. Scopolamine Is an anticholinergic drug
Effective in relieving nausea and vomiting associated with motion sickness
Often used a transdermal patch and place behind the ear

55. Contraindications to use of anti-emetics
When s/s of toxicity can be masked
When use can delay or prevent diagnosis
Reglan is relatively contraindicated in Parkinson’s disease because it further depletes dopamine

56. Management considerations
5HT3 antagonists are 1st choice in chemotherapy induced or postoperative nausea and vomiting
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

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

58. Herbals Efficacy still debated
Ginger may be helpful for tx of nausea and vomiting, studies not conclusive

59. 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-HT3 receptor antagonists are the drugs of choice for this indication
Reglan is alternative but may need to give Benadryl to prevent the EPS
Sometimes use combination of steroid and 5HT3 RA.

60. Laxatives and Cathartics
When stomach and duodenum are distended with food, gastrocolic and duodenocolic reflexes are initiated
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, constipation results

61. 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

62. 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 in those with CAD or hemorrhoids

63. Indications cont.
Relieve constipation in pregnancy, in the elderly; in children with megacolon, and in those w/decreased motility

64. Contraindications
Laxatives and cathartics 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

65. Laxatives Bulk-forming—Citrucel and Metamucil (psyllium)
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. Examples are Colace (docusate) and Surfak.
Saline—magnesium citrate. Nulytely. Increase osmotic pressure in intestinal lumen. Can affect fluids and electrolytes.

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

67. Others
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 electrolyte and water balance.
Sorbitol-monosaccharide that pulls water into the intestinal lumen and has laxative effects. It is given with Kayexalate (potassium removing resin to treat hyperkalemia)

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

69. 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 the hospital

70. 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 limited.

71. Causes of diarrhea Abuse of laxatives Inflammatory bowel diseases
Drug Therapy-pseudomembranous colitis-Clostridium difficile (anaerobic, spore forming rods)
Intestinal infections-E. coli 0157:H7, Traveller’s diarrhea (E. coli, Campylobacter jejuni, Salmonella, Shigella, rotavirus

72. Antidiarrheals Opiate related drugs Paregoric
Motofen (defenoxin with atropine)
Lomotil (diphenoxylate with atropine)

73. Antibacterials Zithromax (azithromycin) for Traveller’s diarrhea
Ciprofloxacin for E. coli, Campylobacter and Shigella
EES-amebiasis
Flagyl (metronidazole) for C. difficile
Bactrim for Traveller’s diarrhea
Vancomycin for C. diff; may even be in the form of enemas

74. Miscellaneous
Questran—useful in Crohn’s disease. 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
Zelnorm—is a 5HT4 receptor agonist. Use in IBS, constipation form.