Digestive system

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. 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

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