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

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)
H.Pylori Agents (Antibiotics)
Antacids
Proton-pump Inhibitors

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
PUD is ulcer formation in the
Esophagus
Stomach
Duodenum
areas of the GI mucosa
that are exposed to gastric acid and pepsin

9. PUD Gastric Acid Pepsin Proton-pump system
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) Cell-protective effects
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?
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
Adjunct therapy in control of upper GI bleeding
Especially in relation to acute stress ulcers
Adverse effects are rare and usually mild

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
Remember: 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

22. Questions: T F - lower esophageal sphincter
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
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!!

27. Where anti-nauseants exert their affects.
Labyrinths is the intricate passages of the inner ear.

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. 6. 5-Hydroxytryptamine 3 (5-HT3 or Serotonin Receptor Antagonists)
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-HT3 receptor 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!