1. Chapter 33
Therapy of Gastrointestinal Disorders: Peptic Ulcers, GERD, and Vomiting

2. Process of Digestion
The organs of the upper GI tract are primarily concerned with digestion and absorption of nutrients
The stomach and small intestine secrete several hormones and enzymes that aid in digestion and absorption
Specialized cells in the stomach produce hydrochloric acid and proteolytic enzymes which break down food particles into an absorbable form
Acetylcholine, gastrin, and histamine are the major stimulators for the release of gastric juices
The mucosal lining of the gi tract is lubricated with secretions of mucus and alkaline fluid that protect it from autodigestion

3. Peptic Ulcer
Open sores that develop on the mucosal lining of the stomach and duodenum
Most common cause is an infection caused by Helicobacter pylori
Can also be caused by long-term use of nsaids and steroids which inhibit secretion of protective mucus and interfere with the normal production of the mucosal lining
Symptoms include periodic pain (heartburn), nausea, loss of appetite, and vomiting
Antibiotic treatment for H.pylori
Antiulcer drug therapy
Reduces gastric acidity
Enhances mucosal barrier defenses
Involves the use of antisecretory drugs and antacids

4. Gastrointestinal Esophageal Reflux Disease (GERD)
Occurs due to regurgitation of digestive juices into the esophagus
Happens as a result of Inappropriate relaxation of the lower esophageal sphincter
Heartburn is the main symptom
GERD drug therapy
Suppresses acid production
Prevents erosion
Provides symptomatic relief

5. Life style modifications
Diet and Lifestyle modifications have an important role in therapy for peptic ulcers and gerd
Stop smoking
Avoid caffeine and alcohol
Reduce stress
Eliminate nsaids if possible
Eat smaller meals
Eliminate foods that trigger/worsen symptoms
Lose weight (if overweight)
Elevate the head of the bed

6. Antisecretory Drugs: Suppression of Gastric Acid
Histamine is a potent stimulator of gastric secretions
Histamine receptors are found in the gastric mucosa
Antihistamine (H2) receptor antagonists
Reduce interaction between histamine and H2 receptors reducing acid secretions
Includes Tagamet, Pepcid, zantac
Used to treat gastric ulcers, gerd, and for patients who must continue nsaid use
Adverse effects are few, especially during short term use
Headache or constipation

7. Antisecretory Drugs Suppression of Gastric Acid
Proton Pump Inhibitors (Prilosec, Nexium, prevacid)
Directly inhibit the system that releases hydrochloric acid
Clinical indications
With antibiotics in treatment of ulcers associated with H. pylori
Benign gastric ulcers and GERD
Promote healing and prevent recurrence
Adverse effects
Abdominal pain, headache, diarrhea, constipation, and nausea

8. Acid Neutralization: Antacids
Clinical indications
Hyperacidity associated with peptic ulcers
Upset stomach
Heartburn, GERD, and acid indigestion
Mechanism of action
React with HCl, forming water and salts- neutralizes acidity
Administered orally
Short duration of action

9. Acid Neutralization: Antacids
Special considerations
Systemic absorption
Most are nonsystemic
Prolonged use of sodium bicarbonate may result in metabolic alkalosis
adverse effects
Chronic use may result in acid rebound
Increased stomach pH (ALKALINE) CAUSES CELLS TO INCREASE SECRETION OF ACID
LONG-TERM USE CAN ALSO INCREASE SODIUM WHICH CAN BE SIGNIFICANT FOR PATIENTS WITH HYPERTENSION OR CONGESTIVE HEART FAILURE (WATER FOLLOWS SODIUM)

10. Prokinetic Drugs for the Management of GERD
Metoclopramide (REGLAN)
Stimulates contraction of the lower esophageal sphincter BY ENHANCING THE ACTION OF ENDOGENOUS ACETYLCHOLINE
PREVENTS REFLUX AND PROMOTES EMPTYING
Treats meal-induced heartburn
Treats chemotherapy-induced vomiting BY ANTAGONIZING DOPAMINE RECEPTORS IN THE CNS

11. Prokinetic Drugs for the Management of GERD
Adverse effects and contraindications
May produce cardiovascular effects such as palpitations and tachycardia
Common adverse effects are fatigue, restlessness, nausea, and diarrhea
Long-term or high-dose use increases the risk of tardive dyskinesia
Contraindicated in patients in whom motility may precipitate Hemorrhage or perforation (bowel perforation or obstruction)
Contraindicated in patients who are epileptic or area receiving drugs that are likely to cause extrapyramidal reactions

12. Management of Emesis Vomiting
Natural defense mechanism that may Signals disease or organ dysfunction
May be involuntary or self-induced
Associated with many causes including flu, pregnancy, motion sickness, ear infections, and certain drugs
Persistent vomiting results in electrolyte, fluid, and acid-base imbalances

13. Management of Emesis
Commonly used antiemetics are antihistamines and phenothiazines that inhibit dopaminergic or cholinergic receptors
Serotonin antagonists (Zofran) prevent serotonin from initiating cholinergic nerves
Antihistamines (reglan) relieve vomiting and exhibit anticholinergic effects
Adverse effects include dry mouth, sedation, drowsiness, diarrhea
Phenothiazines (Promethazine), metoclopramide (reglan), and ondansetron (Zofran) have the potential of producing extrapyramidal reactions
Safety during pregnancy has not been established