Gastrointestinal Disorders

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CHAPTER 13 Gastrointestinal Disorders

I. Gastrointestinal System Anatomy

II. Peptic Ulcer Disease

A peptic ulcer is a sore in the lining of the stomach, esophagus, or the first portion of the small intestine. Peptic ulcers may also be referred to as an ulcer.

1. Peptic ulcers occur when the digestive juices that help food digest damage the walls of the stomach or duodenum. The most common cause is infection with a bacterium called Helicobacter pylori, or H. pylori. Another cause is the long-term use of nonsteroidal anti-inflammatory drugs (NSAID) such as aspirin and ibuprofen (e.g., Motrin, Advil) (Table 13-1). Spicy foods do not cause ulcers, but can aggravate them and make them worse.

C. Signs and symptoms

1. Burning pain is the most common peptic ulcer symptom. The pain is caused by the ulcer and is aggravated by stomach acid contacting the ulcerated area. The pain may last from a few minutes to many hours and may flare up at night. Peptic ulcers also tend to be worse when the stomach is empty.

1. Smoking cessation

2. Decreasing alcohol consumption

3. Controlling acid reflux

4. Dietary modifications (more whole grains, vegetables, fresh fruit; less red meat and fatty foods)

1. Because many ulcers are caused by H. pylori bacteria, an approach to peptic ulcer treatment that eradicates the bacteria and reduces the level of acid in the digestive system is used. The result of the treatment is pain relief and ulcer healing.

2. Histamine H₂ antagonists or H₂ blockers

a) Mechanism of action: reversible H₂ antagonism in gastric parietal cells

(1) Inhibits secretions caused by histamine, gastrin, and muscarinic agonists

(2) Reduces the amount of hydrochloric acid released into the digestive tract

(a) Cimetidine (Tagamet)

(i) Usual adult dose (oral): prophylaxis, 400 mg qhs; active ulcers (short term), 300 mg qid or 800 mg qhs or 400 mg bid for 4 to 8 weeks

(ii) Adverse effects: antiandrogenic effects (gynecomastia, impotence), anticholinergic effects

(iii) Drug interactions: inhibits cytochrome P-450 (CYP) 1A2, 2C9, 3A4; interacts with many prescription and nonprescription drugs; classic drug interactions include narrow-therapeutic index drugs (e.g., theophylline, warfarin, phenytoin)

(b) Ranitidine (Zantac)

(i) Usual adult dose (oral): 150 mg bid or 300 mg qhs

(ii) Adverse effects: well tolerated

(iii) Drug interactions: drugs that require acid for absorption (e.g., ketoconazole)

(c) Famotidine (Pepcid)

(i) Usual adult dose (oral): 20 mg qhs

(ii) Adverse effects: well tolerated

(iii) Drug interactions: drugs that require acid for absorption (e.g., ketoconazole)

(d) Nizatidine (Axid)

(i) Usual adult dose (oral): 150 mg bid or 300 mg qhs

(ii) Adverse effects: well tolerated

(iii) Drug interactions: Drugs that require acid for absorption (e.g., ketoconazole)

a) A combination of antibiotics is usually used to treat H. pylori infections because one antibiotic alone is not usually sufficient to eradicate the organism. (See Box 13-1)

b) Commonly prescribed antibiotics for treatment of H. pylori include amoxicillin (Amoxil), clarithromycin (Biaxin), and metronidazole (Flagyl).

5. Proton pump inhibitors (PPI)

a) Superior to H₂ blockers in the healing, recurrence, and prevention of ulcers. Used preferentially with antibiotics in H. pylori eradication and ulcer treatment regimens.

b) Mechanism of action

(1) Inhibits H⁺/K⁺-ATPase enzyme system at the gastric parietal cell thereby blocking the last step of acid production

c) Adverse effects and precautions

(1) All PPI are generally well tolerated. Occasionally, they may cause nausea, diarrhea, headache or serious allergic-type reactions.

(2) All PPI should be taken 30 minutes before eating (i.e., on an empty stomach).

d) Drug interactions

(1) Omeprazole, lansoprazole, esomeprazole: substrates and inhibitors of CYP450 3A4 phenytoin, warfarin

(2) Rabeprazole, esomeprazole: substrates and inhibitors of CYP450 2C19

(3) All PPI may decrease the absorption of azole antifungals, protease inhibitors, iron salts.

e) Usual adult dose (oral)

(1) Omeprazole (Prilosec): 20 mg qd

(2) Lansoprazole (Prevacid): 15 mg qd

(3) Rabeprazole (Aciphex): 20 mg qd

(4) Esomeprazole (Nexium): 40 mg qd

(5) Pantoprozole (Protonix): 20 mg qd

6. Cytoprotective agents

III. Gastroesophageal Reflux Disease

Table 13-1 Characteristics of H. pylori versus NSAID-induced ulcers

H. pylori	Nonsteroidal anti-inflammatory drugs (NSAIDs)
Direct mucosal damage caused by hypergastrinemia	Direct mucosal damage associated with prostaslandin inhibition
Ulcers are superficial; chronically inflamed	Ulcers are deep; no inflammation
Symptoms: epigastric pain (may be nocturnal), nausea, indigestion, fatigue	Patients are usually asymptomatic; complications cause bleeding perforation

Gastroesophageal reflux disease (GERD), also called acid reflux disease, occurs when liquid from the stomach regurgitates into the esophagus. This liquid may contain stomach acids and bile. In some cases, the regurgitated stomach liquid can cause inflammation (esophagitis), irritation, and damage to the esophagus.

1. Develops when normal protective mechanisms of the esophagus begin to fail

2. Gastric acid enters into the distal esophagus, causing a burning sensation behind the breastbone, and sometimes leads to regurgitation of ingested food.

C. Signs and symptoms

1. Heartburn: a burning sensation in the chest that may spread to the throat

2. Regurgitation

3. Water brash (hypersalivation)

5. Several factors may worsen symptoms of the condition including spicy foods, fatty foods, chocolate, caffeine, tomato sauce, carbonated beverages, mint, alcoholic beverages, large meals, lying down after eating, some medications (e.g., sedatives, tranquilizers, or blood pressure drugs), and cigarette smoking.

D. Complications

1. If GERD persists for a long time it causes esophagitis, ulceration, bleeding, scar, stricture formation, and Barrett’s esophagus

1. Lifestyle modifications

a) Eating slowly

b) Eating three small meals

d) Smoking cessation

e) Sleeping in an upright position

f) Avoiding lying down after eating

2. Mild symptoms

a) Over-the-counter (OTC) antacids

b) OTC H₂ blockers

3. Mild refractory

a) Prescription H₂ blockers

IV. Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn’s disease.

1. The cause of IBD remains unknown. However, current research indicates that IBD most likely involves a complex interaction of factors, including heredity, the immune system, and antigens in the environment.

B. Pathophysiology (Table 13-2)

C. Complications

1. Toxic megacolon

2. Colon cancer

D. Signs and symptoms

1. The symptoms of these two illnesses are similar, which often makes it difficult to distinguish between the two. In fact, about 10% of colitis (inflamed colon) cases cannot be diagnosed as either ulcerative colitis or Crohn’s disease. When physicians cannot diagnose the specific IBD, the condition is called indeterminate colitis.

2. IBD causes chronic inflammation in the gastrointestinal tract and may lead to complications, such as colon cancer. The most common symptoms of both ulcerative colitis and Crohn’s disease are diarrhea (ranging from mild to severe), abdominal pain, decreased appetite, and weight loss. If the diarrhea is extreme, it may lead to dehydration, increased heartbeat, and decreased blood pressure. As food moves through inflamed areas of the gastrointestinal tract, it may cause bleeding.

1. Nonpharmacologic treatment: nutritional support

2. Surgery: for complications (abscess, fistula, perforation)

3. Pharmacologic therapy

d) Antibiotics and typical adult dose

(1) Metronidazole 10–20 mg/kg per day PO; ciprofloxacin 1 g PO qd

(2) Used for perianal fistula

V. Irritable Bowel Syndrome

Table 13-2 Characteristics of Inflammatory Bowel Disease

	Ulcerative colitis	Crohn disease
Anatomic sites	Colon and rectum	Any part of the GI tract
Lesions	Continuous and superficial	Discontinuous
Depth of involvement	Mucosa and submucosa inflammation	Transmural inflammation
Pathologic findings	Polyps	Obstruction due to inflammation Perforation Perianal fistulas

Irritable bowel syndrome (IBS), also called spastic colon, mucous colitis, spastic colitis, nervous stomach, or irritable colon, is a long-term condition that is characterized by abdominal pain, cramping, diarrhea, and constipation. IBS is a functional bowel disorder because the bowel appears normal but does not function properly.

A. Pathophysiology

1. Motility disorders of the GI tract

2. Intestinal secretion

3. Visceral hypersensitivity

1. Although the exact cause of IBS is unknown, it may be due, at least in part, to poor diet, neurotransmitter imbalances, and infections.

C. Clinical presentation

1. Constipation predominant

2. Diarrhea predominant

3. Alternating constipation and diarrhea

D. Signs and symptoms

1. In patients with IBS, the muscles of the colon, sphincters, and pelvis do not contract properly. As a result, patients experience constipation or diarrhea. This causes symptoms of abdominal pain, cramping, bloating, and a sense of incomplete stool movement. Symptoms may improve after the patient has a bowel movement.

1. Nonpharmacologic

a) Dietary modification

b) Stress management

2. Pharmacologic

c) Antispasmodics

(1) Used in patients with abdominal pain

(2) Examples: hyoscyamine (Levsin or Levsinex), dicyclomine (Bentyl), and methscopolamine (Pamine)

d) Antidepressants-Selective Serotonin Reuptake Inhibitors (SSRIs)

(1) Used to improve abdominal pain

(2) Examples: citalopram (Celexa)

VI. Nausea and Vomiting

A. Pathophysiology

1. Three stages

a) Nausea is the subjective feeling of needing to vomit.

b) Retching is a strong, belching-like, rhythmic movement that may or may not be followed by vomiting.

c) Vomiting (emesis) is the forcible expulsion of stomach contents through the mouth.

2. The brain and the GI tract are involved in the processes of nausea and vomiting, which include chemoreceptor trigger zone (CTZ) in the brain, the vestibular system, visceral afferents from the GI tract, and the cerebral cortex. The stimulation of the CTZ sends impulse to the vomiting center. The CTZ contains dopamine, histamine, acetylcholine, serotonin receptors, and neurokinin-1.

C. Signs and symptoms

1. Nausea is a subjective sensation that is difficult to define. It is an unpleasant feeling in the abdomen often associated with the sense of being ill and the urge to vomit. Other related symptoms include increased salivation, loss of color, sweating, tachycardia (increased heart rate), and the urge to defecate.

1. Home treatment

a) Drinking clear liquids only

b) Eating no solid food until the vomiting episode has passed

c) Getting plenty of rest because more movement and exertion may worsen the symptoms

a) 5-HT₃ antagonists

(1) Mechanism of action

(a) Blocks serotonin receptors peripherally and centrally; when the receptors are blocked, emesis is suppressed

(2) Adverse effects

(a) Headache and diarrhea

e) Butyrophenones

(1) Mechanism of action

(a) Blocks D₂ receptors at CTZ

(2) Example and typical adult dose

(a) Haloperidol (Haldol): 1–4 mg PO, IV, or IM q6h as needed

f) Cannabinoids

(1) Mechanism of action

(a) The exact mechanism of action is not well understood. It may be due to its effects on cannabinoid receptors in the central CNS

(2) Example and typical adult dose

(a) Dronabinol (Marinol): 5–20 mg PO q3–6h, or 5 mg/m² q2–4h upto 4–6 doses per day

h) Phenothiazines

(1) Mechanism of action

(a) Inhibits D₂ receptors at CTZ

(2) Examples and typical adult dose

(a) Prochlorperazine (Compazine): 10–20 mg PO, IV, or IM q4–6h

(b) Perphenazine (Trilafon): 2–8 mg PO, IV, or IM q6h

PATIENT PROFILE

Patient Initials: NB

Height: 5’ 6”

Allergies: No known drug allergies (NKDA)

Chief Complaint: NB goes to the pharmacy to ask questions regarding selection of products to treat heartburn. She states troublesome symptoms of heartburn roughly 2 or 3 days a week) within several hours of ingesting a meal. The symptoms began 2 weeks ago. She sometimes experiences the symptoms at night after retiring. She cannot pinpoint any specific dietary items that cause the heartburn to appear. She needs assistance in selecting an over-the-counter (OTC) product. She has been ingesting Tums for symptoms, and these help “a bit,” but the effect does not last long and her heartburn returns.

Social History:

Tobacco use: None

Alcohol use: Minimal, socially only

Exercise: Walking several days per week, some weight training

Levothyroxine 75 mcg PO once daily (hypothyroidism diagnosed 2 years ago, stable)

Laboratory: Not available

PATIENT PROFILE QUESTIONS

1. Certain patients with symptoms consistent with heartburn or gastroesophageal reflux (GERD) are not initial candidates for self-treatment. Which of the following are considered reasons for physician referral?

I. Difficulty swallowing (dysphagia)

II. Persistent symptoms (e.g., >3 months)

III. Symptoms occur >2 times per week

IV. Symptoms occur at night

d. I, II, and III

e. All of the above

Answer: c. If a patient has experienced symptoms intermittently 1–2 or more times per week for just a short period, self-treatment can be pursued for a limited time. The patient should not have had chronic or persistent symptoms for months. To be amenable to self-treatment, a patient should not have any alarm symptoms (e.g., pain or difficulty on swallowing, choking, nausea with vomiting, bleeding, weight loss, chest pain), or symptoms that might indicate other problems (e.g., chest pain, jaw pain, dental erosion, hoarseness of the voice, coughing, or wheezing). The presence of any unusual or alarm symptoms should prompt physician referral.

2. Which of the following would represent the BEST choice for an initial nonprescription (OTC) regimen for NB?

I. AcipHex 20 mg PO once daily

II. Prilosec OTC 20 mg PO once daily

III. Kapidex 30 mg PO once daily

IV. Pepcid AC 20 mg before meals known to cause heartburn

Answer: b. NB can choose an OTC regimen. Either II or IV are potential regimens; the other two (AcipHex, Kapidex) are prescription-only. Pepcid AC is not the best choice for this patient because she cannot identify triggering meals, and symptoms sometimes occur at night hours. However, for many patients, a H₂ antagonist like famotidine is a reasonable choice for heartburn prevention if heartburn symptoms can be tied to a trigger meal (e.g., pasta with tomato sauce) or for treatment of heartburn if symptoms only occur intermittently. A proton-pump inhibitor (PPI) is used OTC when symptoms occur several times (>2 times) per week and would help control symptoms in this patient; this is probably the best choice at this time given her history.

3. NB should also inform her physician of her use of a proton-pump inhibitor (PPI) at her next doctor visit, which is scheduled in 3 weeks. Why might she need to tell her doctor about her heartburn and treatment?

I. Both her choice of antacid (Tums) and a PPI could interfere with her levothyroxine prescription and the maintenance of euthryoid status.

II. If her symptoms are not controlled in 2 weeks, she will need to tell the physician and see if longer term treatment or further evaluation is needed.

III. The PPI could interfere with other prescribed medications, resulting in drug interactions.

d. I, II, and III

Answer: d. All of the above would be reasons for NB to inform her doctor of her use of a PPI. The PPI may cause a change in levothyroxine absorption, and the patient may need to have thyroid function tests monitored more frequently and be aware of symptoms that could indicate hypothyroidism if PPI treatment is continued. If symptoms do not resolve in 2 weeks, the patient should see a doctor for further evaluation, and the need for other tests and or treatments. Because PPIs block stomach acid and also may affect cytochrome P450 (CYP450) isoenzymes, they do have the ability to interfere with other prescription medications. A PPI should not be given with atazanavir, for example, because the PPI substantially decreases the bioavailability of atazanavir; atazanavir requires an acidic environment for oral absorption.

REVIEW QUESTIONS

(Answers and Rationales on page 359.)

1. Lansoprazole is used to treat which of the following?

a. Hypertension

b. Congestive heart failure

c. Gastric reflux (GERD)

d. Peptic ulcer disease

2. Fiber-Con is:

a. used in the treatment of constipation.

b. used in the treatment of diarrhea.

c. to be avoided when taking tetracycline.

d. All of the above

e. None of the above

3. What class of drug is famotidine?

a. H₁ receptor blocker

b. H₂ receptor blocker

c. H₃ receptor blocker

d. Gastrin inhibitor

e. COX-1 inhibitor

4. Which of the following is true of cimetidine?

a. It may cause confusion and dizziness.

b. It may cause hepatic dysfunction.

c. It is useful for the treatment of duodenal ulcers.

5. Histamine can cause all of the following except:

a. Elevated blood pressure

b. Capillary dilitation

c. Gastric hypersecretion

d. Vascular permeability

e. Decreased airway mucus production

6. Which one of the following statements about Dulcolax is true?

a. Normal oral dosing is 50–100 mg.

b. It produces colonic mucosal irritation and fluid secretion.

c. Oral onset of action is 2–4 hours.

d. It is 90% absorbed and secreted in the bile.

e. It should be ingested with a glass of milk for maximum effect.

7. Which of the following may cause breakdown of the protective gastric mucosal barrier?

8. Which of the following statements is/are correct?

a. Atropine, when administered in full doses, causes prolonged inhibition of stomach, duodenum, jejunum, ileum, and colon function.

b. Atropine reduces pancreatic sections.

c. Belladonna alkaloids significantly alter gastric secretions.

d. All of the above

e. None of the above

9. True or False: Increases in blood urea nitrogen (BUN) and serum creatinine (SCr) generally indicate liver damage.

10. Which of the following medications is indicated for treatment of chronic idiopathic constipation in adults?

c. Lubiprostone

d. Opium tincture

e. None of the above

12. Which of the following best describes the mechanism of action of Anzemet?

a. 5-HT₃ antagonist

b. Histamine antagonist

c. Beta-2 antagonist

d. Alpha-2 antagonist

e. None of the above

13. Which one of the following antiemetic medications also decreases gastric emptying time?

b. Metoclopramide

14. Which one of the following drugs is most similar in action to cimetidine?

15. Ranitidine may best be described as a(n):

b. histamine receptor antagonist.

c. proton pump inhibitor.

d. cytoprotective agent.

e. anticholinergic agent.

16. Select the over-the-counter (OTC) anti-nausea medicine that is more effective than cyclizine?

b. Promethazine

c. Diphenhydramine

d. All of the above

e. None of the above

17. Which of the following is an effect of antacids?

a. Inactivation of pepsin at alkaline pH

b. Decreased lower esophageal pressure

c. Increased gastric pH

d. Increased gastric motor activity

18. What is the effect of calcium or magnesium antacids on tetracycline?

a. Increased toxicity

b. Enhanced activity

c. Decreased action

d. Suppression of adverse effects

e. No significant change

19. Which of the following conditions requires consideration of the sodium, magnesium, or phosphate content of a laxative before administration?

b. Congestive heart failure

c. Renal insufficiency

20. Which of the following acts via inhibition of the H⁺/K⁺ ATPase pump?

21. Which of the following is a stimulant cathartic?

c. Sodium citrate

d. Sodium bicarbonate

e. Methylcellulose

22. Which of the following is minimally absorbed systemically?

a. Calcium carbonate

b. Aluminum hydroxide

c. Sodium bicarbonate

23. Which of the following is a correct mechanism of action of lactulose?

a. Induces osmotic diarrhea

b. Reduces fecal pH

c. Increases bacterial assimilation of ammonia

e. All of the above

24. Clearance of which of the following is NOT affected by cimetidine?

a. Theophylline

25. Which of the following is an adverse effect of prostaglandin E₂?

a. Gynecomastia

b. Thrombocytopenia

26. Which of the following will be poorly absorbed in the presence of aluminum hydroxide?

a. Penicillin G

b. Tetracycline

d. Erythromycin

e. Chloramphenicol

27. Which of the following is no longer the most appropriate agent to use in the treatment of peptic ulcer disease?

a. Muscarinic antagonists

b. Prostaglandins

d. Proton pump inhibitors

e. All of the above are appropriate

28. Which of the following is the principal component of emollient laxatives?

a. Magnesium hydroxide

d. Methylcellulose

e. Phenolphthalein

29. Which of the following is a histamine-2 receptor blocker?

d. Metoclopromide

30. Which of the following is NOT an appropriate medication to treat esophagitis?

a. Amitriptilyne

b. Metoclopramide

d. Dexlansoprazole

31. Which of the following is NOT an adverse effect associated with laxative use?

a. Spastic colitis

c. Intestinal obstruction

e. All of the above are potential side effects

32. Which of the following statements about saline cathartics is true?

a. They decrease surface tension of fecal matter.

b. They increase intestinal volume.

c. They are readily absorbed in the stomach.

d. They act more slowly than bulk-forming laxatives.

e. They are safe to use in patients with renal failure.

33. Which of the following is an indication for laxative use?

a. Drug overdose

b. Prevent straining in patients with cardiovascular disease

c. Diverticulosis

d. All of the above

e. None of the above

34. Which of the following is a possible mechanism of laxatives?

a. Increases peristaltic activity

b. Increases stool bulk

c. Lubrication of stool

d. All of the above

e. None of the above

35. Select the statement regarding metoclopramide.

a. It causes extrapyramidal.

b. It blocks peripheral muscarinic synapses.

c. It decreases lower esophageal sphincter pressure.

36. Which of the following statements about sucralfate is true?

a. It increases gastric motility.

b. It enhances Na⁺/K⁺-ATPase activity.

c. It antagonize gastrin.

d. It causes constipation.

e. It antagonizes acetylcholine.

37. Which of the following acts as a saline cathartic?

a. Sodium phosphate

b. Sodium bicarbonate

c. Methylcellulose

The following is a case study. Read the case study and answer the questions after.

A 30-year-old woman presents to her physician with complaints of chest pain for 3 months. She describes the pain as substernal and epigastric, burning, and worse after eating. She also complains of occasional regurgitation of stomach contents. She reports some relief with over–the-counter antacids.

38. What is the mechanism of gastroesophageal reflux?

a. Lower esophageal sphincter relaxation

b. Depressed esophageal mucus production

c. Increased acidity of gastric fluid

d. All of the above

e. None of the above

39. Which of the following is a potential complication of gastroesophageal reflux?

c. Subglottic stenosis

d. Peptic stricture

e. All of the above

40. Which of the following is an appropriate initial treatment for this patient?

c. Dextromethorphan

41. Which of the following is a potential side effect of cimetidine?

a. Constipation

c. Urinary frequency

42. This patient should be counseled to:

a. Elevate the head of her bed.

b. Wait at least 30 minutes after eating before lying down.

c. Avoid aggravating foods.

d. Avoid smoking.

e. All of the above

43. What is the correct dosage of cimetidine for GERD?

a. 300 mg PO bid

b. 400 mg PO qid

c. 400 mg PO qd

d. 400 mg PO tid

e. 1000 mg PO qd

44. Cimetidine may interact with all of the following EXCEPT:

c. cyclosporine

e. All of the above

45. Peptic ulcers are caused by:

b. Long-term NSAID use

46. The most common GERD symptoms are:

a. Laryngitis and hoarseness

b. Heartburn and regurgitation

c. Cough and wheezing

d. Stomach pains and diarrhea

e. Constipation and anal fissures

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