3) Gastrointestinal Agents

What are the 2 common causes of peptic ulcer?

1. Infection with the gram (-) Helicobacter pylori

2. NSAIDs

What are the 3 common treatment approaches for peptic ulcer?

1. Eradicating the H. pylori infection using antimicrobials

2. ↓ gastric acid secretion PPIs or H2 receptor antagonists

3. Providing agents that protect the gastric mucosa from damage (e.g., misoprostol and sucralfate)

Name the agents used in triple and quadruple therapy for H. Pylori-induced gastric ulcers.

Triple therapy: PPI + Amoxicillin + Clarithromycin

Quadruple therapy: PPI + Bismuth subsalicylate + Metronidazole + Tetracycline

How does acetylcholine and histamine induce gastric acid secretion?

1. Receptor-mediated binding of Ach, histamine or gastrin activates protein kinases

2. Protein kinases stimulate the H⁺/K⁺-ATPase proton pump to secrete H⁺ into the stomach lumen in exchange for K⁺

What is the advantage of using PPIs over H2 receptor antagonists in treating peptic ulcer?

PPIs are more superior in suppressing acid production & healing ulcers than H2 antagonists

• esp NSAID-induced ulcers

What are the endocrine side effects of cimetidine?

• gynecomastia

• galactorrhea

List the drugs Cimetidine can interfere with the metabolism of.

1. Warfarin

2. Phenytoin

3. Clopidogrel

Why are PPIs administered as prodrugs?

→ formulated as prodrugs with an acid-resistant enteric coating to protect them from premature degradation by gastric acid while passing through the stomach

• coating is removed in the duodenum’s alkaline environment, where it can be absorbed and transported to the parietal cells where it is converted to its “active form”

What is the long-term side effect of using PPIs?

↑ bone fracture risk in the hip, wrist, spine

What is Misoprostol and its application?

→ analog of prostaglandin E1

• used to prevent NSAID-induced gastric ulcers in high-risk patients

Why is Misoprostol contraindicated in pregnancy?

can stimulate uterine contractions → miscarriage

What are Antacids used to treat?

Symptomatic relief of:

• peptic ulcer disease

• heartburn

• GERD

What is Sucralfate composed of?

aluminum hydroxide + sulfated sucrose

What is the limitation to Sucralfate use?

(-) requires an acidic pH for activation

• shouldn’t be administered with antacids, PPIs, or H2 antagonists

(-) Binds to other drugs and interferes with their absorption

How do chemotherapeutic agents induce vomiting?

• directly activate the medullary chemoreceptor trigger zone (CTZ) or vomiting center

• cause GI cell damage, releasing serotonin, which carries sensory signals to the medulla → emetic/vomitting response

What are the receptors involved in triggering vomiting?

1. Dopamine receptor type 2

2. Serotonin type 3 (5-HT3)

How are laxatives useful in treating constipation?

• accelerate bowel motility

• soften the stool

• ↑ bowel movement freq

What is a downside to using laxatives chronically?

cause electrolyte imbalances

How does castor oil relieve constipation?

1. Castor oil → ricinoleic acid in the small intestine

2. Ricinoleic acid irritates the stomach & promptly ↑ peristalsis

Why should Castor oil not be used in pregnant woman?

stimulates uterine contractions

How does psyllium relieve constipation?

forms “gels” in the large intestine that cause water retention & intestinal distension →

↑ peristaltic activity

What are the sx of irritable bowel syndrome (IBS)?

• Chronic abdominal pain

• Altered bowel habits

What are its 2 main types of IBS?

1. Constipation predominant (IBS-C)

2. Diarrhea predominant (IBS-D)

What does IBD involve?

involves immune-mediated GI tract inflammation in response to bacterial antigens in the intestine

List the 2 common subtypes of IBD.

1. Crohn’s disease (CD)

2. Ulcerative colitis (UC)

Differentiate between Crohn’s and Ulcerative colitis.

Crohn’s Disease

→ can affect any part of the GI tract (mouth to anus) in a noncontinuous (patchy) way

• transmural (full-thickness) inflammation

.

Ulcerative Colitis

→ starts in the rectum and extends continuously through the colon

• inflammation only occurs in the mucosal layer

What are the toxic concerns in using azathioprine? What are the parameters for which the patients need to be monitored?

1. Bone marrow suppression

2. Hepatotoxicity

Pt require regular monitoring of complete blood counts (CBC) and liver function tests (LFTs)

When are TNF-α inhibitors used in ulcerative colitis (UC)?

→ are 2^nd-line agents used in UC patients who:

• fail 5-ASA therapy

• are unresponsive to or dependent on corticosteroids

• have more severe disease