Gastrointestinal - Pharmacology

Question 1

GI therapy

Answer 1

Question 2

H2 blockers

• Examples
• Mechanism
• Clinical use
• Toxicity

Answer 2

• Examples
  
  • Cimetidine, ranitidine, famotidine, nizatidine.
  • Take H2 blockers before you dine.
  • Think “table for 2” to remember H2.
• Mechanism
  
  • Reversible block of histamine H2-receptors –>Ž decreased H+ secretion by parietal cells.
• Clinical use
  
  • Peptic ulcer, gastritis, mild esophageal reflux.
• Toxicity
  
  • Cimetidine is a potent inhibitor of cytochrome P-450 (multiple drug interactions)
    
    • It also has antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased libido in males)
    • Can cross blood-brain barrier (confusion, dizziness, headaches) and placenta.
  • Both cimetidine and ranitidine decrease renal excretion of creatinine.
  • Other H2 blockers are relatively free of these effects.

Question 3

Proton pump inhibitors

• Examples
• Mechanism
• Clinical use
• Toxicity

Answer 3

• Examples
  
  • Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole.
• Mechanism
  
  • Irreversibly inhibit H+/K+ ATPase in stomach parietal cells.
• Clinical use
  
  • Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.
• Toxicity
  
  • Increased risk of C. difficile infection, pneumonia.
  • Hip fractures, decreased serum Mg2+ with long-term use.

Question 4

Bismuth, sucralfate

• Mechanism
• Clinical use

Answer 4

• Mechanism
  
  • Bind to ulcer base, providing physical protection and allowing HCO3– secretion to reestablish pH gradient in the mucous layer.
• Clinical use
  
  • Increase ulcer healing, travelers’ diarrhea.

Question 5

Misoprostol

• Mechanism
• Clinical use
• Toxicity

Answer 5

• Mechanism
  
  • A PGE1 analog.
  • Increased production and secretion of gastric mucous barrier, decreased acid production.
• Clinical use
  
  • Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production)
  • Maintenance of a PDA.
  • Also used to induce labor (ripens cervix).
• Toxicity
  
  • Diarrhea.
  • Contraindicated in women of childbearing potential (abortifacient).

Question 6

Octreotide

• Mechanism
• Clinical use
• Toxicity

Answer 6

• Mechanism
  
  • Long-acting somatostatin analog.
• Clinical use
  
  • Acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors.
• Toxicity
  
  • Nausea, cramps, steatorrhea.

Question 7

Antacid use

• Can affect…
• All can cause…
• Overuse can also cause the following problems
  
  • Aluminum hydroxide
  • Calcium carbonate
  • Magnesium hydroxide

Answer 7

• Can affect…
  
  • Absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying.
• All can cause…
  
  • Hypokalemia.
• Overuse can also cause the following problems.
  
  • Aluminum hydroxide
    
    • Constipation and hypophosphatemia
    • Proximal muscle weakness, osteodystrophy, seizures
    • Aluminimum** amount of feces.**
  • Calcium carbonate
    
    • Hypercalcemia, rebound acid increase
    • Can chelate and decrease effectiveness of other drugs (e.g., tetracycline).
  • Magnesium hydroxide
    
    • Diarrhea, hyporeflexia, hypotension, cardiac arrest
    • Mg = Must go to the bathroom.

Question 8

Osmotic laxatives

• Examples
• Mechanism
• Clinical use
• Toxicity

Answer 8

• Examples
  
  • Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose.
• Mechanism
  
  • Provide osmotic load to draw water out.
  • Lactulose also treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4+.
• Clinical use
  
  • Constipation.
• Toxicity
  
  • Diarrhea, dehydration
  • May be abused by bulimics.

Question 9

Infliximab

• Mechanism
• Clinical use
• Toxicity

Answer 9

• Mechanism
  
  • Monoclonal antibody to TNF-a.
• Clinical use
  
  • Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis.
• Toxicity
  
  • Infection (including reactivation of latent TB), fever, hypotension.

Question 10

Sulfasalazine

• Mechanism
• Clinical use
• Toxicity

Answer 10

• Mechanism
  
  • A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory).
  • Activated by colonic bacteria.
• Clinical use
  
  • Ulcerative colitis, Crohn disease.
• Toxicity
  
  • Malaise, nausea, sulfonamide toxicity, reversible oligospermia.

Question 11

Ondansetron

• Mechanism
• Clinical use
• Toxicity

Answer 11

• Mechanism
  
  • 5-HT3 antagonist
  • Decreasedvagal stimulation.
  • Powerful central-acting antiemetic.
• Clinical use
  
  • Control vomiting postoperatively and in patients undergoing cancer chemotherapy.
  • At a party but feeling queasy? Keep _on dan_cing with ondansetron!
• Toxicity
  
  • Headache, constipation.

Question 12

Metoclopramide

• Mechanism
• Clinical use
• Toxicity

Answer 12

• Mechanism
  
  • D2 receptor antagonist.
  • Increases resting tone, contractility, LES tone, motility.
  • Does not influence colon transport time.
• Clinical use
  
  • Diabetic and post-surgery gastroparesis, antiemetic.
• Toxicity
  
  • Increased parkinsonian effects.
  • Restlessness, drowsiness, fatigue, depression, nausea, diarrhea.
  • Drug interaction with digoxin and diabetic agents.
  • Contraindicated in patients with small bowel obstruction or Parkinson disease (D1-receptor blockade).