gastrointestinal pharmacology

Question 1

Histamine-2 blockers

Cimetidine, ranitidine, famotidine, nizatidine.

MECHANISM Reversible block of histamine H2-receptors –> decreased H+ secretion by parietal cells.

CLINICAL USE Peptic ulcer, gastritis, mild esophageal reflux.

Answer 1

Proton pump inhibitors

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, component of therapy for H pylori, stress ulcer prophylaxis.

Question 2

Antacids

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

Answer 2

Aluminum hydroxide Constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures

Calcium carbonate-Hypercalcemia (milk-alkali syndrome), rebound acid increase

Magnesium hydroxide Diarrhea, hyporeflexia, hypotension, cardiac arrest

Question 3

Bismuth, sucralfate

MECHANISM Bind to ulcer base, providing physical protection and allowing HCO3 – secretion to reestablish pH gradient in the mucous layer. Require acidic environment; usually not given with PPIs/H2 blockers

CLINICAL USE increased ulcer healing, travelers’ diarrhea (bismuth).

Answer 3

Misoprostol

MECHANISM PGE1 analog. increase production and secretion of gastric mucous barrier, decrease acid production

CLINICAL USE Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production). Also used off-label for induction of labor (ripens cervix).

Question 4

Octreotide

MECHANISM Long-acting somatostatin analog; inhibits secretion of various splanchnic vasodilatory hormones.

CLINICAL USE Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors

Answer 4

Sulfasalazine

MECHANISM A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.

CLINICAL USE Ulcerative colitis, Crohn disease (colitis component)

Question 5

Loperamide

MECHANISM Agonist at μ-opioid receptors; slows gut motility. Poor CNS penetration (low addictive potential).

CLINI CAL USE Diarrhea.

Answer 5

Ondansetron

MECHANISM 5-HT3 antagonist;  vagal stimulation. Powerful central-acting antiemetic.

CLINI CAL USE Control vomiting postoperatively and in patients undergoing cancer chemotherapy.

Question 6

Metoclopramide

MECHANISM D2 receptor antagonist. increse resting tone, contractility, LES tone, motility, promotes gastric emptying. Does not influence colon transport time.

CLINICAL USE Diabetic and postsurgery gastroparesis, antiemetic, persistent GERD.

Answer 6

Orlistat

MECHANISM Inhibits gastric and pancreatic lipase –> decrease breakdown and absorption of dietary fats.

CLINICAL USE Weight loss.

Question 7

Laxatives

Bulk-forming laxatives-Psyllium, methylcellulose

MECHANISM

Soluble fibers draw water into gut lumen, forming a viscous liquid that promotes peristalsis

ADVERSE EFFECT

Bloating

Osmotic laxatives-Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose

MECHANISM

Provides osmotic load to draw water into GI lumen

ADVERSE EFFECT

Diarrhea, dehydration; may be abused by bulimics

Stimulants-Senna

MECHANISM

Enteric nerve stimulation –> colonic contraction

Emollients-Docusate

MECHANISM

Promotes incorporation of water and fat into stoo

Answer 7

Aprepitant

MECHANISM Substance P antagonist. Blocks NK1 (neurokinin-1) receptors in brain

CLINICAL USE Antiemetic for chemotherapy-induced nausea and vomiting.