GI - Pharmacology

Question 1

Give 4 examples of H2 blockers.

Answer 1

(1) Cimetidine (2) Ranitidine (3) Famotidine (4) Nizatidine; Think: “Take H2 blockers before you DINE.” to remember -dine & “Table for 2” to remember H2.

Question 2

What is the mechanism and effect of H2 blockers?

Answer 2

Reversible block of histamine H2-receptors => decrease H+ secretion by parietal cells

Question 3

What are 3 clinical uses for H2 blockers?

Answer 3

(1) Peptic ulcer (2) Gastritis (3) Mild esophageal reflux

Question 4

What are 5 major toxicities to associate with H2 blockers, and to which specific H2 blocker(s) does each of these toxicities apply?

Answer 4

CIMETIDINE is a (1) potent inhibitor of cytochrome P-450 (multiple drug interactions); it also has (2) antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased libido in males); can cross (3) blood-brain barrier (confusion, dizziness, headaches) and (4) placenta. Both CIMETIDINE and RANITIDINE (5) decrease renal excretion of creatinine. Other H2 blockers are relatively free of these effects.

Question 5

What are 5 examples of Proton pump inhibitors?

Answer 5

(1) Omeprazole (2) Lansoprazole (3) Esomeprazole (4) Pantoprazole (5) Dexlansoprazole

Question 6

What is the mechanism of proton pump inhibitors?

Answer 6

Irreversibly inhibit H+/K+ ATPase in stomach parietal cells

Question 7

What are 4 clinical uses for proton pump inhibitors?

Answer 7

(1) Peptic ulcer (2) Gastritis (3) Esophageal reflux (4) Zollinger-Ellison syndrome

Question 8

What are 4 toxicities to associate with Proton pump inhibitors?

Answer 8

(1) Increased risk of C. difficile infection, (2) pneumonia. (3) Hip fractures, (4) decreased serum Mg2+ with long-term use

Question 9

What is the mechanism and effect of Bismuth? What other drug acts the same?

Answer 9

Bind to ulcer base, providing physical protection and allowing HCO3- secretion to reestablish pH gradient in the mucous layer; Sucralfate

Question 10

What are 2 clinical uses for Bismuth, sucralfate?

Answer 10

(1) Increased ulcer healing (2) Traveler’s diarrhea

Question 11

What are the mechanism and GI effects of Misoprostol?

Answer 11

A PGE1 analog. Increase production and secretion of gastric mucous barrier, Decrease acid production.

Question 12

What are 3 clinical uses for Misoprostol?

Answer 12

(1) Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production); (2) maintenace of a PDA. (3) Also used to induce labor (ripens cervix)

Question 13

What are 2 toxicities to associate with Misoprostol?

Answer 13

(1) Diarrhea. (2) Contraindicated in women of childbearing potential (abortifacient).

Question 14

In what patient population is Misoprostol contraindicated, and why?

Answer 14

Contraindicated in women of childbearing potential (abortifacient); A PGE1 analog… used to induce labor (ripens cervix)

Question 15

What is the mechanism of Octreotide?

Answer 15

Long-acting somatostatin analog

Question 16

What are 4 clinical uses for Octreotide?

Answer 16

(1) Acute variceal bleeds (2) Acromegaly (3) VIPoma and (4) Carcinoid tumors

Question 17

What are 3 toxicities to associate with Octreotide?

Answer 17

(1) Nausea (2) Cramps (3) Steatorrhea

Question 18

What is the mechanism of Antacid use, and what are the effects on other drugs?

Answer 18

Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying

Question 19

What toxicity can all antacids cause?

Answer 19

All can cause hypokalemia

Question 20

What are 5 toxicities associated with overuse of Aluminium hydroxide antacid?

Answer 20

(1) Constipation and (2) hypophosphatemia; (3) proximal muscle weakness, (4) osteodystrophy, (5) seizures; Think: “aluMINIMUM amount of feces”

Question 21

What are 3 toxicities associated with overuse of Calcium carbonate antacid?

Answer 21

(1) Hypercalcemia, (2) rebound acid increase; (3) Can chelate and decrease effectiveness of other drugs (e.g., tetracycline)

Question 22

What are 4 toxicities associated with overuse of Magnesium hydroxide antacid?

Answer 22

(1) Diarrhea (2) Hyporeflexia (3) Hypotension (4) Cardiac arrest; Think: “Mg = Must Go to the bathroom”

Question 23

What are 4 examples of Osmotic laxatives?

Answer 23

(1) Magnesium hydroxide (2) Magnesium citrate (3) Polyethylene glycol (4) Lactulose

Question 24

What is the mechanism of all osmotic laxatives? Which osmotic laxative has an additional mechanism/use, and what is it?

Answer 24

Provide osmotic load to draw water out; Lactulose also treats hepatic encephalopathy, since gut flora degrade it into metabolite (lactic acid and acetic acid) that promote nitrogen excretion as NH4+

Question 25

What is the clinical use for all osmotic laxatives? Which osmotic laxative has an additional clinical use, and what is it?

Answer 25

Constipation; Lactulose also treats hepatic encephalopathy

Question 26

What are 3 toxicities/risks to associate with osmotic laxatives?

Answer 26

(1) Diarrhea, (2) dehydration; (3) may be abused by bulimics

Question 27

What is the mechanism of Infliximab?

Answer 27

Monoclonal antibody to TNF-alpha

Question 28

What are 5 clinical uses for Infliximab?

Answer 28

(1) Crohn disease (2) Ulcerative colitis (3) Rheumatoid arthritis (4) Ankylosing spondylitis (5) Psoriasis

Question 29

What are 3 toxicities to associate with Infliximab?

Answer 29

(1) Infection (including reactivation of latent TB) (2) Fever (3) Hypotension

Question 30

What is the mechanism of Sulfasalazine? What activates it?

Answer 30

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

Question 31

What are 2 clinical uses for Sulfasalazine?

Answer 31

(1) Ulcerative colitis (2) Crohn disease

Question 32

What are 4 toxicities to associate with Sulfasalazine?

Answer 32

(1) Malaise (2) Nausea (3) Sulfonamide toxicity (4) Reversible oligospermia

Question 33

What is the mechanism of Ondansetron, and what effects does it have?

Answer 33

5-HT3 antagonist; decreases vagal stimulation. Powerful central-acting antiemetic; Think: "at a party feeling queasy? keep ON DANCing with ONDASentron!"

Question 34

What are 2 clinical uses for Ondansetron?

Answer 34

Control vomiting (1) postoperatively and (2) in patients undergoing cancer chemotherapy

Question 35

What are 2 toxicities to associate with Ondansetron?

Answer 35

(1) Headache (2) Constipation

Question 36

What is the mechanism of Metoclopramide, and what effects does it have? What GI function does it not influence?

Answer 36

D2 receptor antagonist. Increase resting tone, contractility, LES tone, motility. Does not influence colon transport time.

Question 37

What are 3 clinical uses for Metoclopramide?

Answer 37

(1) Diabetic and (2) post-surgery gastroparesis, (3) antiemetic

Question 38

What are 10 toxicities to associate with Metoclopramide?

Answer 38

(1) Increase parkinsonian effects. (2) Restlessness, (3) Drowsiness, (4) Fatigue, (5) Depression, (6) Nausea, (7) Diarrhea. Drug interaction with (8) digoxin and (9) diabetic agents. (10) Contraindicated in patients with small bowel obstruction of Parkinson disease (D1-receptor blockade).

Question 39

With what 2 kinds of drugs does Metoclopramide interact?

Answer 39

Drug interaction with digoxin and diabetic agents

Question 40

In what patient population is Metoclopramide contraindicated?

Answer 40

Contraindicated in patients with small bowel obstruction of Parkinson disease (D1-receptor blockade).

Question 41

Draw the gastric cells of the fundus and antrum, including and labeling the different inputs/structures involved in the following pharmacologic pathways: (1) Antacids (2) H2 blockers (3) Muscarinic antagonists (4) Misoprostol (5) Proton pump inhibitors (6) Sucralfate, bismuth (7) Somatostatin (octreotide).

Answer 41

See p. 370 in First Aid 2014 for visual