Gastrointestinal

Pharmacology

GI therapy

Why are misoprostol, sucralfate, and bismuth beneficial in treatment of gastric ulcers?

These drugs have a protective effect on the mucosa underlying ulcers

H2-blockers work on which stomach cell type?

Parietal cells

Muscarinic antagonists work on which two cell types in the stomach?

Enterochromaffin-like cells (with M1 receptors) and parietal cells (with M3 receptors)

Proton pump inhibitors work on pumps that exchange which two ions?

Hydrogen and potassium

H2 blockers

What substance is the endogenous agonist of the H2-receptor?

Histamine

What is the effect of H2-blockers on parietal cells?

Reversible decrease of hydrogen ion secretion

Which H2-blocker has important toxicities that are not seen with other H2-blockers?

Cimetidine

Which adverse effects of cimetidine are seen specifically in males?

Prolactin release, gynecomastia, impotence, decreased libido

By what mechanism does cimetidine cause confusion, dizziness and headaches?

It is able to cross the blood-brain barrier

List three clinical uses of H2-blockers.

Peptic ulcer, gastritis, mild esophageal reflux

Give four examples of H2-blockers.

Cimetidine, ranitidine, famotidine, and nizatidine (remember: Take H2-blockers before you
DINE)

What effect does cimetidine have on the kidneys?

Decreased creatinine excretion

Cimetidine is a potent _____ of P450.

Inhibitor

True or False? Cimetidine is safe during pregnancy.

False; cimetidine crosses the placenta

Which two H2 blockers can decrease the renal excretion of creatinine?

Ranitidine and cimetidine

Proton pump inhibitors

Give at least two examples of proton pump inhibitors.

Omeprazole and lansoprazole

Proton pump inhibitors work by inhibiting _____ _____ _____ in stomach parietal cells.

Hydrogen potassium adenosine triphosphatase

What are the clinical indications for use of proton pump inhibitors?

Peptic ulcers, gastritis, esophageal reflux, and Zollinger-Ellison syndrome

Bismuth, sucralfate

What are two of the infectious indications for bismuth or sucralfate?

Traveler's diarrhea, Helicobacter pylori infection (as part of triple therapy)

What is the mechanism of action of bismuth and sucralfate?

They provide a physical barrier in ulcers to protect from stomach acid

What are the three components of triple therapy?

Metronidazole, bismuth, and amoxicillin or tetracycline

True or False? A proton pump inhibitor can also be used when treating an ulcer caused by
Helicobacter pylori infection.

True (remember: Please MAke Tummy Better for drugs used to treat Helicobacter pylori
infection: proton pump inhibitor, metronidazole, amoxicillin, tetracycline, bismuth)

Misoprostol

Misoprostol functions by increasing the production and secretion of the _____ _____ _____
and decreasing the production of _____.

Gastric mucous barrier; acid

A neonate becomes cyanotic on the third day of life despite 100% supplemental oxygen
administration. The attending orders infusion of a medication and the neonate's oxygen
saturation slowly returns to normal. What medication did the attending order an

Misoprostol; it maintains the patent ductus arteriosus thereby allowing mixing of pulmonary
and systemic circulation in the case of congenital heart disease

A woman with rheumatoid arthritis was recently started on misoprostol because of adverse
effects of her arthritis medicine. What is the adverse effect and the medication that caused it?

Peptic ulcers induced by nonsteroidal antiinflammatory drugs

Misoprostol is a _____ ____ analogue.

Prostaglandin E1

Within what population is misoprostol contraindicated?

Women of childbearing potential; it is an abortifacient

In addition to being an abortifacient, what other toxicity does misoprostol have?

Diarrhea

A woman presents to her OB/GYN at 42 weeks' gestation and is admitted to the hospital. You
look at the orders and see that misoprostol is administered. What is the role of misoprostol in
this patient?

To induce labor

Muscarinic antagonists

Name three major adverse effects caused by muscarinic antagonists.

Tachycardia, dry mouth, and difficulty focusing eyes (anticholinergic adverse effects)

What are the muscarinic antagonists pirenzepine and propantheline used for clinically?

Peptic ulcers (rarely used)

List two muscarinic antagonists that are used to treat peptic ulcers.

Pirenzepine and propantheline

By blocking the M3 receptors on parietal cells, muscarinic antagonists achieve what

effect?

Decreased hydrogen secretion

Muscarinic antagonists block what receptors on enterochromaffin-like cells?

M1 receptors

By blocking the M1 receptors on enterochromaffin-like cells, muscarinic antagonists achieve

what effect?

Decreased histamine secretion

Muscarinic antagonists block what receptors on parietal cells?

M3 receptors

What are the two target cells of muscarinic antagonists when used to decrease acid secretion?

Enterochromaffin-like cells and parietal cells

Antacid use

What effects can antacids have on the efficacy of other drugs?

Interference with absorption, bioavailability, and urinary excretion by altering gastric and
urinary pH and delaying gastric emptying

List three compounds that are commonly used as antacids.

Aluminum hydroxide, magnesium hydroxide, and calcium carbonate

The overuse of the antacid aluminum hydroxide can cause what toxicities?

Constipation, hypophosphatemia, hypokalemia, proximal muscle weakness, osteodystrophy,

seizures

A patient is found to have hypophosphatemia and osetodystrophy. What medication is he

most likely chronically overusing to treat his gastroesophageal reflux disease?

Aluminum hydroxide

Diarrhea, hyporeflexia, hypotension, cardiac arrest and hypokalemia are side effects
of which antacid?

Magnesium hydroxide; remember Mg = Must go to the bathroom

A patient becomes hypotensive and hyporeflexive. She mentions that she has
gastroesophageal reflux disease and takes large amounts of antacids. Which antacid is she
most likely overusing?

Magnesium hydroxide

A patient has a witnessed first seizure. Afterward he complains of recent constipation and
proximal muscle weakness. What medication is he most likely overusing to treat his
gastroesophageal reflux disease?

Aluminum hydroxide; remember Aluminimum amount of feces

A patient who heavily self-medicates her gastroesophageal reflux disease complains of

dizziness and diarrhea. Which antacid is she most likely overusing?

Magnesium hydroxide

Overuse of the antacid calcium carbonate can cause what three toxicities?

Hypercalcemia, rebound acid increase, and hypokalemia

All antacids cause what electrolyte abnormality if overused?

Hypokalemia

Infliximab

What test should be conducted before starting a patient on infliximab?

Purified protein derivative test; this medication can cause reactivation tuberculosis

What is the mechanism of action of infliximab?

It is a monoclonal antibody to tumor necrosis factor-a remember INFLIXimab INFLIX pain on

TNF

What are the adverse effects of infliximab?

Reactivation of latent tuberculosis, hypotension, fever

List two diseases that are treated with infliximab.

Crohn's disease and rheumatoid arthritis

Sulfasalazine

Sulfasalazine is a combination of what two drugs?

Sulfapyridine and mesalamine

What unique mechanism of delivery of mesalamine is created when it is combined with

sulfapyridine?

It is activated by colonic bacteria

What is the function of sulfapyridine?

It is an antibiotic

Sulfasalazine is used to treat what two diseases?

Crohn's disease and ulcerative colitis

A patient is found to have Crohn's ileitis. He asks if he can be started on sulfasalazine. What is
the appropriate response?

Sulfasalazine would be ineffective because it is activated by colonic bacteria and thus has no
effect proximal to the colon

What are the adverse effects of sulfasalazine?

Oligospermia, malaise, nausea, and sulfonamide toxicity

Ondansetron

Ondansetron is used to control vomiting in which two situations?

After an operation and for patients getting cancer chemotherapy (remember: you will not
vomit with ONDANSetron, so you can go ON DANCing)

Ondansetron is an antagonist of what receptor type?

5-hydroxytryptamine3

What are two toxicities of ondansetron?

Headache and constipation

Metoclopramide

What are the clinical uses of metoclopramide?

Diabetic gastroparesis and postsurgical gastroparesis

What are side effects of metoclopramide?

restlessness, drowsiness, fatigue, depression, nausea, diarrhea

What is the mechanism of metoclopramide?

It is a dopamine receptor antagonist

Metoclopramide is contraindicated in patients with what serious gastrointestinal disorder?

Small bowel obstruction, because it is prokinetic and thus will worsen the discomfort of these
patients

With what drugs does metoclopramide interact?

Digoxin and diabetic agents

On what parts of the gastrointestinal tract does metoclopramide act?

The lower esophageal sphincter (it increases tone and contractility), the stomach, and the
small bowel (increases motility); it has no effect on the colon

What specific dopamine receptor is blocked by metoclopramide?

D2 receptor