Gi 3

Front 1

There are many sites on the parietal cell for pharmacology to work. PPIs (Proton pump inhibitors) are acid labile - meaning:

Back 1

PPIs have to be enteric coated capsules or pellets within a capsule, to protect the drug from the stomach acid.

Front 2

Where in the digestive tract are PPIs absorbed?

Back 2

In the intestines

Front 3

TEST Remember that PPIs are a different sort of prodrug which:

Back 3

are NOT converted to active via the 1st pass.

Front 4

How then do the PPIs reach the parietal cells?

Back 4

from the blood

Front 5

PPIs are secreted into the canilculi of the parietal cell and are converted into active form by:

Back 5

acid (sulfenic acid that’s inside the parietal cell)

Front 6

PPIs irreversibly bind to and inhibit the parietal cell’s:

Back 6

active H+/K+ - ATP proton pump. It kills that pump for good.

Front 7

PPI treatment has to be continued because the pumps regenerate. More than 90% of acid secretion is inhibited within 24 hours. When PPIs are discontinued what can occur?

Back 7

Rebound acid secretion. There’s increased gastrin secretion in 5-10% of long-term users.

Front 8

TEST When is the best time to take a PPI?

Back 8

On an empty stomach. Take it 1 hour before your first meal/cup of coffee of the day.

Front 9

Oral bioavailability of all PPI agents decreases by 50% when taken with food. Why is it important to have the PPI administered before food?

Back 9

It has to be there when the pumps start working, and prevent the parietal cell from being stimulated in the first place.

Front 10

The half-life of a PPI is short at about 1.5-2 hours but:

Back 10

it’s duration is 24 hours. It irreversibly binds to pumps, and can even inhibit acid secretion for 1-2 days after a single dose. It’s duration of effect lasts longer than H2 antagonists

Front 11

How are PPIs excreted?

Back 11

Renally, and as primarily INactive metabolite, so adjustments have to be made.

Front 12

PPIs come in IV formulations and in acid stable oral “suspension” preparation. They are generally well tolerated & safe. What are some adverse effects?

Back 12

GI, CNS, GU, possible hip fractures with long-term use, and rebound hypertension

Front 13

Describe the GI adverse effects with PPIs:

Back 13

N/V/D, constipation, flatulence, dark feces (which you have to educate patients about - it’s different then bloody stools), increased LFT

Front 14

Can you take PPIs when pregnant?

Back 14

Depends on patient, but PPIs are to be used cautiously in the first trimester

Front 15

Potentially serious adverse effects include gastric tumors - increased gastric bacterial concentrations - increased risk of enteric infection (C. diff). Why the tumors?

Back 15

The gastric tumors are rare & non-malignant and occur because PPIs stimulate ECL turnover

Front 16

Which drugs will produce significant drug interactions when taken with a PPI?

Back 16

All drugs that undergo rapid first pass metabolism via CYP2C19, or are its substrates or inhibitors. Also, clopidogrel DDI

Front 17

Which drugs require gastric acid for absorption & will have a drug interaction with a PPI?

Back 17

Antifungals like ketoconazole and itraconazole

Front 18

Nutritionally PPIs interfere with the gastric absorption of B12 and it reduces the absorption of what 2 minerals?

Back 18

Calcium & magnesium (think hip fractures)

Front 19

PPIs are considered a first-line treatment. They relieve symptoms & begin to heal duodenal & gastric ulcers more quickly than:

Back 19

H2 antagonists (2-4 versus 4-8 weeks) And, the absolute healing rates are comparable

Front 20

PPIs are the most effective agents for the treatment of:

Back 20

non-erosive & erosive reflux disease, esophageal complications of reflux disease, & extra-esophagela manifestations

Front 21

For non-ulcer dyspepsia the efficacy of PPIs is comparable to H2 antagonists. All PPIs have relatively the same:

Back 21

efficacy

Front 22

TEST List the 5 PPIs:

Back 22

the “-prazoles” Omeprazole. Esomeprazole. Lansoprazole. Pantoprazole. Rabeprazole.

Front 23

GERD. What are the treatment recommendations for GERD?

Back 23

An 8 week course of PPIs for symptom relief and healing of erosive esophagitis.

Front 24

When should maintenance PPI therapy be administered for GERD patients?

Back 24

For patients who continue to have symptoms after PPI is discontinued, and in patients with complications including erosive esophagitis & Barrett’s esophagus.

Front 25

What are the PPI recommendations for GIB (gastric intestinal bleed?)?

Back 25

After successful endoscopic hemostasis (cauterized the bleed) you’ll need to give IV PPI therapy, along with an 80 mg bolus, followed by 8 mg/h continuous infusion for 72 hours. Administer this to patients with active bleeding, a non-bleeding visible clot, or an adherent clot.

Front 26

TEST What will you ned to remember about administering PPIs for a GIB?

Back 26

Remember that you’ll need to give a significant bolus and then continuous infusion for 3 days.

Front 27

Patients with ulcers that have flat pigmented spots or clean bases can receive standard PPI therapy (oral once daily). Would you give PPIs pre=endoscopically?

Back 27

Depends. It may decrease the proportion of patients who have a higher risk stigmata of hemorrhage at endoscopy.

Front 28

SAMPLE QUESTION: Why are PPIs more potent inhibitors of acid secretion than H2 antagonists? a. PPIs inhibit both prostaglandin & histamine stimulation of gastric acid secretion b. PPIs inhibit the H+/K+ ATPase pump which is the final common pathway for acid secretion c. PPIs bind acid - forming protective barrier - whereas H2 antagonists inhibit acid production

Back 28

b. PPIs inhibit the H+/K+ ATPase pump which is the final common pathway for acid secretion