Module 2: PPI

Question 1

What are common indications for PPI’s?

Answer 1

Peptic ulcer disease (PUD)

Gastroesophageal reflux disease (GERD)

Zollinger-Ellison syndrome (tumours in the stomach or small intestine cause the stomach to produce too much acied)

NSAID-associated ulcers

Eradication of helicobacter pylori

Question 2

What are the anticipated clinical outcomes/ treatment goals for PPI’s?

Answer 2

Diminished accumulation of acid in the gastric lumen, with lessened acid reflux.

Healing of duodenal ulcers and esophagitis

Decreased acid secretion in hypersecretory conditions.

Question 3

Describe the MOA of PPI’s?

Answer 3

Inhibit H-K-ATPase, the final step of gastric acid secretion by parietal cells.

PPI’s are a prodrug which accumulate in the the secretory portion of parietal cells. There they undergo acid catalyzed conversion to reactive species. Reactive species interacts with the external surface of the H-K_ATPase that faces the lumen of the secretory space of the parietal cell where it bonds with an enzyme that impairs gastric acid secretion.

Question 4

What are the pharmacokinetics considerations of PPIs:

Answer 4

A: Tablet is enteric-coated; absorption occurs only after tablet leaves the stomach.

D: Unkown.

M: Primarily metabolized by the CYP2C19 and CYP3A4 isoenzymes in the liver; the CYP2c19 isoenzyme exhibits genetic polymorphism (15-20% of Asian patients and 3-5% of White and Black patients may be poor metabolizers and may have significantly increased pantoprazole concentration and an increase risk for adverse effects);

E: inactive metabolites are excreted in urine (71%) and feces (18%)

Question 5

Can PPI’s be used in pregnancy and lactation?

Answer 5

Use only if potential benefits justifies risks to fetus/infant. (not enough research with fetus and generally safe for infants)

Question 6

Can PPI’s be used in the pediatric population.

Answer 6

Yes with caution d/t adverse effects.

Question 7

Can PPI’s be used in the geriatric population?

Answer 7

Appears on Beers list. Risk of C. diff infection, pneumonia, GI malignancies, bone loss, and #’s. Avoid scheduled use for >8 weeks unless for high risk pt’s (e.g. oral corticosteroid or chronic NSAID use) or pt’s with erosive esophagitis, Barrett’s esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance therapy (e.g. failure of H2 antagonist)

Question 8

What are some common expected side effects of PPI’s.

Answer 8

N/A

Question 9

What are some common adverse effects of PPI’s?

Answer 9

Derm: acute generalized exanthematous pustulosis, Eosinophilia and systematic symptoms (DRESS), steven-johnson syndrome, toxic epidermal necrolysis

GI: Clostridioides difficile-associated diarrhea (CDAD)

Misc: Hypersensitivity reactions including: anaphylaxis, angioedema or tubulointerstitial nephritis

Not common but can be assoc with increased risk of chronic kidney disease.

Question 10

What are some significant drug interactions for PPI’s?

Answer 10

Avoid concurrent use with antisecretory agents (H2RAs)

Decreased bioavailability of meds requiring gastric acidity

Can interact via inhibition of CYP2C19 and to a lesser extent CYP3A4.

PPI’s are primarily metabolized by CYP2C19 so inducers of this (e.g. rifampin) will speed up metabolism of PPI’s.

Some PPI’s are CYP2C19 inhibitors - affecting the metabolism of other drugs, increasing their bioavailability

Question 11

Cautions/contraindications associated with PPI’s?

Answer 11

Caution in elderly for increased risk of C.diff and pneumonia.

Malabsorption of minerals and vitamins:
Patients using high doses for >1 yr (increase risk of hip, wrist, or spine #’s and fundic gland polyps)

Pt’s using therapy for > 3yr (increase risk of Vit B12 deficiency)

Pre-existing risk for hypocalcemia

Risk of Zn deficiency (IV)

Question 12

What are monitoring parameters for PPI’s?

Answer 12

Assess routinely for epigastric, abd pain and frank or occult blood in stool, emesis or gastric aspirate.

Monitor bowel function.

Liver function test as may increase ALT, AST, alkaline phosphate, and bilirubin
Monitor serum magnesium and calcium before and periodically during therapy. May cause hypomagnesemia and hypocalcemia
May cause vit B12 deficiency with long-term use (>3 yr). Iv formulation may cause zinc deficiency

Question 13

In general what is peak and duration of PPI’s?

Answer 13

Peak range: 0.5-3.5 hours. NOTE: rameprazole delayed at 2-5 hours

Half-life range: 1-2 hours. NOTE: pantoprazole half-life increased to 3.5-10 hours in CYP2C19 poor metabolizers.