Supportive and Preventive Medicine
Despite short elimination half-lives, PPIs suppress acid secretion for 20 hours or more, permitting
once-daily dosing without requiring gastric pH monitoring.
Tachyphylaxis does not occur with PPIs.
Rebound acid hypersecretion may occur after discontinuation; however, clinical relevance is
unknown.
Adverse effects
Diarrhea, abdominal pain, constipation, nausea
ii.
Headaches
iii.
Rash
iv.
Interstitial nephritis
Hypomagnesemia (3 months or more of therapy)
vi.
Neurologic effects with high-dose intravenous omeprazole (hearing and vision disturbances)
vii.
Hypophosphatemia and metabolic alkalosis when administered with sodium bicarbonate
viii.
Vitamin B12 deficiency
ix.
Increased risk of fractures (hip, waist, and spine)
CDI (definitive cause-effect relationship is not well established)
xi.
Risk of nosocomial pneumonia
Drug interactions
All agents are hepatically metabolized by CYP isoenzymes 3A4 and 2C19.
ii.
Omeprazole is an inhibitor of 3A4, 2C19, 2C9, and 1A2.
iii.
Lansoprazole may induce CYP1A2.
iv.
Clinically significant PPI interactions with clopidogrel through CYP2C19 inhibition have not
consistently been shown to be important.
pH-dependent interactions
Stress-Related Bleeding
Endoscopically evident mucosal damage and occult bleeding rates are reported from historical data;
more contemporary data are lacking (Table 4).
Outcome
Incidence in
ICU Patients
Definition
Endoscopically evident mucosal
damage
75%–100%
Superficial lesions identified on endoscopy
Occult bleeding
15%–50%
Presence of guaiac-positive stools or nasogastric aspirate
Overt or clinically evident bleeding
5%–25%
Appearance of coffee grounds in nasogastric aspirate,
hematemesis, melena, or hematochezia
Clinically important bleeding
1%–5%
Presence of overt bleeding with hemodynamic instability
and/or blood transfusion within 24 hr of the event
Most trials define clinically important GI bleeding as overt bleeding accompanied by one of the
following:
Decrease in blood pressure of 20 mm Hg within 24 hours before or after GI bleeding episode
ii.
Decrease in blood pressure of 10 mm Hg and increase in heart rate of 20 beats/minute or more
on orthostatic change.
iii.
Decrease in hemoglobin of 2 g/dL and transfusion of 2 units of blood within 24 hours of
bleeding OR failure of the hemoglobin concentration to increase after transfusion by at least
the number of units transfused minus 2 g/dL