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