Supportive and Preventive Medicine

Antacids

Dose-dependent neutralization of gastric acid

Not recommended for routine use because of frequency of administration (up to every hour),

adverse effects (diarrhea, constipation, electrolyte abnormalities), and interactions (interferes with

the absorption of some drugs)

Complexes with albumin and fibrinogen to form a viscous, adhesive substance that adheres to

ulcers with a gastric pH less than 4

Not recommended for routine use because of adverse effects (constipation, aluminum toxicity,

hypophosphatemia) and drug interactions by method of chelation; frequency of administration

further complicates administration of other enteral medications

H2RAs

Available agents: Cimetidine and nizatidine as oral; famotidine as oral and intravenous (off-label

use in SUP)

Competitive blockade of histamine receptors on the basolateral membrane of the parietal cells. In

addition, H2RAs inhibit gastrin secretion to reduce acid production; however, they do not reliably

inhibit vagally induced acid secretion.

Alternative pathways (e.g., gastrin, acetylcholine) can be up-regulated in response to the use of

H2RAs, leading to a decrease in gastric pH and explaining the tolerance related to H2RAs. Tolerance

can occur as early as day 2 of H2RA use (World J Gastrointest Pharmacol Ther 2014;5:57-62; Am

J Gastroenterol 1999;94:351-7).

neutrophil activation, reducing inflammation by enhancing cell-mediated immunity, and acting as

a weak free radical scavenger.

Dose-dependent increase in gastric pH

Previous studies of SRMD-related bleeding used either continuous infusion H2RAs or combined

H2RAs with intermittent antacids to maintain a pH greater than 4. Current practice is to use

intermittent administration of H2RAs without pH monitoring.

All H2RAs require renal dosing adjustment.

Adverse effects

Mental status changes such as confusion, hallucinations, agitation, and headaches (mainly

associated with cimetidine, but reported with famotidine in patients with severe renal failure)

ii.

Thrombocytopenia (occurs over several days from hapten formation; may occur within hours

if patient is sensitized)

iii.

Rapid infusion–related hypotension

iv.

Prolongation of corrected QT interval has been reported with famotidine.

Sinus bradycardia

vi.

Risk of nosocomial pneumonia

vii.

Increase in SCr with cimetidine – Competitively inhibits tubular secretion of creatinine

Drug interactions

Cimetidine inhibits cytochrome P450 (CYP) isoenzymes 3A4, 2D6, 2C9, 2C19, and 1A2.

ii.

pH-dependent interactions

PPIs

Available agents: Dexlansoprazole, esomeprazole, lansoprazole, omeprazole (immediate-release

capsule FDA approved for SUP), pantoprazole, and rabeprazole

Agents available (off-label) for SUP: Lansoprazole (oral), omeprazole (oral), and pantoprazole

(oral, intravenous)

Prodrugs activated in the acidic environment of the stimulated parietal cell inhibiting both

histamine-induced and vagally mediated gastric acid by binding and inhibiting active proton pumps

Dose-dependent increase in gastric pH, with maximal activity reached 3 days after initiation