Medication Summary
Immediate and sustained control of gastric acid hypersecretion is the most important aspect of disease management in patients with Zollinger-Ellison syndrome (ZES), because acid hypersecretion is the cause of essentially all the symptoms and early morbidity and mortality.
Once ZES is considered and while appropriate diagnostic tests are conducted, acute acid secretion usually is best controlled with oral administration of a proton pump inhibitor (eg, omeprazole, lansoprazole, rabeprazole, esomeprazole). However, continuous infusion of an H2 antagonist (eg, ranitidine, cimetidine, famotidine), often at high doses, may be necessary for a small proportion of patients requiring rapid control of acid secretion who are unable to take oral medication.
Long-term management of acid secretion with a high dose of a proton pump inhibitor (or H2 blocker) is safe and effective.
Proton pump inhibitors
Class Summary
These agents bind to the proton pump of the parietal cell, inhibiting secretion of hydrogen ions into the gastric lumen. These agents are more effective than H2 blockers in relieving pain and healing ulcers. They are the drugs of choice in ZES. Although the drugs in this class are equally effective, omeprazole is used most commonly. Efficacy and tolerability of parenterally administered proton pump inhibitors in the acute treatment of patients with suspected ZES have not been established.
Omeprazole (Prilosec)
Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump.
Titrate dose to achieve a BAO of 10 mEq/h. Gastric acid hypersecretion usually is controlled with doses < 80 mg/d, but doses up to and even >200 mg/d have been used in some patients.
Lansoprazole (Prevacid)
Inhibits gastric acid secretion. Titrate dose to achieve a BAO of 10 mEq/h. Efficacy and tolerability of IV administration in acute treatment of patients with suspected ZES have not been established.
Rabeprazole (Aciphex)
Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump. Titrate dose to achieve a BAO of 10 mEq/h.
Esomeprazole magnesium (Nexium)
S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+ -ATP pump at the secretory surface of gastric parietal cells. Titrate dose to achieve a BAO of 10 mEq/h.
H2-receptor antagonists
Class Summary
Inhibit the action of histamine on the parietal cell, which inhibits acid secretion. All agents in this class are equally effective. Intravenous administration may be helpful in patients who are unable to take oral medication.
Ranitidine (Zantac)
Inhibits histamine stimulation of the H2 receptor in the gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen concentrations. Titrate dose to achieve BAO < 10 mEq/h.
Cimetidine (Tagamet)
Inhibits histamine at H2 receptors of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations. Titrate dose to achieve BAO < 10 mEq/h.
Famotidine (Pepcid)
Competitively inhibits histamine at H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations. Titrate dose to achieve a BAO of 10 mEq/h.
Chemotherapeutic agents
Class Summary
Indicated in metastatic disease and in patients who are not candidates for surgery. These drugs reduce the tumor size and improve symptoms secondary to metastatic effects of the tumor. A combination of streptozocin, 5-fluorouracil, and doxorubicin has been used, with a response rate of as high as 65%.
Streptozocin (Zanosar)
Inhibits DNA synthesis without significantly affecting the bacterial or mammalian RNA or protein synthesis.
5-Fluorouracil (Adrucil)
Interferes with DNA synthesis by blocking the methylation of deoxyuridylic acid, inhibiting thymidylate synthetase, and, subsequently, inhibiting cell proliferation.
Doxorubicin (Adriamycin, Rubex)
Inhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. The combination of these 2 events can, in turn, inhibit the growth of neoplastic cells.
