Ventricular fibrillation after omeprazole treatment: a case control

Hydrogen-potassium adenosine triphosphatase (H+/K+-ATPase)-target of omeprazole family members- present in gastric parietal cells, plays an essential role in the formation of HCl. It belongs to a family of P-type cation-transporting ATPases also including Ca2+-ATPase and Na+/K+ -ATPase. A 54 years old woman with a mildly degree hypertension (not pharmacologically treated), familiarity for CAD (father deceased after an AMI at the age of 60) and Helicobacter pylori positive gastritis, previously treated with antibiotics and antacid drugs, had being suffering for about two weeks for a gastric pyrosis recurrence. She started oral therapy with omeprazole 20 mg/die, but, still symptomatic, she was treated i.v. with ranitidine and spasmolytics. However, 8 days later, aspecific thoracic pain sensitive to deep inspiration, movements and digital pressure occurred. The ECG didn’t show any sign of acute ischemia and necrosis enzymes were normal. Furthermore, she was treated i.v. with 30 mg ketorolac, and 30 minutes later with 40 mg omeprazole. After few minutes, the patient had ventricular fibrillation, interrupted with a single 200 J DC-shock, and treated with magnesium sulphate in repolarizing solution i.v. The patient maintained always stable sinus rhythm: no further arrhythmias were recorded during her hospitalization and she kept asymptomatic. There were no signs of ischemia at ECG; all ematochemical parameters (CK, CK-MB, LDH, myoglobin and TnI), serum electrolytes, D-dimer and protein C reactive were always normal. In addition to routine laboratory tests, a peripheral blood sample for genetic analysis was taken with patient informed consent. To assess if clinical drugs-related side effects could be ascribe to genetic CYP-dependent drug metabolizing polymorphisms, DNA sample was analyzed. PCR-RFLP and sequencing of mutated CYP2C19 (variants: *2 and *3) and 3A4 (*1B, *2 and *3) alleles isoforms were performed. The homozygous mutations of both CYP isoforms recorded can be responsible of the abnormal omeprazole level and the consequent toxicity. In other words, high plasmatic level of this drug, not adequately metabolized, could target other receptors structurally similar the ones present in the stomach. So due the individual metabolic fingerprint when more than one principal metabolic pathway is “disrupted” serious side effects could be expected.