Dual antiplatelet therapy with clopidogrel and aspirin has been shown to reduce recurrent cardiac events in patients with acute coronary syndromes or those who have undergone coronary artery stent placement. Clopidogrel, a thienopyridine, is a prodrug that is transformed in vivo to an active metabolite by the cytochrome P450 enzyme system. Due to the increased risk of bleeding in patients on dual antiplatelet therapy, concomitant gastrointestinal ulcer prophylaxis with a proton pump inhibitor (PPI) is frequently prescribed. Data from recent studies show that PPIs, which are extensively metabolized by the cytochrome system, may decrease the antiplatelet activity of clopidogrel. This article reviews the metabolism of various PPIs and existing data regarding the drug-drug interaction between PPIs and clopidogrel.

Septic shock, a form of vasodilatory shock associated with high morbidity and mortality, requires early and effective therapy to improve patient outcomes. Current management of septic shock includes the use of intravenous fluids, catecholamines, and vasopressin for hemodynamic support to ensure adequate perfusion. Despite these interventions, hospital mortality rates are still greater than 40%. Practitioners are continuously faced with cases of refractory shock that are associated with poor clinical outcomes. In December of 2017, the Food and Drug Administration approved the first synthetic human angiotensin II, a potent vasoconstrictor, to increase blood pressure in adults with septic or other distributive shock. This approval was based (ATHOS) on the results from the Angiotensin II for the Treatment of High Output Shock study. In this randomized, double-blind, placebo-controlled trial, patients in the angiotensin II group achieved higher rates of target mean arterial pressure and had lower catecholamine requirements in the first 3 hours of therapy compared with patients in the placebo group. There was no significant difference in the 28-day mortality. Safety issues including the risk of thromboembolic events, infection, and delirium have made clinicians cautious in adopting angiotensin II into practice. Ongoing studies are needed to more clearly define the role of this agent and its utility in the management of shock.