The Wong protocol is an attractive option for the rapid desensitization of patients requiring dual antiplatelet therapy with aspirin and clopidogrel in the perimyocardial infarction period.

Cardiac dysrhythmias and cardiac arrest can occur after acute spinal cord injury (SCI). Disrupted sympathetic innervation after SCI results in unopposed parasympathetic activity leading to baseline bradycardia. Hence, vagal stimulation can result in episodes of exaggerated symptomatic bradycardia. Data supporting pharmacologic intervention for treatment of symptomatic bradycardia after SCI are limited. We describe a patient who sustained a high cervical SCI and subsequently developed episodic symptomatic bradycardia. The addition of aminophylline to the patient's therapeutic regimen was associated with resolution of the bradycardia. Throughout her treatment course, the patient's serum theophylline concentrations were 1.9-3.4 mg/L. These levels were consistent with those identified in other case reports describing treatment with methylxanthines to prevent episodic bradycardia after SCI. Our understanding of drug pharmacokinetics and pharmacodynamics in patients with acute SCI is limited and provides an ideal opportunity for further study in this area.

Aspirin (ASA) and clopidogrel have been identified as standard of care in the prevention of major cardiovascular events. Aspirin irreversibly inhibits the cyclooxygenase-1 (COX-1) enzyme, whereas non-steroidal anti-inflammatory drugs (NSAIDs) reversibly inhibit the COX-1 enzyme. An analysis of the literature revealed a statistically significant decrease in clinical benefit of ASA with concomitant administration of ibuprofen. Another NSAID, diclofenac, showed minimal effect on the inhibition of platelet aggregation when administered with ASA. Furthermore, the selective COX-2 inhibitor, rofecoxib, was not shown to influence the effect of ASA. Clopidogrel is metabolized to an active thiol metabolite by the CYP 3A4 enzyme. Some HMG CoA reductase inhibitors have the ability to inhibit the CYP 3A4 enzyme, which can result in a possible interaction if administered concomitantly with clopidogrel. Studies have demonstrated clopidogrel's platelet inhibition being significantly attenuated by atorvastatin. However in a post-hoc analysis, it was demonstrated that there was no difference in clinical outcomes between patients taking clopidogrel and HMG-CoA reductase inhibitors metabolized by and not metabolized by CYP 3A4. Data suggest that the interaction observed involving clopidogrel and HMG-CoA reductase inhibitors appears to be significant in-vitro. Therefore, practitioners should advise patients receiving chronic aspirin therapy to limit the use of ibuprofen and may consider concomitant administration of clopidogrel with HMG-CoA reductase inhibitors without regard for the drug interaction. The intent of this paper is to review the literature discussing possible mechanisms of drug-induced aspirin and clopidogrel resistance and discuss whether the interactions translate into clinical effects.

Antithrombotic, antiplatelet, and fibrinolytic agents are the mainstay for the management of patients with acute coronary syndromes (ACS). In addition to their well-documented efficacy, these pharmacologic agents have the potential for the untoward effect of bleeding. Recent data suggest medication errors related to the dose, duration, and concomitant use of these agents contribute to increasing the risk of hemorrhage in patients treated for ACS. In the event of a major hemorrhage, clinicians should be aware of strategies used to reverse the pharmacologic effects of the offending agent. This paper critically assesses literature directed toward reversal of agents based on drug-specific pharmacodynamic and pharmacokinetic parameters.

The combination of persistent thrombocytopenia and exhaustion of coagulation factors is the likely cause leading to resistance to rFVIIa therapy in this patient.