Faculty Bibliography

Objective. Dabigatran is a direct thrombin inhibitor approved for anticoagulation in non-valvular atrial fibrillation and, in some countries, for thromboembolism prophylaxis following select orthopedic surgeries. Despite decreased rates of thromboembolism, bleeding remains a risk due to the inability to conveniently monitor anticoagulant effect and the lack of a reversal agent. Case series. We present four cases of dabigatran-related bleeding. A 79-year-old man on aspirin, clopidogrel, and dabigatran presented with rectal bleeding and epistaxis. He died despite transfusion and administration of prothrombin complex concentrate. A 73-year-old woman on dabigatran and aspirin survived after transfusion and an emergent sternotomy for cardiac tamponade. An 86 year-old man with kidney disease and thrombocytopenia received packed red blood cells, platelets, and fresh frozen plasma for rectal bleeding while on dabigatran. An 80 year-old man on dabigatran had a subdural hematoma after falling and hitting his head. Serial imaging showed no progression. Conclusion. The absence of a reversal agent for dabigatran raises concern for uncontrollable bleeding and death. Dabigatran's listed contraindications include active bleeding and a history of dabigatran hypersensitivity reaction. Wider use may result in bleeding rates higher than anticipated from clinical trials. Risks factors that may have contributed to bleeding in these patients include concomitant bleeding diathesis, antiplatelet agent use, renal insufficiency, advanced age, and fall risks.

A paradoxical drug reaction constitutes an outcome that is opposite from the outcome that would be expected from the drug's known actions. There are three types: 1. A paradoxical response in a condition for which the drug is being explicitly prescribed. 2. Paradoxical precipitation of a condition for which the drug is indicated, when the drug is being used for an alternative indication. 3. Effects that are paradoxical in relation to an aspect of the pharmacology of the drug but unrelated to the usual indication. In bidirectional drug reactions, a drug may produce opposite effects, either in the same or different individuals, the effects usually being different from the expected beneficial effect. Paradoxical and bidirectional drug effects can sometimes be harnessed for benefit; some may be adverse. Such reactions arise in a wide variety of drug classes. Some are common; others are reported in single case reports. Paradoxical effects are often adverse, since they are opposite the direction of the expected effect. They may complicate the assessment of adverse drug reactions, pharmacovigilance, and clinical management. Bidirectional effects may be clinically useful or adverse. From a clinical toxicological perspective, altered pharmacokinetics or pharmacodynamics in overdose may exacerbate paradoxical and bidirectional effects. Certain antidotes have paradoxical attributes, complicating management. Apparent clinical paradoxical or bidirectional effects and reactions ensue when conflicts arise at different levels in self-regulating biological systems, as complexity increases from subcellular components, such as receptors, to cells, tissues, organs, and the whole individual. These may be incompletely understood. Mechanisms of such effects include different actions at the same receptor, owing to changes with time and downstream effects; stereochemical effects; multiple receptor targets with or without associated temporal effects; antibody-mediated reactions; three-dimensional architectural constraints; pharmacokinetic competing compartment effects; disruption and non-linear effects in oscillating systems, systemic overcompensation, and other higher-level feedback mechanisms and feedback response loops at multiple levels. Here we review and provide a compendium of multiple class effects and individual reactions, relevant mechanisms, and specific clinical toxicological considerations of antibiotics, immune modulators, antineoplastic drugs, and cardiovascular, CNS, dermal, endocrine, musculoskeletal, gastrointestinal, haematological, respiratory, and psychotropic agents.

Although wolf spider venom has been implicated in necrotic arachnidism without acceptably documented verification, limited, prospectively collected data demonstrate a lack of cutaneous necrosis. The infrequent nature of exposure and inherent difficulty in confirming wolf spider bites in humans makes it challenging to study such envenomations. We present the case of a 20 year-old man with confirmed exposure to the wolf spider who developed cutaneous erythema with ulceration following the bite. There was no evidence of skin necrosis. He was treated with aggressive wound care and systemic antibiotics for wound infection, with subsequent resolution of symptoms. This case adds to the limited knowledge regarding wolf spider envenomations and describes the clinical effects and management of wolf spider envenomation.