The risk of serotonin syndrome may also be increased when vortioxetine is combined with other serotonergic drugs, like SSRIs, SNRIs, tricyclic antidepressants (TCAs), triptans, tramadol, tryptophan, buspirone, St Johns wort, fentanyl, and lithium, among others. However, vortioxetine is not considered to be contraindicated with serotonergic medications besides MAOIs. Pharmacology
Pharmacodynamics
Vortioxetine increases serotonin concentrations in the brain by inhibiting its reuptake in the synapse, and also modulates (activates or blocks) certain serotonin receptors. This puts it in the class of serotonin modulators and stimulators, which also includes vilazodone. More specifically, vortioxetine is a serotonin reuptake inhibitor, agonist of the serotonin 5-HT1A receptor, partial agonist of the 5-HT1B receptor, and antagonist of the serotonin 5-HT1D, 5-HT3, and 5-HT7 receptors, as well as an apparent ligand of the β1-adrenergic receptor. In terms of functional activity however, vortioxetine appears to be much more potent on serotonin reuptake inhibition and 5-HT3 receptor antagonism than for its interactions with the other serotonin receptors. Whereas vortioxetine has IC50 or EC50 values of 5.4 nM for the SERT and 12 nM for the 5-HT3 receptor, its values are 120 to 450 nM for the 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT7 receptors. This translates to about 22- to 83-fold selectivity for SERT inhibition and 10- to 38-fold selectivity for 5-HT3 antagonism over activities at the other serotonin receptors.It has been claimed that the serotonin transporter (SERT) and 5-HT3 receptor may be primarily occupied at lower clinical doses of vortioxetine and that the 5-HT1B, 5-HT1A, and 5-HT7 receptors may additionally be occupied at higher doses.
Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food and Drug Administration (FDA) for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). In 2002, it was approved for use during percutaneous coronary interventions in patients who have HIT or are at risk for developing it. In 2012, it was approved by the MHRA in the UK for anticoagulation in patients with heparin-induced thrombocytopenia Type II (HIT) who require parenteral antithrombotic therapy.Argatroban is given intravenously and drug plasma concentrations reach steady state in 1–3 hours. Argatroban is metabolized in the liver and has a half-life of about 50 minutes. It is monitored by PTT. Because of its hepatic metabolism, it may be used in patients with renal dysfunction. (This is in contrast to lepirudin, a direct thrombin inhibitor that is primarily renally cleared). Transitioning to warfarin in individuals with heparin-induced thrombocytopenia
Argatroban is used as an anticoagulant in individuals with thrombosis and heparin-induced thrombocytopenia. Often these individuals require long-term anticoagulation. If warfarin is chosen as the long-term anticoagulant, this poses particular challenges due to the falsely elevated prothrombin time and INR caused by argatroban. The combination of argatroban and warfarin may raise the INR to greater than 5.0 without a significant increased risk of bleeding complications. One solution to this problem is to measure the chromogenic factor X level. A level < 40-45% typically indicates that the INR will be therapeutic (2-3) when the argatroban is discontinued. References
External links
"Argatroban". Drug Information Portal.