Pathways

Ardeparin is a low molecular weight heparin anticoagulant, also known as Normiflo, used to prevent postoperative venous thrombosis. It is created from heparin extracted from porcine intestinal mucosa that has gone through peroxide degradation. Ardeparin acts on antithrombin III, which leads to the inactivation of factor Xa and thrombin inhibiting thrombosis. It is administered subcutaneously and travels to its target in the bloodstream. Some signs of overdose may include excessive bleeding and bruising. Due to its anticoagulant nature herbs and supplements with similar activity should be avoided such as ginseng, ginkgo, ginger and garlic.

Ardeparin is a low molecular weight heparin anticoagulant, that is administered via subcutaneous injection to prevent postoperative venous thrombosis. Ardeparin prevents the formation of deep vein thrombus which may cause leg pain or swelling and pulmonary embolism. Ardeparin targets the coagulation cascade in blood vessels by binding to antithrombin III and increasing its activity. Antithrombin III then inhibits factor Xa, which forms part of the prothrombinase complex together with factor Va. This complex is responsible for cleaving prothrombin to generate thrombin. Antithrombin III also inhibits thrombin (or factor IIa). Thrombin plays a role in the coagulation cascade by cleaving fibrinogen to form the fibrin needed to constitute the fibrin blood clot. Therefore, inhibition of factor Xa and thrombin prevents the generation of fibrin, and as a result, blood clots are unable to form. Side effects from taking ardeparin include rash, anemia, bleeding, nausea/vomiting, constipation, fever and confusion.

Arformoterol is a beta-2 adrenergic receptor agonist that is used as a bronchodilator to treat COPD and chronic bronchitis. It accomplishes this by upon inhalation of the drug by relaxing smooth muscles in the airways to improve breathing. It can be found under the brand name Brovana, and it has a 2 fold greater potency than racemic formoterol. Once arformoterol is administered and it binds to the beta-2 adrenergic receptor, the G protein signalling cascade begins. The alpha and beta/gamma subunits of the G protein separate and GDP is replaced with GTP on the alpha subunit. This alpha subunit then activates adenylyl cyclase which converts ATP to cAMP. cAMP then activates protein kinase A (PKA) which in turn phosphorylates targets and inhibits MLCK through decreased calcium levels causing muscle relaxation. PKA can phosphorylate certain Gq-coupled receptors as well as phospholipase C (PLC) and thereby inhibit G protein-coupled receptor (GPCR) -PLC-mediated phosphoinositide (PI) generation, and thus calcium flux. PKA phosphorylates the inositol 1,4,5-trisphosphate (IP3) receptor to reduce its affinity for IP3 and further limit calcium mobilization. PKA phosphorylates myosin light chain kinase (MLCK) and decreases its affinity to calcium calmodulin, thus reducing activity and myosin light chain (MLC) phosphorylation. PKA also phosphorylates KCa++ channels in ASM, increasing their open-state probability (and therefore K+ efflux) and promoting hyperpolarization. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation of the smooth muscles in the lungs causes the bronchial airways to relax which causes bronchodialation, making it easier to breathe. Some side effects of using arformoterol can include chest pain, anxiety, blurred vision, and chills.

Argatroban is a univalent direct thrombin inhibitor, which means that it binds directly to the active site of thrombin, preventing it from catalyzing the activation of coagulation factors V, XIII and fibrinogen. The drug is injected intravenously, where it can bind any thrombin within the blood stream. This direct binding prevents any other molecules from using thrombin as an enzyme. It prevents catalyzation of factor V to factor Va, which would form the prothrombinase complex and create more thrombin. It also prevents the catalysis fibrinogen or factor I to fibrin, which then polymerizes to form the blood clot. The lack of useable thrombin also prevents the catalysis of factor XIII to factor XIIIa, which is necessary to crosslink the polymerized fibrin to form a water insoluble clot.

Argatroban is a synthetic direct thrombin inhibitor it is recommended for people who have a risk for heparin-induced thrombocytopenia (HIT). The mechanism of action is done by inhibiting thrombin-catalyzed reactions like fibrin formation, it inhibits prothrombin so that fibrin cannot form stopping the formation of a clot. Argatroban is metabolized by the liver through hydroxylation and aromatization. Commonly administered through intravenous injection with a half-life of 30 - 60 minutes and is primarily excreted through the feces, bile and urine. It can interact with food products so it is best to avoid herbs and supplements with anticoagulant and antiplatelet activity such as garlic, ginger, bilberry, danshen, piracetam and ginkgo biloba. Extreme caution with grapefruit products as grapefruit inhibits CYP3A4 metabolism, this enzyme is responsible for metabolizing argatroban leading to increased concentration in the blood. Extreme caution should also be taken with St. John's Wort as it can interact with the drug.

Argatroban is a selective thrombin inhibitor that binds reversibly to the catalytic site and anion-binding exosite inhibiting the cleavage of fibrinogen into fibrin. Unlike bivalirudin, argatroban is not a synthetic peptide but a derivative of L-arginine. Argatroban is used to treat heparin-induced thrombocytopenia as well as to prevent thrombosis. It is used in patients that are undergoing percutaneous coronary intervention or who have a risk in acute coronary syndromes caused by unstable angina or non-ST segment elevation. Thrombin is an important proteinase as it cleaves fibrinogen into fibrin monomers which help form the thrombus that forms the clot at the site of vascular injury. Because Argatroban inhibits thrombin, clotting cannot form which is ideal for heart surgeries and some heart conditions. Argatroban should be monitored as it inhibits clotting so other injuries won't clot and it also can cause blood stagnation. Monitoring changes in hematocrit and blood pressure is extremely important when taking this drug. It is normally administered intravenously so that it is delivered to the site of action right away and can be controlled more easily.

Argatroban is a synthetic derivate of L-arginine and a direct thrombin inhibitor anticoagulant prescribed to patients with heparin-induced thrombocytopenia. Direct thrombin inhibitors bind plasma and fibrin bound thrombin independently of co-factor antithrombin.The inhibition of thrombin reduces the stability of the clot and promotes clot break down. Argatroban does not effect serine proteases like, trypsin, factor Xa, plasmin, and kallikrein. Argatroban is advantageous, particularly for renal failure patients, due to its short-half life and hepatic clearance.