Pathways

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.

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.

Ardeparin, trade name Normiflo, is low molecular weight heparin with anticoagulant effects used to prevent thrombosis. Ardeparin binds and increases antithrombin III activity and inactivates thrombin, factor Xa and coagulation factors XIIa, XIa, plasmin and kallikrein to prevent clot formation. In addition, heparin cofactor II is bound by ardeparin to inhibit thrombin. Plasma proteins have a smaller affinity for low molecular weight heparins than unfractionated heparin. Low molecular weight heparins also don't undergo the rapid degradation of unfractionated heparins. These properties increase ardeparin's bioavailability and give a more predictable anticoagulant activity.

Arbutamine is a synthetic catecholamine non-selective beta-adrenergic agonist. It is administered a closed-loop, computer-controlled drug-delivery system and is indicated to elicit acute cardiovascular responses, similar to a response by exercise. This is used for diagnosing the presence or absence of coronary artery disease in patients who cannot exercise properly and is used to treat conditions including mild or transient episodes of heart block that doesn't require pacing, extreme cases of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation), cardiac arrest until electric shock or pacemaker therapy is available, bronchospasm occurring during anesthesia, and as an adjunct to in the treatment of hypovolemic and septic shock, low cardiac output states, congestive heart failure, and cardiogenic shock. The actions of arbutamine are mostly observed in heart muscle, where it binds to beta-1 adrenergic receptors, and smooth muscle (bronchi, blood vessel, GI tract and uterus), where it exerts it’s effects via beta-2 adrenergic receptors. In the heart, arbutamine binds to and activates the beta-1 adrenergic receptor, which is coupled to the G-protein signaling cascade. Activation of the receptor activates the signaling cascade which leads to activated protein kinase. Protein kinase activates calcium channels in the membrane, causing them to open and allow Ca2+ to enter the cell. Due to this effect, there is high concentration of Ca2+ in the cell. Ca2+ activates the ryanodine receptor on the sarcoplasmic reticulum, which transports Ca2+ from the sarcoplasmic reticulum into the cytosol. the high concentration of Ca2+ in the cytosol binds to troponin to cause muscle contraction. The high concentration of Ca2+ means that more Ca2+ binds to troponin, increasing inotropy. In non-cardiac myocytes, an increase in intracellular Ca2+ increases the slop of phase 4 of the action potential. The threshold is reached faster, therefore, the heart rate is increased. In the smooth muscle, Ca2+-calmodulin complex activates myosin-LC kinase which activates myosin-LC. The activated myosin-LC causes contraction. Arbutamine binds to and activates beta-2 adrenergic receptor, activating the G-protein signaling cascade. The G-protein signaling cascade produces cAMP, which inhibits myosin-LC kinase. This prevents the activation of myosin-LC and as a result, decreases smooth muscle contraction. Possible side effects from taking isoprenaline include headache, dizziness, upset stomach, flushing, fatigue, nervousness, angina, hypotension, hypertension, palpitations, ventricular arrhythmia, tachycardia, adams-stokes syndrome, dyspnea, edema, blurred vision, nausea, vomiting, tremor, weakness. Arbutamine is used over isoprenaline because the degree of hypotension that occurs is less with arbutamine because alpha receptor activity is retained.

Arbutamine is a synthetic catecholamine used to initiate a cardiac stress response to mimic exercise to detect coronary artery disease. Arbutamine has nonselective beta and weak alpha-1-adrenergic activity which causes increased chronotropic activity (increase in heart rate) and inotropic activity (increase myocardial contractility). These effects mimic the cardiovascular effects of exercise. For patients with cardiovascular artery disease, arbutamine can induce myocardial ischemia. Arbutamine is delivered via a computer controlled closed-loop system. The infusion of arbutamine is based off the heart rate feedback. The system monitors heart rate and blood pressure throughout infusion with alarms for physiological changes or problems.