Pathways

Anistreplase, trade name Eminase, is a thrombolytic drug prescribed to treat acute myocardial infarction. The drug is an acylated streptokinase-plasminogen complex. The acylation of the drug renders it temporarily inactive, protecting it from plasmin inhibitors. Anistreplase is deacylated following injection, activating the drug to increase thrombolysis by increasing plasminogen's conversion to plasmin. Plasmin breaks down the fibrin of the thrombus to break up the clot and release arterial blockages. Anistreplase has been shown to be very effective when administered shortly after onset of chest pain. Compared to other thrombolytic drugs, Anistreplase has a longer plasma half-life. It also advantageous as it can be given as a single bolus intravenous injection.

Anistreplase is a plasminogen activator created from recombinant human tissue, used in emergencies such as myocardial infarction and pulmonary emboli. It is administered intravenously and travels throughout the bloodstream to target blood clots by activating plasminogen. Anistreplase converts plasminogen to its active form plasmin by cleaving an arginine-valine bond, plasmin then acts on the fibrin matrix of the blood clot breaking it down into degradation products. Due to its anticoagulant and antiplatelet activity, avoid herbs and supplements with similar activity such as garlic, ginger, bilberry, danshen, piracetam and ginkgo biloba.

Anistreplase is fibrinolytic drug that functions as a recombinant tissue plasminogen activator. It is administered intravenously and used in the emergency treatment of myocardial infarction and pulmonary emboli. It targets plasminogen in blood vessels where these clots occur. The clotting process consists of two pathways, intrinsic and extrinsic, which converge to create stable fibrin which traps platelets and forms a hemostatic plug. The intrinsic pathway is activated by trauma inside the vasculature system, when there is exposed endothelial collagen. Endothelial collagen only becomes exposed when there is damage. The pathway starts with plasma kallikrein activating factor XII. The activated factor XIIa activates factor XI. Factor IX is then activated by factor XIa. Thrombin activates factor VIII and a Calicum-phospholipid-XIIa-VIIIa complex forms. This complex then activates factor X, the merging point of the two pathways. The extrinsic pathway is activated when external trauma causes blood to escape the vasculature system. Activation occurs through tissue factor released by endothelial cells after external damage. The tissue factor is a cellular receptor for factor VII. In the presence of calcium, the active site transitions and a TF-VIIa complex is formed. This complex aids in activation of factors IX and X. Factor V is activated by thrombin in the presence of calcium, then the activated factor Xa, in the presence of phospholipid, calcium and factor Va can convert prothrombin to thrombin. The extrinsic pathway occurs first, producing a small amount of thrombin, which then acts as a positive feedback on several components to increase the thrombin production. Thrombin converts fibrinogen to a loose, unstable fibrin and also activates factor XIII. Factors XIIIa strengthens the fibrin-fibrin and forms a stable, mesh fibrin which is essential for clot formation. The blood clot can be broken down by the enzyme plasmin. Plasmin is formed from plasminogen by tissue plasminogen activator. Anistreplase acts as a tissue plasminogen activator. It binds to clots with fibrin where it causes hydrolysis of the arginine-valine bond in plasminogen, aiding its conversion to plasmin. The plasmin degrades the stable fibrin and causes lysis of the clot. The activity of anistreplase depends on the presence of fibrin. Only small amounts of plasmin are formed from plasminogen when there is no fibrin. Anistreplase in the presence of fibrin obtains a higher affinity for plasminogen, thus leading to its increased activity. Adverse effects such as itching, flushing, skin rash, fever, chills, headache, nausea, sweating, dizziness, muscle aches or tremor can occur from the use of anistreplase.

Ansuvimab (formerly mAb114) is a monoclonal IgG1 antibody derived from a survivor of the 1995 kikwit EBOV (Ebola virus) outbreak. It is directed against the GP1,2 surface glycoprotein of Zaire ebolavirus .It is used for the treatment of Zaire ebolavirus infection in adult and pediatric patients. This drug has been approved by the FDA in 2020. The DP1,2 glycoproteins of EBOV are involved in the the host cell entry and the subsequent viral espape into the cytoplasm. Usually, those glycoproteins bind to various host receptors (lectins, asialoglycoprotein receptor, TIM1), but with the drug, they are blocked. Ansuvimab binds over a region encompassing both the glycan cap and GP1 core, although the glycan cap isnot important in the binding. Also, studies have shown that the GP1 core is important for the GPCL interaction with NPC1 and thus this drug blocks NPC1-GP interactions (endolysosome escape). The drug protect against the entry of the virus in the host cells. Ansuvimab is available as an intravenous injection.

Antazoline is an antihistamine agent used for the symptomatic treatment of nasal congestion and allergic conjunctivitis. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Antazoline also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.

Antazoline is a first-generation ethylenediamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Antazoline is an antihistamine agent used for the symptomatic treatment of nasal congestion and allergic conjunctivitis. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Antazoline inhibits the H1 histamine receptor on blood vessel endothelial cells. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin. Calcium bound calmodulin is required for the activation of the calmodulin-binding domain of nitric oxide synthase. The inhibition of nitric oxide synthesis prevents the activation of myosin light chain phosphatase. This causes an accumulation of myosin light chain-phosphate which causes the muscle to contract and the blood vessel to constrict, decreasing the swelling and fluid leakage from the blood vessels caused by allergens.

Antazoline is an antihistamine agent used for the symptomatic treatment of nasal congestion and allergic conjunctivitis. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.