Pathways

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.

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, 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.

Anisotropine methylbromide is a quaternary ammonium compound. Its use as treatment adjunct in peptic ulcer has been replaced by the use of more effective agents. Depending on the dose, anisotropine methylbromide may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder. In general, smaller doses of anisotropine methylbromide inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion. Quaternary ammonium compounds such as anisotropine methylbromide inhibit the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. By being an antagonist of the M2 receptor on the smooth muscle of the GI tract, this drug inhibits the Gi signalling pathway leading to decreased intracellular calcium levels and muscle relaxation, therefore decreasing the motility of the GI tract. Possible side effects of using anisotropine methylbromide may include constipation, dry mouth, urinary retention, and headache.

Anisotropine methylbromide is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Anisotropine methylbromide passes through the liver and is then excreted from the body mainly through the kidney.

Metabolites of Anisindione are predicted with biotransformer.

Anisindione is a synthetic vitamin K antagonist derived from indanedione that is used only if coumarin-derived anticoagulants such as warfarin or coumadin cannot be taken, due to its side effects. It is also marketed as Miradon or Unidone. Anisindione works as other vitamin K antagonists, by reducing the stores of reduced vitamin K, by inhibiting the vitamin K gamma reductase complex, and preventing the recycling of the vitamin K within the cell. This in turn prevents coagulation factors VIII, IX, X as well as prothrombin, factor II, from activating, which in turn prevents fibrin clots from being formed and stabilized. Anisindione is administered orally and is absorbed in the intestine and enters the liver. There, it inhibits the vitamin K epoxide reductase complex, preventing vitamin K1 2,3-epoxide from being recycled into reduced vitamin K. This leads to less reduced vitamin K to be present in order to react with the precursors of coagulation factors II, VII, IX and X through the vitamin K dependent gamma-carboxylase, and prevents those coagulation factors from being produced. Normally, coagulation factor IX is activated by factor XIa, which then, with the addition of coagulation factor VIII, forms the tenase complex that activates coagulation factor X. Activated coagulation factor Xa then joins with coagulation factor V to form the prothrombinase complex which forms thrombin from prothrombin. Thrombin is then necessary to convert fibrinogen to loose fibrin within the blood plasma, as well as converting coagulation factor XIII into its activated form. The fibrin then is able to polymerizes, and is stabilized into a water insoluble clot by coagulation factor XIIIa. The presence of anisindione and the absence of reduced vitamin K prevents this coagulation cascade from occurring as much due to lack of substrates, and thus helps to prevent blood clotting.

Anileridineb is a synthetic opioid analgesic medication. It is a narcotic pain reliever used to treat severe pain. It can be taken intramuscularly, intravenously, subcutaneously, or orally. Anileridineb binds to mu opioid receptors, stimulating the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as GABA is inhibited. Opioids close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability. Morphine acts at A delta and C pain fibres in the dorsal horn of the spinal cord. By decreasing neurotransmitter action there is less pain transmittance into the spinal cord. This leads to less pain perception.