Global Journal of Science Frontier Research, G: Bio-Tech & Genetics, Volume 22 Issue 2

Modulation of Warfarin Sodium into Warfarin Potassium for Patients with Hypertension Al-Baraa Akram Abstract- Warfarin is an oral anticoagulant drug that has a prolonged duration of action with delayed onset of action; its chemical structure contains sodium atoms, which may be hazardous to hypertensive patients. To solve this problem, sodium atom can be substituted with potassium or lithium atom which can help the patient to relieve hypertension in addition to it essential role as an anticoagulant. Another advantage of this preparation is that it can be used as an antidote against digitalis toxicity, but the warfarin interactions with other drugs are still the same as a cytochrome P450 inhibitor. Warfarin reduces blood clotting by inactivating vitamin K epoxide reductase, which activates vitamin K1, the main component in the blood clotting process. Without sufficient vitamin K1 activation, clotting factors II, VII, IX and X have decreased clotting ability. The anticlotting protein C and protein S have also inhibited, but to a lesser degree. A few timesare required for the clotting process, and these effects can take about five days. Additionally, because this process requires enzymes like VKORC1, patients who take warfarin with polymorphism of these enzymes can require adjustment as genetic factors should be taken into consideration, thus may require lower doses. Keywords: warfain, hypertension, international normalized ratio, therapeutic window, clinical trials, pharmaco- genomics, CYP2C9*3. I. I ntroduction a) History and overview he history of warfarin discovery started in the 1920s in the prairies of North America and Canada. Cattle were dying from internal bleeding without any precipitating cause, which led to a dietary query problem that many farmers complained. They called it sweet clover disease, and at this time, they recommended each other not to feed their cattle the moldy sweet clover hay. But science had a different opinion, a research work funded by the Wisconsin Alumni Research foundation patented in 1941. Variation of dicoumarol was patented as a rat poison in 1948 and then transitioned to the clinical application under the name of Coumadin. The prefix of the name warfarin was derived from WARF (the first letters of Wisconsin Alumni Research Foundation), and the suffix ـــ arin was derived from coumarin. Warfarin first came for large-scale commercial use in 1948 as a rat poison (1). Warfarin was officially approved for human use by the United States food and drug administration (FDA) to treat blood clots in 1954 (2). In 1955 warfarin's reputation as a safe and acceptable treatment was bolstered when American president Dwight Eisenhower took warfarin because of a massive and publicized heart attack (3). This story kick- started the usage of warfarin in coronary heart disease, arterial plaques, and ischemic heart attacks. It is listed in the World Health Organization (WHO) as the essential medicine. Warfarin is available as a generic medication. In 2019 it was the 50 th most prescribed medication in the United States, with more than 14 million prescriptions (4). Figure 1: Chemical structure of warfarin with empirical formula C 19 H 16 O 4 b) Platelet response to vascular injury Physical trauma to the vascular system e.g., punctures or cuts initiate a complex series of interactions between platelets, endothelial cells, and coagulation cascade. This results of formation a platelet-fibrin plug or clot at the site of puncture. c) Coagulation cascade (secondary hemostasis) Series of protease enzymes and their cofactors takes place of phospholipids' surface, platelet, and endothelium which consist of extrinsic, intrinsic, and common pathways that results in the formation of stable fibrin clot as shown in figure 2. T 1 Year 2022 1 © 2022 Global Journals Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Author: faculty of health and life sciences, department of pharmaceutical biotechnology, Portland laboratory in De Montfort University in Leicester (United Kingdom). e-mail: albraaakram94@gmail.com The creation of a thrombus involves many of the same steps as normal clot formation, except this trigger stimulation which is a pathological case in the vascular system.