By Morgan Ahn
(Photo by Marcel Scholte on Unsplash)
Thrombosis and Pulmonary Embolism
Thrombosis and Pulmonary Embolism (PE) are similar medical conditions that bring multiple health effects to humans. Thrombosis is the disease of the creation of blood clots in blood vessels around any part of the body - mainly in the legs and arms. Correspondingly, PE occurs when a blood clot migrates to the lungs, clogging blood flow and disfunctioning it. Given their potential to induce life-threatening consequences, advanced investigations have been conducted to apprehend and address the complexities associated with
thrombosis and PE. According to the Centers for Disease Control and Prevention, 900,000 people in the United States are affected by thrombosis or PE, and 25% of them face sudden death due to the blockage of the blood circulation. (Data) The present project will examine the practicality of Dabigatran as a pharmacological intervention for preventing and treating thrombosis and PE.
Figure 1 Incident rate of Thrombosis and PE by age group (Raptis)
Cause of Thrombosis and Pulmonary Embolism
Thrombosis and PE can be shown in various blood vessels throughout the body, with an eminent association observed in deep vein thrombosis (DVT) cases. DVT typically occurs in the blood vessels borderline (also known as the circumference). However, it can extend to diverse factors, including vascular injury, prolonged immobility, underlying malignancies, excessive body weight, smoking, hormonal contraceptives, pregnancy, and other contributing
conditions. DVT is a severe disease due to its possibility of metastasis into another devastating disease. Countless risk factors also increase an individual's vulnerability to thrombosis, including familial history of blood clots, advanced age, surgical procedures, traumatic incidents, inherited clotting disorders, certain medications, and obesity.
Treatment of Thrombosis and Pulmonary Embolism
The treatment of thrombosis and PE typically involves anticoagulant medications designed to prevent the formation of blood clots. These medications can be given orally or intravenously (injection). Mostly, oral medication is the most popular method for patients, but IV is only used when oral medication is unavailable due to physical conditions. In severe cases, surgery may be necessary to remove a clot or insert a filter into the vein to prevent further clots. However, this project will concentrate on the types of drugs that can cure these diseases and propose them.
Different Types of Drugs for Treatment
There are multiple different types of drugs available for treating thrombosis and PE. Each different drugs have its own risks and limitations, but it depends on the target protein and gene they bind to. The most famous drugs are Warfarin and heparin, which a wide range of patients are available for access. Heparin is a fast-acting anticoagulant that can prevent the formation of newly created blood clots by inhibiting the formation of fibrin, a necessary protein responsible for blood clotting. As mentioned in the previous paragraph, Warfarin is one of the most popular treatments for blood clots. Warfarin inhibits the clotting factors activated by the vitamin K. This is how it ultimately results in the prevention of new clot formation and removal of the existing clots by dissolution. Compared to Heparin, Warfarin is mostly used as an oral medication unless there is a special adjustment needed for the patients. Warfarin is composed of enantiomers, which are “pairs of compounds with the same connectivity but opposite three-dimensional shapes” (Schaller) – S and R. As the chemical structure shown in Figure 2, a three-dimensional structure is noteworthy since Warfarin is one of the few drugs that attach nearly completely to the complement protein: albumin (Gellatly).
Figure 2 Enantiomers of Warfarin
Figure 3 Structure of WarfarinThe 2D structure of Warfarin (left) explicitly indicates the R and S enantiomers. The 3D structure of Warfarin (right) gives an understanding of the binding process. (Warfarin.)
The binding map of Warfarin is shown in Figure 4. As shown in the figure, the yellow molecule is Warfarin, making the pocket bond with the CYP2C9 gene. Looking at the binding area, it is easily shown that the OH functional group has an active binding with the part of the ribbon of the CYP2C9.
Figure 4 Binding map of Warfarin (Lahti)
Adding to the Warfarin and heparin, direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are also used to treat thrombosis and PE. DOACs are relatively newer anticoagulant medications that work by targeting specific clotting factors, such as thrombin or factor Xa, ultimately making it possible to prevent the clots.
Dabigatran works by inhibiting the activity of the thrombin and reducing stroke, systemic embolism, and other clot-related problems. One of the advantages of using dabigatran is that it does not require frequent monitoring of blood tests and involves fewer interactions between different medications and foods. Following is the two-dimensional structure of dabigatran.
Figure 5 Dabigatran compound
It is important to note that the choice of medication for thrombosis and pulmonary embolism treatment depends on several factors, such as the severity of the condition, the patient's age and medical history, and the potential for drug interactions. Therefore, it is crucial to determine the most appropriate treatment process for each patient. Among these choices, dabigatran is going to be the main focused drug for creating analogs depending on the different target purposes.
References
Centers for Disease Control and Prevention. (2023, June 28). Data and statistics on venous thromboembolism. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/dvt/data.html
RM; G. (n.d.). Intravenous warfarin as an alternative for anticoagulation. Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/17542775/#:~:text=Intravenous%20warfarin%20provides%20an%20alternative,heparins%20due%20to%20adverse%20effects
Schaller, C. (2023, January 23). Enantiomers. Chemistry LibreTexts. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Fundamentals/Isomerism_in_Organic_Compounds/Enantiomers#:~:text=Enantiomers%20are%20pairs%20of%20compounds,mirror%20images%20of%20each%20other
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