Novel drug sourced from snake venom
Abstract
The cardiovascular and cerebrovascular diseases have continued to be some of the leading death causes across the globe. In the recent times, the field of medicine has received substantial advancements, particularly in the areas of pharmacological treatment and the prevention of the disorders such as the plasminogen activators, platelets GPIIb/IIIa antagonists and the direct thrombin inhibitors. The development of the novel drug, the tirofiban sourced from the Echis carinatus venom been highly reported to be of great importance. Tirofiban, an anticoagulant factors isolated from Echis carinatus has a variety of immune responses that includes both acute inflammatory responses and this include mast cell degranulation and the adaptive immune responses. Ideally, the anticoagulant factors found in Echis carinatus comprise of the Echicetin and Echesitatin among others. This factor has the ability to bind to platelet glycoprotein Ib (GPIb), which has significant impacts in the inhibition of the aggregation of the platelets. The tirofiban is a primary agent in this case and is regarded as one the common and important glycoprotein IIb-IIIa inhibitors.
Introduction
A variety of the evolutionary distinct animals such as insects, Arachnids, reptiles and the mammals utilise the venoms to protect themselves from their preys and for predation. The recent studies have revealed that the components from venoms have facilitated substantial drug discoveries project in the field of Medicine [5-6]. Ideally, venoms are made up of a sophisticated mixture of various toxic elements that are often injected and delivered to the targeted victim through their bites and strings. In this sense, a move to target a mammalian species by venomous has been reported to bring considerable evolutionary selective pressures with substantially two effects, either to avoid or minimise the toxic effects of the envenomation 1]. On a wider note therefore, the venomous substance from the snake species Echis carinatus has been highly reported to be of great importance and a major discovery in the field of medicine. In this sense, the anticoagulant factors isolated from Echis carinatus has a variety of immune responses that includes both acute inflammatory responses and this include mast cell degranulation and the adaptive immune responses. The venom from E. carinatus therefore, offers a substantial presentation of the first-class haemorrhagic, coagulant and the proteolytic actions and significant effectiveness on blood coagulation.
Ideally, the anticoagulant factors found in Echis carinatus comprise of the Echicetin and Echesitatin among others. This factor has the ability to bind to platelet glycoprotein Ib (GPIb), which has significant impacts in the inhibition of the aggregation of the platelets [2, 3]. The tirofiban is a major agent in this case and is regarded as one the common and important glycoprotein IIb-IIIa inhibitors. The anti-platelets therapies through the use of the tirofiban have the ability to reduce the risks of the adverse coronary events, particularly in the patients who receive percutaneous coronary interventions (PCI) [4]. The snake venoms that exist are classified depending on the ability to expand or reduce the blood clotting process into anti-coagulation and coagulation complex compounds.
Tirofiban and its effects in the body
Platelets are usually activated through the action of different kinds of agonists that include collagen, adenosine diphosphate (ADP), and the thrombin. Ideally, the thromboxane A2 also forms an integral component of the substances in this group. The final step involved he aggregation of the platelets is usually to bind the fibrinogen to activated platelets. During the process, the membrane-protected glycoprotein (GP) complex IIb/IIIa often act as the major fibrinogen’s receptors [1, 2, 3, 4, 5, 6].
Tirofiban a novel compound and a drug sourced from the venom found Echis carinatus is one of the common compounds under this category, which has also been proved to reduce the risks of the adverse coronary events, particularly in the patients who receive percutaneous coronary interventions (PCI) [3]. Ideally, Tirofiban has a higher capacity of reducing other conditions such as the negative vents such as the myocardial infarction (MI) after the treatment and the need for urgent revascularization in people suffering from the unstable angina and the non-Q-wave myocardial infarction [4]. Notably, these actions occurs through various mechanisms and process for limiting the contribution and participation of the platelets in continuous thrombosis. Notably, the effects and the mechanism through which these compound acts involves the inhibition of the crosslinking of the platelets through creating considerable barrier to the processes and events that enhance binding of the fibrinogen to the active receptors of the glycoproteins IIb-IIIa [2-3].
While it is evident that the novel tirofiban is efficient considerably, recent studies have revealed that some of the patients who received this kind of treatment developed recurrent or progressive thrombosis during therapy with the tirofiban. These results offered the indication of the sub-therapeutic dosing. Other patients have also been reported to experience considerable bleeding problems.
Discoveries, development and future treatment
In relation to the characteristics of the glycoproteins IIb/IIIa receptors, investigations of the ligands of the tirofiban’s receptors led to the elaboration of the drug [1]. Ideally, these examination found that tripeptide sequence arginylglycyl-aspartayl (RGD) amount to be less significant to the GP IIb/IIIa receptors [3]. In this sense, the antibodies, particularly the monoclonal or the proteins that consists of the RGD were reported to play greater roles in the inhibition of the IIb/IIIa receptors. Because these factors integrate various complex structures beside the minimal RGD sequence, tirofiban was designed, and characterised by the low molecular weight (MK-383) [4 and 6]. Fundamentally, tirofiban, whose major source is the venom from the snake species Echis carinatus has been approved by the U.S food and Drug Administration for the treatment of the individuals suffering from acute coronary diseases.
Mode of actions of Tirofiban and the treatment of acute coronary syndrome
Prothrombin to Thrombin conversion is an essential reaction in the blood coagulation process in human being. Fundamentally, the physical activation of the prothrombin to the serine proteinase thrombin speeded by the prothrombinase complex comprises of the protease factor Xa, and the cofactor Va and Ca2+. In this sense, the membranes that consists of the anionic phosphates and lipid layers are necessary for the maximum function of this enzyme substance [2-6]. However, research reveals that the activation rate of prothrombin to thrombin is five orders of magnitude low compared to that of prothrombinase complex. The action of the cleavage transforms through the prothrombin-2 instead of the meizothrombin [6].
The glycoprotein IIb/IIIa receptors prove to be crucial anti-platelets factors through the inhibition of the ultimate common pathway of the platelet aggregation [3, 4, 5, and 6]. In this sense, the tirofiban binds with the particular focus to the glycoprotein IIb/IIIa receptors, thereby exerting a wide platelets inhibition. The studies by Byoki and Mirakabadi revealed that the intravenous administration of the tirofiban when combined with the aspirin and heparin has substantial capacity to reduce the negative cardiac events within the patients receiving the percutaneous coronary intervention [1]. It also has similar effects in patients with the acute coronary syndromes. In this sense, therefore, the venom from E. carinatus offers a substantial presentation of the first-class haemorrhagic, coagulant and the proteolytic actions. According to Holmes et al. [2], the proteins such as the Tirofiban, which depict significant effectiveness on blood coagulation and the snake venoms that exist are classified depending on the ability to expand or reduce the blood clotting process into anti-coagulation and coagulation complex compounds. The application of the high-dose bolus tirofiban provide an additional immune in the patients with the greatest risks of the coronary syndromes and other related diseases In this case, the roles of tirofiban is less developed and may have diverse effects on the patients [4].
While it is evident that the drug has depicted a tremendous success over the past few years, minor challenges are also associated with the tirofiban, and therefore constitute to one of the major problems in this area [3]. For instance, patients who received this kind of treatment developed recurrent or progressive thrombosis during therapy with the tirofiban. These results offered the indication of the sub-therapeutic dosing.
Conclusion
It is worth to recognise that large randomised trials that uses tirofiban have significantly demonstrated efficient clinical and long-term survival benefits in virtually people in various age groups. These includes the high-risks patients receiving the percutaneous coronary intervention, as well as those undergoing the elective intracoronary stent intervention. Those who receive medical management in relation to the acute coronary syndromes are also benefit substantially from the drug usage. The application of the high-dose bolus tirofiban offers an extra protection in the patients with the greatest risks of the coronary syndromes and other related diseases In this case, the roles of tirofiban is less developed and may have diverse effects on the patients. While it is evident that the drug has depicted a tremendous success over the past few years, minor challenges are also associated with the tirofiban, and therefore constitute to one of the major challenges in this area. For instance, patients who received this kind of treatment developed recurrent or progressive thrombosis during therapy with the tirofiban. These results offered the indication of the sub-therapeutic dosing. Other patients have also been reported to experience considerable bleeding problems. The developments of the cheap, effective and safe antivenoms have also been reported to be in huge demand globally. To effectively address the challenges associated with the utilization of tirofiban, the components of the venom from Echis carinatus should be effectively established. Such establishment should integrate its Pharmacokinetics and manifestation in the body of the intended patients. In addition, researchers should also focus on establishing the relationships between the effects of tirofiban and other cardiovascular disorders.
References
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