Understanding the Clotting Cascade: A Life-saving Process

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• Executive Summary (an introduction/background to the case study) The clotting cascade is essential in the human body to allow for healing of a broken artery or vein. If we don’t have these clotting factors or clotting cascade it can lead to serious consequences such causing bleeding out eventually leading to death as shown in haemophilia. The clotting cascade consists of primary and secondary haemostasis. Primary haemostasis being the formation vasoconstriction and platelet aggregation at the site of injury and secondary haemostasis being the formation of a clot. In more detail, it starts off with binding of tissue factor VIIa which initiates the coagulation cascade and formation of factor X (thrombin) and eventually fibrin. Platelets …show more content…

Angiolillo, D. et.al, 2007). The drug prevents platelet degranulation and release which expands prothrombic and inflammatory mediators while also inhibiting the transformation of GP IIb/IIIa receptor that forms fibrinogen (J. Angiolillo, D. et.al, 2007). Figure 3. This figure shows the mechanism of action of Clopidogrel (Guzman, F. 2008). Clopidogrel inhibits aggregation for 7 to 10 days which is the average lifespan of a platelet, it produces a dosage dependent effect which begin 2 hours after a single dose and the inhibition is approximately 40% to 60% in adults (L. Buck, M. and D, P., 2010). • Pharmacokinetic Implications ( a description of the mechanism of the patient response) Clopidogrel is taken orally and is rapidly absorbed having a bioavailability of 50% (L. Buck, M. and D, P. 2010). Food doesn’t affect its absorption so it is able to be consumed with or without food (Drugs.com. …show more content…

The metabolic pathway being mediated by the CYP2C19, CYP3A, CYP2B6 and CYP1A2 enzymes. The maximum concentration with a single dose of 300mg loading dose is twice as high as it is after four days of 75mg maintenance dose which occurs approximately 30 to 60 minutes after dosing. Figure 4. This figure shows metabolic activation of Clopidogrel. Bioavailability is determined by intestinal absorption. 85% converted too inactive metabolites via esterase’s and 15% converted to active thiol-containing metabolite by CYP450 enzymes (Agewall et al., 2013). Conversion to 2-oxo-cloipidogrel is catalysed by CYP2C19, CYP1A2 and CYP2B6 while the second step is catalysed by CYP3A4, CYP2B6, CYP2C19, and CYP2C9 which form the active metabolite and binding to the P2Y12 receptors inhibiting ADP-induced platelet activation (Agewall et al., 2013). After 5 days Drugs.com (n.d.) stated that there was 50% excreted in urine with 46% in faeces with a half-life of approximately 6 hours. Clopidogrel being metabolized by CYP2C19 and using other inhibitors of this enzyme results in reduced plasma concentrations (Drugs.com.

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