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Acetyl salicylic acid resistance and inhibition to platelet aggregation
Published in Cut Adeya Adella, Stem Cell Oncology, 2018
D.M. Amoryna, Z. Mukthar, H. Hariman
Platelet aggregation is performed to identify and quantify platelet response and monitor platelet inhibition by drug therapy. It is based on the addition of a platelet agonist to a blood sample (usually platelet-rich plasma). It may be assessed using various agonists such as adenosine di-phosphate (ADP), collagen and others. Arachidonic acid (AA), a precursor of thromboxane A2 and hydroxyl fatty acids liberated from human platelets on activation, converts the enzyme cyclooxygenase-1 (COX-1) into a potent inducer of platelet aggregation. Ingestion of ASA inhibits COX-1 thus inhibits platelet aggregation. The aggregation of platelets is an essential physiologic life-saving process of blood coagulation. The role of platelets in haemostasis involves adherence to sites of injury, activation of internal signalling pathways, aggregation to form plugs and the acceleration of the coagulation reactions to form thrombin. Platelet aggregation, particularly at the site of plaque rupture, results in thrombus formation blocking normal blood circulation in the heart musculature in ACS (Fuster et al., 1996). Platelet function may be impaired if any of the pathways mediated by the activation process by agonists are defective. The objective of this small cohort study is to determine whether an ASA of 50 mg dose is as effective as a 100 mg dose in normal healthy subjects.
Medication: Nanoparticles for Imaging and Drug Delivery
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Aspirin was the model for the class of pharmaceutical agents known as nonsteroidal anti-inflammatory drugs (NSAIDs). Many but not all NSAIDs are derivatives of salicylates; all have similar effects—most act by nonselec-tive inhibition of the enzyme cyclooxygenase, needed to synthesize pros-taglandin and thromboxane. Prostaglandins are local (paracrine) hormones whose diverse effects include transmission of pain information to the brain, modulation of the hypothalamic thermostat, and regulating inflammation. Thromboxanes are involved in aggregation of platelets that form blood clots. Aspirin can irreversibly block the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation. This is the mechanism of aspirin’s anticoagulant effects used to reduce the incidence and severity of heart attacks. A side effect is a general reduction in the ability of the blood to clot, which may result in excessive bleeding with the use of aspirin.
Analgesic, Anti-Inflammatory, Antipyretic, and Anesthetic Drugs: Dealing With Pain, Inflammation, and Fever
Published in Richard J. Sundberg, The Chemical Century, 2017
But no one knew how aspirin worked until the early 1970s, when John Vane and collaborators showed that it inhibited formation of prostaglandins.2 Vane shared the 1982 Nobel Prize in Medicine for this discovery.a The first enzyme in the biosynthetic pathway to prostaglandins is cyclooxygenase-1 (COX-1), so aspirin and related drugs became known as COX-1 inhibitors. The prostaglandins are biosynthesized from arachidonic acid, a highly unsaturated 20-carbon fatty acid. The cyclooxygenase enzyme contains a heme group that functions to form peroxides and hydroperoxides and a second site that converts these to hydroxyl and carbonyl groups.3 The two sites are linked by electron transfer. The key intermediate is prostaglandin endoperoxide (shown as PGH2 in Fig. 13.1), which gives rise to the prostaglandins and two related types of compounds, the thromboxanes and prostacyclin. As a group, these compounds are called eicosanoids, referring to their 20-carbon structures. Several of the prostaglandins are vasodilators and also effect blood clotting. The thromboxanes tend to be prothrombotic, vasoconstrictors and promote platelet aggregation. Prostacyclin (also called PGI2) has the opposite effects, acting as a vasodilator and inhibiting platelet aggregation. The balance between these effects is a critical aspect of their biological function. The eicosanoids are involved in several other important biological processes including, kidney function, asthma, maintenance of gastrointestinal mucosa, induction of sleep, and aspects of reproduction.
Applications of omega-3 polyunsaturated fatty acid supplementation for sport performance
Published in Research in Sports Medicine, 2019
Jordan D. Philpott, Oliver C. Witard, Stuart D.R. Galloway
EPA is known to replace arachidonic acid in the phospholipid layer of platelet cell membranes following n-3PUFA ingestion (Lorenz, Spengler, Fischer, Duhm, & Weber, 1983). As a consequence, platelet aggregation may be reduced due to a reduction in levels of thromboxane A within the plasma. Platelets mediate the wound healing process via blood clotting. Thus, in theory a decrease in platelet aggregation may increase bleeding time. Consistent with this notion, a recent study also suggests that n-3PUFA supplementation may reduce platelet aggregation in healthy individuals and therefore increase bleeding time following surgery or lacerations (McEwen, Morel-Kopp, Chen, Tofler, & Ward, 2013). However, human studies examining the influence of n-3PUFA supplementation on bleeding time and severity have generally shown mixed results. A recent systematic review found no difference in bleeding risk with n-3PUFA supplementation in different populations, including athletes (Begtrup, Krag, & Hvas, 2017). However, the interpretation of this systematic review may be influenced by variations in the dose and duration of n-3PUFA supplementation between studies. Overall, although n-3PUFA supplementation may reduce platelet aggregation there appears to be no effect on bleeding rates following surgery. Therefore, unless athletes are ingesting a high dose of n-3PUFA, concerns over bruising and bleeding following an injury during sport appear unfounded.
Fabrication of swellable PEGylated hydrogel by free radical polymerization for controlled delivery of non-steroidal anti-inflammatory drug; characterization and statistical analysis
Published in Particulate Science and Technology, 2023
Ariba Baloch, Mahmood Ahmad, Muhammad Usman Minhas, Syed Faisal Badshah, Kashif Barkat, Muhammad Suhail, Nadia Shamshad Malik
Ketorolac is an anti-inflammatory and antipyretic agent. The anti-inflammatory, antipyretic, and analgesic effects are due to the inhibition of prostaglandin synthesis in the body tissues by competitive blocking of at least two cyclooxygenase (COX) iso-enzymes, COX-1 and COX-2, which promote blocking of prostaglandin synthesis, resulting in decreased production of precursors of prostaglandin and thromboxane from arachidonic acid. Ketorolac is one of the good candidates to be formulated in controlled and sustained-release dosage forms, thereby simplifying the dosage regimen and improving the patient compliance.
In Vitro models for thrombogenicity testing of blood-recirculating medical devices
Published in Expert Review of Medical Devices, 2019
In both static incubation and dynamic flow loop models, the quality of the blood is essential. It should be fresh, as platelet and leukocyte function is diminished after 4 h [78]. Atraumatic blood collection, using a 21gauge needle, is needed to minimize venostasis and platelet activation [1]. Additionally, ASTM F-2888 specifies that blood should be taken from human donors who have not taken aspirin, acetaminophen, naproxen, warfarin, heparin, or ibuprofen for 10 days. These drugs interfere with the coagulation process, and therefore, diminish coagulation response. Aspirin and naproxen are part of the non-steroidal anti-inflammatory (NSAID) class of drugs that block cyclooxygenases, part of the inflammatory cascade. Aspirin is used as an anti-platelet agent because of its inhibition of downstream production of thromboxane A2 within platelets, increasing fibrin clot porosity [79]. Naproxen acts similarly through the inhibition of thromboxane B2 [80]. Systemic platelet function is only restored after platelets are replaced. Ibuprofen and acetaminophen decrease platelet activity reversibly. Warfarin is a Vitamin K antagonist that prevents the synthesis of factor X and prothrombin [81]. Blood from donors who have consumed any of these drugs should not be used for in vitro thrombogenicity testing because of decreased coagulation activity. An important consideration for the blood used in an in vitro thrombosis study is the anticoagulant used and its concentration. The two most common anticoagulants that are used in in vitro flow loops are lithium heparin and sodium citrate. Clinically, heparin is the most common anticoagulant used in ECMO, VAD, or dialysis therapies while sodium citrate is infrequently used because it irreversibly binds calcium. In order to restore normal coagulation properties of citrated blood, calcium must be added into the blood before use in an in vitro test. The choice of which anticoagulant is most appropriate can depend on the requirements of the post-test analysis of blood or comparison to clinically relevant conditions. While heparin is more common, citrated blood can provide a distinct advantage for in vitro models because of the ease of handling and stability of citrated blood before use in a study. The level of anticoagulation for blood used in an invitro flow loop should ideally be donor specific because of high variability in the coagulability of blood in different species and between donors.