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Aspirin in Myocardial Infarction by Pharm Jimmy Aiden

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The use of aspirin in the management of myocardial infarction by pharm jimmy aiden

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Aspirin in Myocardial Infarction by Pharm Jimmy Aiden

  1. 1. BY PHARM. JIMMY AIDEN Pharmacy Department Federal Teaching Hospital, Gombe 27th Feb., 2015 ANTIPLATELETS (ASPIRIN) IN THE MANAGEMENT OF MI
  2. 2. • Overview of Myocardial Infarction • Platelet • Adhesion • Activation • Aggregation • Introduction on Aspirin • Synthesis of Aspirin • Structural Activity Relationship of Aspirin OUTLINE
  3. 3. • Mode of Action of Aspirin • Indications of Aspirin • Pharmacokinetic data of Aspirin • Dosage • Adverse Effects • Contraindications • Interactions • Discussion • Conclusion OUTLINE cont.
  4. 4. OVERVIEW OF MI • Myocardial infarction is defined as necrosis of heart muscle caused by ischaemia 1 • Myocardial ischaemia generally occurs as a result of coronary artery occlusion, usually due to thrombosis at the site of a recently ruptured atheromatous plaque • The immediate consequence of coronary occlusion is myocardial ischaemia, which leads to impaired contractility, arrhythmias, and eventually myocardial cell death.
  5. 5. • The lay term 'heart attack' describes both sudden cardiac death and myocardial infarction. • Management of acute myocardial infarction therefore involves both early treatment of the acute condition, and long-term therapy in survivors to reduce risk and to treat and prevent complications. OVERVIEW OF MI cont.
  6. 6. • Blood clots do not usually form in normal arteries. However, a clot may form if there is some atheroma within the lining of the artery • Atheroma is like fatty patches or plaques that develop within the inside lining of arteries • Plaques of atheroma may gradually form over a number of years in one or more places in the coronary arteries. Each plaque has an outer firm shell with a soft inner fatty core. OVERVIEW OF MI cont.
  7. 7. • A crack develops in the outer shell of the atheroma plaque, this is called plaque rupture. This exposes the softer inner core of the plaque to blood. This can trigger the clotting mechanism in the blood to form a blood clot. OVERVIEW OF MI cont.
  8. 8. OVERVIEW OF MI cont.
  9. 9. OVERVIEW OF MI cont. Management of acute attacks • Oxygen • Morphine + Metoclopramide • Aspirin (150-300mg) chewed or dispersed in water • Streptokinase • Nitrates • β- blockers • ACEI’s • Anticoagulants
  10. 10. Long-term Management • Aspirin • β-blockers • ACEI’s • Nitrates • Statins OVERVIEW OF MI cont.
  11. 11. PLATELETS Adhesion, Activation, and Aggregation
  12. 12. PLATELETS • Also called "thrombocytes", are blood cells whose function (along with the coagulation factors) is to stop bleeding. • Platelets have no nucleus: they are fragments of cytoplasm which are derived from the megakaryocytes. • The main function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium.
  13. 13. PLATELET Cont.
  14. 14. PLATELET ADHESION
  15. 15. PLATELET ADHESION Cont. • adhering platelets undergo a dramatic conformational change to an irregular sphere with multiple philopodious increasing their surface area contact.
  16. 16. • Platelet activation begins seconds after adhesion occurs. It is triggered when collagen from the subendothilium, and/or tissue factor from the media and adventitia bind with their respective receptors on the platelet. • Thromboxane A2 synthesis increases during activation: it is secreted and acts on both its own thromboxane receptors (the so-called "out-in" mechanism), and those of other platelets. These receptors trigger intraplatelet signaling, which converts GPIIb/IIIa receptors to their active form to initiate aggregation. PLATELET ACTIVATION
  17. 17. PLATELET ACTIVATION Cont.
  18. 18. • Aggregation begins minutes after activation, and occurs as a result of turning on the GPIIb/IIIa receptor, which allows these receptors to bind with vWF or fibrinogen. PLATELET AGGREGATION
  19. 19. PLATELET AGGREGATION Cont.
  20. 20. ASPIRIN (Low dose)
  21. 21. INTRODUCTION OF ASPIRIN • Also known as acetylsalicylic acid is a salicylate drug, often used as an analgesic, as an antipyretic and as an anti-inflammatory medication.2 • Aspirin is part of a group of medications called nonsteroidal anti-inflammatory drugs (NSAIDs) • Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane A2 which under normal circumstances binds platelet molecules together to create a patch over damaged walls of blood vessels. 3
  22. 22. • The active ingredient of Aspirin was first discovered from the bark of the willow tree in 1763 by Edward Stone of Wadham College, Oxford University. He had discovered salicylic acid, the active metabolite of aspirin.4 • Due to irreversible binding, platelets exposed are affected for the remainder of their lifespan (7-10 days) and recovery of normal platelets function occurs at a rate consistent with platelet turnover. INTRODUCTION cont.
  23. 23. SYNTHESIS
  24. 24. STRUCTURAL ACTIVITY RELATIONSHIP Acetylsalicylic Acid Acetylated organic molecules exhibit increased ability to cross the selectively permeable blood–brain barrier.
  25. 25. MECHANISM OF ACTION
  26. 26. MECHANISM OF ACTION cont.
  27. 27. INDICATIONS • Initial and long-term management of Myocardial infarction. • Management and Prophylaxis of Ischaemic stroke • Pyrexia, Pain, and Inflammation • Migraine • After coronary artery bypass surgery • Patients with prosthetic heart valve
  28. 28. PHARMACOKINETIC DATA • Bioavailability: 80-100% • Protein Binding: 80–90% • Half-life : 15-20 hrs • Metabolism: Hepatic, (CYP2C19 and possibly CYP3A). Also hydrolysed to salicylate in the gut wall by esterase enzyme • Excretion: Urine (80–100%), sweat, saliva, feces1
  29. 29. DOSAGE • Acute Ischaemic Stroke: 150-300mg as a single dose given within 48hrs of onset and 75- 150mg daily reduces the risk of having another stroke. • Myocardial infarction: 150-300mg for initial management. While a dose of 75-150mg is given for long-term management to reduce the rate of reinfarction.
  30. 30. ADVERSE EFFECTS • Bronchospasm: inhibition of COX pathway activates the 5-lipoxygenase pathway
  31. 31. ADVERSE EFFECTS cont. • Gastrointestinal upset and Haemorrhage
  32. 32. CONTRAINDICATIONS • Active peptic ulceration • Hypersensitivity to Aspirin • Children and adolescents below 16 yrs except in Kawasaki disease • Haemophilia and other bleeding disorders • Severe renal or hepatic impairment • Lactation
  33. 33. INTERACTIONS • Aluminium and Magnesium containing Antacids (excretion of ASA by alkaline urine) • Corticosteroids ( plasma salicylate conc. due to renal clearance and induction of hepatic metabolism ) • Heparin : Enhanced anticoagulant effect of heparin due to its antiplatelet effect. • Ibuprofen: Antagonism of the antiplatelet and cardioprotective effect of Aspirin and GI side effects. • Warfarin ( risk of bleeding )
  34. 34. INTERACTIONS cont. • Methotrexate (interference with renal elimination and may also displace it from its protein binding site. Excretion reduced and hence toxicity ) • Spironolactone: Impairs the tubular secretion of canrenone the main active metabolite of spironolactone. Consequently inhibiting the natriuretic properties of spironolactone. (antagonism of diuretic effect)
  35. 35. • Valproic acid and Phenytoin: Enhanced effect due to their displacement from their plasma protein binding site. • Acetazolamide: Salicylate-induced displacement from its plasma protein binding site and reduced renal clearance, hence toxicity. INTERACTIONS cont.
  36. 36. DISCUSSION • Aspirin is an inhibitor of the enzyme cyclo-oxygenase, the action being considered to be due to an irreversible acetylation process. • In blood platelets such enzyme inhibition prevents the synthesis of thromboxane A2, a compound which is a vasoconstrictor, causes platelet aggregation, and is thus potentially thrombotic. • In blood vessel walls the enzyme inhibition prevents the synthesis of prostacyclin, which is a vasodilator, has anti-aggregating properties, and is thus potentially anti-thrombotic.
  37. 37. DISCUSSION cont. • The duration of these effects, however, may differ, with the effects on the vascular tissue generally being shorter than the effects on the platelets. • The difference may be explained by the fact that vascular cells regain the ability to regenerate prostacyclin in a few hours but platelets are unable to re-synthesise cyclo-oxygenase, which results in no new thromboxane A2 being produced for about 24 hours until more platelets are released by the bone marrow
  38. 38. CONCLUSION • Inhibition is cumulative on repeated dosage, and it has been estimated that a daily dose of 75- 100 mg will result in virtually complete suppression of platelet thromboxane synthesis within a few days. Large doses of 150 to 300 mg can produce maximum suppression almost instantaneously. • Cost advantage of Vasoprin® over Clopidogrel and less possibilities of drug-drug interactions as compared to that of the clopidogrel .
  39. 39. CONCLUSION cont.
  40. 40. REFERENCES 1. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J 2000; 21: 1502–13. 2. Brayfield, A, ed. (14 January 2014). "Aspirin". Martindale: The Complete Drug Reference. Pharmaceutical Press. Retrieved 3 April 2014. 3. Lewis, H. D.; Davis, J. W.; Archibald, D. G.; Steinke, W. E.; Smitherman, T. C.; Doherty Je, J. E.; Schnaper, H. W.; Lewinter, M. M.; Linares, E.; Pouget, J. M.; Sabharwal, S. C.; Chesler, E.; Demots, H. (1983). "Protective Effects of Aspirin against Acute Myocardial Infarction and Death in Men with Unstable Angina". New England Journal of Medicine 309 (7): 396–403. doi:10.1056/NEJM198308183090703. PMID 6135989. 4. Stone Edmund (1763). "An Account of the Success of the Bark of the Willow in the Cure of Agues. In a Letter to the Right Honourable George Earl of Macclesfield, President of R. S. from the Rev. Mr. Edmund Stone, of Chipping- Norton in Oxfordshire". Philosophical Transactions of the Royal Society of London 53: 195–200. doi:10.1098/rstl.1763.0033. JSTOR 105721
  41. 41. THANK YOU

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