This document discusses the use of aspirin in the management of myocardial infarction. It begins with an overview of myocardial infarction and the platelet mechanisms involved in clot formation. It then discusses aspirin, including its introduction, mechanism of action inhibiting platelet activation, and indications for use in acute myocardial infarction and long-term management. The document outlines aspirin's pharmacokinetics, dosage, adverse effects, interactions, and concludes that aspirin's irreversible inhibition of platelet thromboxane synthesis provides cost-effective prevention of reinfarction.

1. BY
PHARM. JIMMY AIDEN
Pharmacy Department
Federal Teaching Hospital, Gombe
27th Feb., 2015
ANTIPLATELETS (ASPIRIN) IN THE
MANAGEMENT OF MI

2. • Overview of Myocardial Infarction
• Platelet
• Adhesion
• Activation
• Aggregation
• Introduction on Aspirin
• Synthesis of Aspirin
• Structural Activity Relationship of Aspirin
OUTLINE

3. • Mode of Action of Aspirin
• Indications of Aspirin
• Pharmacokinetic data of Aspirin
• Dosage
• Adverse Effects
• Contraindications
• Interactions
• Discussion
• Conclusion
OUTLINE cont.

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. • 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. • 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. • 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. OVERVIEW OF MI cont.

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. Long-term Management
• Aspirin
• β-blockers
• ACEI’s
• Nitrates
• Statins
OVERVIEW OF MI cont.

11. PLATELETS
Adhesion, Activation, and Aggregation

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. PLATELET Cont.

14. PLATELET ADHESION

15. PLATELET ADHESION Cont.
• adhering platelets undergo a
dramatic conformational
change to an irregular sphere
with multiple philopodious
increasing their surface area
contact.

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. PLATELET ACTIVATION Cont.

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. PLATELET AGGREGATION Cont.

20. ASPIRIN
(Low dose)

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. • 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. SYNTHESIS

24. STRUCTURAL ACTIVITY RELATIONSHIP
Acetylsalicylic Acid
Acetylated organic molecules exhibit increased
ability to cross the selectively permeable
blood–brain barrier.

25. MECHANISM OF ACTION

26. MECHANISM OF ACTION cont.

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. 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. 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. ADVERSE EFFECTS
• Bronchospasm: inhibition of COX pathway
activates the 5-lipoxygenase pathway

31. ADVERSE EFFECTS cont.
• Gastrointestinal upset and Haemorrhage

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. 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. 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. • 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. 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. 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. 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. CONCLUSION cont.

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. THANK YOU