Pharmacology
Cardiovascular
What is the mechanism of aspirin as an anti-platelet:
Answer:
Aspirin irreversibly inhibits cyclooxygenase and blocks the platelet production of thromboxane A2 (TXA2), thus inhibiting platelet aggregation.Aspirin (Antiplatelet)
Pharmacology / Cardiovascular
Last Updated: 7th June 2022
Antiplatelet drugs decrease platelet aggregation and inhibit thrombus formation in the arterial circulation, because in faster-flowing vessels, thrombi are composed mainly of platelets with little fibrin.
Mechanism of Action
Aspirin irreversibly inhibits cyclooxygenase and blocks the platelet production of thromboxane A2 (TXA2), a powerful inducer of platelet aggregation. The endothelial cells of the vascular wall produce a prostaglandin, prostacyclin (PGI2), which is a physiological antagonist of TXA2, causing inhibition of platelet aggregation. Platelets cannot synthesise new enzyme but the vascular endothelial cells can, and the balance is shifted to the anti-aggregatory effects of PGI2.
Indications
Low-dose aspirin may be indicated in:
- Primary prevention of cardiovascular events in some people when the risk is particularly high
- Secondary prevention of cardiovascular events in people with:
- Angina
- Myocardial infarction
- Stroke and transient ischaemic attack
- Peripheral arterial disease
- Atrial fibrillation (although anticoagulants are usually used)
Contraindications
Low-dose aspirin should be avoided in:
- People with a history of true hypersensitivity to aspirin or salicylates (symptoms of hypersensitivity to aspirin or salicylates include bronchospasm, urticaria, angioedema, and vasomotor rhinitis)
- People with active pathological bleeding, such as peptic ulcer or intracranial haemorrhage
- People with suspected stroke, until intracranial haemorrhage has been excluded by brain imaging
- People with haemophilia or another haemorrhagic disorder (including thrombocytopenia)
- Children younger than 16 years of age (due to risk of Reye's syndrome)
Cautions
Low-dose aspirin should be used with caution in:
- People who may be at high risk of increased bleeding — for example those receiving treatment with warfarin, NSAIDs, corticosteroids, or other drugs known to increase bleeding
- People with asthma (may precipitate bronchospasm)
- People with uncontrolled blood pressure
- If using for primary prevention of cardiovascular events, do not initiate aspirin until blood pressure is less than 150/90 mmHg
- For secondary prevention, benefits of antiplatelet treatment outweigh risks, and treatment should not be delayed while controlling blood pressure
Side Effects
Low-dose aspirin may result in:
- Increased absolute risk of major bleeding, major gastrointestinal bleeding, and intracranial bleeding
- Gastrointestinal adverse effects including bleeding, ulceration and dyspepsia
- Bronchospasm and asthma attacks in patients with asthma
Interactions
The risk of bleeding is increased when low-dose aspirin is combined with other drugs that can increase the risk of bleeding such as other antiplatelet drugs, NSAIDs, oral and parenteral anticoagulants, selective serotonin reuptake inhibitors (SSRIs) and corticosteroids. Consider the need for gastroprotection with a proton pump inhibitor (such as omeprazole) or a histamine antagonist (such as ranitidine).
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
