See our physiology of haemostasis page to understand how platelets work to form clots and why blocking ADP and glycoprotein IIb/IIIa can be helpful.

Antiplatelet drugs:

• COX 1 inhibition (aspirin)
• Platelet phosphodiesterase inhibition (dipyridamole)
• ADP binding inhibition (clopidogrel, prasugrel, ticagrelor)
• Glycoprotein IIb/IIIa receptor antagonists (abciximab, eptifibatide, tirofiban)
• Dextran 70
• Epoprostenol (Prostacyclin PGI2)

Aspirin

• Uses: Analgesia, secondary prevention, anti-inflammatory
• Presentation: Tablets and IV
• Dose: 75mg low, 300mg high
• MOA: Low dose – platelet COX inhibition only = reduced TXA2 induced platelet aggregation and ongoing vessel wall synthesis of prostacyclin and prostaglandins unaltered
• Pharmacokinetics: Weak acid, pKa =3
• Absorption: Unionised in stomach, allowing gastric absorption
• Distribution: 85% protein bound by albumin
• Metabolism: Hydrolysed by intestinal and hepatic esterases to salicylate -> further hepatic metabolism to salicylic acid and glucuronide derivatives
• Elimination: Urine, enhanced excretion in alkaline conditions
• Overdose: Presents with sweatiness, tinnitus, blurred vision, tachycardia, pyrexia, hyperventilation, initially respiratory alkalosis by direct stimulation of respiratory centre, then metabolic acidosis as more drug is absorbed. Rarely causes GI bleeds, N+V, oliguria, pulmonary oedema, coaguloapthy, hypokalaemia, hypoglycaemia, encephalopathy. Treat with activated charcoal, forced alkaline diuresis, haemo-filtration and haemo-dialysis.
• Reye’s syndrome: Aspirin linked widespread mitochondrial damage, fatty changes in liver and liver failure, encephalopathy and cerebral oedema, mortality rate 40%. Not used under 12 years of age unless specifically indicated eg Still’s disease.

Platelet phosphodiesterase inhibition

Dipyridamole

Mechanisms:

• Stops platelets adhesion to damaged vessel walls by stopping adenosine uptake
• Potentiates prostacyclin which reduces platelet activation
• At high doses, inhibits platelet phosphodiesterase activity resulting in increased cAMP levels and lower intraplatelet calcium levels – reducing release of platelet factors
• Potent coronary artery vasodilator, used in conjunction with thallium-201 during myocardial imaging

ADP binding inhibition

Clopidogrel, prasugrel and ticagrelor

Mechanism: Irreversibly prevents ADP from binding to its receptor on the platelet surface, preventing the glycoprotein IIb/IIIa receptor transforming to its active form

Used in secondary prevention, stroke, and after stenting of coronary arteries to prevent stent thrombosis

Effects start 2 hours after oral dose but effects seen after 3-7 days of treatment so stop for 7 days preoperatively to prevent bleeding

Glycoprotein IIb/IIIa receptor antagonists

Abciximab (monoclonal antibody with high affinity for platelet glycoprotein IIb/IIIa receptor) – 20 minute half life, but has residual activity in circulation for 15 days.

Eptifabide (cyclic heptapeptide with lower receptor affinity) – plasma half life of 200 minutes and 50% renal clearance.

Tirofiban (intermediate receptor affinity) renal and faecal clearance

All three given IV for patients with intermediate or high risk after acute coronary syndrome where angiography is scheduled within 96 hours.

Complications = thrombocytopaenia and bleeding risk

Dextran

Dextran 40 and 70 have anticoagulant activity by inhibiting vWF and reducing platelet adhesiveness. Improved microcirculatory flow from volume expansion. Not used clinically very often due to risk of fluid overload, allergic reactions and anaphylaxis. Cross matching by rouleaux formation is impaired (they reduce red cell aggregation). Renal failure can occur.

Epoprostenol (Prostacyclin PGI2)

Stimulates adenylate cyclase -> cAMP rises -> intracellular Ca2+ reduces -> inhibits platelet adhesion and aggregation. Additional fibrinolytic effect. Side effects: hypotension, tachycardia and headache from vasodilation.