14) Antiplatelets

Question 1

In healthy endothelium how is platelet aggregation inhibited ?

Answer 1

Prostacyclin produced and released by endothelial cells bind to platelet receptors
=> Increases [cAMP] in platelets
=> Decreases Ca2+ prevent platelet aggregation
=> Decrease platelet aggregatory agent
=> Stabilises GPIIb / IIIa receptors

Question 2

COX - Inhibitor
> Example  
> MOA 
> Side effects 
> Interactions 
> When is it indicated
> Dose

Answer 2

Aspirin
> Inhibits COX-1 Mediated production of thromboxane A2 and reduced platelet aggregation

Side effects:
> Bleeding Time prolonged => Haemorrhagic Stroke ; GI Bleeding
> Reye’s Syndrome
> Hypersensitivity
> 3rd Trimester - Premature closure of the Ductus Arteriosus

Interactions:
> Other antiplatelet and anticoagulants

Indication:
> 2o prevention of Stroke, TIA and Acute Coronary Syndromes
> 2o prevention of MI in stable Angina or Peripheral Vascular Disease
> often prescribed with other antiplatelet agents
> Gastric protection for long term use in at risk patients

Dose = 300mg loading dose (Chewable)

Question 3

ADP Receptor Antagonists 
> Example
> MOA 
> Side effects 
> Interaction
> Indications

Answer 3

Examples:
> Clopidogrel - Slow onset ; irreversible
> Prasugrel - Rapid onset ; irreversible
> Ticagrelor - Rapid onset ; reversible

MOA:
> Inhibit binding of ADP to p2y12 receptor -> Inhibit activation of GPIIb/IIIa receptors

Side effects:
> Bleeding
> GI upset - Dyspepsia and Diarrhoea
> Possible renal and hepatic Impairment

Interaction:
> Requires CYPs so any drug that uses up affects its cation
> Use other PPIs
> Co prescribed with other antiplatelet and anti coagulant or NSAIDs - Bleeding
> Stop 5-7 days prior to surgery

Indications:
> Clopidogrel used when aspirin is contraindicated
> NSTEMI and STEMI patients with stent up to 12 months
> Stop before CABG
> Ischaemic stroke and TIA long term 2o prevention
> Prasugrel with Aspirin in ACS patients undergoing PCI (Percutaneous Coronary Intervention) up to 12 months

Question 4

Gylcoprotein IIb/IIIa inhibitors 
> Examples 
> MOA 
> Side Effects 
> Interactions

Answer 4

Examples
> Abciximab

MOA:
> Blocks binding of fibrinogen and von Willebrand factor
> Antibody body blocks GPIIb/IIIa receptors

Side Effects:
> Bleeding
> Adjust disorder for body weight, thrombocytopenia , hypotension, bradycardia

Interactions:
> Other anti platelet and anticoagulant

Question 5

Phosphodiesterase Inhibitors 
> Example 
> MOA 
> Side Effects 
> Interactions
> Indication

Answer 5

Example:
> Dipyridamole

MOA:
> Inhibits cellular reuptake of adenosine
=> Increased [Adenosine]
=> Inhibits platelet aggregation via A2 receptors
> Phosphodiesterase inhibitor which prevents cAMP degradation -> inhibit Expression of of GPIIb/IIIIA

Side Effects:
> Flushing
> Headache
> Hypersensitivity

Interaction:
> Caution with anti hypertensives, anti platelets and anticoagulants

Indications:
> 2o prevention of ischaemic stroke and TIAs
> Adjunct for prophylaxis of thromboembolism following valve replacement

Question 6

Fibrnolytic Agents
> Examples
> MOA
> Side effects

Answer 6

Examples
> Streptokinase
> Alteplase

MOA:
> Dissolve fibrin meshwork of thrombus

Side effects:
> Bleeding
> Streptokinase can only be used once as anti bodies develop