Anti-platelet and Fibrinolytic Drugs

Question 1

List the following for: COX inhibitor

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications
• Important drug reactions

Answer 1

Anti-platelet

Aspirin

COX inhibitor

• Hepatic hydrolysis to salicylic acid
• Irreversibly inhibits COX-1 (inhibits production of thromboxane A2 and reduces platelet aggregation)
• Used at low non-analgesic doses (75 mg)
• Gastrointestinal irritation
• GI bleeding (peptic ulcer)
• Haemorrhage (stroke)
• Hypersensitivity
• Reye’s syndrome - avoid <16 years
• Hypersensitivity
• 3rd trimester (premature closure of ductus arteriosus)
  COX-1 polymorphisms - lack of efficacy in some
• Other antiplatelet and anticoagulants

Question 2

List the following for: ADP receptor antagonists

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications
• Important drug reactions

Answer 2

Anti-platelet

Clopidogrel
Prasugrel
Ticagrelor

ADP receptor antagonists
- Inhibit binding of ADP to P2Y12 receptor
- Inhibit activation of GPIIb/IIIa receptors
(Independent of COX pathway)

• Bleeding
• GI upset (dyspepsia and diarrhoea)
• Thrombocytopenia (rare)
• High bleed risk patients with renal and hepatic impairment (caution)

Requires CYPs for activation
- CYP inhibitors - omeprazole, ciprofloxacin, erythromycin, some SSRIs need to consider use of other PPIs with clopidogrel
- Ticagrelor can interact with CYP inhibitors and inducers
- Other antiplatelet and anticoagulant agents or NSAIDs (caution)
In most cases need to be stopped up to 7 days prior to surgery

Question 3

List the following for: Phosphodiesterase inhibitors

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Important drug reactions

Answer 3

Anti-platelet

Dipyridamole

Phosphodiesterase inhibitors

• Inhibits cellular reuptake of adenosine so increased [adenosine]
• Inhibits platelet aggregation via adenosine (A2) receptors
• Also acts as a phosphodiesterase inhibitor, prevents cAMP degradation to inhibit expression of GP2b/3a
• Vomitting and diarrhoea
• Dizziness
• Antiplatelets and anticoagulants
• Adenosine

Question 4

List the following for: GP2b/3a inhibitors

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Important drug reactions

Answer 4

Anti-platelet

Abciximab

GP2b/3a inhibitors

• Blocks glycoprotein 2b/3a receptors to prevent binding of fibrinogen and vWF
• Targets final common pathway
• Bleeding
• Other antiplatelets and anticoagulants

Question 5

List the following for: Fibrinolytics

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Important drug reactions

Answer 5

Alteplase (tPA) - Stroke
Streptokinase - MI

Streptokinase
Alteplase

Fibrinolytics

• Dissolve fibrin meshwork of thrombus
• Increases conversion of plasminogen to plasmin (required for fibrin clot to be broken down into fibrin degradation products)
• Bleeding
• Other antiplatelets and anticoagulants