CPT14 - Antiplatelet and Fibrinolytic Drugs

Question 1

5 features of cyclo-oxygenase inhibitors as an anti-platelet

Examples
Mechanism
Efficacy x3
Usage x4
Contraindications x4

Answer 1

1.) Examples - aspirin (75mg)

2. ) Mechanism - irreversibly inhibits COX-1 enzymes
   - prevents formation of TXA2 from arachidonic acid
   - thromboxane A2 is a platelet aggregating agent
3. ) Efficacy
   - low dose aspirin (75mg) is the antiplatelet
   - inhibition lasts lifespan of the platelet (7-10 days) because there is no nuclei to produce more COX-1
   - COX-1 polymorphisms –> variable efficacy
4. ) Usage
   - always given after an MI w/ an ADP antagonist
   - secondary prevention of stroke, TIA, ACS
   - after primary PCI (stent) to ↓ischaemic complications
   - long term uses requires gastric protection (PPI)
5. ) Contraindications
   - ↑bleeding time: haemorrhagic stroke, GI bleed
   - Reye’s syndrome and hypersensitivity
   - T3 of pregnancy (early closure of ductus arteriosus)

Question 2

6 features of ADP receptor antagonists as an anti-platelet

Examples x3
Mechanism
PK/PD x3
Usage
Contraindications x3
Caution x2

Answer 2

1. ) Examples - clopidogrel, prasugrel, ticagrelor,
   - all administrated orally

2.) Mechanism - prevents action of fibrinogen and vWF
- blocks binding of ADP to P2Y12 receptors, inhibiting
GPIIb/IIIa receptors needed for fibrinogen and vWF

3. ) PK/PD
   - clopidogrel and prasugrel are pro-drugs
   - they are also irreversible inhibitors of P2Y12 whilst ticagrelor acts reversible at a different site
   - clopidogrel is slow onset whilst others are rapid onset
4. ) Usage - always given for up to 12 months
   - w/ aspirin after an MI (NSTEMI or STEMI w/ stent)
   - secondary prevention of stroke, TIA
   - prasugrel + aspirin in ACS patients undergoing PCI
   - clopidogrel when aspirin is contraindicated
5. ) Contraindications
   - active bleeding, history of intracranial haemorrhages
   - before surgery: clopidogrel 7 days, ticagrelor 5 days
6. ) Caution
   - CYP inhibitors/inducers
   - hepatic and renal problems (activation and clearance)

Question 3

4 features of glycoprotein IIb/IIIa inhibitors as an anti-platelet

Example
Mechanism x2
Usage
Contraindications x5

Answer 3

1. ) Example - abciximab
   - administrated by bolus IV infusion
2. ) Mechanism - blocks binding of fibrinogen and vWF
   - antibody blocks GPIIb/IIIa receptors
   - most effective anti-platelet since it targets the final common pathway –> ↑risk of bleeding

3.) Usage - specialist use in high risk PCI

4. ) Contraindications - bleeding
   - dose adjustment needed for body weight
   - thrombocytopenia, hypotension, bradycardia

Question 4

5 features of phosphodiesterase inhibitors as anti-platelets

Examples
Mechanism x2
Usage x2
Cautions x3
Side-Effects x3

Answer 4

1.) Examples - dipyridamole

2. ) Mechanism - 2 different ways:
   - ↓ cAMP degradation –> ↓expression of GPIIb/IIIa
   - inhibits cellular reuptake of adenosine which inhibits platelet aggregation via A2 receptors
3. ) Usage
   - secondary prevention of ischaemic strokes and TIA
   - prophylaxis of thromboembolism after valve replacemnt
4. ) Cautions
   - w/ adenosine (too much adenosine)
   - w/ anti-hypertensives (can cause hypotension)
   - w/anti-coagulants (risk of bleeding)
5. ) Side Effects
   - flushing, headache, hypersensitivity

Question 5

4 features of fibrinolytic agents

Examples x2
Mechanism
Usage x2
Contraindications x3

Answer 5

1.) Examples - streptokinase and alteplase

2. ) Mechanism - increase fibrin degradation
   - activate plasminogen to form plasmin
3. ) Usage
   - after an MI where primary PCI can no longer be used
   - alteplase used in acute ischaemic stroke <4.5 hours
4. ) Contraindications
   - bleeding, history of intracranial haemorrhages
   - streptokinase only used once (antibodies develop)

Question 6

Management of a myocardial infarction

Initial Therapy for an NSTEMI or Unstable Angina x8
Initial Therapy for a STEMI x10
Long-Term Management of a STEMI x5

Answer 6

1. ) Initial Therapy for an NSTEMI or Unstable Angina
   - MONAA: morphine, oxygen, nitrates, anti-emetics, aspirin
   - ticagrelor (grace score >3%), enoxaparin (LMWH)
   - ß-blockers (CCB if contraindicated)
2. ) Initial Therapy for a STEMI
   - oxygen, nitrates, morphine, antiemetic
   - aspirin, clopidogrel or ticagrelor (prasugrel if PCI)
   - PCI or fibrinolytic w/ heparin to remove the clot
   - PCI used if within 12 hrs of onset of symptoms and can be given within 90mins of diagnosis
   - GPIIb/IIIa inhibitor in high-risk patients undergoing PCI
   - ß-blockers and ACEi
3. ) Long-Term Management of a STEMI
   - ACEi, ß-blocker, statin, (aspirin + ticagrelor/clopidogrel)