IC3- Thrombolytics (fibrinolytics)

Question 1

What is the MOA of fibrinolytics (esp alteplase)?

Answer 1

It is a recombinant tissue-type plasminogen activator (tPA) that binds to plasminogen → conversion of plasminogen to plasmin → mediates fibrinolysis

Question 2

When are thrombolytics used?

Answer 2

Only used in dire situations when a clot threatens irreversible damage or death as they increase risk of embolism

Question 3

What is the reversal agent of (-teplases)?

Answer 3

Tranexamic acid and aminocaproic acid (compete for lysine binding site on plasminogen and plasmin → block interaction with fibrin)

Used to reverse states of excessive fibrinolysis (excessive bleeding)

Question 4

What is the advantage of the -teplases over the -kinases?

Answer 4

-teplases bind preferentially to clot-associated plasminogen, activating plasmin at the clot

Question 5

ADEs of -teplases? (7)

Answer 5

• *Haemorrhage/ bleeding
• Ventricular arrhythmias
• Hypotension
• Oedema
• Cholesterol embolisation
• Venous thromboembolism
• Hypersensitivity and anaphylaxis (rare but severe)

Question 6

Contraindication of -teplases? (3)

Answer 6

• Active bleeding
• Hx of intracranial haemorrhage
• Recent (within last 3 months) intracranial/ intraspinal surgery, serious head injury or stroke

Question 7

Caution in? (7)

Answer 7

Caution in pts with:
- Major surgery within 10 days
- Risk of bleeding (eg. peptic ulcer)
- Cerebrovascular disease
- Mitral stenosis
- Atrial fibrillation
- Acute pericarditis
- Subacute bacterial endocarditis

Question 8

DDIs of -teplases?

Answer 8

↑ bleeding risk 🩸:
- Antiplatelets (esp dipyridamole, aspirin) and anticoagulants (esp warfarin, heparin)

↓ alteplase level (hence fibrinolytic activity):
- *Nitroglycerin