Thrombolytic Agents

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Thrombolytics: MOA - Clot Demolition Crew

  • Primary Goal: Rapid dissolution of existing intravascular thrombi by initiating fibrinolysis.
  • Core Action: Convert plasminogen (inactive proenzyme) to plasmin (active enzyme). 📌 Plasmin Pulverizes Pathologic clots!
  • Plasmin's Role: A serine protease that degrades the fibrin mesh of the clot into soluble fibrin degradation products (FDPs).
  • Activators:
    • Endogenous: e.g., tissue Plasminogen Activator (t-PA).
    • Exogenous (Drugs): Directly/indirectly activate plasminogen.

⭐ Thrombolytics achieve their effect by converting plasminogen to plasmin, which then degrades fibrin clots.

Fibrinolysis pathway diagram

Thrombolytics: Agents - Fibrin's Nightmare

Key agents used to dissolve intravascular clots by converting plasminogen to plasmin, which degrades fibrin.

AgentGen.Fibrin SpecificityAntigenicityt½ (min)Key Features
Streptokinase1stLowHigh20-25Bacterial origin, allergy, hypotension
Urokinase1stLowLow15-20Human origin, less antigenic
Alteplase (tPA)2ndHighLow4-6Recombinant, short t½ (infusion), fibrin-bound
Reteplase (rPA)3rdModerate (<Alteplase)Low13-16Longer t½, bolus admin., better penetration
Tenecteplase3rdHighest (>Alteplase)Low20-24↑ Fibrin specificity, PAI-1 resistant, single bolus

📌 Mnemonic (Generations): Silly Unicorns Always Race Turtles. (1st: SK, UK; 2nd: Alteplase; 3rd: Reteplase, Tenecteplase).

Thrombolytics: Uses - Clots: Time to Go!

These drugs dissolve existing fibrin clots by converting plasminogen to plasmin. Administered IV.

Key Indications & Therapeutic Windows:

  • Acute MI (STEMI):
    • Within <12 hours of onset (ideal <6 hours).
    • Door-to-needle time goal: <30 minutes.
    • PCI preferred if available timely (<90-120 min from first medical contact).
  • Acute Ischemic Stroke:
    • IV Alteplase within <4.5 hours of symptom onset.

    ⭐ For acute ischemic stroke, IV thrombolysis (e.g., with alteplase) is indicated within 3 to 4.5 hours of symptom onset in eligible patients.

  • Massive Pulmonary Embolism (PE):
    • If hemodynamically unstable.
  • Extensive Deep Vein Thrombosis (DVT):
    • E.g., phlegmasia cerulea dolens, iliofemoral DVT.

📌 Mnemonic: "Time is Tissue!" Critical windows save lives.

  • Stroke: <4.5h
  • STEMI: <12h

Monitoring:

  • Primary risk: Bleeding (intracranial, GI).
  • Neuro status, vital signs, signs of reperfusion (e.g., arrhythmia resolution in MI).

t-PA mechanism of action on thrombus

Thrombolytics: Risks - Handle With Care!

  • Adverse Effects:
    • Bleeding: Major risk (ICH, GI).
    • Allergy/Anaphylaxis (esp. Streptokinase).
    • Hypotension.

⭐ The most devastating adverse effect of thrombolytic therapy is intracranial hemorrhage (ICH); meticulous patient selection is crucial.

  • Contraindications:
    AbsoluteRelative
    Active bleed, Prior ICHSevere HTN (>185/110 mmHg)
    Recent surgery/trauma (<3 wks)Recent internal bleed (<2-4 wks)
    Intracranial neoplasm/AVM, Aortic dissectionPregnancy, Active PUD, Anticoagulants (INR >1.7)
  • Bleeding Management:
    • Stop thrombolytic.
    • Supportive care.
    • Reversal: Aminocaproic acid, Tranexamic acid, FFP, Cryoprecipitate.

High‑Yield Points - ⚡ Biggest Takeaways

  • Mechanism: Convert plasminogen to plasmin for fibrinolysis.
  • Examples: Streptokinase (antigenic), Alteplase (t-PA, fibrin-selective), Tenecteplase.
  • Major adverse effect: Bleeding (e.g., intracranial hemorrhage).
  • Antidotes: Aminocaproic acid or Tranexamic acid.
  • Key indications: Acute MI, ischemic stroke (window period), PE.
  • Contraindications: Active bleeding, recent surgery/trauma, hemorrhagic stroke history, severe uncontrolled HTN.

Practice Questions: Thrombolytic Agents

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Flashcards: Thrombolytic Agents

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