test 4 Flashcards
1
Q
Common Characteristics of thrombolytic agents: mechanism of action
A
- All act either directly or indirectly to convert plasminogen to plasmin
* Cleaves fibrin and lyses thrombin
2
Q
Common Characteristics of thrombolytic agents: Therapeutic Use
A
- Used to treatment DVT, PE, and arterial thrombosis with MI
* Intracoronary delivery of drug to achieve revascularization
* 2 – 6 hour therapeutic window - Restore catheter and shunt function
- Dissolve clots that result in strokes
3
Q
Common Characteristics of thrombolytic agents: Adverse Effects
A
- Hemorrhage
* Do not distinguish between fibrin from unwanted thrombus and fibrin of a beneficial hemostatic plug - Contraindicated in pregnancy, CVA history, intracranial bleeding, metastatic cancer, and patients with healing wounds
4
Q
Thrombolytic Drugs: Alteplase
A
- Alteplase is formerly known as tissue plasminogen activator (tPA)
* Recombinant tPA
* Lower affinity for free plasminogen
* Binds to fibrin in a clot and converts entrapped plasminogen to plasmin
* “fibrin selective” - Approved for treatment of MI, PE, and acute ischemic stroke
- Half-life: less than 5 minutes
- May cause orolingual angioedema
* Especially with ACE inhibitors
5
Q
Thrombolytic Drugs: Reteplase
A
- Smaller derivative of recombinant tPA
- Half-life: 18-23 minutes
- Approved only for use in acute MI
- Off-label use
* DVT, PE
6
Q
Thrombolytic Drugs: Tenecteplase
A
- Recombinant tPA
- Half-life: 20-24 minutes
- Approved only for use in acute MI
7
Q
Thrombolytic Drugs: Streptokinase
A
- Extracellular protein
* Purified preparation of group C β-hemolytic streptococci - Forms active complex with plasminogen
* Converts plasminogen to plasmin - Complex also catalyzes degradation of fibrin, fibrinogen, V, VII
- Half-life: 18-25 minutes
- Rarely used due to new agents
* No longer available in US
8
Q
Thrombolytic Drugs: Urokinase
A
- Produced naturally in the kidneys
- Therapeutic urokinase
* Isolated from cultures of human kidney cells - Activates plasminogen to yield plasmin
- Half-life: ~ 12 minutes
- Approved only for lysis of PE
- Off-label use
* Treatment of acute MI, DVT, arterial thromboembolism
9
Q
Drugs Used to Treat Bleeding
A
• Aminocaproic acid (Amicar) • Tranexamic acid • Protamine sulfate • Vitamin K1 /phytonadione
10
Q
Aminocaproic acid (Amicar)
A
- Inhibits plasminogen activation, thereby inhibiting plasmin activation
* Reducing fibrinolysis - Used to treat post-op bleeding
- Adjunctive therapy in hemophilia
- Half-life: 2 hours
11
Q
Tranexamic acid
A
- Inhibits the activation of plasminogen to plasmin
- Similar to Amicar
- 10 times more potent than Amicar
- Half-life: 3 hours
- Uses: post-op bleeding and hemophilia therapy
12
Q
Protamine Sulfate
A
- Originally isolated from fish sperm
- Now produced through recombinant biotechnology
- Used to reverse the anticoagulant properties of heparin
* Binds heparin forming a stable complex
13
Q
Protamine Sulfate side effects
A
- Hypersensitivity
- Shortness of breath
- Flushing
- Bradycardia
- Hypotension (when rapidly injected)
- Weak anticoagulant (large doses)
14
Q
Vitamin K1
A
- Essential cofactor for the γ-carboxylase enzyme
* γ-carboxylation activates coagulation cofactors - Used in treatment of coagulation disorders caused by vitamin K deficiency
- Antidote for bleeding caused by coumadin therapy
- Administration: oral, SC, IV
- IV administration preferred for treatment of bleeding
* Infuse slowly – minimize hypersensitivity - 24 hours to reduce INR
15
Q
Two types of Thrombate and ATryn
A
- Thrombate III
• Made from pooled human plasma - ATryn
• Made from milk of genetically engineered goats
