Fibrinolytics Flashcards
What is haemostasis?
Cessation of blood loss from a damaged vessel.
What is thrombosis?
A pathological condition resulting from inappropriate activation of haemostatic mechanisms.
What characterizes venous thrombosis?
Usually associated with stasis of blood; small platelet component and large component of fibrin.
What characterizes arterial thrombosis?
Usually associated with atherosclerosis; large platelet component.
Define thrombus.
A blood clot formed in situ within the vascular system, impeding blood flow.
What is the role of thrombin in blood clotting?
Converts soluble fibrinogen to an insoluble meshwork of fibrin.
What are the two limbs of the clotting cascade?
In vivo (extrinsic) pathway - Rapid; in vitro (intrinsic) pathway - Slow.
What is the function of calcium ions in coagulation?
Essential for activation of factors IXa, VIIa, and Xa.
What is haemophilia A caused by?
Lack of factor VIII.
What is the primary use of antithrombotic drugs?
To treat thrombosis.
What are the three classifications of antithrombotic drugs?
- Antiplatelet drugs
- Anticoagulants
- Fibrinolytic agents
What is the action of heparin?
Inhibits plasma antithrombin III.
What are common adverse effects of heparin?
- Bleeding
- Thrombocytopaenia
- Hypersensitivity reactions
- Osteoporosis
What is the mechanism of action of low molecular weight heparins?
Accelerates action of antithrombin III, increasing inactivation of factor Xa.
What is the main use of direct thrombin inhibitors?
Directly inhibit thrombin without relying on antithrombin III.
What is dabigatran used for?
Prevention of venous thromboembolism and stroke in atrial fibrillation.
What is the mechanism of action of warfarin?
Inhibits the reduction of vitamin K, preventing carboxylation of factors II, VII, IX, and X.
What is streptokinase and its primary use?
A plasminogen activating protein used to reduce mortality in acute myocardial infarction.
What are the adverse effects of streptokinase?
- Nausea
- Headache
- Dizziness
- Low blood pressure
- Mild fever
- Bleeding
What is epsilon amino-caproic acid (EACA)?
A lysine analogue that inhibits plasminogen activation and is used to check fibrinolysis associated bleeding.
What is the treatment for overdose of heparin?
Protamine sulfate.
Fill in the blank: The drug _______ is a recombinant tissue plasminogen activator.
Alteplase
True or False: Direct thrombin inhibitors require monitoring of activated partial thromboplastin time (aPTT).
False
What is the primary indication for using antifibrinolytic drugs?
To counteract the effect of fibrinolytic agents and bleeding due to their use.
What can rapid intravenous injection of certain drugs cause?
Hypotension, bradycardia, and possible arrhythmias.
What is a limitation of the large dose needed for specific treatments?
Tranexamic acid is mostly preferred.
What is the initial priming dose of tranexamic acid?
5 g oral/i.v., followed by 1 g hourly till bleeding stops (max. 30 g in 24 hrs).
What is the mechanism of action of tranexamic acid?
Inhibits plasminogen activation and thus prevents fibrinolysis.
List some clinical uses of tranexamic acid.
- Treat bleeding or risk of bleeding following prostatectomy or dental extraction
- Menorrhagia (excessive menstrual blood loss)
- Life-threatening bleeding following thrombolytic drug administration.
How much more potent is tranexamic acid compared to EACA?
7 times more potent.
What are the main side effects of tranexamic acid?
- Nausea
- Diarrhoea.
What can occur infrequently as a side effect of tranexamic acid?
- Thromboembolic events
- Disturbed colour vision
- Allergic reactions.
What is the typical dosage range for tranexamic acid?
10–15 mg/kg 2–3 times a day or 1–1.5 g TDS oral, 0.5–1 g TDS by slow i.v. infusion.
What are antiplatelet drugs used for?
Interfere with platelet function and are useful in the prophylaxis of thromboembolic disorders.
What receptors do platelets express on their surface?
Several glycoprotein (GP) integrin receptors.
What happens when reactive proteins like collagen react with platelet receptors?
Platelet activation and release of pro-aggregatory and vasoconstrictor mediators.
What forms a ‘platelet plug’ in arteries?
The binding of fibrinogen and von Willebrand factor (vWF) to platelet GPIIb/IIIa receptors.
In which type of thrombosis are antiplatelet drugs more useful?
Arterial thrombosis.
Which substance synthesized in the intima of blood vessels inhibits platelet aggregation?
Prostacyclin (PGI2).
What is the role of platelets in atherogenesis?
They play a role in atherosclerotic plaque formation leading to coronary artery heart disease.
What is the mechanism of action of aspirin as an antiplatelet drug?
Inhibits cyclo-oxygenase irreversibly and inhibits platelet thromboxane (TX)A2 synthesis.
What are the gastrointestinal side effects of aspirin?
Irritation of the stomach lining, gastrointestinal upset, ulcers, and bleeding.
What is clopidogrel and how does it function?
A prodrug that irreversibly inhibits P2Y12 receptors and inhibits platelet aggregation.
What is the clinical effect of clopidogrel in relation to aspirin?
Its clinical effect is additive with aspirin.
What is prasugrel used for?
Acute coronary syndrome (ACS).
How does ticagrelor differ from other antiplatelet drugs?
It is reversible but non-competitive.
What do antagonists of GPIIb/IIIa receptors do?
Inhibit diverse agonists activating GPIIb/IIIa receptors.
What is dipyridamole used for?
As a vasodilator for angina pectoris and in addition to aspirin for stroke or transient ischemic attack.
List some clinical uses of antiplatelet drugs.
- Acute myocardial infarction
- Prevention of myocardial infarction in patients at high risk
- Cerebral ischemic attack (ministrokes) or thrombotic stroke
- Prevent recurrence in atrial fibrillation.
What is the primary action of antiplatelet drugs?
To prevent arterial thrombosis.
