Term 2 Pharm - Anti-Coagulation Drugs Flashcards
What are the major adverse effects of anti-coagulants?
- Major adverse effect is bleeding (frequently life-threatening or fatal)
- Account for the highest number of adverse events of all drug classes
- But they are still lifesaving
What are the Anti-platelet agents?
- Cyclooxygenase inihibitors
- ADP-receptor inhibitors
- GPIIb/IIIa antagonists
What are the Anticoagulants?
- Heparin
- Vitamin K antagonists
- Parenteral direct thrombin inhibitors
- Target specific oral agents (TSOACs)
What causes Thrombosis?
Thrombosis occurs when there is a breakdown in the balance between thrombogenic factors and protective mechanisms
What are common Thrombogenic Factors?
- Endothelial cell disruption
- Activation of platelets
- Activation of blood
- coagulation
- Inhibition of fibrinolysis
- Stasis
What are some Protective Mechanisms against thrombosis?
- Intact endothelium
- Neutralization of coag factors by endogenous - factors
- Dilution of clotting factors by blood flow
- Clearance of activated factors by the liver
- Fibrinolysis
Definition of a Thrombus
Thrombus = Blood Cells + Fibrin Clot
Definition of an Embolus
Embolus = Thrombus far from home (Thrombus = Blood Cells + Fibrin Clot)
Arterial Thrombus
- Occurs in association with pre-existing vascular disease, e.g., atherosclerosis in areas of disturbed flow
- Occurs under conditions of high flow
- Predominantly platelet aggregates bound by fibrin strands
- Causes tissue ischemia by obstructing flow or embolizing to distal circulation
*Arterial clots are usually formed by vascular damage
Venous
- Generally lower limbs; other sites especially with associated thrombophilia
- Occurs under conditions of low flow, stasis
- Composed of red cells and fibrin with relatively fewer platelets
- Obstruct venous return; venous inflammation; pulmonary emboli
*Venous clots are usually formed by stasis
Common Indications for Anticoagulation
Primary prevention of thrombosis (Venous) - Hospitalization - Surgery - Immobilization - Cancer
(Arterial)
- Stroke in atrial fibrillation
- Myocardial infarction
- Mechanical heart valves
- Peripheral arterial occlusion
Secondary prevention
Treatment of acute thrombosis
Choice of agent depends on mechanism of thrombosis
Type of anti-coag depends on venous or arterial thrombosis, explain…
For Arterial – anti-platelets
For Venous – down regulation of coag
Describe Primary Hemostasis (Primary Hemostatic Plug)
- Platelet Adhesion
- To sub endothelium
- Via collagen – vWF – platelet receptor GpIb - Activation/degranulation/shape change
- Collagen
- Soluble agonists - Aggregation
- Via fibrinogen -platelet receptor GpIIb/IIIa - Support of coagulation
- Exposure of PS/PE
Anti-Platelet Agents
Agents
- COX inhibitors
- ADP P2Y12 receptor antagonists
- Clopidogrel
- Prasugrel
- Ticagrelor
- Dipyridimole
Indicated for prevention of arterial thrombosis
Prolong bleeding time/PFA-100
Acetylsalicylic Acid (Aspirin: ASA)
- Aspirin inhibits platelet aggregation by irreversible
acetylation of platelet cyclo-oxygenase (COX) - Aspirin prevents formation of thromboxane A2 and therefore inhibits TXA2 mediated platelet aggregation
- Rapid absorption, peak platelet effect at 1 hour (3-4 hours for enteric coated)
- Half-life is 15-20 minutes BUT effect on platelets is IRREVERSIBLE
(Lasts for entire 7-10 day lifespan of platelets. 10-15% of circulating platelets are replaced every 24 hours. Must discontinue the drug 10 days in advance of invasive procedures for complete restoration of normal platelet function) - No effect on platelet adhesion
Aspirin Adverse Effects
B/c irreversible COX (cyclooxygenase) inhibitor
inhibitor!
- Major side effects are gastrointestinal and are dose-related
(GI upset, ulcer, bleed) - Not associated with major bleeding in patients with normal baseline hemostasis
- Bleeding is increased with concurrent use of anticoagulants, some supplements
- Exacerbates bleeding tendency in patient with bleeding disorders (be careful for surgery)
- Elderly are more susceptible
Reversible COX Inhibitors
- Nonsteroidal anti-inflammatory agents
(Ibuprofen)
(Naproxen) - Reversible inhibition of COX
- Platelet function is restored when the drug is cleared
For ibuprofen
- Rapid absorption of oral dose; peak effect 1-2 hours
- Half-life is ~2 hours
- Essentially all of the drug is excreted (urine) 24 hours after the last dose
- Holding the drug for 1-2 days preoperatively is sufficient
For naproxen
- Half life is 12-17 hours
- Must discontinue several days before surgery
Uses for Aspirin as an Antithrombotic Agent
- Primary and secondary prevention of arterial thrombosis
- Inferior to anticoagulants for stroke prevention in atrial fibrillation, mechanical heart valves
- Reduces disorders associated with placental insufficiency (e.g., preeclampsia)
- Efficacious for prevention of venous thromboembolism in limited situations (e.g., hip fracture surgery)