15) Anticoagulant Therapy Flashcards
What are the constituents of Virchow’s triad?
Hypercoagulability
Endothelial damage
Stasis
What factors/conditions can affect hypercoagulability?
Smoking OCP Heart valves Malignancy Protein C and S deficiency SLE
What factors/conditions can cause endothelial damage?
Atheroma
HTN
Toxins (cigarettes)
What factors/conditions cause stasis?
Venous - immobility
Arterial - cardiac abnormality (AF)
What is the mechanism of action of warfarin?
Inhibits production of vitamin K dependent clotting factors
What are the vitamin K depending clotting factors?
Prothrombin (II), VII, IX, X
Describe the onset and offset time of warfarin:
Slow onset Slow offset (need to stop 3 days before surgery)
Describe the pharmacokinetics of warfarin (ADME):
Good GI absorption
Heavily protein bound
Metabolised in liver by cytochrome P450
What are some adverse effects of warfarin?
Teratogen (trimester 1) and can cause brain haemorrhage (T3)
Excessive bleeding - intracranial, epistaxis, GI
How can warfarin be monitored?
Prothrombin time
INR
What is the prothrombin time?
Citrated plasma clotting time
What is the INR?
Standard value of PT between labs
What drugs can inhibit the hepatic metabolism of warfarin?
Amiodarone, quinolone, metronidazole, alcohol
What drugs increase warfarin’s effect?
Aspirin
Cephalosporins (reduce vit K from gut bacteria)
NSAIDs
What drugs are inhibitors of warfarin?
Anti-epileptics
Rifampicin
St John’s Wort
When is warfarin used?
DVT, PE, AF, prosthetic valves
How can the action of warfarin be reversed?
Stop warfarin and give: IV vit K, fresh frozen plasma or prothrombin complex concentrate
Describe the structure of heparin:
Glycosaminoglycan with a glucose backbone
What is the mechanism of action of unfractionated heparin?
Activate anti-thrombin III that de-activates factors Xa, IIa, IXa
What clotting factor is affected by low molecular weight heparin?
Xa
How do unfractionated and LMWH heparin vary in structures?
Unfractionated: variable length heparin chains (20kDa)
LMWH: small chains (4kDa)
How do unfractionated and LMWH heparin vary in route of administration?
Unfractionated: IV
LMWH: SC
Why is unfractionated heparin able to inhibit thrombin, when LMWH can’t?
To catalyse inhibition of thrombin by ATIII, heparin has to bind to molecules simultaneously and only unfractionated is large enough to do this
Describe the onset and offset time of heparin:
Rapid onset and offset of action
Describe the pharmacokinetics of LMWH (ADME):
Poor GI absorption
High bioavaliability
Long half life
How can unfractionated heparin be monitored?
Activated partial thromboplastin time
When is heparin used?
Prevention of thromboembolsim (post op, immobility)
DVT/PE and AF
Acute coronary syndromes
Pregnancy
What are some of the adverse effects of heparin?
Bruising/bleeding
Heparin induced thrombocytopenia
Osteoporosis
Explain heparin-induced thrombocytopenia:
Heparin and PF4 on platelets are immunogenic, IgG complexes form activating more platelets until platelets are depleted and get thromboses in area
How should heparin induced thrombocytopenia be managed?
Stop heparin and add hirudin
How can heparin be reversed?
Stop heparin and if actively bleeding give protamine sulphate
Name some antiplatelet drugs:
Aspirin
Clopidogrel
Dipyridamole
Glycoprotein IIb/IIIa inhibitors
What is the mechanism of action of aspirin?
Inhibition of thromboxane A2 production by COX enzymes
What is the mechanism of action of clopidogrel?
Inhibits P2Y12 ADP receptor involved in platelet activation
When is clopidogrel given?
ACS and PCI
What is the mechanism of action of dipyridamole?
Phosphodiesterase inhibitor - positive ionotrope and vasodilator
When is dipyridamole given?
Secondary prevention of stroke
How do glycoproteins IIb/a receptor antagonists work?
Block fibrinogen from binding to these receptors which causes platelet aggregation
When are glycoprotein IIa/b receptor antagonists used?
High risk ACS, post PCI
