Anticoagulants, antiplatelet and antifibrinolytic drugs Flashcards
What is the process of haemostasis?
- Constriction of damaged vessels
- Mechanical blockage of the hole by a platelet plug
- Coagulation cascade
- Fibrinolysis
What stimulates platelet aggregation? （4 points)
ADP
Thromboxane A2
Fibrinogen
Thrombin
What is thrombolysis?
Fibrin mesh prevented from increasing and slowly dissolved by the enzyme plasmin
What can be used to prevent or treat atherosclerosis as well as arterial and venous thrombosis?
Antiplatelet therapy
Anticoagulant therapy
Thrombolytic therapy
What are the different types of antiplatelet drugs?
Cyclooxygenase inhibitors
ADP receptor antagonists
Adenosine re-uptake inhibitors
What are some indications for antiplatelet therapy?
Previous myocardial infarction
Acute myocardial infarction
Previous stroke or TIA
Acute stroke
Stable angina
Intermittent claudication
Atrial fibrillation
What are some examples of antiplatelet drugs?
Aspirin
Clopidogrel
Prasugrel
Dipyridamole
What roles do antiplatelet drugs play in acute cardiac events?
Reduce the risk of complications eg aspirin in unstable angina
Improve prognosis eg aspirin in acute MI
What is the mechanism of aspirin?
Irreversibly inhibits the synthesis of thromboxane A2 in the platelet by blocking the enzyme cyclooxygenase
What is thromboxane A2?
A prostaglandin that promotes platelet aggregation
How long does the effect of aspirin last?
7-10 days
How can dental professionals manage the increased risk of postoperative haemorrhage in patients who take aspirin?
Limit initial treatment area
Consider carrying out treatments with higher post-op bleeding complications in a staged manner, where possible, over multiple visits
Local measures (packing with haemostatic agent eg Surgicel, suturing)
Aspirin (___mg/day) is used therapeutically for long-term maintenance or ___________ in patients with established CVD/post-___________ __________ surgery as well as reducing the risk of _______________ disorders.
75, prophylaxis, coronary bypass, thromboembolic
What are some contraindications to aspirin?
Allergy
Age <12y/o (risk of Reye’s Syndrome)
Active peptic ulceration
Recent gastrointestinal bleeding
Recent intracranial haemorrhage
Bleeding disorders
Severe liver disease
Warfarin
How does clopidogrel work?
ADP receptor antagonist
Inhibits ADP-induced platelet aggregation
How is clopidogrel safer than aspirin?
Lower risk of gastrointestinal bleeding
Less haematological toxicity
When is clopidogrel prescribed in combination with aspirin?
For patients suffering from acute coronary syndrome
In the prevention of atherosclerotic events in peripheral artery disease, or following MI or stroke
If complications occur whilst on aspirin, what can be prescribed alternatively?
Clopidogrel
Dipyridamole is a __________ and _________ __________ inhibitor as well as a potent __________. It modifies various aspects of platelet function such as _________, _________ and __________,
Phosphodiesterase, adenosine reuptake, vasodilator,
adhesion, aggregation, survival
Dipyridamole is used as an _______ for oral anticoagulants for the prophylaxis of ________ associated with prosthetic heart valves. It is also used as an alternative or an ________ to aspirin following a __________ or transient ischaemic attack (TIA).
Adjunct, thromboembolism, adjunct, stroke
Heparin works as an anticoagulant by enhancing the activity of ______________ III, which neutralises _________ ___________ IXa, Xa, XIa, XIIa. This inhibits ________ by inactivating __________, therefore impairing _______ function.
Antithrombin, clotting factors, thrombin, prothrombin, platelet
Why can heparin only be given parenterally?
Heparin is a large, highly ionised molecule that is poorly absorbed from the gut
Is heparin given in low or high doses subcutaneously?
Low
What dosage is heparin given intravenously?
High doses
Where is heparin metabolised in?
The liver
Where are heparin’s metabolites excreted?
Via the kidney
After intravenous injection, how long does it take for heparin to work?
Immediate onset of action
How are low molecular-weight heparins (LMWH) given?
Subcutaneously
What is used to monitor the effectiveness of anticoagulation of heparin?
aPTT (activated partial thromboplastin time)
What can reverse the effects of heparin/what can be given when heparin causes haemorrhage?
Protamine sulphate (1mg for every 100 units of heparin)
What are low molecular weight heparins (LMWH)?
Short chains of polysaccharide
What are the advantages of LMWH?
Once daily dosing
No need to monitor aPTT
Smaller bleeding risk
Reduced risk of thrombocytopenia
Lower risk of allergy
Subcutaneous administration
Outpatient use (deep vein thrombosis and pulmonary embolism no longer require hospitalisation)
What are the unwanted effects of heparin?
Haemorrhage, most commonly in GIT
Transient thrombocytopaenia
Allergy
Long term may cause osteoporosis, alopecia and hypoaldosteronism
Impaired liver function
What is warfarin?
Coumarin-derived oral anticoagulant
How does warfarin work?
Inhibits vitamin K-dependent clotting factors (II, VII, IX and X)
What are the pharmacokinetics of warfarin?
Absorbed by GI tract
Extensively protein bound (98%)
Plasma half-life is 35-37 hours
Metabolised in the liver
Metabolites excreted in the urine and faeces
What is warfarin used for?
Prevent deep vein thrombosis
Treat pulmonary embolism
Prevent risk of embolisation in patients with atrial fibrillation
Prevent emboli from developing on prosthetic heart valves
What drugs does warfarin interact with (and should be avoided from prescribing together)?
Aspirin
Fluconazole, miconazole (antifungal)
Erythromycin (antibiotic)
Metronidazole (antibiotic)
Will patients need to stop their anticoagulant therapy before undergoing dental surgical procedures?
No, if INR < or = 4
If INR>4, what can be done before patients undergo dental surgical procedure?
Consult with the prescriber of warfarin to adjust the dose eg by stopping for a couple of days prior to the surgical procedure
Is the risk of stopping anticoagulant therapy greater than the risk of prolonged bleeding?
Yes
What are thrombolytics?
Plasminogen activators
Promote the breakdown of thrombin by activating plasminogen to form plasmin
What are some examples of thrombolytics?
Streptokinase
Alteplase
What are some indications of accelerated thrombolysis?
Peripheral arterial thrombosis
Coronary arterial thrombosis/myocardial infarction
Venous thromboembolic disease
When should INR be checked?
When a procedure that involves a risk of significant bleeding is to be carried out
What are some examples of direct oral anticoagulants (DOAC’s)?
Dabigatran
Rivaroxaban
How does dabigatran work?
Thrombin inhibitor
How does rivaroxaban work?
Direct factor Xa inhibitor
Is the activity of dabigatran reflected in the INR?
No, therefore there is no point checking the patient’s INR
What is the advantage of using dabigatran compared to warfarin?
LInear dose-response with dabigatran. Warfarin has a lot of complications due to its being highly protein-bounded.
Why do haematologists like DOAC’s?
More predictable response
What is the negative aspect of DOAC’s?
Cannot check their activity using INR
According to SDCEP, what procedures are classed under low risk of bleeding for patients taking DOACs?
Simple extractions (1-3 teeth)
Incision and drainage
Detailed periodontal examination
RSI
Restorations with sub-gingival margins
According to SDCEP, what procedures are classed under higher risk of bleeding for patients taking DOACs?
Complex (surgical)/adjacent (teeth side by side) extractions
Flap raising procedures
Gingival re-contouring
Biopsies
How to manage patients taking dabigatran undergoing higher-risk procedures?
If dabigatran is taken twice a day, miss morning dose and take evening dose - providing it is >4 hours after haemostasis
How to manage patients taking rivaroxaban undergoing higher-risk procedures?
Delay dose to 4 hours post haemostasis
