Anticoagulants Flashcards
Describe the intrinsic pathway of the coagulation cascade
- Abnormal / damaged surface
- Kininogen released
- Formation of XIIₐ from XII
- Formation of XIₐ from XI
- Formation of IXₐ from IX
- Formation of Xₐ from X (VIIIₐ catalyst)
Describe the extrinsic pathway of the coagulation cascade
- Trauma / tissue damage
- Formation of VIIₐ from VII
- Formation of Xₐ from X (tissue factor catalyst)
Describe the common pathway of the coagulation cascade
- Formation of thrombin (IIₐ) from prothrombin (II) (Xₐ and Vₐ catalyst)
- Formation of fibrin (Iₐ) from fibrinogen (I)
- Formation of cross-linked fibrin clot (XIIIₐ catalyst)
Name 4 types of anti-coagulant drugs
- Heparin
- Coumarins
- Direct Thrombin Inhibitors
- Direct Factor Xₐ Inhibitors
Where do anticoagulants tend to target?
Veins
What are 2 types of heparin?
- Unfractionated (UFH)
2. Low molecular weight (LMWH)
Give an example of a LMWH drug
Enoxaparin sodium
Name 2 reasons why may LMWH drugs be preferable to UFH
- Longer duration
2. More predictable anticoagulant effect
Describe the mechanism of action of heparin
- Binds to and activates anti-thrombin III (ATIII)
- LMWH-ATIII complex inactivates Xₐ
- UFH-ATIII complex inactivates Xₐ and thrombin
Why are heparin drugs not administered orally?
Large, highly charged molecules so cannot be absorbed by the GIT
Describe the ADME of UFH
- Given IV (or subcutaneously)
- Immediately active
- T½ = 40-90 minutes
- T½ increases at higher dose as metabolic pathways in liver saturate
Describe the ADME of LMWH
- Given subcutaneously
- Longer T½ (once or twice daily dose)
- Renal excretion
- Caution in renal failure
What 3 clinical conditions may heparin be used to treat?
- Thromboembolic disease
- Acute coronary system
- Acute peripheral arterial occlusion
Name 2 uses of heparin other than treatment of clinical conditions
- Prevention of thromboembolic disease
2. Extracorporeal circuits (haemodialysis)
Why are heparins used instead of warfarin in pregnancy?
Heparin molecules are too large to cross the placenta
What are 5 adverse effects of heparin?
- Haemorrhage
- Reduced aldosterone secretion (hyperkalaemia)
- Osteoporosis and alopecia (rarely)
- Hypersensitivity reactions
- Thrombocytopenia
What is thrombocytopenia?
Reduced platelet count
How is UFH monitored?
- UFH given as IV bolus then infusion adjusted by activated partial thromboplastin time
How does APTT allow for the adjustment of UFH?
- APTT uses thromboplastin with no tissue factor activity
- Tests intrinsic and final common pathways
How can LMWH monitoring be carried out?
- LMWH does not affect APTT
- If need to assess, effect can measure Factor Xₐ activity
- Rarely done due to predictability
Give an example of a coumarin drug
Warfarin
Describe the mechanism of action of warfarin
- Inhibitor of Vitamin K epoxide reductase
- Prevention of regeneration of reduced Vitamin K
- Blocks synthesis of Vitamin K-dependent clotting factors
What are 3 uses of warfarin?
- Prophylaxis and treatment of thromboembolic disease
- Prophylaxis in atrial fibrillation
- Prophylaxis with prosthetic heart valves fitted
What value is used to monitor warfarin?
International Normalised Ratio
What are 5 adverse effects of warfarin?
- Haemorrhage
- GI upset
- Teratogen
- Alopecia
- Skin necrosis
Name 5 contraindications of warfarin
- Pregnancy
- Active bleeding
- Recent peptic ulcer
- Uncontrolled severe hypertension
- Bacterial endocarditis
What 4 things can cause variation in warfarin effects?
- Diet
- Disease
- Genetic variation
- Drug interactions
What 3 diseases can cause a variation in warfarin effects?
- Acute liver disease
- Congestive heart failure
- Small bowel disease
What 2 results of genetic variation can cause a variation in warfarin effects?
- Vitamin K epoxide reductase
2. Cytochrome P450-2C9
Name 4 drugs which increase the effects of warfarin
- Metronidazole
- Erythromycin
- Fluconazole
- Cimetidine
Name 3 drugs which reduce the effect of warfarin
- Rifampicin
- Barbiturates
- Carbamazepine
Name a type of drug which is used as a safer alternative to coumarin drugs
Direct Acting Oral Anticoagulants (DOAC)
Name 2 examples of DOAC drugs and their targets
- Dabigatran - Thrombin IIₐ inhibitor
2. Apixaban - Direct Xₐ inhibitor
What are 3 clinical uses of DOAC drugs?
- Treatment of thromboembolic disease
- Prophylaxis of thromboembolic disease
- Prophylaxis of stroke in non-valvular atrial fibrillation
What are 5 adverse effects of DOAC drugs?
- GI upset
- Abdominal pain
- Dyspepsia
- Thrombocytopenia
- Haemorrhage
Name 5 drugs which interact with DOAC drugs
- Other anticoagulants (Warfarin)
- Significant enzyme inhibitors (Fluconazole)
- NSAIDs (Naproxen)
- P-gp1 enzyme inhibitors (clarithromycin)
- P-gp1 enzyme inducers (carbamazepine)
Name 3 advantages of DOAC drugs compared to warfarin
- Orally available with faster onset
- No need for monitoring INR
- Less toxicity and interactions
Name 3 disadvantages of DOAC drugs compared to warfarin
- More frequent dosing required
- Lack of reversal agents
- Less known about efficacy and safety
What are 4 contraindications of DOAC drugs?
- Pregnancy
- Artificial heart valve present
- Liver disease
- Malignancy
How do fibrinolytic drugs function?
Activate conversion of plasminogen to plasmin which dissolves fibrin strands of clot
Name 2 examples of fibrinolytic drugs
- Streptokinase
2. Alteplase
What are 2 clinical indications of fibrinolytic drugs?
- Given IV for acute pulmonary embolism
2. Reduce mortality early post myocardial infarction or ischaemic stroke
Name 4 side effects of fibrinolytic drugs
- Bleeding
- Breakaway embolus formation
- Reperfusion arrhythmias
- Hypersensitivity reactions
How do anti-fibrinolytic (pro-coagulant) drugs function?
Inhibit the activation of plasminogen to plasmin and/or stabilise fibrin clot
Name 2 examples of anti-fibrinolytic drugs
- Tranexamic acid
2. Desmopressin
What is the mechanism of action for tranexamic acid?
Synthetic analogue of lysine which binds to plasminogen preventing plasmin from binding to and degrading fibrin
What is the mechanism of action of desmopressin?
Modified form of vasopressin which activated V₂ receptor coupled to stimulation of van Willibrand’s factor release from endothelium
What are 2 side effects of anti-fibrinolytic drugs?
- GI upset
2. Hypotension
What are 2 clinical indications of anti-fibrinolytics?
- Control persistent haemorrhage after tooth extraction
2. Given with Factor VIII as standard therapy for haemophilia
