Anti-Thrombotics (Anti-Coagulants & Anti-Platelets) Flashcards
Anti-Coagulants
= Blood thinners that delay blood clotting
DOACS = Warfarin, Rivaroxaban/Apixaban, Dabigatran
PARENTERAL = Heparin, LMWH (Dalteparin, Enoxaparin), Fondaparinux
* DOACS*
Direct Factor Xa (Protease) Inhibitors
Drugs = Rivaroxaban, Apixaban
Mechanism = inhibit liver-made Factor Xa (protease)
Factor Xa = cleaves prothrombin –> thrombin (CF)
Uses = VTE, PE, DVT, AF/Stroke
+ No blood test required for PT
- INC. risk of GI bleed = dark brown/black/red stools
Vitamin K Antagonist
Drug = Warfarin
Mechanism:
= Inhibits enzyme Vitamin K epoxide reductase
= Carboxylation of glutamic acid residues
= Inhibits PT (Factor II), CF’s (VI, IX, X) activation
Uses = DVT, PE, AF, Heart Valve replacement
+ Vitamin K antagonist
- INC. risk in bleeding (provide VK antidote)
- Low VK = high PT = INC. bleeding risk
PARENTERAL
Unfractioned Heparin (UFH)
= Mucopolysaccharides (short duration, rapid onset)
Mechanism:
= Bind to activate Factor Xa + thrombin
= Activate anti-thrombin III by INC. affinity for serine proteases
LMWH
Drugs = Enoxaparin, Dalteparin, Fondaparinux (SC injection)
Mechanism = bind to Factor Xa but not thrombin
Uses = VTE, DVT, hospital prophylaxis, PE, ACS
Difference between UFH & LMWH?
= UFH binds to Factor Xa and thrombin
= LMWH binds to Factor Xa only
Ant-Platelets
= Keep clots from forming by keeping blood clots from sticking together
Uses = MI, stent, CABG, TIA, Stroke
Aspirin
Mechanism:
= Irreversible COX-inhibitor (acetylates COX enzymes)
= Selectively inhibit thromboxane production
= Reduces platelet aggregation ability
Dose = 75mg/day
Uses = ACS, MI (75mg daily + 300mg LD), stroke
- GI tract irritation (give with PPI for long term)
- Increased bleeding risk
- Hypersentivity reactions
Clopidogrel
Mechanism:
= Irreversible purine antagonist
= Prodrug activated by CYP2C19 in liver
= Binds to P2Y2 receptor to block calcium induced release of ADP
Uses = ACS, stents, CVS, AF
- Bleeding, dyspepsia, diarrhoea
- (Prodrug) CYP2C19 interactions = DEC. efficacy (thus ovoid Omeprazole)
Ticagrelor
Mechanism:
= Reversible purine antagonist
= Binds to P2Y2 receptor at allosteric site
= Not a prodrug, so doesn’t need hepatic activation
+ Faster onset than Clopidogrel
+ First choice
+ Easier to stop pre-surgery
- Dyspnea, bleeding
Thrombolytics
Drugs = Alteplase, Streptokinase
Mechanism = convert plasminogen to plasmin (degrades fibrin strands)
Alteplase = selective for fibrin bound plasminogen
Statins
Drugs = Simvastan, Atorvastatin Mechanism: = Inhibit HMG-CoA Reductase = Prevents HMG-CoA --> Mevalonic acid conversion = Reduce cholsterol levels
+ Effective in evening time (once in evening)
- Muscle pain/cramps
- DON’T TAKE CLARYTHROMYCIN!
Which of the following drugs could be used to treat deep vein thrombosis?
Dalteparin
An 80 year old man is bought to the emergency department by his daughter whio is his carer. She explains to you that noticed a small amount of blood in his urine (haematuria) earlier today which is confirmed on the urine dipstick. His blood pressure is normal and he feels well. He is currently taking warfarin for thromboprophylaxis as he has a diagnosis of atrial fibrillation. His target INR is 2-3 and a month ago was 2.7. You request an emergency INR which is reported as 8.2.
Which option would provide the most appropriate immediate course of action?
Give vitamin K by slow intravenous infusion
A 75 year old gentleman is admitted with left sided upper limb weakness for 2 hours that then completely resolves. He is seen by the stroke team who diagnose a transient ischaemic attack and suggest simvastatin 40mg amongst other medication for secondary prevention.
Which of the following options would be most appropriate to communicate to the patient?
When taking clarithromycin, the statin should be stopped
Which of the following enzymes are inhibited by statins to reduce plasma cholesterol?
HMG-Co-reductase
ou are called about a 67 year old woman with an INR of 6.1 (target 2-3). She has a past medical history of myocardial infarction and atrial fibrillation. She appears well and examination reveals no bleeding. She has completed a course of erythromycin for a chest infection one week ago. Her current prescription is bisoprolol (2.5 mg oral daily) and warfarin 3mg daily.
Select the most appropriate option with regard to her anticoagulation.
Omit warfarin for 2 days and recheck her INR
Which dose regimen is the most appropriate for the administration of oral statins?
Once daily in the evening
What effect will an inhibitor of the liver enzyme CYP2C9 have on the INR of a patient stabilised on warfarin?
Increase the INR (+ INC. plasma concentration)
What is the mechanism of action for the anticoagulant effects of warfarin?
Vitamin K epoxide reductase inhibitor
Which of the following drugs is a thrombolytic agent selective for fibrin bound plasminogen?
Alteplase
Which of the following drugs is an irreversible purine receptor antagonist?
Clopidogrel
