3-Antithrombotic Agents Flashcards
Aspirin (MOA, dose dep effects)
- MOA: irreversible acetylation of serine residue of COX-1
- Dose Dep:
- Low dose = COX 1 specific inhibitor (only decreases TXA2 synthesis)
- High dose = binds other COX forms (decrease synthesis of other PGs as well)
Thienopyridines (MOA & Name 4 types)
MOA: Antiplatelet drugs: Irreversibly inhibit ADP receptors on platelets (thus inhibit activation of GPIIb/IIIa receptors/platelet aggregation)
- Ticagrelor
- Ticlopidine
- Clopidogrel
- Prasugrel
Ticlopidine (Class, MOA, Metabolism)
- Class: Antiplatelet: irreversibly inhibit ADP receptors
- MOA: P2Y12 ADP platelet receptor
- Metabolism: Prodrug (parent drug inactive)
Clopidogrel (Class, Metabolism)
Plavix:
1. Class: Antiplatelet: irreversibly inhibit ADP receptors
2. Metabolism: Primarily metabolized by CYP 2C19
(Some genetic populations lack this enzyme: drug stuck in prodrug form)
Ticagrelor (Class, Metabolism, Other)
- Class: Antiplatelet: REVERSIBLY inhibit ADP platelet receptor
- Metabolism: NOT a prodrug (direct acting)
- Other: Faster onset/Greater inhibition of platelet aggregation than Clopidogrel
Name 3 GPIIb/IIIa Antagonists
- Abciximab (monoclonal antibody)
- Tirofiban (fibrinogen analogue)
- Eptifibatide (fibrinogen analogue
(inhibit final common pathway for platelet aggregation)
What 3 situations are Anti-Platelet drugs used for?
- MI prophylaxis
- Arterial occlusions leading to stroke
- Arterial platelet issues (venous platelets like DVT would use Warfarin)
Which GPIIb/IIIa antagonist is not specific for GPIIb/IIIa & undergoes clearance via reticuloendothelial cells?
Abiciximab
Eptifibatide & Tirofiban are cleared renally and are specific
What are GP2b/3a antagonists indicated (2)?
- Treatment of unstable coronary syndromes
2. Adjunct to reduce risk of periprocedural MI following percutaneous coronary interventions
Warfarin (MOA)
Anti-Coagulant:
- Inhibits VitK-epoxide reductase -> decreases Vit-K dep molecules:
- Coagulation factors II, VII, IX & X
- Protein C & S (which inhibit factors V & VIII)
How is Warfarin transported throughout the blood? Significance?
- 99% plasma protein bound (inactive)
- 1% free (active)
- Drugs w/ high plasma protein binding capacity (DM drug Sulfonylureas) kick Warfarin off plasma proteins and increase free, active Warfarin = increased bleeding risk
Warfarin (metabolism & 3 associated alleles)
Metabolism: CYP 2C9
Alleles:
- 1* = normal warfarin metabolized
- 2** = 70% warfarin metabolized (30% less warfarin broken down) = increased risk of bleeding
- 3*** = 10% warfarin metabolized (90% less warfarin broken down) = super increased risk of bleeding
When would you use Warfarin?
Venous thrombolytic issues (DVT)
Warfarin (advantages & disadvantages)
Advantages: - Oral - Cheap Disadvantages: - Bleeding - Cross placenta (switch pregnant women to Heparin)
What 2 products would you administer for Warfarin reversal? Which has a more immediate action?
- Fresh Frozen Plasma + Vitamin K
- FFP = more immediate action (Vit K takes time to induce synthesis of coagulation factors)
What is the HASBLED score?
- Used in clinic to measure risk of warfarin
- Max score of 9
- Score over 3 = high risk of bleeding
- HASBLED = Hypertension (1), Abnormal renal/liver fxn (2), Stroke (1), Bleeding (1), Labile INRs (1), Elderly (1), Drugs/Alcohol (2)
Name 7 drugs that inhibit CYP 2C9? Significance w/ relation to Warfarin?
“Pams Off”
- Paroxetine
- Amiodarone
- Metronidazole
- Sulfonamides
- Omeprazole
- Fluconazole
- Fluoxetine
Decrease metabolism, thus increase active blood levels of Warfarin = increase risk of bleeding
Name 3 drugs that induce CYP 2C9? Significance w/ relation to Warfarin?
RPC
- Rifampin
- Phenobarbital
- Carbamazepine
Increase metabolism, thus decrease active blood levels of warfarin = decrease risk of bleeding
4 herbals that potentiate warfarin effects?
- Garlic
- Ginger
- Ginko
- Feverfew
What is INR? Target INR?
- INR = normalizes PT ratio by adjusting for the variability in the sensitivity of different thromboplastins
- Target INR: 2-3
Name 3 Warfarin dosing recommendations
- Individualize dose according to INR
- Loading dose controversial (may increase bleeding/may offer more rapid protection)
- Low initiation doses are recommended for elderly/frail/hepatic failure/malnourished patients
Heparin (MOA, Conventional vs. LMWH)
- MOA: bind/enhance Antithrombin III (inhibits FII (thrombin) & X)
- Conventional Heparin aka Unfractionated Heparin (UFH):
- Binds ATIII & Thrombin directly - Low molecular weight heparin (LMWH):
- Only binds ATIII
- Higher specificity for Factor X
How would you reverse Heparin?
Protamine Sulfate
PS is a base & Heparin is an acid
Name 3 Low Molecular Weight Heparins (LMWH)
TED
- Tinzaparin
- Enoxaparin
- Dalteparin
Which LMWH has a lower incidence of Hep-Induced-Thrombocytopenia?
Enoxaparin
Fondiparinux (Class/Target)
- Class: Synthetic Heparin
2. Accelerates ATIII binding to FX ONLY (not FII)
Name 3 Direct Thrombin Inhibitors (DTI)
BALD
- Bivalrudin (derived from saliva of leech)
- Argatroban
- Dabigatran (Pradaxa)
How do you reverse Direct Thrombin Inhibitors?
You don’t. They have no antidotes.
Name 2 oral Xa antagonists. When are these indicated?
- Roxirivaban
- Abixaban
Indications:
- Thromboprophylaxis in A-fib
- Reduce recurrent events after acute coronary syndromes
Name 3 examples of fibrinolytic drugs.
TUS
- tPA
- Urokinase
- Streptokinase
Name 2 anti-fibrinolytic drugs
- Aminocaproic acid
2. Tranexamic acid
