Pharmacology - Anticoagulants Flashcards
Anticoagulants – venous thrombosis include:
Heparins
Vitamin K antagonist
Direct thrombin inhibitors
Direct Xa inhibitors
Cox inhibitor
P2Y12 (ADP receptor) inhibitors
GPIIbIIIa (fibrinogen receptor) inhibitors
Phosphodiesterase inhibitors
These are what kinds of drugs?
Antiplatelet Drugs - arterial thrombosis
T/F: Anticoagulants do not lyse already formed clots, but prevent their further propagation
True
Use TPA for acute thrombosis
use Anticagulants to prevent thromboses in low shear environments is heart in a-fib, valvular disease and valve replacement
These are \_\_\_\_\_\_\_ drugs: Aspirin Dipyramole Clopidogrel Presugrel Ticagrelor Abciximab Eptifibatide Tirofiban
Antiplatelet drugs - used in arterial thrombosis
These are _____ drugs:
Alteplase
Tenecteplase
Reteplase
Fibrinolytic drugs
lyse clots acutely
Class Warfarin:
Vitamin K antagonist
MOA Warfarin:
Blocks Vitamin-K-dependent gamma-carboxylation of factors II, VII, IX, X, protein C and S
- 7-9-10-2* remember this
- *does not affect already synthesized factors
Thrombin is aka:
activated factor 2 (clotting cascade)
Unfractionated and low molecular weight heparin act on what parts of the clotting cascade:
10a, thrombin
Apixaban and Rivaroxaban act on what part of the clotting cascade?
They are direct 10a inhibitors
Reversibly bind active site of 10a
Therapeutic Uses:
Apixaban
Rivaroxaban
DVT/PE prophylaxis
Side effects:
Apixaban
Rivaroxaban
Bleeding (duh, they’re anticoagulants)
Skin necrosis is a side effect of what anticoagulant?
Warfarin
Other side effects:
bleeding;
thrombosis is a warfarin side effect bc of protein C lowering
Therapeutic use of warfarin for long-term anticoagulation is particularly useful bc it lacks what toxicity?
Warfarin has no major organ toxicities, so OK for lifelong therapy
Mode of administration of unfractionated heparin is IV for what 2 reasons?
Big molecule
short half life
T/F: Dosing of unfractionated heparin can be unpredictable bc it binds to everything basically, ie cell surface glycoproteins, vitronectin, platelet factor four etc.
True
The binding to factor 4 makes a highly immunogenic compound that is responsible for HIT
MOA Unfractionated Heparin
Binds antithrombin
Heparin-AT complex inactives IIa, Xa, IXa, XIa, XIIa
Uses: unfractionated heparain
prevention/tx of venous thromboembolism
MOA:
Dalteparin
Enoxaparin
LMWH
inhibits thrombin less effectively than factor Xa
longer half life, less monitoring necessary
What anticoagulant is preferred for use in pregnancy?
Enoxaparin
indirect thrombin inhibitor
LMWH
monitor with heparin assay instead of PTT (unfractionated heparin)
What test do you use to monitor warfarin therapy?
PT (expressed as INR)
Too low warfarin can cause clots bc:
warfarin also inhibits the carboxylation of anticoagulants protein S and C, which may induce thromboembolism (for example at the onset of therapy)
To avoid it, warfarin is always started while on heparin.
Bivalirudin
Argatroban
Dabigatran
These drugs are:
Direct thrombin inhibitors
MOA: Direct thrombin inhibitors
Bivalirudin
Argatroban
Dabigatran
Inactivate thrombin both bound and unbound to fibrinogen
Bind to the catalytic site of thrombin
Immediate onset
No antidote (under development)
Therapeutic Uses:
Bivalirudin
Argatroban
percutaneous coronary intervention (PCI)
monitor with PTT
Therapeutic Use: Dabigatrain
DVT/PE
Afib
What anticoagulantis preferred for use in cancer patients?
Unfractionated heparin
Therapeutic uses:
Dalteparin
Enoxaparin
Use in pregnancy;
unstable angina
Dosing of warfarin is difficult because:
- Competes with Vitamin K
– Vitamin K is influenced by diet, diarrhea, laxatives, antibiotics, fat absorption - > 99% is bound to albumin – Interference by other drugs
- Hepatic metabolism
– Enhanced by barbiturates, rifampin
– Inhibited by metronidazole, amiodarone, disulfiram……. - Fluctuation of the cascade
How would you reverse the effects of warfarin?
- Stop warfarin
- Give vitamin K
- Give Prothrombin factor concentrate (Kcentra: Factors II, VII, IX, X, Protein C+S)
- Give fresh frozen plasma (FFP) (until recently, this was common practice)
Name the direct Xa inhibitors.
Rivaroxaban
Apixeban
reversibly bind active site of Xa
for DVT/PE prophylaxis
Even though Apixaban did well in clinical trials, still the only anticoagulant preferred for valvular disease is:
warfarin
MOA: Fibrinolytics
Alteplase
Tenecteplase
Reteplase
activate plasminogen –> plasmins
lyse clots
for STEMI
Therapeutic Use: Alteplase
STEMI, acute stroke, PE
How is Tenecteplase differenct from the other fibrinolytics (Alteplase, Reteplase)?
Clot-specific, long half-life
Therapeutic Uses: Antiplatelet Drugs Aspirin Dipyramole Cilostazol Clopidogrel
Myocardial infarction (MI)
Stroke/Transient Ischemic attack (TIA)
Peripheral arterial disease (PAD)
Percutaneous coronary intervention (PCI)
MOA Abciximad
MAB against GP2b/3a
MOA:
Dipyramole
Cilostazol
Phophodiesterase (PDE) inhibitor –> increase in platelet cAMP
Dipyridamole --Used alone or with aspirin --Secondary stroke prevention Cilostazol – Peripheral arterial disease – Also reduces smooth muscle proliferation and intimal hyperplasia
MOA Clopidogrel
P2Y12 (ADP Receptor) Blocker
prevent and treat ACS, stroke, PVD, angina, stent
T/F: Dabigatran is a prodrug.
True
Direct thrombin inhibitor
metabolized in the liver to active form
Take a moment to read about the αIIbβ3- Integrin (GPIIb/IIIa, Fibrinogen Receptor) Inhibitors (antiplatelet family).
They are Parenteral drugs
Abciximab
– monoclonal antibody: Fab’2 fragment of chimeric mouse/human – immune response prevents repeated use
– effective for 24-48 hours
Eptifibatide
– rattlesnake venom peptide fibrinogen analog
– rapid onset, short half-life and reversible action
Tirofiban
– tyrosine derivative fibrinogen analog
The effects of cytokines, such as IL-1, are mediated by receptors that cause:
tyrosine phosphorylation
other autacoids – histamine, serotonin, the kinins, and eicosanoids – bind to G- protein-coupled membrane receptors that are themselves not tyrosine kinases
The NSAIDs inhibit the cyclooxygenases, which convert arachidonic acid into prostacyclins, prostaglandins, and thromboxanes. They do not inhibit:
lipoxygenase, which converts arachidonic acid into the leukotrienes.
