Anticoagulants Flashcards
heparin sulfate
Indirect Thrombin Inhibitor
Catalyzes antithrombin activity
Linear polysaccharide so has to be give parenterally
Pentasaccharid structure is active
Binds antithrombin, causes conformational change that results in activation through increase in flexibility of REACTIVE SITE LOOP
Inhibits
IIA
IXA
XA
Source: Extracted from poricne/bovine sources
Mixture of smaller molecular weight fragments
Can be toned down to low molecular weight heparin (<7,000 MW)
INDICATION:
- DVT or PE
- Useful in prophylaxis of venous thrombosis and in cases of DIC
Toxicity:
Bleeding, allergy, thrombosis, and osteoporosis
Heparin induced thrombocytopenia (systemic hypercoaguable state that occurs in UFH for a 7 days
Never administer IM (hematoma)
Requires close monitoring (PTT)
Reversal initiated by protamine sulfate
Removed from blood by:
- Saturable: Reticuloendothelial system
- Non-Saturable: RENAL
rivaroxaban
Anticoagulant
New
Oral administer
Factor Xa Inhibitor
No monitoring needed
Short half-life
NO GOOD REVERSAL
Maximum inh. of factor Xa occurs four hours after dose
Once daily dose
Liver, Renal, and Fecal biliary clearance
warfarin
Anticoagulant
Blocks vitamin K dependent factors
II, VII, IX, X, Factor C and s
Inhibits vitamin K metabolism, disrupts POSTTRANSLATIONAL gamma-carboxylation of glutamate residues
Partially inhibits synthesis, not degradation
- Makes it depend on factor half life for effectiveness
Increased INR: 2 to 3
Patients who start warfarin are put on heparin for “warfarization
Due to levels of protein C and S dropping faster than proclotting factors
Toxicity:
- bleeding
- skin necrosis
- teratogenesis
- thrombosis
Interacts with numerous other drugs, diets, disease states
Cleared by:
- Kidney
- Liver
Reversal
- Vit K
- Fresh-frozen plasma
- Recombinant factor VIIa
protamine sulfate
Heparin antagonist
Highly cationic peptide that binds heparin to form a stable ion pair inhibiting function
menadione
Warfarin antidote
Vitamin K
dalteparin
Low molecular weight heparin
Enhances antithrombin activity on Factor X
Use cautiously in patients with renal insufficiency
Available for prophylaxis and treatment,
Do not require laboratory monitoring
Neutralize via protamine but is incomplete, does not work on fondaparinux
Metabolism: Kidney
enoxaparin
Low molecular weight heparin
Enhances antithrombin activity on Factor X
Use cautiously in patients with renal insufficiency
Available for prophylaxis and treatment,
Do not require laboratory monitoring
Neutralize via protamine but is incomplete, does not work on fondaparinux
Metabolism: Kidney
Fondaparinux
Just pentasaccharide
Enhances antithrombin activity on Factor X
Use cautiously in patients with renal insufficiency
Available for prophylaxis and treatment,
Do not require laboratory monitoring
Neutralize via protamine but is incomplete, does not work on fondaparinux
Metabolism: Kidney
argatroban
Direct Thrombin Inhibitor
Parenteral
Hepatic clearance
Small molecule
IV only due to short half life
bivalirudin
Direct Thrombin Inhibitor
Parenteral
Hepatic clearance
20% renal clearance
20 amino acid peptide
lepirudin
Direct Thrombin Inhibitor
Parenteral
Renal clearance
65 aa protein
tissue plasminogen activator
Fibrinolytic Drug
Indications:
- Massive venous thrombosis
- Pulmonary emboli
- Acute MI
Human
Non-allergenic
Shortest half life
streptokinase
Fibrinolytic Drug
Indications:
- Massive venous thrombosis
- Pulmonary emboli
- Acute MI
Streptococcus
Allergic Reactions
Long half life
Urokinase
Fibrinolytic Drug
Indications:
- Massive venous thrombosis
- Pulmonary emboli
- Acute MI
Human
Non-allergic
Short half life
abciximab
Antiplatelet Drug
Chimeric monoclonal antibody
Target platelet IIb/IIIa receptor complex
- Functions as receptor for fibrinogen and vitronectin and Von Willebrand Factor
Administer Parenterally
aspirin
Antiplatelet Drug
Inhibit synthesis of thromboxane A2 by irreversible acetylation of COX
Most commonly used antiplatelet drug
Cardiovascular indications
- Reduce TIA
- Prevent stroke
- Primary and secondary prevention of MI
- Prevention coronary restenosis following MI/fibrinolytic therapy or bypass grafting
Side Effects:
- Excessive bleeding
clopidogrel
Antiplatelet Drug
Thienopyridine derivative that reduce platelet aggregation by Irreversibly blocking P2Y12 receptor on platelets
No effect on prostaglandin metabolism
Standard for patients undergoing coronary stent
Useful in patients who cannot tolerate aspirin
Fewer adverse effects and requries less dosing than ticolpidine and is therefore preferred
Activated by: CYP2C19
- Genetic variability in this populaiton
prasugrel
Antiplatelet Drug
Thienopyridine derivative that reduce platelet aggregation by Irreversibly blocking P2Y12 receptor on platelets
No effect on prostaglandin metabolism
Standard for patients undergoing coronary stent
Useful in patients who cannot tolerate aspirin
Fewer adverse effects and requries less dosing than ticolpidine and is therefore preferred
Prasugerel decreases platelet aggregation more rapidly and consistently
Effective in MOST INDIVIDUALS
Activation through HYDROLYSIS NOT OXIDATION
ticlopidine
Antiplatelet Drug
Thienopyridine derivative that reduce platelet aggregation by Irreversibly blocking P2Y12 receptor on platelets
No effect on prostaglandin metabolism
Standard for patients undergoing coronary stent
Useful in patients who cannot tolerate aspirin
Adverse Effect:
- Nausea
- Dyspepsia
- Diarrhea
- Hemorrhage
- Leukopenia (1%)
tirofiban
Antiplatelet Drug
IIb/IIIa inhibitor
Target receptor complex which functions as receptor for fibrinogen, vWF, and vitronectin
Smaller molecule with similary properties to eptifibatide
Administer parenterally
