Coagulants, Anticoagulants and Thrombolytics Flashcards
Aspirin
- Oral antiplatelet agent
- Irreversible inhibition of COX
*reduces prostaglanding synthesis (and thus thromboxane A2), which reduces platelet aggregation
- Use: FDA evidence supports aspirin in preventing ANOTHER heart attack or stroke in pts who have ALREADY had one
NSAIDs
- Oral antiplatelet agent
- Reversible inhibition of COX
*reduces prostaglandin synthesis, which reduces platelet aggregation
*aspirin is the COX inhibitor of choice due to its irreversible inhibition
Ticlopidine
- Oral antiplatelt agent
MOA
- Inhibits platelet function by inducing a thrombasthenia-like (decreased platelet function) state
- Irreversibly inhibits ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions (same as clopidogrel)
USE
- Prevention of stroke in pts. w/ history of TIA or thrombotic stroke (only if intolerant of or aspirin fails), and in combination w/ aspirin to prevent coronary stent thrombosis
SIDE EFFECTS
- Nausea, dyspepsia, diarrhea, hemorrhage, leukopenia and TTP
Clopidogrel (PLAVIX)
- Oral antiplatelet
MOA
- Prodrug that requires activation via cytochrome P450 enzyme isoform CYP2C19
*FDC recommends genotyping pts. to identify a SNP in CYP2C19 that reduces metabolism of clopidogrel (pts. would be at risk of cardiovascular events)
*also, drugs that impari CYP2C19 function (ex. omeprazole (proton pump inhibitor), shoud be used w/ caution
- Irreversible block (irreversible covalent binding) of the ADP receptor on platelets
*irreversibly inhibits ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions
USE
- Unstable angina or non-ST-elevation acute MI (NSTEMI) in combination w/ aspirin; for STEMI; or recent MI, stroke, or peripheral artery disease
- Cardiovascular conditions prone to clot formation
SIDE EFFECTS
- Thrombotic thrombocytopenic purpura (TTP) and only rare neutropenia (so usually preferred over ticlopidine)
Prasugrel (EFFIENT)
- Oral antiplatelt
MOA
- Inhibits platelet activation and aggregation mediated by the ADP receptor
USE
- Like clopidogrel acute coronary syndrome (w/ or w/o aspirin)
SIDE EFFECTS
- Major and minor bleeding risk increased over clopidogrel
CONTRAINDICATIONS
- Pts w/ TIA history or stroke due to increased bleeding risk
Ticagrelor (BRILINTA) MOA
- Oral antiplatelt agent
MOA
- Reversible antagonist of ADP receptor
*does not require bioactivation = faster onset
USE
- Acute coronary syndromes in combination w/ low dose aspirin
*PLATO trial (compared to clopidogrel in acute coronary syndrome pts.; it is superior in primary end point of cardiovascular death or stroke (but increased noncardiac surgical bleeding)
SIDE EFFECTS
- (In addition to bleeding) shortness of breath (at rest), after a small amount of exercise, or after any physical activity; chest pain; and fast, slow, pounding, or irregular heartbeat
GPIIB/IIIA
- Receptor on platelets that fibrinogen binds to
- Ligands for it contain an Arg-Gly-Asp (RGD) sequence motif
*important for binding
Abcixamab (REOPRO)
- Injectable antiplatelet agent
MOA
- GpIIb/IIIa antagonist (chimeric monoclonal antibody against IIb/IIIa complex)
USE
- Percutaneous coronary intervention and acute coronary syndromes
SIDE EFFECTS
- Bleeding
Tirofiban (AGGRASTAT)
- Injectable antiplatelet agent
MOA
- GpIIb/IIIa antagonist
USE
- non-ST elevation acute coronary syndrome
*short half-life (continuous infusion)
SIDE EFFECTS
- Minor bleeding
Dipyridamole (PERSANTINE)
- Vasodilator that also inhibits platelet function (oral or IV)
MOA
- Inhibits adenosine uptake and inhibits cGMP phosphodiesterase (cAMP and cGMP are inhibitory to platelet adhesion and aggregation)
USE
- When used alone has little or no effect
*in combination w/ aspirin to prevent cerebral ischemia
*in combination w/ warfarin as a prophylaxis of thromboemboli for prosthetic heart valves
SIDE EFFECTS
- Chest pain, angina exacerbation (IV), abnormal ECG, headache (IV), dizziness, ST-T changes abdominal discomfort (oral), extrasystole
Cilostazol (PLETAL)
- Antiplatelet agent
MOA
- A new phosphodiesterase inhibitor (also promote vasodilation and inhibits platelet aggregation)
USE
- Claudication (cramping pain in the leg induced by exercise, typically caused by peripheral vascular disease)
SIDE EFFECTS
- hedache, diarrhea, abnormal stools, infection, rhinitis, pharyngitis, dizziness, palpitations, peripheral edema, back pain, dyspepsia
CONTRAINDICATIONS
- CHF of any severity
Heparin
- Injectable indirect thrombin inhibitor
- IV or subQ
- Mixture of sulfated mucopolysaccharides
- Binds to endothelial cells and variety of plasma proteins
MOA
- Enhances the activity of anti-thrombin III (AT-III)
- AT-III inhibits factors thrombin (IIa), IXa, Xa, XIa and XIIa
- High-molecular weight heparin fractions have high affinity for AT-III and inhibit all “3”, most especially IIa and Xa
*w/ Xa inactivated less IIa made too
- Low-molecular weight fractions mainly inhibits Xa
*enoxaparin, dalteparin and tinzaparin
*similar efficacy as unfractionated w/ increased bioavailability in injection site and less frequent dosing
USE
Prevention and treatment of:
- deep venous thrombosis (in vivo)
- pulmonary embolism (in vivo)
- arterial thrombosis (in vivo)
- hemodialysis (in vitro)
- indwelling vascular catherters (in vitro)
- laboratory blood samples (in vitro)
SIDE EFFECTS
- Unwanted bleeding (mucous membranes, open wounds, intracranial, GI), allergic reactions, hair loss
- Heparin induced thrombocytopenia > skin necrosis
- Long-term use assoc. w/ osteoporosis and fractures (mineralocorticoid deficit)
- Close monitoring needed
Protamine Sulfate
- Heparin antagonist
- Stably complexes w/ heparin
Fondaparinux (ARIXTRA)
- Injectable indirect thrombin inhibitor
- IV or subQ
- Related to heparin
MOA
- Enhances the activity of anti-thrombin III
- Only enhances AT-III ability to inactive Xa; thus less thrombin formed (indirect thrombin inhibitor)
USE
- DVT/acute PE (treatment and prophylactic) and acute coronary syndrome
SIDE EFFECTS
- Some cross-reactivity w/ heparin antibodies, so some cases of HIT; anemia, fever, nausea, rash, constipation, edema, headache, insomnia, vomiting
- No monitoring needed
Bivaliruden (ANGIOMAX)
- Injectable direct thrombin inhibitor
- IV (no IM injection)
MOA
- specific and reversible bivalent direct thrombin inhibitor
- Rapid on and off (t1/2 = 25min.)
USE: (w/ aspirin)
- Unstable angina in pts. undergoing percutaneous transluminal coronary angioplasty (PTCA)
- Percutaneous coronary intervention (PCI) w/ provisional use of GpIIb/IIIa inhibitor
- W/ or at risk of HIT or heparin-induced TTP and thrombosis syndrome
SIDE EFFECTS
- back, general pain, nausea, hemorrhage, headache, hypotension, injection site pain, insomnia, pelvic pain, hypertension, anxiety, vomiting, bradycardia, dyspepsia, abdominal pain, fever, nervousness
