anti-thrombotics, anti-coagulants, antiplatelets, and thrombolytics Flashcards
thrombosis
when a clot blocks veins or arteries and can lead to many medical conditions
clot in the brain
ischemic stroke/transient ischemic attack (TIA)
clot in the lungs
pulmonary embolism (PE)
clot in the appendages
DVT
clot in coronary artery leading to myocardial death
heart attack
hemostasis
physiologic process by which bleeding stops
intrinsic pathway- contact activation pathway
turned on when blood makes contact with collagen after trauma to a blood vessel wall
cascade starts with activation from factor XII to factor XIIa and proceeds until factor X is activated to factor Xa
intrinsic pathway- contact activation pathway
extrinsic pathway- tissue factor pathways
turned on by trauma to the vascular wall-which triggers release of tissue factor (AKA thromboplastin)
cascade starts with activation from factor VII to factor VIIa and proceeds until factor X is converted into factor Xa
extrinsic pathway-tissue factor pathway
tissue plasminogen activator (tPA)
activates conversion from plasminogen to plasmin
found in endothelial cells-continuously released but increased when stimulation of certain endothelial cells
antiplatelet drugs
primarily used to prevent arterial clots
aspirin indications
ischemic stroke, TIAs, chronic stable angina, coronary stenting, acute myocardial infarction
aspirin contraindications
use in children and teens with viral infection (Reye’s syndrome)
aspirin ADRs
GI bleeds
hemorrhagic stoke
aspirin metabolism/excretion
no renal or hepatic adjustments needed
aspirin MOA
irreversible inhibitions of COX- decreases thromboxane A2 production thus reduces platelet activation
clopidogrel
plavix
Plavix indications
acute coronary syndrome (STEMI and NSTEMI), ischemic stroke, peripheral atherosclerotic disease
Plavix US boxed warning
diminished effects in CYP 2C19 poor metabolizers
Plavix MOA
irreversible blocks P2Y12 component of ADP receptors on the platelet surface- effects last the duration of the platelet’s life
Plavix contraindications
active pathological bleeding (peptic ulcer, intracranial hemorrhage, etc.)
Plavix ADRs
bleeding
Plavix metabolism/excretion
no hepatic or renal dosage adjustment needed
must be metabolized by CYP2C19 into active drug
CYP2C19 is inhibited by PPIs
American College of Cardiology, American Heart Association, and American College of Gastroenterology issued a consensus document that PPIs may reduce the antiplatelet effects but not enough to diminish effects
prasugrel MOA
irreversibly blocks P2Y12 component of ADP receptors on platelet surface
prasugrel contraindications
active pathologic bleeding, prior TIA or stoke
prasugrel ADRs
bleeding
Prasugrel metabolism/excretion
no renal or hepatic adjustments needed
Prasugrel US Boxed Warning
Significant sometimes fatal bleeding – Avoid in patients with active pathological bleeding or a history of TIA or stroke
In patients 75 or older – use is generally not recommended – increased risk of fatal and intracranial bleeding – lacks additional benefit
Do not use in patients likely to need urgent coronary artery bypass graft (CABG) surgery – discontinue 7 days prior to surgery (most agents are 5)
Additional risk factors for bleeding – weight <60 kg, propensity to bleed or history of bleeding, concomitant medications that increase risk of bleeding (NSAIDs, warfarin, fibrinolytics)
Suspect bleeding in any patient who is hypotensive
If possible, manage bleeding without discontinuing prasugrel – discontinuing, particularly in the first few weeks post-acute coronary syndrome, increases the risk of a secondary event
Ticagrelor US Boxed Warnings
bleeding risk: avoid in patients with pathologic bleeding or history of intracranial hemorrhage
aspirin doses >100 mg daily reduce the effectiveness and should be avoided
Ticagrelor MOA
reversible P2Y12 inhibition
reduces platelet activation
Ticagrelor contraindications
active pathologic bleeding or history of intracranial hemorrhage
Ticagrelor ADRs
dyspnea
Ticagrelor metabolism/excretion
no hepatic or renal adjustments needed
Cangrelor MOA
reversible P2Y12 inhibition
reduces platelet activation
Cangrelor contraindications
significant active bleeding
Cangrelor ADRs
bleeding
Cangrelor metabolism/excretion
no renal or hepatic adjustment needed
vorapaxar MOA
PAR-1 antagonist
inhibits platelet aggregation
Vorapaxar contraindications
history of stroke, TIA, intracranial hemorrhage
active pathological bleeding
Vorapaxar ADRs
bleeding
Vorapaxar metabolism/excretion
no hepatic or renal adjustments needed
Glycoprotein IIB/IIIA inhibitors
Eptifibitide and Tirofiban
Eptifibitide and Tirofiban MOA
reversible blockade of Gp IIb/IIIa receptors on platelets and thereby inhibit the final step of aggregation
prevent aggregation stimulated by all factors including collagen, TXA2, ADP, thrombin, and PAF
Eptifibitide and Tirofiban contraindications
active abnormal bleeding within the previous 30 days or history of bleeding diathesis
history of stoke within 30 days or history of hemorrhagic stroke
major surgery within the preceding 6 weeks
Eptifibitide and Tirofiban ADRs
bleeding
Dipyridamole MOA
inhibits the uptake of adenosine into the platelets – prevents platelet activation/aggregation
Dipyridamole contraindications
Use in children and teens with viral infections (Reye’s Syndrome)
Dipyridamole ADRs
bleeding
GI disturbances
Dipyridamole metabolism/excretion
avoid use in severe liver and renal impairment
drugs for thromboembolic disorders
antiplatelets
anticoagulants
fibrinolytics
inhibit platelet activation
antiplatelets
decrease formation of thrombin
anticoagulants
promote breakdown of fibrin in thrombi
fibrinolytics
antiplatelet drugs
aspirin (NSAIDs)
P2Y12 antagonists/thienopyridines
protease-activated receptor-1 antagonist (PAR-1)
glycoprotein IIb/IIIa inhibitor
phosphodiesterase/adenosine deaminase inhibitor
anticoagulant drugs
vitamin K antagonist
antithrombin activators
direct thrombin inhibitors
direct factor Xa inhibitors
fibrinolytics
Alteplase
Tenecteplase
Retavase
warfarin
inhibits the synthesis of clotting factors
vitamin K antagonist
Warfarin
antithrombin activators
heparin, enoxaparin, fondaparinux
direct thrombin inhibitors
argatroban
bivalirudin
dabigitran
direct factor Xa inhibitors
apixaban
rivaroxaban
edoxaban
coumadin
warfarin
coumadin US boxed warnings
bleeding risk-monitor INR on all treated patients
coumadin indications
myocardial infarction, thromboembolic complications (PE, DVT, stroke, Afib, cardiac valve replacement)
coumadin MOA
vitamin K antagonist
inhibits synthesis of clotting factors II, VII, IX, and X and proteins C and S via inhibiting vitamin K epoxide reductase complex 1 (VKORC1) and decreasing activation of the factors
coumadin ADRs
bleeding
coumadin metabolism/excretion
adjusting dose in kidney function may need to happen- no robust guidelines
liver function plays a significant role in anticoagulant response-monitor INR closely
warfarin contraindications
hemorrhagic tendencies
recent or potential surgery on spine or eyes
malignant, uncontrolled hypertension
pericarditis or pericardial effusion
bacterial endocarditis
patients with high potential for non-compliance
pregnancy/breast feeding
vitamin K, phytonadione indications
hemorrhage prevention in newborns (intracranial)
warfarin antidote
vitamin K, phytonadione as a warfarin antidote
reverses hypoprothrombinemia and bleeding- perioperatively or in the case of severe bleeds
vitamin K, phytonadione MOA
required for synthesis of prothrombin and clotting factors VII, IX, and X- essential for coagulation cascade
vitamin K, phytonadione ADRs
essentially no storage- metabolism and secretion occur rapidly
vitamin K, phytonadione metabolism/excretion
no renal or hepatic adjustments needed
foods that interact with warfarin
vitamin K containing foods- decreased INR and effects- leafy greens, mayonnaise, others
foods that increase effects, alcohol, cranberries, cherries, grapefruit
warfarin drug interactions
sulfa-antibiotics
acetaminophen
carbamazepine, phenobarbital, rifampin
sulfa-antibiotics and warfarin interaction
sulfa-antibiotics displace warfarin on albumin
significant bleeding risk (Bactrim)
acetaminophen and warfarin interactions
increase INR
carbamazepine, phenobarbital, rifampin and warfarin interactions
powerful inducers in CYP system-decrease warfarin effects
heparin indications
anticoagulation- prophylaxis and treatment of thromboembolic disorders, prevention of clotting in arterial and cardiac surgery, anticoagulation for blood transfusions, extracorporeal circulation and dialysis procedures
heparin MOA
potentiates the actin of antithrombin III, inactivating thrombin and factor Xa which prevents the conversion of fibrinogen to fibrin
heparin contraindications
severe thrombocytopenia (<100,000)
history of HIT
uncontrolled active bleeding
heparin ADRs
bleeding, thrombocytopenia
localized reactions in SubQ administration- bruising, irritation, hematoma
heparin metabolism/excretion
no renal or hepatic adjustments needed
aspirin routes
81 mg daily- maximal effects on platelet function
325 mg- indicated in initial treatment for an acute event
dipyridamole/aspirin routes
oral caps (not enough aspirin for primary prevention of MI)
vitamin K, phytonadione routes
oral tabs
IV/IM
warfarin clinical pearls
in patients with new onset DVT/PA or other active clots, warfarin is started at the same time as parenteral anticoagulation (enoxaparin, heparin) and is continued for a minimum of 5 days AND until the INR >2.0 for 24 hrs
heparin routes/doses
IV (full-dose, treatment dose): algorithm based on following anti-Xa or activated partial thromboplastin time (aPTT) levels
bolus given if effect is needed immediately- active PE, STEMI
SubQ (prophylaxis): 5000 units q8h-q12h 7500 units q8h in morbidly obese
heparin induced thrombocytopenia (HIT)
potentially fatal immune-mediated disorder that results in rapid platelet count drops and potentially paradoxical increase in clotting
antibodies are developed against heparin-platelet complexes causing damage to the vascular endothelium- increases clotting and decreases platelets
protamine indications
heparin neutralization
protamine US boxed warnings
hypersensitivity reactions
protamine MOA
forms a stable salt with heparin and nullifies anticoagulant activity
protamine route
IV
protamine ADRs
bradycardia, flushing, hypotension
protamine metabolism/excretion
no renal or hepatic adjustments needed
enoxaparin
lovenox
low-molecular-weight heparin
Lovenox indications
acute coronary syndromes, DVTs/PEs, VTE prophylaxis
Lovenox US boxed warnings
spinal/epidural hematoma
Lovenox MOA
shortened derivative of heparin - has anti-Xa and antithrombin activity - has more Xa than thrombin inactivation
Lovenox contraindications
history of HIT
active major bleeding
Lovenox routes
subcutaneous
Lovenox ADRs
anemia
hemorrhage
Lovenox metabolism/excretion
renal adjustments needed at CrCl <30 mL/min (40 mg daily –> 30 mg daily, 1 mg/kg q12h –> 1 mg/kg q24h)
avoid in severe renal impairment (CrCl <20 mL/min)
Lovenox subcutaneous dosin
full dose/treatment dose: 1 mg/kg q12h or 1.5 mg/kg q24h
prevention/prophylaxis: 40 mg q24h or 30 mg q12h
intermediate dosing: 60 mg q12h or 1 mg/kg q24h
Fondaparinux indications
DVT/PE treatment, VTE prophylaxis
does not promote HIT, although it can still lower platelets
can be used in patients with history of HIT but not in active HIT
Fondaparinux US boxed warnings
spinal/epidermal hematomas
Fondaparinux MOA
selective indirect inhibitions of factor Xa
no activity with thrombin
Fondaparinux contraindications
severe renal impairment (CrCl <30 mL/min), body weight <50 kg (prophylaxis), active major bleeding, bacterial endocarditis
Fondaparinux ADRs
anemia/bleeding
Fondaparinux metabolism/excretion
renal adjustments needed
no hepatic adjustments needed
Argatroban indications
prophylaxis of treatment of thrombosis in patients with HIT or history of HIT
anticoagulant for PCI in patients with HIT or history of HIT
argatroban MOA
direct inhibition of thrombin
Argatroban contraindications
major bleeding
Argatroban ADRs
bleeding, hypotension
Argatroban metabolism/excretion
hepatic adjustments needed
no renal adjustments needed
dosed off of bilirubin and monitored with aPTT
Bivalirudin indications
anticoagulant used in patients undergoing primary PCI and PCI facilities
given in combo with aspirin and P2Y12 inhibitos
Bivalirudin MOA
direct thrombin inhibitor
Bivalirudin contraindications
active major bleeding
Bivalirudin ADRs
bleeding, hypotension
Bivalirudin metabolism/excretion
renal adjustments needed
no hepatic adjustments
Dabigatran indications
DVT/PE treatment and prevention, Atrial fibrillation, VTE prophylaxis in total hip arthroplasty
Dabigatran US boxed warnings
Thrombotic Events – premature discontinuation increases risk of thrombotic events
Spinal/epidural hematoma
Dabigatran MOA
direct thrombin inhibitor
Dabigatran contraindications
active bleeding, patients with mechanical heart valves
Dabigatran ADRs
bleeding
GI disturbances
Dabigatran metabolism/excretion
indication dependent- avoid use in DVT/PE for renal dysfunction, dose adjust for Afib
no hepatic adjustments needed
direct factor Xa inhibitors indications
Afib, VTE treatment and prophylaxis, VTE prophylaxis in hip and knee arthroplasty
direct factor Xa inhibitors US boxed warnings
premature discontinuation increases risk of thrombotic events
spinal/epidural hematoma
direct factor Xa inhibitors contraindications
active bleeding
direct factor Xa inhibitors ADRs
bleeding
direct factor Xa inhibitors metabolism/excretion
renal adjustments needed-drug specific
rivaroxaban
xarelto
xarelto additional indications
stable coronary artery disease to reduce risk of CV events
peripheral artery disease to reduce risk of thrombotic events
VTE prophylaxis in acutely ill
Xarelto dosing
Afib: 20 mg with evening meal
VTE: 15 mg bid x 21 days then 20 mg daily with evening meal
CAD/PAD: 2.5 mg bid
Apixaban
eliquis
Eliquis dosing
Afib: 5 mg bid
VTE: 10 mg bid x 7 days, then 5 mg bid
Edoxaban dosin
Afib: 60 mg daily
VTE: 30-60 mg daily
Edoxaban use not recommended if
CrCl >95 mL/min
Thrombolytic (fibrinolytic)
given to remove thrombi that have already formed
used for acute myocardial infarctions, massive pulmonary embolism, acute ischemic stroke
three thrombolytic agents available
altepase
tenecteplase
retaplase
alteplase indications
acute ischemic stroke
pulmonary embolism
STEMI
alteplase MOA
initiates fibrinolysis by converting plasminogen to plasmin in a thrombus- dissolves the clot
alteplase ADRs
bleeding
Alteplase metabolism/excretion
no hepatic or renal adjustments needed