Mod 1 Lecture 1 Flashcards
what is the common venous clot
DVT -> PE
what is virchows triad
stasis
vessel wall injury
hypercoaguability
what is the treatment for DVT
anticoagulant drugs or thrombolytics
what are arterial clots
medium sized arteries (carotid, optical)
endothelial damage in atherosclerosis, states of low flow -> thrombosis/emboli
emboli from heart in Afib; MI and stroke
what do arterial clots block
block delivery of oxygen (Painful)
what is the treatment of arterial clots
anti-platelet drugs and thombolytics
what is the goal of antiplatelets
slow platelet aggregation
what is the goal of anticoagulation agents
slow down clotting via interference with fibrin formation
what is the goal of fibrinolytics
dissolve clots
antidotes exist for most anticoagulation meds
what is the goal of anticoagulants and antithrombotic meds
prevention of heart attack, stroke, PE or DVT
also, prevent complications of Afib, CHF, and genetic or acquired hypercoagulability
what is the purpose of thomboxane A2
causes shape change and activation of GPIIB/IIIa receptors
what is the purpose of ADP
causes release of granules and activation of GPIIb/IIIa receptors
what is the purpose of GPIIb/IIIa receptors
when active, bind fibrinogen and crosslink platelets together
what fibrinolyzes the clot after platelet aggregation
plasmin
what type of agent are aspirin, clopidogrel, abciximab
anti-platelet agents that prevent platelet activation
what type of agents are heparin and warfarin
classical anticoagulants - prevent formation of fibrin clots (venous thrombus )
what type of agents is dabigatran
“new” thrombin inhibitor
what type of agent is tPA and anistreplase
fibrinolytic agents - break down existing clot
what antiplatelet drugs are P2Y12 ADP receptor inhibitors (platelet antagonists)
clopidogrel (Plavix)
Prasugrel (Effient)
Ticlopidine (Ticlid)
Ticagrelor (Brilinta)
what are antiplatelets that are GPIIb/IIIa receptor inhibitors
abciximab (reoPro)
Eptifbatide (integrilin)
Tirofiban (aggrastat)
what are antiplatelets that are phosphodiesterase inhibitors
dipyridamole (Persantine)
Cilostazol (pletal)
what is the MOA of aspirin
inhibits COX-1 IRREVERSIBLY
inhibition of platelet aggregation is the result
what is COX1 important for
key enzyme involved in the synthesis of platelet thromboxane A2 (prostaglandin pathway)
when is aspirin indicated
primary prevention of heart attack and stroke
used for clot risk reduction after surgery
secondary prevention in pts with hx of CAD, DM, PVD, CVA, TIA
and DAPT
what does DAPT stand for
Dual Anti-platelet therapy
when is DAPT recommended
after CABG, PCI (stent), stroke, TIA for 2 weeks
when is aspirin contraindicated?
bleeding risk (elderly, GI)
tinnitus (makes it worse)
perioperative: intracranial, intramedullary or posterior eye surgeries
when should ASA 81 be discontinued peri-operatively
intracranial, intramedullary or posterior eye surgeries
what is the MOA of Clopidogrel
Irreversibly blocks P2Y12 ADP receptors on platelet surface -> decrease ADP-stimulated aggregation
when does clopidogrel have reduced effectiveness
in patients who are poor metabolizers
what is the goal of clopidogrel
prevent further atherosclerotic events in MI and unstable angina
ACS and coronary angioplasty
when is clopidogrel used
DAPT with 81mg ASA for Bare-metal stent (BMS), Drug eluting stent (DES), Acute coronary stent (ACS) and TIA/minor ischemic stroke
how long is clopidogrel typically used
usually no longer than 12 months
what is a DAPT score greater than or equal to 2 mean
favorable benefit/risk ratio for prolonged DAPT
a DAPT score of less then 2 is associated with what
in-favorable benefit/risk ratio
when should P2Y12 ADP receptor inhibitors be avoided
episodes of active bleeding
history of bleeding (GI, Intracranial)
what is Clopidogrel used to prevent
CVD event in recent MI, CVA, RAP and prevent thrombosis in ACS with or without PCI stent
what is generally the first-line antiplatelet drug
Clopidogrel (plavix)
when should Clopidogrel be stopped prior to a lifesaving surgery
at least 5 days prior to surgery
what is the medication when Clopidogrel does not work or the patient is a fast metabolizer
Ticagrelor (brilinta)
what is Ticagrelor
ONLY REVERSIBLE P2Y12 inhibitor
taken with low dose aspirin (DAPT)
what is Parsugrel (effient)
second P2Y12 inhibitor
approved in aCS and after MI
increased antiplatelet activity, so less CV death, MI, stroke
increased risk of bleeding, especially >75yo
when should parsugrel be avoided
history of bleeding (especially > 75yo)
what is the risk of Ticlopidine (ticlid)
risk of thrombocytopenia, agranulocytosis and TTP (Thrombotic thrombocytopenia purpura)
No longer sold in the US due to serious life threatening hematologic AE
what do GPIIb/IIIa inhibitors bind to
bind to platelet GPIIb/IIIa receptor complex
bind to vWF and fibroinogen
what is the purpose of GPIIb/IIIa inhibitors
inhibit action of platelet aggregation
use with ASA and heparin
when are GPIIb/IIIa inhibitors used
with ASA and heparin during balloon angioplasty, coronary stent placement, PCI, if needed to prevent further clot formation
what is a Humanized monoclonal antibody
Abciximab (ReoPro)
administered IV
what is the adverse effects of abciximab
bleeding
what is tirofibran used for
reduces rate of thrombotic CV events VERY RARELY USED
can be used in NSTEMI with PCI
IV infusion
what is the risk of Tirofibran use
hx of bleeding
what needs to be monitored with Tirofibran
aPPT
what is inhibited with prosphodiesterase inhibitors
inhibit conversion of cAMP to AMP
inhibit platelet aggregation
encourages vasodilation - can cause rebound headaches
what medication is used for stress tests to induce reflex tachycardia
Dipyridamole (persantine)
causes vasodilation
when isDipyridamole used
rarely used, but when used, is in fixed combo with ASA (Aggrenox) for secondary stroke prevention
when is Cilostazol used
intermittent claudication (legs) in PVD
what is the effect of cilostazol
vasodilatory and anti-platelet effects
increasses HDL cholesterol
when is cilostazol contraindicated
heart failure
what are the adverse effects of Cilostazol
headache and GI upset and many drug interactions (CYP inhibitor)
what are platelet activating supplements
fish oil
dong quai
garlic, ginger, gincko, ginseng, green tea
what is the MOA of Heparin
“indirect” agent (does not act by iteself)
binds to and activates anti-thrombin(ATIII) and increases anti-thrombin activity 1000-fold
what does heparin/anti-thorombin complex lead to
inactivation of thrombin (factor IIa) and other clotting factors (IXa and Xa)
what is the purpose of heparin
prevent and allow body to break down thromboembolism
PE, DVT, TIA, ACS (MI)
sometimes used initially in Afib or Prosthetic vales and hemodialysis and heart/lung bypass machines
what are the types of heparin
Unfractionated and Low Molecular weight Heparin
both bind to anti-thrombin, inactivate Xa and thrombin, inhibit formation of fibrin
Injectable
what should be avoided when using Heparin
NSAIDs - bleeding and renal dysfunction risks
what is the unset of unfractionated heparin
rapid onset with a short half life
how is unfractionated heparin administered
Infuse or subQ
what are the side effects of unfractionated heparin
bleeding
osteoporosis
hyperkalemia (via aldosterone suppression)
elevation in transaminases (transient)
what is HIT
Heparin induce thrombocytopenia
what is a risk of unfractionated heparin
HIT (heparin induced thrombocytopenia)
immune mediated, life threatening disease state
increased risk for clotting
STOP heparin ASAP and start alternative anticoagulant
what is the antidote to unfractionated heparin
Protamine sulfate
- although rarely used due to short half life of heparin except after bypass surgery
LMWH have lower risk for
HIT and osteoporosis
when is LMWH contraindicated
do not use if spinal or epidural catheters, use 4 hours after removal - prevents spinal hematoma
what are the different types of LMWH
Enoxaparin (lovenox)
Dalteparin (Fragmin)
Tinzaparin (Innohep)
what needs to be checked regularly in patients on heparin
Platelets checked daily or multiple times a day to ensure HIT does not take place
what is the indications for enoxaparin (Lovenox)
DVT/PE treatement and DVT prophylaxis in knee/hip replacement and abdominal surgerys
prophylactic anticoag for immobilized
what are the adverse effects of lovenox
peripheral edema
when is Dalteparin used
primarily in patients with malignancy, more effective than warfarin in reducing risk of recurrent embolic events
what are the risks of Tinzaparin
increased risk of death in elderly, especially if renal insufficiency in DVT, PE or both
what is the MOA of Warfarin
inhibition of Vitamin K
inhibits formation of fibrin
what is the importance of Vitamin K
co-factor in carboxylation/activation of several clotting factors (factor II, VII, IX and X)
what needs to be monitored with warfain use
PT/INR
what medication is weight base and also safe with pregnancy
Enoxaparin
what does warfarin bind to
albumin - rapid absorption
what can reverse warfain
Vitamin K infusion
what drugs increase bleeding/potentiate Warfarin activity
ASA - inhibition of platelets
Heparin - inhibits clotting factors
Antibiotics - cut bacteria Vit K production
what drugs decrease warfarin activity
barbiturates, phenytoin - induction of metabolizing enzymes
Vitamin K - promote clotting factor synthesis
Cholestyramine - reduce absorption
what medication is used as a bridge for coumadin therapeutic onset
enoxaprin (lovenox)
what are the indications of Warfarin use
DVT/PE treatment - prevent clot from growing while the body dissolves the plug
Prophylaxis thrombic event in: Afib, atrial flutter, prosthetic heart vales, recurrent DVT, perioperative (TKA,THA)
what is the INR goal range
1.0 - 3.0 for most
what is the INR goal for mechanical valve patients
2.5-3.5
what is Dabigatran (pradaxa)
direct anti-thrombic agent
first warfarin alternative
“not inferior to warfarin in preventing CVA”
what are the adverse effects of Dabigatran
bleeding (more GI)
what is the antidote for Dabigatran
Idarucizumab (Praxbind) - monocolonal antibody that removes dabigatran
what can happen with the discontinuation of dabigatran
can cause rebound thrombosis
what is Argatroban (Acova)
direct thrombin inhibitor
- binds to thrombin, inhibits converstion to fibrinogen ->fibrin
IV only
what is Argatroban used for
anticoagulant prophylaxis or treatment for HIT
also used in PCI if patient is at risk of HIT with heparin agent
what needs to be monitored when taking Argatroban
ACT (active clotting time) and in patients with hepatic impairment (dose should be decreased)
What are Factor Xa Inhibitors / DOAC
Fondaparinux (arixtra) injection
Rivaroxaban (Xarelto) oral
Apixaban (eliquis) oral
what is the MOA for fonduparinux
binds to anti-thrombin III, consider as an alternative to heparin in pts with history of HIT
No binding to Plasma protein - no direct effect on thrombin
what is the use for fonduparinux
prevent DVT in orthopedic surgery and treatment for PE/DVT
what is Rivaroxaban used for
DVT/PE prevention and treatment and stroke prevention in non-valvular Afib
what are the risks of Rivaroxaban
highest risk of GI bleeding of the Factor Xa inhibitors, more liver/kidney risk
lower risk of serious and fatal bleeding events than warfarin
what is apixaban used for
DVT/PE prevention after THA/TKA
effective in stroke prevention in non-valvular Afib
better than warfarin, less bleeding
what is the MOA for fibrinolysis
medically-induced degradation of clots
- activation of endogenous protease
- plasminogen activated to plasmin
- plasmin breaks down fibrin clots
when are fibrinolytics more effective
against new formed thrombi in acute MRI, Aterial and venous thrombosis and PE
what are the risks of Fibrinolytics
hemorrhage by destruction of therapeutic clots as well as pathologic clots
what are the types of Fibrinolytic drugs
Anisterplase
Urokinase
Alteplase (tPA)
what is Antisterplase
plasminogen/streptokinase activator complex
purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme’s active site
what is the MOA for anisterplase
catalyzes conversion of inactive plasminogen to plasmin - combines with pro-activator plaminogen
what are the risks of antistreplast
high indiscriminate bleeding
what is urokinase
from urine, similar to streptokinase
only indicated for PE
neither used much anymore
what is tPA
endogenous activator of plasminogen to plasmin converstion
preferentially activates plaminogen bound to fibrin
produces by recombinant DNA technology
what does tPA stand for
tissue plasminogen activator
what is reteplase (r-PA)
genetically engineered, similar derivative of tPA = faster and more potent
administered IV for acute MI - off label for massive PE and DVT
what is tenecteplast (TNK-tPA)
genetically engineered, smaller derivative of tPA
longer half life than rPA
higher affinity for fibrin than alteplase
administered IV for acute MI - off label for massive PE and DVT
