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90 Cards in this Set

  • Front
  • Back
anticoagulation drugs
indirect thrombin inhibitors, direct thrombin inhibitors, vit K antagonist, factor Xa inhibitor
Indirect thrombin inhibitor
heparin, fondaparinux
direct thrombin inhibitors
hirudin, bivalirudin, lepirudin, argatroban, dabigatrom
vitamin K antagonist
warfarin
factor Xa inhibitor
rivaroxaban
Thrombolytic Drugs
streptokinase, anistreplase, urokinase, alteplase, reteplase, tenecteplase,
antplatelet agents
aspirin, clopidogrel, ticlopidine, abiciximab, eptifibatide, tirofiban
Drugs used to facilitate clotting
vitamin K, clotting factors, fibrinoltic inhibitors, serine protease inhibitors
clotting factors
7,8,9,10, FFP, cryoprecipates
fibrinolytic inhibitors
aminocaproic acid
serine protease inhibitors
aprotinin
component factor 1
fibrinogen
component factor 2
prothrombin
component factor 4
calcium
component factor 7
proconvertin
component factor 8
Antihemophilic factor (AHF)
component factor 9
Christmas factor
component factor 10
Stuart Prower factor
Disorders treated by anticoagulants
venous thrombosis, arterial thrombosis, embolism
endogenous anticoagulants
antithrombin, protein C and protein S
Antithrombin (AT or AT III)
a serine protease inhibitor, inactivates clotting factors 2,9,10
protein C
vitamin K dependent serine protease, activated by thrombin to APC, Degrades cofactor 5 and 8
protein C deficiency may display
increased thrombosis
Protein S
vitamin K dependent glycoprotein. Free form acts as a cofactor to Protein C
Indirect thrombin inhibitor
Heparin (UFH, LMWH) fondaparinux
indirect thrombin inhibitors activity is mediated through
their interaction with antithrombin (AT). Inactivate thrombin, 2,9, 10, 11, 12. Heparin increases lipoprotein lipase
Heparin (UHF)
a mixture of sulfated mucopolysaccharides, extracted from porcine gut or bovine lung
Clinical use of Heparin
use parenterally (IV,SC), do not use IM (risk of hematoma). Short half life, preferred for pregnant women
LMWH
enoxaparin dalteparin tinzaparin
clinical LMWH
inhibit Xa (less effect on thrombin), less frequent dosing and less side effects/tox, no routine monitoring of aPTT
monitoring heparin effect UFH level
close monitoring of the activated partial thromboplastin time (aPTT) or by protamine titration or anti Xa units
monitoring of heparin effect LMWH level
weight based dosing. aPTT measured only in obesity, pregnancy and renal insufficiency
Heparin toxicity
bleeding, HIT, allergy, hair loss/alopecia, osteoporosis/fracture (long term use)
Bleeding in Heparin
major adverse effect close monitoring needed, increase in elderly, female, and pt's with renal failure
HIT
heparin induced thrombocytopenia, an immunohematological disorder (hypercoagulation ) in pts treated with UFH for > than 7 days. Esp surgical pts. Venous thrombosis is the most common
if HIT noticed what should you do
discontinue use and use a direct thrombin inhibitor or fondaparinux
Cause of HIT
development of Abs against heparin/platelet factor 4 complex.
when is HIT suspicious
decreased platelet count, new thrombus, thrombocytopenia
reversal of heparin action
discontinue the drug and use an antagonist (protamine sulfate)
Heparin is contraindicated in
active bleeding, intracranial hemorrhage, advanced liver/kidney disease, severe hypertension, infective endocarditis, active tuberculosis…. Gi ulcer, hemophilia, purpura, threatened abortion, visceral carcinoma
Heparin is avoided in
post surgery of brain, spinal cord, eyes, pts undergoing LP, pregnant unless clearly indicated
Fondaparinux
long half life (sub Cu) effective in the prevention/treatment of venous thromboembolism, alternative anticoagulant in pts with HIT
direct thrombin inhibitors
hirudin, bivalirudin, lepirudin, argatroban, dabigatran
special about hirudin and bivalrudin
bivalent DTI's which also bind to the substrate recognition
how do direct thrombin inhibitors work
binding directly to the active site of thrombin
Hirudin
isolated from leech saliva, bivalent irreversible thrombin inhibitor
Lepirudin
a recombinant form of hirudin. Used in pts with HIT. Caution in pts with renal insufficiency
Bivalirudin
bivalent reversible thrombin inhibitor also inhibits platelet activation. IV, rapid on off action short half life
argatroban
used in pts with thrombosis and HIT. IV, short half life. Monitor aPTT, liver clearance (caution in liver disease). Increased international normalized ratios (INRs)
attributes of an ideal anticoagulant
oral, rapid onset, wide therapeutic range, predictable therapeutic effect, no food or drug-drug interactions
oral anticoagulants currently
Dabigatran, warfarin, rivaroxaban
dabigatran
oral prodrug, fast onset of action, assess renal function prior to prescription. Contraindicated in renal failure. No antidote. Reports of fatal bleeding
warfarin
vitamin K epoxide reductase. Blocks the gamma carboxylation of the glutamate residue in prothrombin 7, 9, 10 protein Cand S (8-12 hr delay in action)
warfarin special
racemix misture, potency S>>R, long half life, slow onset and slow offset
warfarin contraindications and adverse rxn
cross the placenta, hemorrhage in the fetus, serious birth defect( affect other fetal proteins in the bones and blood). Adverse reaction skin necrosis aka WISN, decrease protein C activity
warfarin clinical
oral, std dose 5-10 mg, adjustment of the prothrombin time (PT). Extrinsic pathway 1 week. PT should be increased. Therapeutic range is define by INR. Recommended INR for prophylaxis and treatment of thrombotic disease is 2-3
Reversal of warfarin action
stop the drug, admin vit K1, fresh frozen plasma, prothrombin cplx, rFIIa
factor Xa inhibitor
rivaroxaban
special for rivaroxaban
oral, fast onsel, liver metabolism (cyp3a4), no monitoring. Drug interaction with p450 inducers inhibitors
rivaroxaban antidote
factor Xa
Thrombolytic Drugs
streptoinase, anistreplase, urokinase, tPA, alteplase, reteplase, tenecteplase
streptokinase
bacterial protein, binds to activate plasminogen. Potential allergic rxn (no repeat use)
anistreplase
complex of human plasminogen and streptokinase
urokinase
human enzyme directly converts plasminogen to active plasmin
alteplase and reteplase
recombinant tissue plasminogen activators (tPA's, preferentially activate the fibrin bound plasminogen
tenecteplase
mutant tPA, longer half life
clinical uses of thrombolytic drugs
IV for pulmonary embolism, DVT and ascending thrombophlebitis. Management of acute MI
Recombinant t PA's are also used in
acute ischemic stroke
antiplatelet drugs
ADP receptor antagonists, thromboxane inhibitor, IIIa/Iib receptor antagonist
thromboxane inhibitor
aspirin
aspirin
irreversibly inhibits the synthesis of thromboxane A2, promary prophylaxis of MI 325 mg/d
antiplatelet drugs Adp receptor antagonists
clopidogrel and ticlopidine
MOA of antiplatelet drugs
inhibit the ADP receptor P2y12 on platelet, prevent thrombosis.
clopidogrel special
prodrug
adv rxn ticlopidine
GI tox, hemorrhage, TTP, neutropenia
clopidogrel adv rxn
less adverse effects, avoid concomitant use with PPI's ie omeprazole due to redued antiplatelet activity
antiplatelet drugs 3a/2b receptor antagonists
abciximab, eptifibatide, tirofiban
abciximab
chimeric mab against 2b/3a receptor, blocks activation of the Iib/3a receptor and vibronectin receptor
eptifibatide
analog of the delta chain of fibrinogen, blocks the binding of fibrinogen to the 2b/3a receptor
tirofiban
smaller molecule similar to eptifibatide
Factor 11 deficiency
hemophilia C, 2nd most common bleeding disorder among women
factor 7 deficiency
serum prothrombin converse accelerator. Diagnosed in newborns (bleeding into the brain as a result of traumatic delivery)
Agents used to facilitate clotting
vitamin k, antiplasmin drugs, clotting factors
vitamin K
fat soluble, found in leafy green veggies and synthesized by bacteria. Used to treat excessive warfarin or vitamin K deficiency
What is given to all newborns
Vitamin K1
fibrinolytic inhibitors
aminocaproic acid, aprotinin
aminocaproic acid
synthetic inhibitor of fibrinolysis. Competitivly inhibits plasminogen activation
administration of aminocaproic acid
loading dose when IV (>30 min to avoid hypertension)
adverse effects of aminocaproic acid
intravascular thrombosis, hypotension
aprotinin
serine protease inhibitor, inhibits figrinolysis by free plasmin, reduces bleeding from surgery.