Antiplatelet Drugs, Anticoagulants And Fibrinolytics Flashcards
What is activated partial thromboplastin time (PPT)
Laboratory test used to monitor the anticoagulant effect of unfractionated heparin and direct thrombin inhibitors
What is antithrombjn III
An endogenous anticlotting protein that irreversibly inactivates thrombin and factor Xa.
What are the names of the glycoproteins on the Platelet surface
Glycoprotein 2b/3a
How do glycoproteins primarily aggregate platelets
Binding to fibrin
What is the weight of unfractionated heparin
5000-30,000
What is the weight of fractionated heparin
2000-6000
What is the prothrombin time (PT)
Laboratory test used to monitor the anticoagulant effect of warfarin
What is in the Virchows triad
Endothelial injury
Abnormal blood flow
Hypercoagulability
What are the three types of anticlotting drugs
Anticoagulants
Thrombolytics
Anti platelets
What drugs facilitate clotting
Replacement factors, Vitamin K, Antiplasmin drugs
List the drugs associated with anticoagulants
Heparin
Direct thrombin inhibitors
Direct factor Xa inhibitors
Warfarin
List the drugs associated with thrombolytics
Tissue Plasminogen Activator (tPA derivative)
Streptokinase
List the drugs associated with anti platelets
Aspirin
Glycoprotein 2b/3a inhibitors
Adenosine diphosphate inhibitors
Phosphodiestrase (PDE)/ adenosine reuptake inhibitors
What pathway does
I heparin
II warfarin
target
Intrinsic
Extrinsic
What is the MOA of
I Heparin
II Warfarin
Inactivates thrombin and factor Xa
Inhibits Synthesis if clotting Factors
What is the route of administration for
I Heparin
II Warfarin
IV or SubQ
PO
True or false Heparin crosses the placenta or into breast milk but Warfarin doesn’t
False, Warfarin crosses the placenta (teratogenic) but Heparin doesn’t
How long is the offset of
I Heparin
II Warfarin
Rapid (minutes)
Slow (hours)
How long is the duration of
I Heparin
II Warfarin
Brief (hours)
Prolonged (days)
True or false Heparin has lesser drug interactions than Warfarin which has many
True
How is
I Heparin
II Warfarin
Eliminated
Renally
Hepatically
What is used to monitor
I Heparin
II Warfarin
PTT
PT
What is the antidote for
I Heparin
II Warfarin
Protamine
Phytomenadione (Vitamin K)
What are the low molecular weight anitthrombin III activators
Enoxaparin
Dalteparin
What are the Vitamin K antagonists
Warfarin
Phenprocoumon (Acenocoumarol)
What are the drugs associated with being thrombin inhibitors
Hirudin Argatroban Bivalirudin Davila Tran Desirudin Lepirudin
What are the drugs associated with being Heparin and LMWH
Heparin Ardeparin Dalteparin Danaparoid Exoxaparin Tinzaparin
What are the drugs associated with being Direct Factor Xa inhibitors
Apixaban
Edoxaban
Rivaroxaban
What is the source of injectable heparin and LMWH
Procine intestinal mucosa
Bovine lung
Heparin and LMWH is associated with the family of _______ ________
Sulphated glycosaminoglycan
What is the molecular weight range of injectable heparin
5000-40000 daltons
What is the molecular weight of LMWH
1000-10,000 daltons using gel filtration chromatography
What is the MOA of Heparin
Cofactor of Antithrombin III
Increases the rate of ANTIII reaction by 1000
Also increase in activation of IX, Xa, XIa, XIIa and protein C and S
1:10 binding ration with all factors
What is the MOA of LMWH
Have only one binding site for ANTI- III
Therefore increase inactivation of IX, Xa, XIa and XIIa
True or false, only the LMWH is active in the invivo and in vitro method
False both Heparin and LMWH
True or false , LMWH doesn’t inactivate IIa
True
True or false, only long chains of Heparin can inhibit the action of factor Xa by binding to antithrombin (AT)
False, any size heparin chain can inhibit the factor Xa
True or false, in order to inactivate thrombin (IIa), the heparin molecule must be long enough to bind to both antithrombin and thrombin
True, it must be long in order to bind to both antithrombin and thrombin
What type of Heparin would you use to inactive thrombin
Unfractionated Heparin
LMWH binds only to ______ and therefor increases inactivation of Factors __________
Antithrombin III and IXa, Xa, XIa and XIIa
Why is LMWH, more prescribed than Heparin
Less monitoring
More predictable anticoagulant response
Same efficacy as heparin
True or false, Heparin is polar
True
What is the :
I. Way of Administrating
II. Onset
Of heparin
IV and subcutaneous,
Fast, 60 minutes
What is the bioavailability of Heparin after SC
20%
Why is the initial loading dose required
5000 U
Explain the reason as to why Heparin is unpredictable
Non-specific binding to plasma proteins, endothelial cells, Macrophages
vWF- need to saturate
What is the half life of Heparin
40-90 minutes
The aPPT for monitoring Heparin should not be
> 2.5 X normal
True or false, the Ti for Heparin is low
True
How is Heparin eliminated
Internalized and destroyed by Reticulocyte-endothelial system, heparinase enzyme
What are the advantages of LMWH vs UH
Less inhibition of platelet function Lower incidence of Thrombocytopenia and Thrombosis (HIT Syndrome)
How does the use of LMWH Lower the risk of thrombocytopenia or HIT
Less interaction with platelet factor 4
Fewer heparin- dependent lgG antibodies
What are the adverse drug reactions of Heparin
Inhibits aldosterone- hyperkalemia= HIT potential
Causes necrosis due to Protein C
Anticoagulant
Initial transient reduction in platelet count
Thrombocytopenia usually occurs 2-14 days after the start of therapy
____% patients receiving heparin
____% patients receiving LMWH
5%
1%
HIT Incidence rates for
Thrombosis
Amputations
Death
30-50%
20%
30%
What is used during Heparin Overdose
Protamine sulphate
How is Protamine sulphate given
Slow IV
Given at 1Mg/ 100 U of heparin remaining
Protamine sulphate is given routinely after________ surgery to reverse effects of Heparin
Cardiac
What is the adverse effects of Protamine Sulphate
Histamine release
True or false, Heparin and LMWH are both given at 5000 U
True
What is the bioavailability of LMWH after SC
90%
What is the half life of LMWH
T times longer than heparin
Why is there no monitoring required for LMWH
There is no change in aPTT
True or false, Heparin is more expensive than LMWH
False LMWH is more expensive
What is the difference between the Thrombin inhibitor drugs and heparin drugs
Heparin drugs require the binding of Antithrombin III in order to inhibit the binding of Thrombin
What are the names of the Thrombin inhibitor drugs that are taken via IV
Hirudin
Lepuridin
What is the name of the Thrombin inhibitor that is taken orally
Dinihatran etexilate
True or false , Thrombin inhibitors are approved for treatment of anticoagulant when there is or the potential for HIT
True
How is hirudin produced
Synthesized via recombinant DNA technology
How is Hirudin eliminated
Hepatic metabolism
What is the half life of hirudin
2 and a third hours
What are the adverse effects of Hirudin
Liver injury, Renal insufficiency
True or false, Heparin blocks the activation of Clotting factors while Warfarin speeds up the inactivation of The clotting Factors
False, it is the other way around
What is the oral coagulant for warfarin
Coumarin
Where is Coumarin prepared from
Clover leaves
What is the MOA of Warfarin
Competively inhibits the Vitamin K epoxide reductase complex 1 (-VPORC1), which is essential for activating the Vitamin K available in the body
Through this method, Warfarin can deplete functional Vitamin K reserves and therefore reduce synthesis of active clotting Factors
What is the half life for Warfarin in cofactors (hrs) VII IX X II Protein C Protein S
6 24 36 60 8 30
Where is Warfarin eliminated and by what enzyme
Liver CYTP450
Is Warfarin polar or non polar
Non polar
What is the onset of Warfarin
Slow - 48 hours
What is the duration of Warfarin
4-5 days
What is the half life range of Warfarin
25-60 hours
True or false, Warfarin is well absorbed
True pK 2-8 hours
What Aretha ADR/ toxic effects of Warfarin
Diarrhea
Overdose - bleeding
Skin necrosis
Drug interactions
What is used to treat Warfarin
Vitamin K
True or false, Warfarin has a low TI
True
What is the therapeutic range of warfarin
2-3
What is the
i. onset of plasma in the reversal of warfarin
ii. duration
Rapid but short lasting
What is the onset of Vitamin K in the reversal of of warfarin
ii. duration
Vitamin K- not rapid but lasts 1-2 weeks
True or false, It is advised to use vitamin k if you are planning on restarting warfarin within next week
false
Warfarin Induced Skin Necrosis usually occurs in what range after initiation
3-6 days
True or false, Warfarin induced skin necrosis is common
False it is rare
What persons are most likely to be affected by Warfarin Induced skin necrosis
Obese women
Postmenopausal women
What is the treatment for Warfarin induced skin necrosis
Heparin
Which drug inhibits liver enzymes
Cimetidine
Cimetidine ______ clearance of Warfarin
Decreases
What drugs increase the clearance of Warfarin
Barbiturates, rifampin, phenytoin
Which drugs induces liver enzymes
Barbiturates, rifampin, phenytoin
How does Disulfiram affect interactions with Warfarin
Causes Displacement from plasma proteins, thereby increasing free warfarin
How does Broad Spectrum Antibiotics affect drug interaction with Warfarin
Decrease absorption of Vitamin K, decreases clotting factors
Increases Warfarin activity
What type of Anti-clotting drug decreases the formation of chemical signals that promote platelet aggregation
Antiplatelet drugs
Anti platelet drugs are mainly administer for what specific cases
Specific Prophylaxis of arterial thrombosis
During management of heart attacks
What are the different types of antiplatelet drugs
COX/TXA2 inhibitor
IIB/IIIA receptor antagonists
P2Y12 ADP receptor blockers
Phosphodiesterase Inhibitor
What are the different P2Y12 ADP receptor blockers
Ticlopidine
Clopidogrel
Prasugrel
Ticagrelor
What are the different IIB/IIIA receptor antagonists
Abciximab
Eptifibatide
Tirofiban
What are the different phosphodiesterase inhibitors
Dipyridamole
What is the name of a COX/TXA2 inhibitor
Aspirin
TXA2 is a potent inducer of platelets _________
Aggregation
Aspirin acetylates ________ inhibiting platelet aggregation for a range of _________ days
Cyclooxygenase-1 (COX-1)
5 or 7 days
What is the MOA of aspirin
irreversible inhibition of COX 1
In platelets prevents formation of TX A2 which prevents platelet aggregation
What is the oral Dose of Aspirin
160-320mg/d
What is the onset of Aspirin
30-60 mins
Where is Aspirin eliminated
Liver
What is the duration of Aspirin
7-9 days
What is the adverse reaction of Aspirin
GIT irritation
What is the MOA of Dipyridamole
Inhibits phosphodiesterase = cAMP
cAMP competes with ADP for binding site = blocking response to ADP
High amounts of AMP decreases Ca2+ concentration, therefor decreasing aggregation of platelets
What is Dipyridamole usually used with
Aspirin or Warfarin
In ______ doses, Dipyridamole can be used as a vasodilator
High
Dipyridamole has a _____ efficacy
low
What is Dipyridamole used for
Prophylactic use
How is Dipyridamole excreted
Liver metabolizes and then is excreted by bile
True or False, Dipyridamole is well absorbed
True
What is the adverse effects of Dipyridamole
Headaches, Dizziness
Overdoses= hypotension
True or false, Dipyridamole has a high PPB
True
What is the PK of Dipyridamole
75 minutes
What are the ADP receptor antagonists
Ticlopidine (Ticlid)
Prasugrel
Clopidogrel (Plavix)
Ticagrelor
True or False, Dipryidamole doesn’t affect bleeding time
True
True or False, ADP receptor antagonists don’t affect bleeding time
False, they do
Dipyridamole inhibits the reuptake of _______
Adenosine
ADP receptor antagonists work by inactivating the platelet _______ by irreversibly binding to the receptor, thus having a prolonged action
P2Y12 (ADP)
ADP receptor antagonists work by inhibiting the binding of _______ (factorI) to activated platelet
Fibrinogen
What is the route of administration for Clopidogrel
Oral
What is the PK of Clopidrogrel
2 hours
What is the Pro-drug activated by
CYP450 (2C19)
What is the onset of Clopidrogel
4-8 days
What is the duration of Clopidrogel
14 days
What is ADR of Clopidrogrel
Diarrhea, bleeding
What is the MOA of GPIIb/IIIa receptor antagonist
Blocks the binding of fibrinogen and Von Wilebrand Factor to the glycoprotein IIb/IIIa on the surface of the platelet.
What is the monoclonal antibody to the Glycoprotein IIIa/IIb
Abcixmab
What are the platelet IIb/IIIa antagonists
Eptifibatide, Tirofiban
GPIIb/IIIa antagonists increase the risk of bleeding, particularly at the site of _______
Arterial access
True or false, Abcixmab irreversibly binds to the GPIIb/IIIa
True
Abcixmab is used with _______
Aspirin and Heparin
What is the route of administration for Abcixmab
IV fusion
What is the onset of Abcixmab
rapid
What is the half life of Abcixmab
10 minutes
What is the duration of Abcixmab
48 hours
What are the adverse effects of Abcixmab
Fever headaches, thrombocytopenia
Where is Abcixmab metabolized
Liver
What are the Thrombolytic Drugs
Streptokinase
What drugs are used to lyse already formed clots
Thrombolytic drugs
What are two tissue- plasminogen activators
Reteplase, Tenecteplase
(more expensive)
(Only used in emergency setting )
What is the MOA of Fibrinolytic drugs
Increase the conversion of plasminogen to plasmin
only used in emergency setting
What is streptokinase dependent on
Plasminogen Availability
What is streptokinase given with
Hydrocortisone IV
What is the half life of streptokinase
40-80 hours
What is the duration of streptokinase
12 hours
What is the adverse effects of Fibrinolytics
Antibody formation
Where are Fibrinolytics metabolized
Liver