Anticoagulants and Fibrinolytics Flashcards
Review the coagulation cascade
**see below**
What are the 2 sources of heparin?
Pig intestine and cow lung…yuck
Describe the MOA of heparin
(Unfractionated) Heparin binds to and potentiates the effects of anti-thrombin (which you will recall inhibits thrombin -factor 2, and factor 10a)
What are the indications of unfractionated heparin? (4)
What value do you use to monitor heparin at therapeutic doses and what is the effect of heparin on this value?
Heparin used for DVT prophylaxis (e.g. for hospitalized pts to prevent clotting) and venous TE, a-fib, ACS
Therapeutic doses monitored by aPTT. Heparin increases the aPTT
A unique side effect of heparin is ___
2 other adverse effects of heparin are ___ and ___
A unique side effect of heparin is heparin-induced thrombocytopenia
2 other adverse effects of heparin are bleeding and injection site pain
Describe how heparin-induced thrombocytopenia occurs
HIT is caused by an antibody reaction against heparin:
When heparin is introduced, IgG abs bind to the PF4 proteins on heparin, which causes profound platelet aggregation and activation and excess thrombin formation - induces prothrombotic state
Platelets therefore decrease in HIT because they’re being consumed
***
A characteristic decrease in platelets occurs 5-10 days after exposure (for a first exposure), and is noted by a 50% or more drop in platelets
What is the difference in MOA between unfractionated heparin and low molecular weight heparin?
Which one is IV and which one is not?
Recall that the longer molecules wrap around thrombin whereas LMW heparin doesn’t affect thrombin so it mainly has activity for factor 10a
Unfractionated heparin is given IV whereas LMW isn’t
___ is LMW heparin used for DVT prophylaxis, VTE, A-fib (among other conditions), and is given subcutaneously (hint: -parin drugs)
Enoxaparin is LMW heparin used for DVT prophylaxis, VTE, A-fib (among other conditions) and is given subcutaneously
___is an ultra LMW heparin that potentiates the effects of antithrombin only to Factor10a, and can be safely used in pts with previous history of HIT
Fondaparinux is an ultra LMW heparin that potentiates the effects of antithrombin only to Factor10a, and can be safely used in pts with previous history of HIT
What class of drugs are argatroban and bivalirudin?
Argatroban and Bivalirudin are IV direct thrombin inh’s
Name 2 indications of IV direct thrombin inhibitors
IV direct thrombin inhibitors are mainly indicated for HIT and ACS
Name the IV anticoagulant therapies (3)
Unfractionated heparin
LMW heparin (fondaparinux)
IV direct thrombin inhibitors
Which clotting factors are Vitamin-K dependent?
Briefly describe the Vitamin K cycle. The inhibition of which enzyme will result in decreased Vit K dependent clotting factors?
Vitamin K dependent clotting factors: 2, 7, 9 and 10
**see image for cycle**
The inhibition of Vitamin K reductase will result in decreased Vit K dependent clotting factors
Describe the mechanism of action of Warfarin
Name 2 reasons why the S isomer of warfarin is important
Warfarin blocks Vit K epoxide reductase >> depletion of Vit K-dependent clotting factors
The S isomer works the most on Vitamin K reductase, and is metabolized by CYP2C9 in the liver
***
Note that warfarin is useful for production of clotting factors but is not useful for circulating clotting factors
The anticoagulant effects of warfarin are dependent on ___
T/F: Proteins C and S are generally depleted before the other factors, which could induce a pro-thrombotic state in the initial day of starting warfarin
Name 3 adverse effects of warfarin
The anticoagulant effects of warfarin are dependent on the half-life of clotting factors
T/F: Proteins C and S are generally depleted before the other factors, which could induce a pro-thrombotic state in the initial day of starting warfarin - True
3 adverse effects of warfarin: bleeding, rare skin necrosis and rare calciphylaxis
Besides warfarin, name 2 other oral anticoagulants
2 other oral anticoag’s: direct oral anticoags and oral direct thrombin inhibitors
___ are the 1st line treatment for VTE and a-fib (barring any contraindications for use)
Why are these drugs overall better than warfarin? (3)
DOACs are the 1st line treatment for VTE and a-fib (barring any contraindications for use)
DOACs are better than warfarin because they cause less intracranial hemorrhage, have fewer drug interactions and have roughly the same efficacy as warfarin
Fill in the blanks (what oral direct drugs have the effects indicated below?)
Oral direct anticoagulants:
Direct Thrombin inh: Dabigatran
Direct Factor 10a inh: -xaban drugs
___ is an oral direct thrombin inhibitor that is renally eliminated (monitor renal function), causes ___ (adverse effect) and is contraindicated w/ ____
Dabigatran is an oral direct thrombin inhibitor that is renally eliminated (monitor renal function), causes dyspepsia and is contraindicated w/ strong P-glycoprotein inhibitors/inducers
****The dyspepsia seen with this drug is caused by the tartaric acid that is in the capsule covering the drug** (one of the inactive ingredients)
****P glycoprotein is an influx pump involved with dabigatran absorption***
Which drugs are oral Factor Xa inhibitors? (3) (hint: -xaban drugs)
Rivaroxaban
Apixaban
Edoxaban
**note that these drugs are renally eliminated; rivaroxaban and apixaban are also hepatically metabolized; contraindicated w/ strong CYP3A4 or P glycoprotein inducers/inhibitors
Why does rivaroxaban have to be taken w/ a large meal?
___ is dose reduced based on age, weight, and serum Cr
___ is contraindicated in pts with good renal function (likely due to faster elimination)
Rivaroxaban has to be taken with a large meal because absorption of the drug is much lower with a small meal than with a large meal
Apixaban is dose reduced based on age, weight, and serum Cr
Edoxoban is contraindicated in pts with good renal function (likely due to faster elimination)
Why wouldn’t you use DOACs in pts with mechanical valves?
People with mechanical valves are at a high risk of thrombosis (related to a whole of factors that you can google if you like. Something about flow, the valve thrombogenicity etc etc)
Which class of drugs is referred to as a “clot buster”?
This class of drugs is primarily indicated for ___ (3)
Fibrinolytics, aka “clot busters” are primarily indicated for STEMI, acute ischemic stroke, and massive pulmonary embolism
Describe the mechanism of action of fibrinolytics
**see below**
Basically plasminogen is activated by tissue activator >> plasmin >> breaks down fibrin and fibrinogen to degradation products
Fibrinogen can be freely circulating or it can be bound to fibrin
The fibrin specificity often dictates the risk of bleeding – if plasminogen is bound to fibrin and we activate the plasminogen, fibrin will be broken down (which is the whole point of a clot buster)
The main fibrinolytics are ___ and ___. Which one is the most fibrin specific?
The main fibrinolytics are alteplase (t-PA) and tenecteplase (TNK)
TNK is the most fibrin specific
Name 4 conditions in which fibrinolytics would be contraindicated
Active bleeding
Severely uncontrolled hypertension (>185/110; want to reduce risk of intracranial bleeding so need to lower BP first)
Recent surgery or serious head trauma
Active anticoagulation use
