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Ch. 51 Anti-Coag, Anti-platelet, Thrombolytic Drugs - KEY POINTS
Fibrin is produced by 2 pathways (intrinsic and extrinsic pathways) and they converge at which clotting factor?
the active form of plasminogen serves to degrade the fibrin meshwork of clots.
The thrombolytic drugs (stroptokinase, alteplase) act by promoting conversion of plasminogen to PLASMIN
The drugs for thromboembolic disorders fall into 3 major groups
3. thrombolytic drugs
Anticoagulants (heparin, warfarin) disrupt
the coagulation cascade
thereby, suppress fibrin production
Anti-platelet drugs (aspirin, clopidogrel (Plavix), inhibit what?
Thrombolytic drugs (alteplase, streptokinase) promote what?
lysis of fibrin, causing dissolution of the thrombi
Arterial thrombi are BEST prevented with which class of drugs?
Anti-platelet drugs (aspirin)
Venous thrombi are BEST prevented with what class of drugs?
Anti-coagulants (heparin, warfarin)
Anti-coagulants are drugs that
reduce the formation of fibrin
Warfarin inhibits the synthesis or activity of clotting factors?
inhibits the SYNTHESIS of clotting factors, including factor Xa and thrombin
All other anti-coagulants inhibit the synthesis or activity of clotting factors?
inhibit the ACTIVITY of clotting factors (either factor Xa, thrombin or both
Heparin suppresses coagulation by
helping Anti-thrombin inactivate thrombin and factor Xa
Heparin is administred through what 2 routes?
IV or subcut
Heparin is a preferred anti-coagulant for use during
2. & in situations that require rapid onset of anti-coag effects such as
Heparin is also used for patients undergoing
open heart surgery
low dose therapy is used to prevent
post-op venous thrombosis
Anti-coagulation effects of HEPARIN DRIP within
minutes of IV admin
What is the MAJOR ADVERSE EFFECT of Heparin?
Severe Heparin induced bleeding can be treated with what antidote?
- a drug that binds to heparin and stops it from working
Heparin Induced Thrombocytopenia (HIT) is a
potentially fatal condition caused by development of antibodies against heparin-platelet protein complexes
Heparin Induced Thrombocytopenia HIT should be suspected whenever
1. platelet counts fall significantly
2. or when thrombosis develops despite adequate anti-coagulation
Heparin is CONTRAINDICATED for patients with
2. uncontrollable bleeding
Heparin must be used with EXTREME CAUTION in all patients who have
a high likelihood of bleeding
Heparin therapy is monitored by measuring what lab?
The target aPTT is how many seconds?
Antidote for severe Heparin OD
Low molecular weight Heparins are produced by
breaking molecules of unfractionated heparin into smaller pieces
Unfractionated Heparins inactivate what?
factor Xa and thrombin equally
Low molecular weight Heparins inactivate what?
only factor Xa
LMW heparin's plasma levels are more predictable than
What type of schedule is LMW heparin on?
LMW heparin's plasma levels are predictable, therefore they can be administered on a fixed schedule with no need for routine lab monitoring
LMW heparins can be used at home
LMW heparins are approved for what 3 things?
1. PREVENTION of DVT following
- abdominal surgery
- hip replacement
- knee replacement
2. Tx of established DVT with or without PE.
3. PREVENTION of ischemic complications in patients with
- unstable angina
- non-Q wave MI
Compared with unfractionated heparin, LMW heparins have
higher bioavailability and longer half-lives.
Direct Thrombin Inhibitors work by
direct inhibition of THROMBIN
Hence, they differ from the heparin life anti-coags, which inhibit THROMBIN INDIRECTLY (by enhancing anti-thrombin activity)
What is one Direct Thrombin Inhibitor prototype?
what is the effect of greatest concern with Direct Thrombin Inhibitor dabigatran (Pradaxa)?
Warfarin is the only
oral anti-coag currently available
Warfarin prevents what?
the activation of Vitamin K synthesis (hence why foods with vitamin K must be avoided when taking coumadin)
thereby, blocks the biosynthesis of vitamin K depending clotting factors
Warfarin is readily absorbed following oral dosing. Once in the blood, what % of coumadin binds to albumin?
Anti-coagulant responses to warfarin develop
slowly and persisnt for several days after warfarin is discontinued
Warfarin is employed most frequently for what?
long term prophylaxis of thrombosis
3 specific indications for Warfarin are
1. prevention of VENOUS THROMBOSIS and associated PE
2. prevention of thromboembolism in patients with prosthetic heart valves (higher INR)
3. prevention of thrombosis during A fibb (higher INR)
Warfarin therapy is MONITORED by measuring what?
PT & INR
What is the INR target for MOST patients?
2 - 3
what is the MAJOR COMPLICATION of warfarin therapy?
Moderate Warfarin OD is treated with what antidote?
Can warfarin be used during pregnancy?
The drugs can cause
- fetal malformation
- CNS defects
- optic atrophy
Drugs that promote bleeding such as Heparin and Aspirin do what when taking with Warfarin?
INCREASE the risk of bleeding in patients taking warfarin.
When patients are on Warfarin, instruct them to avoid
ALL DRUGS (prescript and non-perscrip) that have NOT been approved by the MD.
Dietary Vitamin K can REDUCE the Anti-Coag effect of Warfarin.
Rich dietary sources include
- canola oil
- soybean oil
- green leafy veggies
Aspirin and other Anti-platelet drugs suppress what?
thrombus formation in arteries
Aspirin inhibits platelet aggregation by
causing irreversible inhibition of CYCLOOXYGENASE
Since platelets are unable to synthesize NEW CYCLOOXYGENASE, inhibition
persists for the life of the platelet (7-10days)
Aspirin is given for
1. PRIMARY prophylaxis od MI
2. PREVENTION of MI recurrence
3. PREVENTION of stroke in patients with Hx of transient ischemic attacks
When used to suppress platelet aggregation, aspirin is admin. in
typically 80 - 325 mg/day
Even in low doses, aspirin increases the RISK of what?
GI bleed and hemorrhagic stroke
Another Anti-platelet is Clopidogrel (PLAVIX) which cause (class)
irreversible blockade of ADP receptors on the platelet surface, thereby preventing ADP stimulated aggregation.
Indications for clopidogrel (PLAVIX) ADP inhibitor includes:
1. recent stroke
2. acute coronary syndromes
Anti-platelet Drug class Glycoprotein IIb/IIIa Antagonists include the following drugs?
1. tirofiban (Aggrastat)
2. eptifibatide (Integrilin
3 abciximab (ReoPro)
The GP IIb/IIIa antagonists receptor blockers (abciximab) ReoPro inhibit what?
the FINAL common step in the platelet aggregation and hence are the MOST EFFECT ANTI-PLATELET DRUGS AVAIL
The GP IIb/IIIa antagonists are used
short term to prevent ischemic events in patients with acute coronary artery syndrome and those undergoing PCI
The MAJOR SIDE EFFECT of GP IIb/IIIa antagonists (ReoPro, Integrillin, Aggrastat) is
A client is to undergo a coronary angioplasty. The nurse acknowledges that which drug is used primarily for preventing reocclusion of coronary arteries following a coronary angioplasty?
Thrombolytic Drugs are given to
remove thrombi that have ALREADY formed.
vs. anti-coags which are given to PREVENT thrombus formation.
Thrombolytic Drugs (streptokinase, alteplase tPA) are used to
dissolve existing thrombi (rather than prevent thrombi formation)
Thrombolytic drugs work by
converting plasminogen to PLASMIN, an enzyme that degrades the fibrin matrix of thrombi.
Thrombolytic therapy is most effective when
STARTED EARLY (within 2-6 hours of Sx onset and pref. sooner)
For patients with acute MI, tPA is slightly more effective than
streptokinase BUT costs more and causes intracranial bleeding
Streptokinase may cause
significant HYPOTENSION soon after dosing.