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Cardio 1: Anti-Coagulants
Heparin
29
Medical
Graduate
10/04/2013

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Cards

Term
What is unfractionated heparin?
Definition

Heparin is composed of heterogenous glycosaminoglycan chains 

This heterogenous mixture is called regular or unfractionated heparin 

Term
What is low MW heparin (LMWH)
Definition

These are the smallest fragments issoalted from heparin 

These are going to have a completely different prolife than unfractionated heparin 

Term
What is the function of anti-thrombin-III?
Definition

-Formed by the liver

-Inhibits thrmobin in the presence of heparin or heparin-like substances

-Inhibits activated coagulation factos in both the instrinic + common       pathway including:

          Thrombin

          IXa

          Xa

          XIa

          XIIa + Kallikrein

-NO activity against VIIa (extrinsic pathway) 

 

Term
What is the most important anti-coagulant effect of anti-thrombin?
Definition
Inhibition of thrombin + Factor Xa
Term

What is the MOA of heparin?

**Detailed MOA**

Definition
  • Activates anti-thrombin-III and catylsizing the reaction between anti-thrombin-III and thrombin (factor IIa) and anti-thrombin-III and factor Xa
  • This is going to cause inhibition of thrombin and Factor Xa 
  • Heparin is an anti-coagulant drug!!!
Term
What effect is heparin going to have on PT and aPTT time?
Definition
  • Increases aPTT and PT but PT is affected less 
  • But at HIGH plasma concentration of heparin, PT will also be prolonged 
Term
Heparin ROA
Definition
  • Heparin is a large molecule + is destroyed by the GI tract
  • Can ONLY be administed IV or subcutaneously
  • Intramuscular injection is contraindicated b/c hematoma formation
Term
Heparin pharmacokinetics (Onset)
Definition
  • Since heparins activity is based on binding to anti-thrombin-III + clotting factors, its onset of action is going to be determined by rate of apperance into the plasma
  • When rapid anticoagulation is required, IV-bolus injection is used with continuous IV infusion 
  • When slower onset is needed (prophylaxis to surgery) a subcutaenous injection of heparin/LMWH is used 
Term

Continous IV infusion of heparin:

When is it used?

Advantages?

Disadvantages? 

Definition
  • Used after intial bolus injection to maintin heparin levels.  Rate is adjusted based on aPTT test
  • Advantages:  Immediate onset of anti-coagulant effect and stable blood concentrations
  • Disadvantages:  Long term use may cause hypervolemia, discomfort, and needs to be monitored carefully 
Term
When do you use heparin subcutaneous low dose?
Definition
  • Prophylaxis treatment (before surgery and after until discharged) 
Term
What are extracorpeal uses of heparin?
Definition
  • Used to flush out IV lines 
  • They are "heparinized" to prevent coagulation 
Term
Monitoring of heparin?
Definition
  • Remember that your monitoring is MAINLY going to be aPTT time because PT time is not altered much unless you have super high doses
  • aPTT = 1.5-2.5X control 
Term

Heparin pharmokinetics (excretion/termination)

Half-life? 

Definition
  • 50% is excreted unchanged in the urine 
  • Remainder is metabolized by the liver 
  • Half-life dependent on dose

-B/c binding of UFH (unfractionated heparin) binds to plasma proteins via a saturable process 

-And Binding of heparin to plasma proteis = limits bioavailability 

Term
Heparin toxicity?
Definition
  • Hemorrhage:  Caused by overdose or undiagnosed disease 
  • Hematoma:  If given IM or SC injection
  • Heparin-induced thrombocytopenia:
  • Hyperkalemia:  Heparin decreases aldosterone.  So be careful especially for patients that are on ACE-I or ARBs 
  • Acute hypersensitivity, alopecia, platelet aggregation, osteoporosis (after 1 yr treatment), priapism 
Term
How does HIT work? What is it?
Definition
  • Factor IV = calcium 
  • Caused by Ab against Heparin-Factor IV complex
  • Ag-Ab complex forms, binds to Fc receptors on platelets, causing platelet aggregation, and paradoxical thrombosis 
  • Can be treated with direct thrombin inhibitors 
Term
Heparin contraindications
Definition
  • Active bleeding:  Always know the potential of bleeding before giving this.  So look at PT and occult bleeding!
  • Severe hypertension/vascular aneurysm (risk of bleeding)
  • Hemophilia, thrombocytopenia
  • Intracranial hemorrhage 
  • Active tuberculosis 
  • Ulcerative lesions of GI 
  • Threated abortion
  • Visceral carcioma 
  • Should withdraw in surgery of eye, brain, or spinal cord 
  • Do not give to patients undergoing lumbar puncture or anesthetic block 
Term
Can you give heparin to pregnant women?
Definition

ONLY when clearly indicated

Even though does not cross the placenta 

Term
Heparin indictions?
Definition
  • Treatment + prophylaxis of:  DVT or PE
  • Extra-corporeal circulation b/c of IN-VITRO effects
  • Prophylaxis of post-op + recumbence thrombosis 
  • MI + unstable angina
  • DIC
Term
***Treatment of MI***
Definition
  1. Aspirin immediately + O2 + Nitroglycerin + Morphine 
  2. Thrombolytic therapy 
  3. Heparin-IV 
Term
Heparin OD treatment
Definition
  • Immediately withdraw if bleeding complication occurs on heparin
  • Protamine sulfate DOC for heparin OD:  Binds to and inactivates heparin because of its strong + charge
Term

Protamine sulfate

Use

SE

Definition

-Use: For heparin OD or bleeding complications induced by heparin

-SE:  Thrombotic complications

        Can cause transient hypotension if given too fast

        Anaphylactic reaction may occasionally occur 

Term
MOA of LMWH vs Heparin
Definition
  • Factor II = prothrombin
  • Heparin:  Heparin binds to anti-thrombin-III which then binds to Factor Xa or factor-IIa.  Factor Xa does not need another binding site other than anti-thrombin-III so it its activity is suppressed.  Factor-IIa does require another binding site for its suppression that heparin DOES have.
  • LMWH:  LMWH bidns to anti-thrombin-III which then can bind to factor Xa or IIa.  Factor Xa does not require another binding site for its suppression so it is suppressed.  Factor IIa (thrombin) REQUIRES another binding site for its suppression but LMWH does NOT have it.  So factor-IIa activity is NOT suppressed
Term
LMWH use
Definition
  • Has a greater ratio of decreasing factor Xa to thrombin (IIa) activity and so has LESS of a platelet activity.  
  • This is to help decrease bleeding side-effets while still retaining anti-coagulation activity
  • This is ESPECIALLY used to prevent DVT in surgical patients
Term
What are the advantages of LMWH vs Heparin?
Definition
  • Greater bioavilability after SC adminitration 
  • Longer duration of anti-factor Xa activity that allows decreased dosing intervals
  • Linear pharmacokinetcs 
  • Less side-effects
  • Does NOT require monitoring of aPTT
Term
LMWH Drugs
Definition
  • Enoxaparin sodium
  • Dalteparin 
  • Tinzaparin 
Term

Fondaparinux MOA

Benefit?

Definition
  • Analog of heparin that inhibits factor-Xa but not thrombin (so acts like a LMWH)
  • Does NOT bind to platelet factor-IV (calcium) and so does NOT cause HIT 
Term

Benefits of fondaparinux vs heparin

Negatives of fondaparinux

Definition
  • Benefit:  Does not induce HIT b/c does NOT bind to platelet factor-IV
  • Negative: Does NOT modify the PT, aPTT time, bleeding time, or platelet function so monitoring isnt possible
Term
Fondaparinux ROA + SE
Definition
  • SE:  Similar to that of enoxaparin
  • ROA:  SC injection 
Term
Fondaparinux Use
Definition
  • Prophylaxis:  Prevent DVT after fracture or surgery 
  • Administered w/warfarin in acute DVT or acute PE when initial therapy is administered in the hospital 
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