Anticoagulants Flashcards
Heparin
Anticoagulant
Uses;
- Prophylaxis and Treatment of DVT
- prevents clots in cardiac bypass/ ECMO/ dialysis machine
- Tx unstable angina and systemic embolism associated with acute MI
- maintains potency in intravenous cateter
MOA:
NO Fibrinolytic therapy or anticoagulant effect alone
-acts as a co-actor when bound to anti-thrombin III (endogenous) and potentiates anti-thrombin III effects x 1000
-anti-thrombin inactivated thrombin and other coag factor (9, 10, 11, 12) and plasmin; also prevents conversion of fibrinogen to fibrin (blocks stabilization of clot)
-heparin also binds to factor II which also inhibits thrombin
Dose;
Prophylaxis; SQ 5,000 units q 8-12
first dose 2 hrs before surgery unless regional planned
Cardiopulmonary bypass;
-initial; 300 units/kg
-maintenance; 100units/kg/hr
Reversal Agent; Protamine; 1 mg neutralizes 100 units of circulating heparin
Pharmacokinetics;
onset; immediate with IV
-SQ varies from 20min - 2 hrs
E1/2t; dose deponent (bigger dose longer 1/2t)
-Vd; minimal (not lipid soluble; doesn’t cross BBB/ placenta)
-Pb; high?
- metabolized by the liver
- 50% excreted unchanged by kidneys
Side Effects; -hemorrhage -unexplained bruising -thrombocytopenia -heparin induced thrombocytopenia (HITT) d/c heparin immediately if this occurs
Contraindicated;
- Hx of HITT
- uncontrolled active bleeding
- severe HTN
- suspected intracranial hemorrhage
- bleeding risk
- monitor for S/S of bleeding
- D/C heparin infusion 4 -5 hrs before surgery ad check PTT level
- heparin can be given 1 hr after after neuraxial anesthesia
- epidural catheter can be removed 2- 4 hrs after last dose of heparin if placement was atraumatic
Transexamic acid (TXA)
Antifibrinolytics, Procoagulant, Lysine analog
Uses;
- help patients who are hemorrhaging to stop hemorrhaging
- Reduce Blood loss and need for transfusion are reduced in surgical patients
MOA;
- TXA will directly inhibit plasmin at high doses
- Tranexamic acid competitively inhibits plasminogen activation by binding to the kringle domain (in place of lysine or plasminogen)
- This blocks the conversion of plasminogen to plasmin that would cause fibrinolysin
- Blocking the conversion prevents active plasmin enzyme from degrading fibrin clots, fibrinogen, and other plasma proteins, including the procoagulant factors V and VIII.
Alternative MOA hypothesis has been suggested: TXA improves survival via reduction of pro-inflammatory plasmin activity
Dose;
Loading dose; 1g in 100cc of NS over 10 min
Followed by; 1g in 100cc of NS over 8 hours
*Best effect if given within 3 hours of injury
Pharmacokinetics;
- onset; 5 -15 min
- E1/2t; 2 -11 hrs
- DOA; 3 hours
- Vd; 9 – 12 L
- Pb; 3% (does not bind to albumin)
-95% excreted unchanged by the kidneys (Reduce dose in renal disease)
Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min),
Side Effects;
- Seizures (GABA blockade in frontal cortex)
- Vision changes – particularly color vision
- Ureteral obstruction and bleeding
- Renal toxicity
- No increase of risk for thromboembolic events based on current evidence (no risk of stroke, MI, etc.)
Contraindicated;
Do not administer in the same line as blood products, rFVIIa or Penicillin
Renal Failure (check serum creatinine; if high means creatinine clearance is decreased and then drug excretion will be decreased and dosing amount and schedule must be adjusted)
Should be stored between 15 - 30C (56 - 86F)
Protamine
Procoagulant
Heparin Antagonist
inhibitor of anticoagulation and fibrinolysis
Uses;
- Reverse heparin after cardiac bypass surgery
- Tx heparin OD
- mild anticoagulant effect alone
MOA;
- combines with heparin to form an inactive stable compound with no anticoagulant effects
- compound is 1:1 (protamine:heparin)
- protamine binds to all FREE heparin
- heparin bound to anti-thrombin III may or may not get reversed
- *when used alone protamine has mild anticoagulant effects on platelets and fibrinogen
Dose;
Infusion; <5mg/min (give slow)
Reversal of heparin after surgery; 1 mg of protamine our 100 units of heparin
Pharmacokinetics;
Side Effects;
Protamine
Heparin Antagonist
inhibitor of anticoagulation and fibrinolysis
Uses;
- Reverse heparin after cardiac bypass surgery
- Tx heparin OD
- mild anticoagulant effect alone
MOA;
- combines with heparin to form an inactive stable compound with no anticoagulant effects
- compound is 1:1 (protamine:heparin)
- protamine binds to all FREE heparin
- heparin bound to anti-thrombin III may or may not get reversed
- *when used alone protamine has mild anticoagulant effects on platelets and fibrinogen
Dose;
Infusion; <5mg/min (give slow)
Reversal of heparin after surgery; 1 mg of protamine our 100 units of heparin
*after administration check ACT and compare with baseline ACT -see if further dosing needed
Pharmacokinetics;
DOA; 20 min
Eliminated via the reticuloendothelial system (in the liver?)
Clears faster than heparin (heparin rebound can occur)
Side Effects;
- usually dependent on the infusion r/t histamine release (infusion must be <5mg/min)
- some SE are from protamine/ heparin induced thromboxane A2 release from platelets release; Pretreatment with Cox inhibitor can attenuate these see effects
- hypotension
- bronchoconstriction
- facial flushing
- tachycardia or Bradycardia
- pulmonary hypertension (especially in cardiac bypass setting)
Contraindicated;
- hypersensitivity
- allergy to seafood
Caution;
-decreased LV function more prone to decrease SBP
Stable for 2 weeks at room temp
