(3) Blood & Inflammation: Anti-coagulants & Thrombolytics (1.1-1.4) Flashcards
What enzyme catalyzes the final step of the coagulation cascade?
Thrombin
(Factor II, and crosslinking of fibrin occurs via Factor XIII)
What coagulation factor activates thrombin?
Factor Xa
ROA: Direct factor Xa inhibitors
Oral
What protein mediates Heparin’s effects?
Antithrombin III
Which coagulation factors does Heparin inhibit?
(1) Factor IIa
(2) Factor Xa
Which clotting time does heparin most affect?
PTT
(activated partial thromboplastin time)
Indications (3) : Heparin
(1) DVT prophylaxis
(2) Pulmonary embolism prophylaxis
(3) Acute MI
ROA: Heparin
IV
What is the antigenic target in Heparin-Induced Thrombocytopenia?
Platelet Factor 4
Adverse Effects (4) : Heparin
(1) Heparin-induced thrombocytopenia
(2) Hypoaldosteronism
(3) Osteoporosis
(4) Type IV RTA
* (Type 4 renal tubular acidosis)*
What drug reverses the effects of Heparin?
Protamine sulfate
What is the difference LMWH and Heparin?
LMWH is more specific for Factor Xa
Does LMWH or Heparin have a longer half life?
LMWH
How is LMWH eliminated?
Renally
(Whereas Heparin is eliminated by the liver)
Which anticoagulant is indicated in pregnancy?
Heparin
(or LMWH)
Why doesn’t LMWH require routine monitoring?
↓ Risk of HIT
MOA: Fondaparinux
≅ LMWH
(Although even more specific for ATIII)
Which indirect thrombin inhibitor has the lowest risk of HIT?
Fondaparinux
Suffix: Direct thrombin inhibitors
(1) “-rudin”
(2) “-gatro-“
Suffix: Direct factor Xa inhibitor
“-xaban”
Other than Warfarin, what class of anticoagulant is used in long term therapy of atrial fibrillation?
Direct factor Xa inhibitors
Treatment: Heparin-induced thrombocytopenia
Direct thrombin inhibitors
What’s the goal INR value in Warfarin therapy?
2-3
Indications (2) : Warfarin
(1) Prophylaxis in atrial fibrillation
(2) DVT prophylaxis
Which anticoagulant is a teratogen?
Warfarin
What causes an initially hypercoagulable state in Warfarin therapy?
Early inhibition of Protein C
Why do we need to monitor patients early in Warfarin therapy?
Warfarin induced skin necrosis
(Common initial presentation of Protein C/S deficiency)
What drug should be coadministered early in Warfarin therapy?
Heparin
How is Warfarin reversed?
(1) Delayed: Administer Vitamin K
(2) Immediate: Plasma transfusion
How is Warfarin metabolized?
CYP-450
What does the damaged vascular endothelium expose which activates platelets?
(1) vWF
(2) Collagen
Which platelet receptor does vWF bind?
GP1b
Which platelet receptor does ADP bind?
P2-Y12
What effect does serotonin release from platelets have?
(1) ↑ Platelet aggregation
(2) Vasoconstriction
Which COX isozyme is responsible for synthesizing TXA2?
COX-1
Which COX isozyme is only active during inflammation?
COX-2
MOA: Aspirin
Irreversibly inhibits COX-1 and COX-2
Suffix: ADP receptor inhibitors
“-grel”
Which cardiovascular diseases are antiplatelet drugs used in?
(1) Peripheral artery disease
(2) MI and Acute coronary syndromes
What route of administration should Aspirin be given in the setting of acute MI?
Chewable aspirin
What is dual antiplatelet therapy used for?
Prevent coronary stent thrombosis
What ADP receptor inhibitor does NOT have the suffix “-grel”?
Ticlopidine
Which antiplatelet agent is associated with granulocytopenia?
Ticlopidine
What platelet receptor does Fibrinogen bind?
GP IIb/IIIa
Name 3 drugs which block GP IIb/IIIa
(1) Abciximab
(2) Eptifibatide
(3) Tirofiban
* (Ab-6-imab = gp2 x gp3)*
Adverse Effect: GP IIb/IIIa inhibitors
Thrombocytopenia
Name 2 PDE inhibitors used as antiplatelet agents
(1) Dipyridamole
(2) Cilostazol
What effect does Cilostazol have on vasculature?
Arterial vasodilation
Indication: Cilostazol
Claudication symptoms
Adverse Effect: Cilostazol
Coronary steal
(a phenomenon where an alteration of circulation patterns leads to a reduction in the blood flow directed to the coronary circulation)
What are the fibrinolytic agents?
(1) tPA
(2) Streptokinase
Suffix: Recombinant tPA drugs
“-teplase”
What effect on clotting time do fibrinolytic agents have?
↑ PT and PTT
What circulating product is formed as a result of clot degradation?
D-dimer
When can fibrinolytics be used to treat acute ischemic stroke?
Within 3-4.5 hours
Indications (4) : Fibrinolytics
(1) Acute ischemic stroke
(2) Deep venous thrombosis
(3) Pulmonary embolism
(4) Acute myocardial infarction
What is the time frame for percutaneous coronary intervention?
Within 2 hrs
Adverse Effect: Thrombolytic therapy
Hemorrhagic stroke
Contraindications (3) : Thrombolytic therapy
(1) Recent head trauma
(2) Recent intracranial surgery
(3) Severe hypertension
Which thrombolytic can cause anaphylaxis?
Streptokinase
(Derived from Streptococcus ∴ foreign protein ∴ immunogenic)
What drugs can be used to reverse fibrinolytic therapy?
(1) Aminocaproic acid
(2) Tranexamic acid
MOA: Aminocaproic Acid
Inhibits plasminogen activation