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Flashcards in Anticoagulants Deck (41)
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1

Anticoagulants

Heparin, Enoxaparin, Lepirudin, Dabigatran, Rivaroxaban, Warfarin

2

Fibrinolytics

Streptokinase, Alteplase

3

Antithrombotics

Aspirin, Clopidogrel, Vorapaxar, Abciximab

4

Thrombogenesis

Immediate hemostatic response of a damaged vessel, Vasospasm
Within seconds, Platelets stick to the exposed collagen of the damaged endothelium, Platelet adhesion
& then to each other, Platelet aggregation
Platelet plug quickly arrests bleeding
Must be reinforced by fibrin for long-term effectiveness

5

White thrombus

Forms in high-pressure arteries & decreases arterial flow, Stasis triggers fibrin formation → Stroke, MI

6

Red thrombus

Can form around a white thrombus or in low-pressure veins, Platelets form a long tail consisting of a fibrin network in which RBC are enmeshed → DVT → PE

7

Blood Coagulation

Blood coagulates by the transformation of soluble fibrinogen → insoluble fibrin
At each step of this cascade, a clotting factor, i.e., zymogen undergoes limited proteolysis & becomes an active protease, VII is activated to VIIa
Protease activates the next clotting factor, Until a solid fibrin clot is formed

8

Regulation of Coagulation & Fibrinolysis

Blood coagulation must be confined to the smallest possible area to achieve local hemostasis in response to bleeding, Without causing disseminated coagulation or impaired blood flow

9

Blood contains ________ that rapidly inactivate the coagulation proteins as they leave the site of injury, e.g.,

protease inhibitors; antithrombin

10

Critical step in fibrinolysis

Conversion of inactive plasminogen into the proteolytic enzyme plasmin

11

Heparin

about 50 monosaccharides in a chain
Greatly increases the rate of activity of antithrombin, Heparin (-) binds with antithrombin (+) which inhibits serine protease clotting enzymes

12

Heparin inhibits

Inhibits clotting factors IIa (thrombin) & Xa, (IXa, XIa, & XIIa)

13

Heparin uses

Thrombosis/Embolism: Prophylaxis (e.g., after major surgery) & active Treatment (e.g., PE, DVT)
Disseminated Intravascular Coagulation (DIC)

14

Heparin side effects

Hemorrhage (<10%) anywhere in the body (e.g., GI)
Allergy (chills, fever, urticaria)
Thrombocytopenia (HIT) (Heparin induces antibodies which destroy platelets, also attack the lining of blood vessels which can trigger a coagulation cascade
HIT can cause stroke & other thrombotic complications which can be life threatening)

15

Heparin antidote/Hep's activity measured by

protamine; aPTT

16

Heparin drug interactions

Cephalosporins, penicillins, NSAIDs (ex aspirin)

17

Enoxaparin mech of action

(smaller version of heparin) more sensitive for Xa than IIa

18

Enoxaparin therapuetic uses

DVT prophylaxis
DVT Tx (+/- PE)
Unstable angina/Non-Q-wave MI

19

Enoxaparin side effects/drug interactions

similar effects to heparin, also hematomas; interacts w/ same drugs as heparin

20

Rivaroxaban mech of action; thera uses

Direct Xa inhibitor; Atrial fibrillation: Prevent → Stroke, Systemic embolism
Prophylaxis of DVT: Knee, Hip replacement

21

Rivaroxaban side effects and pharmacodynamics

Hemorrhage: Spinal or Epidural anesthesia or puncture; CYP3A4, P-gp
Severe renal & hepatic impairment (↑AUC)

22

Lepirudin; thera use

Polypeptide analog of hirudin → Hirudo medicinalis (leech); Heparin-induced thrombocytopenia

23

Lepirudin, Argatroban, Dabigatran mech of act

Inhibits thrombin (IIa) by binding to it (1:1 stoichiometry)

24

Lepirudin side efect; pharmocokinectics

Allergy- Antibody inhibition b/c of yeast expression; Adjust dose with hepatic function

25

Dabigatran; Therapeutic uses

Prodrug; Atrial fibrillation: Prevent systemic embolism, Stroke

26

Dabigatran side effects; pharmaco

Hemorrhage (intracranial bleeding), Less bleeding with dabigatran vs. warfarin, GI (dyspepsia, gastritis);
Adjust dose with renal function, Rifampin (P-gp)

27

Warfarin

Racemic mixture, S-enantiomer 4 x more potent; Therapeutic efficacy, Measured by international normalized ratio (INR), Therapeutic range, 2.0 to 3.0

28

Warfarin mech of action and therap uses

Vitamin K analog & thus blocks the gamma-carboxylation of several glutamate resides in clotting factors II, VII, IX & X; Venous thrombosis: prophylaxis & treatment
Atrial fibrillation: prevent embolization

29

Warfarin side effects

Hemorrhage
Necrosis (gangrene of the skin)
Hypercoagulation (transient)
Warfarin blocks the biosynthesis of protein C which inactivate clotting factors Va, VIIIa (via proteolysis), Because of the slow onset of anticoagulation with warfarin therapy, Heparin tx is used for the 1st 5 days
Birth defects (facial, CNS)
Abortion

30

treatment of warfarin hemorrhaging

D/C warfarin, Give Vitamin K1 (phytonadione), Give Plasma, Give Factor IX concentrate

31

warfarin drug interactions

Bleeding
PK: Amiodarone, Metronidazole, Fluconazole Sulfamethoxazole/Trimethoprim, Clopidogrel
PD: Aspirin, Ceftriaxone, Ginkgo biloba
Clotting
PK: Phenobarbital, Rifampin, Carbamazepine, St. John’s Wort, Cholestyramine
PD: Vitamin K, Hydrochlorothiazide

32

mech of action of Streptokinase, Alteplase

Converts plasminogen into plasmin which degrades fibrin & fibrinogen

33

thera uses Streptokinase, Alteplase

Acute myocardial infarction (S,A)
Pulmonary embolism (S,A)
Deep vein thrombosis (S)
Arterial thrombosis & embolism (S)
Occluded arteriovenous cannulae (S)
Acute ischemic stroke (A)

34

side effects Streptokinase, Alteplase

Hemorrhage
Lysis of fibrin at vascular injury
Systemic plasmin inhibits factors V & VIII
Allergy (anaphylaxis, S)

35

aspirin mech of action

Inhibits the synthesis of thromboxane A2, Irreversible acetylation of COX-1/2, Anuclear platelet, Can’t synthesize more COX during its 10-day lifetime
Thromboxane A2 function: platelets c shape, release granules, & aggregation

36

aspirin uses, side effects

1o prophylaxis of MI & TIA ;
Bleeding, GI Ulcers

37

Clopidogrel mech of action and therapeutic use

P2Y12 receptor antagonist, therefore it interferes with platelet membrane function by inhibiting ADP-induced platelet-fibrinogen binding & subsequent platelet-platelet interaction ; Arterial thromboembolism prophylaxis: Prevent Myocardial infarction, Stroke

38

Clopidogrel side effects and pharmacodynamics

Thrombocytopenia, Leukopenia, Thrombotic Thrombocytopenic Purpura; Bioactivated 1o by CYP2C19 & Inhibitor of CYP2C9

39

Vorapaxar mech of action and thera use

Mechanism of action:
Protease-activated receptor-1 (PAR-1) antagonist, Inhibits thrombin mediated activation of platelets
Therapeutic use:
Myocardial infarction, Peripheral artery disease, ↓ thrombotic cardiovascular events, With ASA + Clopidogrel

40

Vorapaxar side effects and drug interactions

Hemorrhage: contraindicated in patients with 1. active bleeding conditions, 2. history of TIA, 3. stroke & 4. intracranial bleeding, Anemia, Retinopathy (diplopia); CYP3A4 substrate, Anticoagulants (e.g., NSAIDs, SSRIs, warfarin)

41

Abciximab mech of action, thera use, side effect

Mechanism of action
Inhibits the glycoprotein IIb/IIIa receptor of platelets →
↓ platelet aggregation w/ fibrinogen & vWF
Therapeutic use
Acute coronary syndrome: percutaneous coronary intervention (PCI) used with aspirin &/or heparin
Side Effect
Thrombocytopenia