Anticoagulants

Question 1

Anticoagulants

Answer 1

Heparin, Enoxaparin, Lepirudin, Dabigatran, Rivaroxaban, Warfarin

Question 2

Fibrinolytics

Answer 2

Streptokinase, Alteplase

Question 3

Antithrombotics

Answer 3

Aspirin, Clopidogrel, Vorapaxar, Abciximab

Question 4

Thrombogenesis

Answer 4

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

Question 5

White thrombus

Answer 5

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

Question 6

Red thrombus

Answer 6

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

Question 7

Blood Coagulation

Answer 7

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

Question 8

Regulation of Coagulation & Fibrinolysis

Answer 8

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

Question 9

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

Answer 9

protease inhibitors; antithrombin

Question 10

Critical step in fibrinolysis

Answer 10

Conversion of inactive plasminogen into the proteolytic enzyme plasmin

Question 11

Heparin

Answer 11

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

Question 12

Heparin inhibits

Answer 12

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

Question 13

Heparin uses

Answer 13

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

Question 14

Heparin side effects

Answer 14

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)

Question 15

Heparin antidote/Hep’s activity measured by

Answer 15

protamine; aPTT

Question 16

Heparin drug interactions

Answer 16

Cephalosporins, penicillins, NSAIDs (ex aspirin)

Question 17

Enoxaparin mech of action

Answer 17

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

Question 18

Enoxaparin therapuetic uses

Answer 18

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

Question 19

Enoxaparin side effects/drug interactions

Answer 19

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

Question 20

Rivaroxaban mech of action; thera uses

Answer 20

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

Question 21

Rivaroxaban side effects and pharmacodynamics

Answer 21

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

Question 22

Lepirudin; thera use

Answer 22

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

Question 23

Lepirudin, Argatroban, Dabigatran mech of act

Answer 23

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

Question 24

Lepirudin side efect; pharmocokinectics

Answer 24

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

Question 25

Dabigatran; Therapeutic uses

Answer 25

Prodrug; Atrial fibrillation: Prevent systemic embolism, Stroke

Question 26

Dabigatran side effects; pharmaco

Answer 26

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

Question 27

Warfarin

Answer 27

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

Question 28

Warfarin mech of action and therap uses

Answer 28

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

Question 29

Warfarin side effects

Answer 29

``` 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 ```

Question 30

treatment of warfarin hemorrhaging

Answer 30

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

Question 31

warfarin drug interactions

Answer 31

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

Question 32

mech of action of Streptokinase, Alteplase

Answer 32

Converts plasminogen into plasmin which degrades fibrin & fibrinogen

Question 33

thera uses Streptokinase, Alteplase

Answer 33

``` 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) ```

Question 34

side effects Streptokinase, Alteplase

Answer 34

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

Question 35

aspirin mech of action

Answer 35

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

Question 36

aspirin uses, side effects

Answer 36

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

Question 37

Clopidogrel mech of action and therapeutic use

Answer 37

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

Question 38

Clopidogrel side effects and pharmacodynamics

Answer 38

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

Question 39

Vorapaxar mech of action and thera use

Answer 39

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

Question 40

Vorapaxar side effects and drug interactions

Answer 40

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)

Question 41

Abciximab mech of action, thera use, side effect

Answer 41

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