test 3 part 2

Question 1

Anticoagulants classified as

Answer 1

• indirect or direct thrombin inhibitors

Question 2

Heparin

Answer 2

• Mixture of straight-chain polysaccharide molecules with a wide range of molecular weights
  * (3000-30,000 Da)
• Activity is dependent upon endogenous anticoagulant antithrombin (AT) /antithrombin III (ATIII)
  * Inhibits coagulation enzymes
  * IIa, IXa, Xa, XIa, XIIa
• Unique pentasaccharide sequence permits binding to ATIII

Question 3

How does heparin work

Answer 3

• Binds reversibly to ATIII and greatly accelerates the rate which ATIII inactivates coagulation enzymes
  * IIa (thrombin) and Xa

Question 4

Low Molecular Weight Heparins (LMWHs)

Answer 4

• Mixture of smaller heparin fractions with molecular weights between 4000 – 6000 Da
• Binds reversibly to ATIII and greatly accelerates the rate which ATIII inactivates coagulation enzymes
  * More selective for Xa inhibition

Question 5

Heparin/LMWHs: Therapeutic Uses

Answer 5

• Prevention of venous thrombosis
• Prevention of post-op DVTs and PE
• Dialysis and cardiac surgery
• Prevent embolisms in patients with a-fib
• Maintain patency of IV injection devices
• Anticoagulant of choice for treating pregnant women
  * Does not cross the placenta

Question 6

Heparin/LMWHs: Pharmacokinetics

Answer 6

•Heparin administered IV
or SC
        • Onset of action
                • IV: a few minutes
                • SC: 1-2 hours
• LMWHs administered SC
        • Onset of action
                • SC: 4 hours

Question 7

Intravenous half-life difference between heparin and LMWHs

Answer 7

Heparin: 2 hours
LMWHs: 4 hours

Question 8

Anticoagulant response difference between heparin and LMWHs

Answer 8

Heparin: vardiable
LMWHs: predictable

Question 9

Bioavailability difference between heparin and LMWHs

Answer 9

Heparin: 20%
LMWHs: 90% (because it’s less protein bound)

Question 10

Major adverse effects difference between heparin and LMWHs

Answer 10

Heparin: frequent bleeding
LMWHs: Less frequent bleeding

Question 11

Setting for therapy difference between heparin and LMWHs

Answer 11

Heparin: hospital
LMWHs: Hospital and outpatient

Question 12

Heparin/LMWHs: Pharmacokinetics

Answer 12

• Taken up by monocyte/macrophage system
• Depolymerized and desulfonated to inactive products in the liver
• Metabolites are excreted into the urine
• Renal insufficiency prolongs the half-life of LMWHs

Question 13

Heparin/LMWHs: Adverse Effects

Answer 13

• Bleeding
• Hypersensitivity
• Thrombocytopenia (HIT)
• Osteoporosis
  * Long-term heparin therapy

Question 14

Fondaparinux

Answer 14

• Used to treat DVT and PE
• Prevention of venous thromboembolism (VTE)
  * Orthopedic and abdominal surgery
• SC administration
• Half-life (17-21 hours)
• Bleeding is major side effect
• HIT less likely
• No reversal

Question 15

Warfarin (Coumadin)

Answer 15

• Inhibits vitamin K epoxide reductase
  * Results in depletion of the reduced form of vitamin K
  * Vitamin K dependent clotting factors
  * II, VII, IX, X
• Vitamin K is a cofactor for carboxylation of glutamate residues of the vitamin K dependent clotting factors
• Decreased levels of factors (II, VII, IX, X) results in decreased thrombin generation
• Monitored using INR as a therapeutic index
  * INR = 2.0 – 3.0 (most patients)
  * INR = 2.5 – 3.5 (mechanical valves)
• Peak effect
  * 72-96 hours
• Reversal
  * Vitamin K administration
  * Takes ~ 24 hours

Question 16

Warfarin (Coumadin): Therapeutic Uses

Answer 16

• Prevention and treatment of DVT and PE
• Stroke prevention
• Stroke prevention in patients with a-fib and/or prosthetic valves
• Prevention of VTE during orthopedic or gynecologic surgery

Question 17

Warfarin (Coumadin): Pharmacokinetics

Answer 17

• Oral administration
• 100% bioavailability
• Highly protein bound
  * Variability in therapeutic response
• Cross placental barrier
• Half-life – 40 hours
  * Highly variable
• Excreted in feces and urine
• Numerous drug interactions

Question 18

Warfarin (Coumadin): Adverse Effects

Answer 18

• Hemorrhage
• Skin lesion and necrosis
• Purple toe syndrome
  * Rare
• Teratogenic

Question 19

Rivaroxaban and Apixaban

Answer 19

• Oral inhibitors of factor Xa
• Both bind to Xa
  * Preventing conversion of prothrombin (II) to thrombin(IIa)
• Half-life: 5-9 hours
• Rivaroxaban
  * Prevention of DVT, PE, and stroke (nonvalvular a-fib)
• Apixaban
  * Prevention of stroke (nonvalvular a-fib)

Question 20

Argatroban

Answer 20

• Synthetic direct thrombin inhibitor
• Reversibly binds thrombin
• Alternative to heparin in patients with HIT
• Parenteral administration

Question 21

Argatroban use

Answer 21

• Used in prevention or treatment of VTE in patients with HIT
• Used during PCI in patients with HIT
• Half-life: 39-51 minutes
• Metabolized in liver
  * Can be used in patients with renal impairment
• Monitored using aPTT
• Bleeding is major side effect

Question 22

Bivalirudin (Angiomax) /Desirudin

Answer 22

• Synthetic direct thrombin inhibitors (free and clot bound)
• Alternative to heparin in patients with HIT
• IV administration
• Half-life: 25 minutes
• Bleeding is major side effect
• Desirudin
  * Prevention of DVT in patients undergoing hip replacement

Question 23

Dabigatran (Pradaxa)

Answer 23

• Oral direct thrombin inhibitor (free and clot bound)
• Half-life: 12-14 hours
• Approved for:
  * Prevention of stroke
  * Systemic embolism
  * In patients with nonvalvular a-fib
• Side effects:
  * Bleeding
  * GI disturbances
• Contraindicated in patients with mechanical or bioprosthetic valves
• Abrupt discontinuation should be avoided
  * Cause increased risk for thrombotic events