Lecture 10: Drugs for PAD and DVT

Question 1

What are the 5 Parenteral indirect thrombin/Xa inhibitors? (H/E/D/T/F)

Answer 1

heparin

enoxaparin, dalteparin, tinzaparin

fondaparinux

Question 2

What are the 2 Parenteral direct thrombin inhibitors? (B/A)

Answer 2

bivalirudin, argatroban

Question 3

What is the Oral coumarin derivative?

What are the 2 Oral antiplatelet phosphodiesterase inhibitors? (D/C)

Answer 3

CD: warfarin

PDEI: dipyridamole, cilostazol

Question 4

What are the 3 Oral direct Factor Xa inhibitors? (R/A/E)

What is the Oral direct thrombin inhibitor?

Answer 4

XaI: ribaroxaban, apixaban, endoxaban

TI: dabigatran

Question 5

What is the biggest risk factor associated with PAD development?

What complications does PAD lead to?

Answer 5

SMOKING
- also diabetes, obesity, high BP/cholesterol, inc. age

Comp: limb ischemia (GANGRENE) and stroke

Question 6

What is Cilostazol and what is it clinically used for?

Who is it contraindicated in?

Answer 6

• type 3 phosphodiesterase inhibitor that prolongs cAMP in platelets and cells = vasodilation/dec. platelet aggreg.
  use: intermittent claudication (walking causing leg cramps)

CI: pts. with HEART FAILURE (dec. survival in Class III/IV pts)

Question 7

Heparin

What is its MOA, what does it block, and what is its antidote?

How does it affect pregnancy?

Answer 7

MOA: binds to/activates antithrombin III to inhibit Factor Xa and thrombin (blocks generation and inactivates thrombin)

• large negative charge, cannot cross membranes

Antidote: Protamine
Pregnancy: doesn’t cross placenta, so CAN use in pregnancy

Question 8

Heparin

What are 3 major contraindications to use? (T/B/S)

What is Heparin-induced Thrombocytopenia?

Answer 8

1. thrombocytopenia
2. uncontrollable bleeding
3. surgery involving brain, eye, spinal cord

Heparin-induced Thrombocytopenia

• reduced platelet counts w/paradoxical inc. in thrombotic events
• Abs to heparin-platelet complexes

LMW heparins can also cause thrombocytopenia and severe bleeding

Question 9

Enoxaparin, Dalteparin, Tinzaparin

What is their MOA, what are they used for, and what is their antidote?

How do they affect pregnancy?

Answer 9

MOA: shorter length heparin molecules that selectively block Factor Xa but NOT thrombin; used for DVT and red thrombus prevention

• FIRST CHOICE TREATMENTS FOR DVT
• easier to use (can be used at home; long 1/2 lives)

Antidote: protamine
Pregnancy: SAFE

Question 10

Fondaparinux

What is its MOA, what is it used for, and what is its antidote?

How is it administered and what does it NOT potentially cause in patients?

Answer 10

MOA: synthetic pentasaccharide that selectively inhibits Factor Xa and prevents DVT

• more effective than Enoxaparin, but inc. bleeding risk
• can be used in conjunction with Warfarin
• administered SubQ with 17-21 hr 1/2 life

Antidote: NONE (not affected by protamine)
- does NOT cause Heparin-induced Thrombocytopenia

Question 11

Bivalirudin (Hirudin-analog)

What is its MOA, what drug is it commonly used with, and how is it administered?

What is its antidote?

Answer 11

MOA: synthetic peptide that directly (reversibly) inhibits thrombin; given w/GP IIb/IIIa antagonists in pts. undergoing coronary angioplasty

• must be given IV like heparin (expensive though!!)
  Antidote: NONE

Question 12

Argatroban

What is its MOA, what is it used for, and how is it administered?

What patient population is it used in?

Answer 12

MOA: directly binds to catalytic site of thrombin and reduced new thrombus development, specifically pts. with Heparin-induced thrombocytopenia
- treatment monitored with aPTT

• given IV (short half-life)

Question 13

Warfarin

What is its MOA, what is it used for, and what is it NOT useful for?

What is a consideration when using this drug?

Answer 13

MOA: vitamin K antagonist that dec. production of active forms of calcium-dependent clotting factors (2, 7, 9, 10) and protein C/S (anti-clotting factors)

• for long-term thrombosis prophylaxis
• for mechanical heart valves and atrial fibrillation
• NOT useful for emergencies (delayed effects)

remember: slow onset and slow offset, monitor frequently when other drugs are added/subtracted

Question 14

Warfarin

What is a major complication of use and how can it be corrected?

What is its effect in pregnancy?

Answer 14

MC: BLEEDING; if occurs, discontinue immediately

• effects can be reversed with Vitamin K (12-24 hrs)
• give fresh blood for quick change
• can cause cutaneous necrosis (loss of Protein C causes procoagulant state)

Pregnancy: DO NOT USE ON PREGNANT PTS
- crosses the placenta

has greatest affects on Factor VII and Protein C

Question 15

Rivaroxaban (Apixaban, Endoxaban)

What is its MOA, what are its 2 uses, and what is its antidote?

How does it affect pregnancy?

Answer 15

MOA: direct inhibitor of Factor X (binds in active center); used for DVT prevention and stroke prevention in pts with nonvalvular A Fib (not as good w/mechanical valve)

Antidote: andexanet alfa
Pregnancy: appears UNSAFE
- do NOT use with other anticoagulants
- avoid in pts. with renal/hepatic involvement

Question 16

Rivaroxaban

What are its 5 advantages over Warfarin? (R/F/LBR/FI/NM)

Answer 16

1. rapid onset
2. fixed dosage
3. lower bleeding risk
4. fewer drug interactions
5. no need for INR monitoring

Question 17

Dabigatran

What is its MOA, what is it used for, and what is it contraindicated in?

What is its antidote?

Answer 17

MOA: reversible direct thrombin inhibitor that has advantages over Warfarin (no monitor, lower bleeding risk, same dosing)

• used for stroke and systemic embolism prevention
• in pts. with nonvalvular Atrial Fibrillation

CI: pts. with MECHANICAL HEART VALVES
- also pills are unstable (bleeding major concern)

Antidote: idarucizumab