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Pharmacology > Antiplatelet Agents > Flashcards

Antiplatelet Agents Flashcards

1
Q

Which drugs affect hemostasis?

A
  1. Heparin-like
  2. Oral agents
    - warfarin
    - direct acting IIa and Xa inhibitors
  3. Antiplatelet agents
    - aspirin
    - clopidogrel
    - GP inhibitors (angioplasty)
  4. Medical devices
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2
Q

What drugs affect thrombolysis?

A

Plasminogen activators

  • alteplase
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3
Q

What is the goal of anticoagulation?

A

To diminish the activity of Factors Xa and IIa (thrombin)

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4
Q

What are examples of antithrombin III catalysts??

A
  • heparin
  • enoxaparin
  • fondaparinux
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5
Q

What are examples of thrombin inhibitors?

A
  • dabigatran
  • rivaroxaban
  • apixaban
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6
Q

What is an inhibitor of clotting factor synthesis?

A

warfarin

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7
Q

What’s the difference between fractionated and unfractionated heparin?

A

unfractionated = larger

fractionated = smaller

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8
Q

What is the pH of heparin?

A

acidic

made from porcine intestine or bovine lung

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9
Q

Antithrombin III catalysts MOA

A

Activate anti thrombin III so that it can bind to and inactivate factors IIa and Xa clotting factors.

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10
Q

True/false: heparin is NOT consumed in the reaction (binding to antithrombin III)

A

True. It is NOT consumed. It is a catalyst

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11
Q

Unfractionated heparin MOA

A

accelerates the reaction. Can bridge thrombin/antithrombin molecules, which speeds up the reaction of ATIII and IIa

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12
Q

LMW heparin MOA

A

No bridge. Can accelerate the interaction of ATIII with Xa.

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13
Q

Fondaparinux MOA

A

Pentasaccharide that binds to ATIII, inhibits Xa activity.

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14
Q

Which of the heparins requires routine monitoring?

A

heparin

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15
Q

True/false: heparin does not cross the placenta.

A

True

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16
Q

Heparins: adverse effects

A

BLEEDING

hypersensitivity

thrombocytopenia

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17
Q

What is the best way to monitor the anticoagulant action of heparin?

A

aPTT (increase)

maintain 2x control time

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18
Q

What is Heparin-induced thrombocytopenia? (HIT)

A

Antibodies againsed heparin-platelet factor 4 complexes. Bind to Fc receptors on adjacent platelets >> aggregation. = antibody mediated thrombocytopenia with paradoxical thrombosis

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19
Q

True/False: warfarin is contraindicated in HIT.

A

True.

A direct thrombin inhibitor is preferred, fondaparinux or argatroban.

20
Q

Contraindication for heparin

A
  • hypersensitivity
  • active bleeding
  • threatened abortion
  • infective endocarditis
  • surgical procedures
21
Q

What is the heparin antagonist?

A

protamine sulfate

ion pairs with heparin to form a stable complex. BE CAUTIOUS: excess PS has anticoagulant activity. Adverse effects = dyspnea, bradycardia, hypotension

22
Q

Indications for LMW heparin

A
  • DVT, clots

- CONTRAINDICATED in HIT

23
Q

Indications for Fondaparinux

A
  • PE, DVT
  • thromboprophylaxis for hip/knee surgery

- use for HIT

24
Q

Thrombin inhibitors MOA

A

Agents that bind to and directly inhibit the activity of key clotting factors.

25
Q

Warfarin MOA

A

decreases synthesis of active coagulation factors

inhibits addition of the gamma-carboxy groups to the clotting factors

= inactive factors

26
Q

What is warfarin’s MOA in relation to vitamin K?

A

It blocks the enzyme VKORCI, which is key to recycling (reduction) of vitamin K.

27
Q

What is important to know about the time frame for using warfarin clinically?

A

It takes time, 8-12 hrs for the drug to act; full activity takes several days.

28
Q

Warfarin Adverse effects

A
  1. BLEEDING
  2. Fetal hemorrhage; abn bone formation
  3. Inhibition of protein C and S >> procoagulant states
29
Q

Vitamin K and Warfarin

A

Warfarin = structural analog of vit. K (isomers)

S form is 4x more active

30
Q

Warfarin drug interactions

A

metabolized by CYP2C9

Vitamin K-large doses can reverse warfarin action

31
Q

Dabigatran

Rivaroxaban

Apixaban

A

orally direct acting inhibitors

32
Q

Dabigatran

A

Prodrug >> hydrolysis

Adverse effects = BLEEDING (esp GI), slightly higher MI risk

Drug interactions: p-glycoprotein transport (ketoconazole + rifampin)

33
Q

Are there antidotes to dabigtran and rivaroxaban?

A

NO

*also very expensive drugs

34
Q

Rivaroxaban

A

Adverse effect = BLEEDING

Drug interactions: p-glycoprotein and Cyp 3A4

35
Q

Desirudin MOA

A

Direct acting thrombin inhibitor

  • no need for ATIII
    • one to one complex with thrombin*

was lepirudin

36
Q

Bivalrudin MOA

A

20 AA direct inhibitor

37
Q

Argatroban MOA

A

must be IV

blocks catalytic site of thrombin (reversible)

use in HIT

38
Q

Abciximab MOA

A

blocks GP IIB/IIIa receptors

  • an integrin, receptor for fibrinogen and vWF

adjunctive for angioplasty

39
Q

Clopidogrel (&prasugrel) MOA

A

Antiplatelet

ADP pathway: P2Y1 and P2Y12 receptors activated at the same time >> activate platelets

Clopidogrel inhibits activation P2Y12 irreversibly

**alternative for apteints who cannot tolerate aspirin (no effect on prostaglandin pathway)

40
Q

What happens when you combin clopidogrel and aspirin?

A

synergy

41
Q

What is unique about the metabolism of heparin?

A

metabolized by the RES

42
Q

What is unique about the metabolism of dabigatran?

A

Is NOT metabolized

renal excretion

43
Q

Prasugrel

A

newer member of class

contraindicated in cerebrovascular disease

44
Q

Adverse effect of Clopidogrel

A

rash, diarrhea, abdominal pain, dyspepsia, bleeding

45
Q
A

Pharmacology (9 decks)

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