Antiplatelet Drugs Flashcards

1
Q

What is the enzyme that breaks down membrane lipids to create arachidonic acid?

A

Phospholipase A2

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2
Q

What are the two pathways arachidonic acid can enter? (Name the two enzymes)

A

Cyclooxygenase (eventually makes thromboxanes and prostaglandins)

Lipoxygenase
(makes leukotrienes)

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3
Q

Describe the methods of Platelet Aggregation Assays

A

Take a patient’s plasma and subject it to different factors (ADP, thrombin, TRAP (agonist), epi, 5HT, collagen, ristocetin). See how well the platelets aggregate (measured by light transmission)

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4
Q

What is the difference between a primary and secondary aggregation?

A

Secondary aggregations are irreversible. Primary aggregations are reversible.

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5
Q

Light granules contain?

A

Platelet Factor 4 )heparin cofactor)
Beta-thromboglobulin
PDGF

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6
Q

Dense granules contain?

A
ADP
Serotonin
Epinephrine
Ca2+
Histamine
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7
Q

Aspirin

MOA

A

Blocks COX1 and COX2 enzymes through acetylation. Prevents formation of thromboxane, leading to anticoagulation.

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8
Q

Cyclooxygenase Inhibitors

A

Celecoxib

Selective for COX2, but do have some antiplatelet effects

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9
Q

List the ADP Receptor Inhibitors

A
Ticlopidine
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
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10
Q

What are the oral ADP receptor inhibitors? What is the only IV ADP receptor inhibitor?

A

Cangrelor is the only IV agent.

Ticlopedine, Clopidogrel, Prasugrel, and Ticagrelor are oral ADP receptor inhibitors.

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11
Q

The ADP receptor inhibitors are prodrugs that require metabolic transformation EXCEPT for…

A

Ticagrelor

Cangrelor

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12
Q

Which ADP receptor inhibitor tends to have a high variability in patient response? If a patient is resistant to that drug, which drug should you substitute with?

A

Clopidogrel has high variation in patient response (30% inactivity)

Use Prasugrel if a patient is not responding to clopidogrel

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13
Q

Dipyridamole

MOA

A

Coronary vasodilator

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14
Q

Cilostazol

MOA and Indication?

A

Phosphodiesterase inhibitor used in intermittent claudication

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15
Q

What are the GP IIb/IIIa inhibitors?

A

Abciximab
Tirofiban
Eptifabatide

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16
Q

What is the thrombin receptor inhibitor? (Very new drug)

A

Vorapoxar

17
Q

Aspirin

Mechanisms of Resistance

A

Mainly due to a mutation in COX2 enzyme.

The resistance may cause recurrent ischemic events in patients who are on aspirin.

18
Q

ADP Receptor Inhibitors

MOA

A

Block the ADP receptor on the surface of platelets, blocking the upregulation of GP IIb/IIIa receptors in platelet activation/aggregation

19
Q

Which antiplatelet drug is used in every dual/triple antiplatelet therapy?

A

Aspirin is used everywhere!

May be used with clopidogrel (block ADP receptors), GP IIb/IIIa inhibitors, Dipyridamol (coronary vasodilator), Cilostazol (phosphodiesterase inhibitor)

20
Q

Antiplatelet Drugs Clinical Applications

A
  1. Cerebrovascular disease
    - TIA
    - Complete stroke
  2. Coronary artery disease
    - Acute MI
    - Unstable Angina
  3. Saphenous vein coronary artery bypass grafts
  4. Peripheral vascular disease
    - Venous thrombosis
    - Peripheral arterial disease (PAOD, intermittent claudication)
  5. Small Vessel Disease
    - TTP
  6. Prevention of thrombus formation on artificial surfaces
21
Q

Drug Interactions with Antiplatelet Agents

Which interactions can cause increased bleeding?

A

Thrombolytic agents (urokinase, streptokinase, TPA)
Heparin
Warfarin
Antithrombin agents (hirudin, bivalirudin, argatroban)

22
Q

Aspirin blocks the conversion of AA to…? Where?

A

Thromboxane in the platelets. Low dose aspirin does not inhibit production of prostacyclins in the endothelium because it does not get through the thicker endothelial wall.

23
Q

Which drug is an inhibitor of lipoxygenase?

A

Zileuton

Used in management and treatment of asthma

24
Q

List two leukotriene antagonists

A

Montelkast - asthma and seasonal allergies

Zarirlukast- asthma treatment

25
Q

Fish Oil Pharmacology

Mechanism of antiplatelet action

A

Omega 3 Fatty Acids (alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid)

Inhibit thromboxane A2
Lead to production of thromboxane A3, which is inactive in platelet action