Chapter 40 - Antiplatelets

Question 1

Normal platelet levels

Answer 1

150-350 x 10^9/L

Question 2

Normal preventative measures of platelet aggregation

Answer 2

1) endothelium NO and prostacyclin 2) endothelial ADPase expression - degrade ADP

Question 3

Platelet lifespan

Answer 3

8-10 days

Question 4

Activation of platelets

Answer 4

1) exposed tissue factor 2) subendothelial collagen 3) vWF 4) fibronectin interact with glycoprotein on platelets platelets release ADP and thromboxane A2

Question 5

Effect of ADP in platelet aggregation

Answer 5

1) ADP cross link platelets together

Question 6

Thromboxane A2 in platelet aggregation

Answer 6

Vasoconstriction and further recruitment of platelets

Question 7

Glycoprotein IIb/IIIa receptor

Answer 7

Exposes on surface of platelet when activated ligates divalent fibrinogen to bridge platelet promotes aggregation

Question 8

Platelet function and molecular targets

Answer 8

FIGURE 40.1

Question 9

ASA effect

Answer 9

1) irreversibly acetylates COX-1 (cyclooxygenase) 2) decrease prostaglandin H2 and thromboxane A2 3) prevent platelet aggregation 4) high doses of ASA inhibit COX-2 –> antinflammatory effects

Question 10

Time to action of ASA after ingestion

Answer 10

1 hour enteric takes 3-4 hours chewing 20 min

Question 11

Risk of bleeding with ASA treatment

Answer 11

1-3% / year

Question 12

Allergy to ASA

Answer 12

0.3%

Question 13

Clopidogrel key points

Answer 13

1) adenosine diphosphate receptor antagonist 2) thienopyridines 3) prodrug 4) activated by hepatic cytochrome 450 5) irreversibly inhibits P2Y12 ADP receptor on platelet

Question 14

Dose of plavix

Answer 14

75mg - takes a day to have effect 300-600 mg loading - rapid onset 2 hours

Question 15

GI hemorrhage with plavix

Answer 15

2%

Question 16

drug interactions with plavix

Answer 16

PPI = inhibitor of CYP2C19 –> decrease ability of plavix to become activated

Question 17

Ticlopidine

Answer 17

Block P2Y12 ADP receptor also via CYP450

Question 18

Complication with ticlopidine

Answer 18

1) Neutropenia 2) Aplastic anemia 3) TTP

Question 19

Ticagrelor action

Answer 19

1) binds ADP P2Y12 receptor non-competitively and reversibly 2) metabolized by CYP3A4

Question 20

Dose of ticagrelor

Answer 20

180 mg loading then 60-90 mg BID

Question 21

half life of ticagrelor

Answer 21

7-9 hours

Question 22

Time to maximum inhibition of ticagrelor

Answer 22

2 hours

Question 23

Prasugrel key points

Answer 23

irreversibly blocker P2Y12 use in TIA/stroke

Question 24

Dose of prasugrel

Answer 24

60 mg then maintenance 10 mg daily

Question 25

Cangrelor

Answer 25

reversibly bind P2Y12

Question 26

Dose of cangrelor

Answer 26

30 mcg/kg bolus before PCI then 4 mcg/kg/min for 2 hours

Question 27

time to action and half life of cangrelor

Answer 27

time to action \< 2 min half life 3-6 minutes platelet function return to normal in 60 min after cessation

Question 28

Glycoprotein IIB/IIIA inhibitors

Answer 28

Abciximab = monoclonal antibody eptifibatide, tirofiban = peptide antagonists

Question 29

Dose of glycoprotein IIB/IIIA inhibitor

Answer 29

Abciximab 0.25 mg/kg before PCI then 0.125 mcg/kg/min Eptifibatide 180 mcg/kg then 2 mcg/kg/min Tirofiban 25 mcg/kg then 0.15 mcg/kg/min

Question 30

Side effect with glycoprotein IIB/IIIA inhibitor

Answer 30

5% thrombocytopenia worst with abciximab

Question 31

Half life of glycoprotein IIB/IIIA inhibitor

Answer 31

Abciximab - 30 min Eptifibatide 2.5 hours Tirofiban - 2 hours stop 2-4 hours before surgery; abciximab needs 12 hours because of slow dissociation

Question 32

Dipyridamole effect

Answer 32

inhibit activity of adenosine deaminase and phosphodiesterase --\> increase cAMP --\> vasodilation and inhibit platelet aggregation

Question 33

Aggrenox

Answer 33

200 mg Dipyridamole + 25 mg asa BID

Question 34

Side effects of dipyridamole

Answer 34

1) headache 2) dizziness 3) skin rash 4) GI upset 5) chest pain

Question 35

Dipyridamole half life

Answer 35

10-12 hours

Question 36

Protease activated receptor 1 inhibitor

Answer 36

Vorapaxar inhibit thrombin-induced and thrombin receptor agonist peptide (TRAP) induced platelet aggregation half life 3-4 days takes 1 week to get 80% activity dose 2.5 mg daily with ASA Contraindicated in stroke, TIA, ICH

Question 37

CAPRIE trial

Answer 37

1) plavix vs asa 2) 19185 patients 3) recent stroke, MI or PAD symptomatic 4) plavix had has slightly less risk of stroke, MI or death 5.32 vs 5.83

Question 38

TRA 2P trial

Answer 38

Vorapaxar for secondary prevention of ischemic events Reduced hospitalization for acute limb ischemia and need for peripheral revasc

Question 39

ACC/AHA guideline for perioperative management of CAD

Answer 39

FIGURE 40.4