Coagulation Pharm

Question 1

Three things triggered in a platelet upon ECM binding

Answer 1

Adhesion/Shape Change
Secretion
Aggregation

Question 2

First step of platelet activation

Answer 2

Adhesion mediated by GP 1b binding to collagen
Gp1b binding to VWF bridged to collagen
Shape change facilitates binding

Question 3

Second step of platelet activation

Answer 3

Secretion: Degran. and release of ADP, Thromboxane, Sero.

These cause recruitment of platelets and vasoconstriction

Question 4

Third step of platelet activation

Answer 4

Step two triggers expression of GPIIb/IIIa to bind fibrinogen
Forms temporary hemostatic plug
Fibrin stabilizes and anchors agregated platelets

Question 5

How do COX-1 inhibitors work

Answer 5

Inhibition of platelet Cox1, interfering with platelet aggregation via TXA2
Prolongs bleeding time
Prevents arterial thrombi formation

Question 6

Maximally effective dose of Aspirin

Answer 6

50-320 mg/day

Question 7

High doses of ASP inhibit production of

Answer 7

Prostacyclin

Question 8

Indications for ASA?

Answer 8

Prevents coronary thrombosis in unstable angina
Adjunct to thrombolytic therapy
Reduces recurrence of thrombotic stroke

Question 9

Cinical actions of ASA?

Answer 9

Prolonged bleeding time
No change of PT
Hemostasis returns to normal 36 hours after most rec

Question 10

Important info to know about ADP receptors in coagulation

Answer 10

P2Y1 – Couples to Gq-PLC-IP3-Ca pathway
P2Y12 – Couples to Gi and AC inhibition

Both must be activated to activate platelets via ADP

Question 11

Important P2Y12 ADP receptor inhibitors

Answer 11

Clopidogrel
Ticlopidine
Prasugrel
Ticagrelor

Question 12

How long do ADP inhibitor effects last?

Answer 12

Several days after last dose

Question 13

Why do people use Clopidogrel over Ticlopidine

Answer 13

Clopidogrel has a lower toxicity profile. Ticlo may induce TTP

Question 14

Who would you prescribe Clopidogrel for?

Answer 14

Acute Coronary Syndrome (MI, Stroke, PVD, Stent)

Question 15

Important details about Prasugrel?

Answer 15

Used for Acute Coronary Syndrome, PCI
Faster onset of action
Increased potency due to rapid metabolism by Cyp450

Question 16

Important details about Ticagrelor?

Answer 16

Binds to an allosteric site – reversible binding
Requires no bioactivation
Faster onset than clopedogrel

Question 17

Which CYP activated Clopidogrel

Answer 17

CYP 2C19

Question 18

Which P2Y12 ACP receptor drugs are prodrugs

Answer 18

Clopidogrel, Prasugrel

Question 19

Name G IIb/IIIa Receptor Inhibitors

Answer 19

Eptifibatide
Tirofiban
Abciximab

Question 20

Important Eptifibatide details

Answer 20

Inhibits fibrinogen binding to decrease platelet activation
IV bolus followed by infusion up to 72 hours
Duration of 6-12 hrs
Derived from Rattlesnake Venom

Question 21

Important Tirofiban details

Answer 21

Reversible inhibitor
Administered in IV, 2 hr plasma life
More than 90% inhibition of platelet aggregation after 30 mins

Question 22

How is Tirofiban typically used

Answer 22

Combined with heparin to treat Acute Coronary Syndrome

Question 23

Important details about Abciximab

Answer 23

Ab about Gp 11b/IIIa
IV bolus + Infusion
LONGER DURATION OF ACTION – Bleeding

Question 24

Why should you use Abciximab

Answer 24

Prevent thromboembolism in coronary angioplasty

Combined with t-PA for early MI treatment

Question 25

Important Phosphodiesterase-3 Inhibitors

Answer 25

Dipyridamole

Cilostazol

Question 26

What do Phosphodiesterase-3 Inhibitors do?

Answer 26

Activation related to cAMP PDE inhibition opposing P2Y12 action

Question 27

What is Dipyridamole used for?

Answer 27

Combined with Warfarin to prevent embolization from prosthetic heart valves.
Used with ASA to prevent cerebrovascular ischemia

Question 28

What is Cilostazol used for?

Answer 28

Intermittent claudication

Question 29

Protease Activated receptor inhibitors

Answer 29

Vorapaxar

Atopaxar (phase 2 trials)

Question 30

How do protease activated receptors work?

Answer 30

Proteolytic cleavage of PAR-1 on platelet surface

PARs are GPCRs coupled to release of Ca from stores

Question 31

Important Vorapaxar details?

Answer 31

Prophylactic for MI, PAD
Used w/ ASA or Plavix
Half Life 3-4 days (lasts for days after stopping drugs)
Contra – Stroke, TIA, or Hemorrhage history