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Pharmacology - Test #4 > Coagulation Pharm > Flashcards

Flashcards in Coagulation Pharm Deck (31):
1

Three things triggered in a platelet upon ECM binding

Adhesion/Shape Change
Secretion
Aggregation

2

First step of platelet activation

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

3

Second step of platelet activation

Secretion: Degran. and release of ADP, Thromboxane, Sero.
These cause recruitment of platelets and vasoconstriction

4

Third step of platelet activation

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

5

How do COX-1 inhibitors work

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

6

Maximally effective dose of Aspirin

50-320 mg/day

7

High doses of ASP inhibit production of

Prostacyclin

8

Indications for ASA?

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

9

Cinical actions of ASA?

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

10

Important info to know about ADP receptors in coagulation

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

Both must be activated to activate platelets via ADP

11

Important P2Y12 ADP receptor inhibitors

Clopidogrel
Ticlopidine
Prasugrel
Ticagrelor

12

How long do ADP inhibitor effects last?

Several days after last dose

13

Why do people use Clopidogrel over Ticlopidine

Clopidogrel has a lower toxicity profile. Ticlo may induce TTP

14

Who would you prescribe Clopidogrel for?

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

15

Important details about Prasugrel?

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

16

Important details about Ticagrelor?

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

17

Which CYP activated Clopidogrel

CYP 2C19

18

Which P2Y12 ACP receptor drugs are prodrugs

Clopidogrel, Prasugrel

19

Name G IIb/IIIa Receptor Inhibitors

Eptifibatide
Tirofiban
Abciximab

20

Important Eptifibatide details

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

21

Important Tirofiban details

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

22

How is Tirofiban typically used

Combined with heparin to treat Acute Coronary Syndrome

23

Important details about Abciximab

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

24

Why should you use Abciximab

Prevent thromboembolism in coronary angioplasty
Combined with t-PA for early MI treatment

25

Important Phosphodiesterase-3 Inhibitors

Dipyridamole
Cilostazol

26

What do Phosphodiesterase-3 Inhibitors do?

Activation related to cAMP PDE inhibition opposing P2Y12 action

27

What is Dipyridamole used for?

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

28

What is Cilostazol used for?

Intermittent claudication

29

Protease Activated receptor inhibitors

Vorapaxar
Atopaxar (phase 2 trials)

30

How do protease activated receptors work?

Proteolytic cleavage of PAR-1 on platelet surface
PARs are GPCRs coupled to release of Ca from stores

31

Important Vorapaxar details?

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