Coagulation Pharm Flashcards
Three things triggered in a platelet upon ECM binding
Adhesion/Shape Change
Secretion
Aggregation
First step of platelet activation
Adhesion mediated by GP 1b binding to collagen
Gp1b binding to VWF bridged to collagen
Shape change facilitates binding
Second step of platelet activation
Secretion: Degran. and release of ADP, Thromboxane, Sero.
These cause recruitment of platelets and vasoconstriction
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
How do COX-1 inhibitors work
Inhibition of platelet Cox1, interfering with platelet aggregation via TXA2
Prolongs bleeding time
Prevents arterial thrombi formation
Maximally effective dose of Aspirin
50-320 mg/day
High doses of ASP inhibit production of
Prostacyclin
Indications for ASA?
Prevents coronary thrombosis in unstable angina
Adjunct to thrombolytic therapy
Reduces recurrence of thrombotic stroke
Cinical actions of ASA?
Prolonged bleeding time
No change of PT
Hemostasis returns to normal 36 hours after most rec
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
Important P2Y12 ADP receptor inhibitors
Clopidogrel
Ticlopidine
Prasugrel
Ticagrelor
How long do ADP inhibitor effects last?
Several days after last dose
Why do people use Clopidogrel over Ticlopidine
Clopidogrel has a lower toxicity profile. Ticlo may induce TTP
Who would you prescribe Clopidogrel for?
Acute Coronary Syndrome (MI, Stroke, PVD, Stent)
Important details about Prasugrel?
Used for Acute Coronary Syndrome, PCI
Faster onset of action
Increased potency due to rapid metabolism by Cyp450
Important details about Ticagrelor?
Binds to an allosteric site – reversible binding
Requires no bioactivation
Faster onset than clopedogrel
Which CYP activated Clopidogrel
CYP 2C19
Which P2Y12 ACP receptor drugs are prodrugs
Clopidogrel, Prasugrel
Name G IIb/IIIa Receptor Inhibitors
Eptifibatide
Tirofiban
Abciximab
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
Important Tirofiban details
Reversible inhibitor
Administered in IV, 2 hr plasma life
More than 90% inhibition of platelet aggregation after 30 mins
How is Tirofiban typically used
Combined with heparin to treat Acute Coronary Syndrome
Important details about Abciximab
Ab about Gp 11b/IIIa
IV bolus + Infusion
LONGER DURATION OF ACTION – Bleeding
Why should you use Abciximab
Prevent thromboembolism in coronary angioplasty
Combined with t-PA for early MI treatment
Important Phosphodiesterase-3 Inhibitors
Dipyridamole
Cilostazol
What do Phosphodiesterase-3 Inhibitors do?
Activation related to cAMP PDE inhibition opposing P2Y12 action
What is Dipyridamole used for?
Combined with Warfarin to prevent embolization from prosthetic heart valves.
Used with ASA to prevent cerebrovascular ischemia
What is Cilostazol used for?
Intermittent claudication
Protease Activated receptor inhibitors
Vorapaxar
Atopaxar (phase 2 trials)
How do protease activated receptors work?
Proteolytic cleavage of PAR-1 on platelet surface
PARs are GPCRs coupled to release of Ca from stores
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
