A-29. Drugs used coagulation disorders I: Antiplatelet agents. Flashcards
TXA2 Synthesis Inhibitors
Acetylsalicylic acid (aspirin)
P2Y12 Receptor (ADP receptor) Antagonist
Clopidogrel, prasugrel, ticagrelor
ticlopidine, cangrelor
PAR-1 Antagonist
Vorapaxar
GpIIb/IIIa (vWF/fibrinogen receptor) Antagonist
abciximab, eptifibatide, tirofiban
PDE Inhibitors
dipryidamole and cilostazol
Antiplatelet drugs are used for arterial or venous thrombotic disorders?
Arterial thrombotic disorder
MOA of Acetlysalicylic Acid
- Irreversible inhibition of COX enzyme
- Decreased synthesis of both TXA2 (platelet activator/aggregator) and prostacyclin (platelet/vasodilator)
Where is TXA2 and prostacyclin formed?
TXA2 is formed in platelets, which doesn’t synthesize new COX once it is inhibited.
Prostacyclin is formed by endothelium which synthesizes new COX.
Indications of Acetylsalicylic Acid
- ) Primary/Secondary Prophylaxis of Arterial Thromboemboli
- As in unstable angina, MI, angioplasty, cerebrovascular issues - ) Pain, fever, inflammation
Loading dose of acetylsalicyclic acid
250-500 mg given acutely
Kinetics of Aspirin
Good oral absorption, high plasma protein binding, first pass metabolism to salicyclic acid in liver
Side effects of Aspirin
Bleeding, peptic ulcers
P2y12 inhibitors (thienopyridines) MOA
non-competitive inhibition of P2Y12- an ADP receptor on platelets
P2y12 inhibitor kinetics
Prodrugs activated in the liver (except ticagrelor and cangrelor)
Good oral absorption
High protein binding
Have a good synergistic effect with other anti-platelet drugs
Ticagrelor and cangrelor are reversible inhibitors which do not require activation by CYP enzymes
Indications of P2Y12 inhibitors
cardio/cerebrovascular disorders
Side effects of P2Y12 inhibitors
- ) GI upset and minor bleeding
2. ) Leuko-/thromboctopenia- rare, worse with ticlopidine (regular CBCs for 1st three months)
P2Y12 inhibitors interactions
CYP2C19 inhibitors i.e. omeprazole, fluoxetine, fluconazole inhibit clopidogrel activation
PAR-1 Antagonist (Vorapaxar) MOA
Inhibits platelet PAR-1 (protease-activated receptor) leading to decreased platelet activation by thrombin
Kinetics of PAR-1 Antagonist (Vorapaxar)
Good oral absorption; metabolized by CYP enzymes
Indications of of PAR-1 Antagonist (Vorapaxar)
- ) Myocardial Infarction- as secondary prophylaxis
2. ) Peripheral Arterial Thrombi- in combination with aspirin
Contraindication of PAR-1 Antagonist and side effect
bleeding (contraindication and side effect), TIA, and stroke
GPIIb/IIIa Receptor Antagonist (Abciximab) MOA
high affinity mAB against GpIIb/IIIa receptor complex causing irreversible antagonism of vWF.fibrinogen binding by GpIIb/IIIa
(also binds endothelial cells and vitronetin receptors)
Kinetics of abciximab
IV admin; short metabolic (30 min) but lon biological half-life (18-24 hours)
Indications of abciximab
PCI procedures for treatment of acute coronary syndrome
Side effects of abciximab
- ) Bleeding- major bleeding in 4%; severe bleeding may require platelet transfusion
- )Thrombocytopenia- in 1%; monitor platelet counts
- )hypotension, bradycardia, nausea, vomiting
Eptifibatide and tirofiban are both _______ antagonists of GpIIb/IIIa
kinetics
competitive antagonist
Given via IV; short 2-4 hours duration of action; more thrombocyte-selective than abciximab
Dipyridamole
MOA
Indication
Complications
PDE and adenosine uptake inhibition leading to vasodilation and platelet inhibition
Indication: Heart valve thrombus prophylaxis- only effective with warfarin
Complications: coronary steal syndrome with high IV doses
-healthy coronaries dilate while stenotic ones already at max dilation do not leading to coronary circulation is stolen by already-healthy vessels
Cilostazol is used for?
Newer PDE inhibitor for the treatment of intermittent claudication
Antiplatelet drugs may skew which test?
Bleeding time is increased
