Antiplatelets Flashcards
know
durg, classificaiton, MOA, Epidural implications
Thienopyridine P2Y12 ADP-Receptor Antagonists
- Ticlopidine (Ticlid®)
- Clopidogrel (Plavix®)
- Prasugrel (Effient®)
• Non-Thienopyridine P2Y12 ADP-Receptor Antagonists)
- Ticagrelor (Brilinta®)
* Cangrelor (Kengreal®
• Glycoprotein IIb/IIIa Receptor Inhibitors/Antagonists
- Abciximab (Reopro®)
- Eptifibatide (Integrilin®)
- Tirofiban (Aggrastat®)
ASA Mechanism of action
inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase-1 (COX-1) enzyme, thereby preventing the formation of thromboxane A2, which is a potent platelet aggregate and potent vasoconstrictor
The effects of preventing platelet aggregation last for the
lifetime of the platelet
(7-10 days) since ASA produces irreversible inhibition of platelet cyclooxygenase-1
Aspirin absorption
•
Rapidly absorbed in stomach & upper intestine
• Rapidly cleared from the body (t1/2 =______) but the effects of aspirin on platelets are irreversible and last for the life of the
20 min; platelet (7-10 days)
Non-enteric coated plasma levels peak 30 to 40 minutes
Inhibition of platelet function occurs within 1 hour
• Enteric coated plasma levels peak 3 - 4 hours
ASA should be stop about
7-10 days
in general you dont have to
Dipyridamole
• Is both_____and _________
a vasodilator and antiplatelet agent
Mechanism of action of dipyridamole (1)
- Dipyridamole inhibits cyclic nucleotide phosphodiesterases, the enzyme that degrades cyclic adenosine monophosphate to 5′-AMP, resulting in the intraplatelet accumulation of cyclic AMP, which
inhibits platelet aggregation
Mechanism of action of dipyridamole (2)
- Dipyridamole inhibits the uptake of adenosine into platelets and endothelial cells, which results in an increase in local adenosine concentrations that acts on platelet adenosine A2 receptors thereby stimulating platelet adenylyl cyclase which increases platelet cAMP
levels & cAMP inhibits platelet aggregation
cyclic aMP tells platelets
non-adhere
Stop dipyridamole
• Discontinue 24 hours prior to surgery
Ticlopidine (Ticlid®)
• Thienopyridine Class Antiplatelet Agent
Ticlopidine (Ticlid®)
• Mechanism of action
The active metabolite then binds irreversibly to P2Y12 receptors on the surface of platelets and inhibits ADP induced platelet aggregation and activation
• Inhibits platelet function for the life span of the platelet (7-10 days)
Ticlid
• Is a prodrug that requires the liver for metabolic
KNOw FOR BOARDS • Hold 10 days prior to surgery and hold 14 days prior to placement of neuraxial anesthesia
KNonw for boards
Clinical use has all but been eliminated due to newer agents and due to ticlopidine’s risk of ____
causing severe neutropenia (ANC <
500/µL) and thrombotic thrombocytopenia purpuria (TTP)
Thienopyridine Class Antiplatelet Agent one agent
Clopidogrel
Mechanism of action of Clopidogrel
Is a prodrug that requires several liver CYP 450 enzymes for a 2-step metabolic conversion into its active metabolite. The active metabolite then binds irreversibly to P2Y12 receptors on the surface of platelets and inhibits ADP induced platelet aggregation and activation
Clopidogrel –>Inhibits platelet function for the life span of the platelet_______
(7-10 days)
For clopidogrel: Concomitant use of drugs that inhibit the CYP 450 enzymes used to metabolize clopidogrel to its active metabolite results in_______ plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition
reduced
Clopidogrel, stop -_______ piror to surgery or elective surgery
7 days
Prasugrel (effient)
Is a more potent inhibitor of platelet aggregation than
clopidogrel and achieves more consistent and complete
inhibition of ADP-induced platelet aggregation. The trade off for this potent inhibition is a greater risk of bleeding from prasugrel compared to clopidogrel!
**Contraindications for PRASUGREL (EFFIENT)
• Any previous TIA or stroke (higher mortality)
Prasugrel
Discontinue at least 7 days prior to ANY surgery
Ticagrelor is
• Non-thienopyridine class antiplatelet agent
• Ticagrelor and its active metabolite bind
REVERSIBLY to P2Y12 receptors on the surface of platelets and inhibit ADP induced platelet aggregation and activation
• Ticagrelor and its active metabolite are approximately
equipotent
• Ticagrelor is not a prodrug and ________require metabolic activation –
DOES NOT
Discontinue ticagrelor how many days prior to surgery
5 days before
Contraindicated while epidural
catheter in place hold time before placement
Ticlopidine 14 dyas
Clopidogrel 7 days
Prasugrel 7 days
Ticagrelor 7 days
kengreal (Cangrelor ) used as an
Used as an adjunct to PCI in the management of ACS patients
Mechanism of action of Cangrelor
• Cangrelor is a direct P2Y12 platelet receptor inhibitor that blocks ADP-induced platelet activation and aggregation.
Cangrelor binds selectively and reversibly to the P2Y12
receptor to prevent further signaling and platelet activation
Immediate onset and rapid offset______(medication) how soon does it take for platelet function to return to normal?
Cangrelor
Platelet functions return to normal in 60 minutes
• Metabolism of Cangrelor
• Cangrelor is deactivated rapidly in the circulation by
dephosphorylation to its primary metabolite, a nucleoside
Half life of Cangrelor
3-6 minutes
No consideration for _____and ______in patients receiving cangrelor
liver and kidney
**Vorapaxar (Zontivity®)
**protease-activated receptor 1 (PAR-1) antagonist/inhibitor
**Vorapaxar (Zontivity®) Mechanism of action
Vorapaxar is a competitive, protease-activated receptor 1 (PAR-1) antagonist that inhibits thrombin-induced and
thrombin receptor agonist peptide (TRAP)-induced platelet aggregation
Antiplatelet Agents: Glycoprotein IIb/IIIa
Antagonists Available in United States
Abciximab (Reopro®)
• Eptifibatide (Integrilin®)
• Tirofiban (Aggrastat®)
All have different MOA
GIIb/IIIa antagonists Mechanism of action
bind competitively (reversibly) to the GP IIb/IIIa receptor on platelets and prevent the binding of fibrinogen, von Willebrand factor, and/ or other adhesive ligands to the GP IIb/IIIa receptor and thus inhibit platelet aggregation
If patients on GIIb/IIIA they cannot
cannot go to surgery/epidural catheter
Only us Giib/IIIa
as continuous IV
Glycoprotein IIb/IIIa Antagonists:
Surgical Implications
• Abciximab
Typically discontinued__________
72 hours before surgery
- Eptifibitide and Tirofiban
* Typically discontinued
24 hours before surgery
Can cause bleeding
GIIb/GIIIa
hold time before placement
Abciximab 48 hours
EptifibatideΨ 4-8 hours
TirofibanΨ 4-8 hours
Fibrinolytic agents
• These agents are called fibrinolytic or thrombolytic agents because they act as plasminogen activators since they convert endogenous proenzyme plasminogen into the fibrinolytic enzyme plasmin and plasmin then degrades fibrin into fibrin split products
____is a major structural component of a thrombus
Fibrin
Fibrin-specific agents
• These agents act preferentially on plasminogen molecules that are located within a fibrin clot and produce limited conversion of plasminogen into plasmin in the absence of fibrin, thus causing a limited systemic effect
• This fibrin specificity decreases systemic activation of
plasminogen and the resulting degradation of circulating
fibrinogen
Plasminogen
can be free or bound to a clot
Non-Fibrin-Specific Agents (aka: First generation agents)
•
Streptokinase (Streptase®) – No longer available in the U.S.A
• Urokinase (Abbokinase®) – No longer available in the U.S.A
Fibrin-Specific Agents (aka: Second generation agents)
- Alteplase (Activase®, Cathflo®Activase®)
- Reteplase (Retavase®)
- Tenecteplase (TNKase®)
**Fibrinolytic/Thrombolytic Agents
Absolute contraindications
CASKAKI
Any prior intracranial hemorrhage/hemorrhagic stroke
- Ischemic stroke within 3 months
- Known structural cerebral vascular lesion
- Arteriovenous malformation, Aneurysm
- Known intracranial neoplasm
- Suspected aortic dissection
- Active Internal bleeding or bleeding diathesis
- Considerable facial trauma or closed head trauma in past 3 months
Fibrinolytic/thrombolytics
Relative contraindications
• Severe hypertension (SBP >180 and/or DBP >110)
• History of chronic poorly controlled hypertension
• INR 2-3 on warfarin
• Recent trauma, major surgery, prolonged CPR, minor head trauma,
internal bleeding within past 2-4 weeks
• Active peptic ulcer disease
• Streptokinase exposure > 5 days earlier or prior allergic reaction to streptokinase
• Pregnancy
• Age > 75 years
• Known intracranial pathology (dementia)
• Streptokinase is a
non-enzymatic fibrinolytic agent produced by beta-hemolytic streptococci
Streptokinase Mechanism of action
Rather, streptokinase binds non-covalently
to plasminogen (or binds to plasmin) to form a
streptokinase:plasminogen activator complex, and THIS
COMPLEX then acts on other plasminogen molecules to
generate plasmin
It binds to Plasminogen
Plasmin
plasmin bind to plasmin split products and break down clot
****Pharmacologic Properties of Fibrin-Specific
Thrombolytics
• Mechanism of action
• All available fibrin-specific thrombolytic agents have the same general mechanism of fibrinolysis
****• When introduced into systemic circulation, alteplase, reteplase, and tenectaplase preferentially bind to fibrin within a thrombus and enzymatically convert the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis. Plasmin breaks down fibrin into fibrin-split products. Fibrinogen, a
precursor to fibrin, is also degraded by plasmin
• They produce limited conversion of plasminogen in the absence of fibrin
Alteplase (Activase®)
• Is a serine protease that acts as a tissue plasminogen activator and is manufactured by recombinant DNA technology
Chemically identical to endogenous tPA
Alteplase
• Plasma t1/2 = rt-PA
< 5 min (shorter than streptokinase)
_____ metabolism is the major clearance mechanism for rt-PA
Liver
only medication arpproved for Ischemic stroke
Alteplase
rt-PA administration
- Administer within 3 hours of stroke symptom onset
- It is also appropriate to use within 3 to 4.5 hour window (there are additional inclusion criteria than 3 hour criteria)
Catheter placement
NOOOO
