16. Anti thromb/plat drugs Flashcards
The pharmacologic treatment of NSTEMI, UA, and STEMI is similar, and is consists of
antithrombotic/antiplatelet agents, statins, beta adrenergic
blockers and nitrates.
These are all examples of: Cyclooxygenase inhibitors • Aspirin – ADP receptor inhibitors • Clopidogrel • Prasugrel • Ticagrelor – Glycoprotein IIb/IIIa inhibitors Abciximab • Eptifibatide
Anti-Plats Drugs
Coag Cascade: series of transformations of proenzymes to activated enzymes resulting in the formation of _______which converts soluble fibrinogen to insoluble
fibrin
thrombin (IIa)
Key actions in CoAg cascade:
– activation of Factor X to Xa
– conversion of prothrombin(II) to thrombin (IIa)
– thrombin-mediated transformation of fibrinogen to fibrin (the GLUE)
Factors II, IX, X, VII depend on synthesis of:
Vit K
What is the point of convergence between
extrinsic pathway and intrinsic pathway
Factor Xa
Why do we want to accelerate lysis of occlusive intracoronary thrombosis in STEMI with Fibrinolytics?
– Restore coronary blood flow
– Limit myocardial damage
– Translate to increased survival rate and fewer complications
What patients benefit from fibrinolytic therapy?
Pts with STEMI:
Patients with UA or NSTEMI do not benefit from
fibrinolytic therapy
Alteplase (tPA) is what type of drug therapy?
Recombinant tissue-type plasminogen activators
Mech of action of tPA
Transforms the inactive precursor plasminogen
into active protease plasmin, which lyses fibrin clots
• No matter which thrombolytic is used, the
key point is that need to be
administered ASAP, ideally within 30 min of patient’s presentation at hospital
Complication of tPA?
Bleeding
lytic state for older fibrinolytics (streptokinase)
What patients should we NOT put on fibrinolytics (tPA)?
therapy could impair necessary fibrin clots w/i circulation
– Active peptic ulcer
– Recent stroke
– Recovering from recent surgery
In patients with STEMI,
the earlier the patient presents, and the earlier the artery can be recanalised, the better:
• degree of reversibility and extent of myocardial necrosis are both:
Which is better: an open artery or closed artery?
both time dependent
an open artery is better than a closed artery.
Goals of Anti-Coags
inhibit activation of thrombin by Xa
Directly inhibit thrombin
Decrease production of functional prothrombin
Interfere with coagulation cascade and impair secondary
hemostasis
Anti-Coags
enoxaparin, dalteparin are examples of
Low molecular weight heparins
What additional side effect besides bleeding in unfractionated Heparin is:
heparin-induced thrombocytopenia (HIT)
Side effect of all ‘heparins’
bleeding
LMWH (enoxaparin and dalteparin) as well as fondaparinux advantage over UFH is
longer half-life and more predictable bioavailablity
less bleeding, less risk of HIT
Direct Thrombin Inhibitor
Bivalirudin
INhibits independent of antithrombin and acts on circulating and clot-bound thrombin
Bivalirudin (direct thrombin inhibitor)
Unstable angina patients undergoing percutaneous coronary intervention should use
Bivalirudin
Bivalirudin should be used for patients:
Unstable angina patients undergoing percutaneous coronary intervention
Does Bivalirudin cause thrombocytopenia?
NOPE
Whats the issue with thrombin bound to fibrin?
thrombin bound to fibrin within a thrombus remains enzymatically active and protected from inactivation by antithrombin— can locally activate plateletes causing thrombus growth
Whats the difference in how Heparin and Direct Thrombin inhibitors (Bivalirudin) act on throbmin?
- Heparin only inactivates circulating thrombin
* Direct thrombin inhibitors inactive free and fibrin-bound
Clopidogrel, Ticlopidine, Prasugrel and Ticagrelor are all examples of
Thienopyriadines: Anti-Plat drugs
Abciximab and Eptifbatide are examples of?
GP 11b/IIIa receptor antagonists
Plat activation is associated with increase in:
Ca++ in numerous different mechanisms
Aspirin irreversibly acetylates:
cyclooxygenase-1 in platelet
What effect does aspirin have on thromboxane?
- Blocks production of thromboxane
* Platelets lack nuclei so permanant effect of aspirin
What is the role of prostacyclin in platelets?
Inhibits platelet aggregation: EC’s make this and can regenerate and make more of this to keep platelets from being activated vs aspirin which is irreversible
Aspirin use in patients with
CVD for Secondary Prevention
What benefit does aspirin used in patients with unstable angina, acute myocardial infarction (MI), history of MI provide?
– Reduces incidence of future fatal and nonfatal coronary events
What benefit does aspirin provide in patients with chronic stable angina without a history of MI?
Decreases occurrence of subsequent MI and mortality
What benefit does aspirin provide in patients who have had a minor stroke or transient cerebral ischemic attack
Reduces rate of future stroke and CV events
What benefit does aspirin have in patients who have undergone coronary artery bypass surgery?
Decreases chance of graft occlusion
What pts should use asprin?
Shouldn’t use it?
Low dose for those with clinical manifestations of coronary artery disease
DONT use in health individuals
Mech of action of Thienopyridines; clopidogrel, ticlopidine, prasugrel and ticagrelor:
Inhibit ADP-mediated activation of platelets
• ADP simultaneously activates two purinergic
receptors, P2Y1 and P2Y12
– P2Y1 –> increase PLC –> increase calcium
– P2Y12 –> decrease cAMP–>increase calcium
Inhibit ADP-mediated activation of platelets
• ADP simultaneously activates two purinergic
receptors, P2Y1 and P2Y12
Thienopyridines
Which thienopryidines are irreversible?
clopidegrel, prasurgrel
Which thienopryadines are reversible?
ticagrelor
Drugs inhibit P2Y12 receptor
Thienopryidines
What is the advantage of reversible platelet
inhibitors?
If patient requires surgery (like coronary bypass surgery) and is taking drug like
clopidogrel (or aspirin), waiting period is
necessary to prevent platelet function to
return to normal.
– Life span of the platelet?
– 7-10 days
Clopidogrel, ticlopidine and
prasugrel are____
(which is more readily metabolized?)
pro-drugs
– Prasugrel more readily metabolized and increased potency
Side effects of Thienopryidines
Side effects include bleeding and GI related symptoms
Thienopryidine associated with life threating adverse effects such as severe neutropenia and thrombitic purpura
Ticlopidine
Clopidogrel is metabolized by
CYP2C19
– Variability of response in patients
with CYP2C19 polymorphisms
What drug do we need to be careful of administering with Clopidogrel?
Co-administration with protein pump inhibitor (omeprazole) a concern since PPI inhibit CYP2C19
As monotherapy, drugs are modestly superior to aspirin
in reducing risk of myocardial infarction
– Increased risk of side effects
– Increased cost
Thienopryidine
Combination of______ with aspirin has increased
benefit compared to aspirin alone
– Increased bleeding risk
clopidogrel
Mech of Abciximab
blocks access of fibrinogen, vWF and other adhesive
molecules to the GP IIb-IIIa receptor
blocks access of fibrinogen, vWF and other adhesive
molecules to the GP IIb-IIIa receptor
Abciximab
Mech of Eptifibatide
Contains a sequence motif that binds specifically to GP
IIb-IIIa receptors
Both Abciximab and Eptifibatibe are Glycoprotein IIb/IIIa Receptor Antagonists:
Which one is competitive?
Eptifibatibe is competitive
Abciximabe is non-competitive
Indications of Abciximab or Eptifibatibe?
Patients undergoing PCI, including angioplasty or
stent placement
Patients undergoing PCI, including angioplasty or stent
placement OR Patients with unstable angina and myocardial infarction, often with LMWH
Eptifibatibe
What other drugs do we use or can we use when giving Abciximab?
In combination with aspirin and heparin (or LMWH)
• Also used with alteplase for thrombolysis
All you need to know about Dipryidamole
Occasionally prescribed to patients that
cannot tolerate aspirin; relatively ineffective
• Mechanism of action-unclear, may increase in platelet cAMP
• Blocking phosphodiesterase
• Blocking cellular uptake and destruction of adenosine
• Given alone, the drug has no proven cardiac
benefits
Dabigitran
Rivaroxaban
are what kinds of drugs?
New oral anticoags
Whats the benefit of Dabigitran and rivaroxaban?
reduce the risk of stroke and systemic embolism in
patients with nonvalvular atrial fibrillation
Rivaroxaban inhibits:
Dabigitraban inhibits
Xa
Thrombin
