Pharmacology of Platelet Inhibitors

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Questions and Answers

What is the primary effect of phosphodiesterase inhibitors on cyclic AMP levels?

They prevent the degradation of cAMP, increasing its levels. (correct)

They convert cAMP to AMP, enhancing platelet activation.

They block all calcium-mediated signaling pathways.

They decrease cAMP levels, increasing platelet aggregation.

What mechanism is primarily responsible for the inhibition of platelet activity by cAMP?

Sequestration of cytosolic Ca2+. (correct)

Increased Ca2+ absorption.

Direct inhibition of thrombin.

Activation of ADP receptors.

Which of the following is a recommended approach for using Dipyridamole in therapy?

Use it in combination with warfarin. (correct)

Combine it with aspirin for maximum efficacy.

Administer it alone for immediate antiplatelet effect.

Apply it as a monotherapy in acute ischemic events.

What kind of receptor does Vorapaxar act on as a PAR-1 antagonist?

Protease-activated receptor 1. Signup and view all the answers

What kind of adverse effect is associated with the use of Dipyridamole?

Coronary vasodilation. Signup and view all the answers

What correlation has been observed regarding platelet function testing and antiplatelet therapy?

Low responsiveness correlates with a high rate of ischemic events. Signup and view all the answers

Which of the following represents a limitation of tailoring antiplatelet therapy based on platelet response?

Definitive proof in clinical trials is still lacking. Signup and view all the answers

What is the main therapeutic action of phosphodiesterase inhibitors in the context of platelet aggregation?

Increasing the levels of cAMP to reduce aggregation. Signup and view all the answers

What is a common characteristic of GPIIb/IIIa antagonists?

They reduce platelet activation through broad-spectrum inhibition. Signup and view all the answers

Which of the following is a disadvantage of GPIIb/IIIa antagonists?

They require parenteral administration only. Signup and view all the answers

What is the mechanism of action of abciximab?

It prevents the binding of fibrinogen to activated GPIIb/IIIa receptors. Signup and view all the answers

Which of the following is NOT a common GPIIb/IIIa antagonist?

Clopidogrel Signup and view all the answers

Which patient population is most likely to benefit from ADP antagonists like Clopidogrel?

Patients with aspirin intolerance Signup and view all the answers

What is a potential adverse effect of using abciximab?

Increased risk of bleeding. Signup and view all the answers

What is the primary mechanism of action of Clopidogrel?

Noncompetitive inhibition of P2Y12 receptors Signup and view all the answers

Which statement regarding phosphodiesterase inhibitors (PDEI) is true?

They increase cAMP levels in platelets. Signup and view all the answers

How is Clopidogrel metabolized to its active form?

By CYP2C19 and CYP3A4 in the liver Signup and view all the answers

What limitation is associated with the immunogenicity of abciximab?

It limits its use to single administration. Signup and view all the answers

How do GPIIb/IIIa antagonists primarily affect platelet function?

By reducing the activation of platelets. Signup and view all the answers

Which factor can lead to resistance to Clopidogrel therapy?

Polymorphisms in CYP2C19 Signup and view all the answers

Which of the following is a common side effect of antiplatelet therapy, including Clopidogrel?

Gastrointestinal bleeding Signup and view all the answers

What class of drugs does Prasugrel belong to?

ADP receptor antagonist Signup and view all the answers

Which statement is true regarding the activation of Clopidogrel?

It is a prodrug activated by CYP enzymes Signup and view all the answers

Which subtype of ADP receptors is primarily targeted by Ticagrelor?

P2Y12 Signup and view all the answers

Study Notes

Phosphodiesterase Inhibitors

Phosphodiesterase inhibitors (PDEIs) prevent the degradation of cyclic adenosine monophosphate (cAMP) leading to increased cAMP levels.
Increased cAMP levels inhibit platelet activity, reducing platelet aggregation and clot formation.
This action is independent of the agonist, resulting in broad-spectrum inhibition.
cAMP opposes the effects of calcium ions (Ca2+) by sequestering it.
Dipyridamole (Persantine®) is a phosphodiesterase inhibitor that increases cAMP levels, inhibiting platelet activity.
Dipyridamole is recommended for use in combination with warfarin.
It can cause coronary vasodilation as an adverse drug reaction (ADR).

ADP Antagonists

ADP receptor activation triggers platelet activation and clot formation.
ADP antagonists can therefore reduce clot formation.
They are useful in aspirin-intolerant patients.
ADP activates purinergic receptors, particularly the subtypes P2Y1 and P2Y12.
Clinically used ADP antagonists include:
- Clopidogrel (Plavix®)
- Prasugrel (Effient®)
- Ticagrelor (Brilinta®)

Clopidogrel (Plavix®)

Clopidogrel is a prodrug that requires activation via metabolism in the liver by CYP2C19 and CYP3A4 enzymes.
It is a noncompetitive (irreversible) ADP (P2Y12) receptor antagonist.
Patients with poor CYP2C19 metabolism may produce less of the active metabolite and experience resistance to clopidogrel's antiplatelet effects.

GPIIb/IIIa Antagonists

GPIIb/IIIa antagonists reduce platelet activation independent of activating agonists, providing broad-spectrum inhibition.
These antagonists are primarily used for parenteral (intravenous) administration.
Common GPIIb/IIIa antagonists include:
- Abciximab (Reopro®): a monoclonal antibody
- Eptifibatide (Integrelin®): a synthetic cyclic peptide
- Tirofiban (Aggrastat®): a non-peptide
Abciximab prevents fibrinogen binding to activated GPIIb/IIIa receptors, inhibiting platelet aggregation and clot formation.

Abciximab (ReoPro®)

Abciximab is a monoclonal antibody Fab fragment that acts as an essentially irreversible antagonist of GPIIb/IIIa receptors.
It is administered intravenously.
Abciximab reduces the risk of restenosis but can cause bleeding as an ADR.
It has drawbacks such as immunogenicity, limiting its administration to single doses, and requiring parenteral administration.
Patients may develop an allergy to the drug after a single administration.

Zontivity® (Vorapaxar)

Vorapaxar is a first-in-class approved antiplatelet medication that acts as a protease-activated receptor 1 (PAR-1) antagonist.
It was approved on May 8, 2014.

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Description

This quiz tests your knowledge on phosphodiesterase inhibitors and ADP antagonists, focusing on their mechanisms, effects on platelet activity, and clinical applications. You'll learn about agents like Dipyridamole, their role in preventing clot formation, and their adverse effects. Perfect for students and professionals in pharmacology.