Antiplatelets

Question 1

P2Y12 Receptor Blockers (ADP blockers/Thienopyridines)

Answer 1

MOA: They block the binding of ADP to a specific platelet receptor P2Y12, thereby inhibiting platelet activation for CARDIAC indications.

Ticlopidine (Ticlid®): SE: Neutropenia, TTP. (Has fallen out of favor).

Clopidogrel (Plavix®):** irreversible** inhibitor of P2Y12 receptors. It is a prodrug: that needs to be activated by CYP2C19, the activity of which is genetically controlled & variable among populations. Omeprazole: is a strong inhibitor of CYP2C19, pantoprazole is NOT!

Prasugrel (Effient®): Less affected by 2C19 inhibitors than Plavix, more effective but with a higher risk of bleeding. Avoid in patients older than 75 years.

Ticagrelor (Brilinta®): A newer reversible ADP inhibitor. Not a prodrug. Indicated for acute coronary syndromes. Causes dyspnea, and more bleeding than Plavix.

Cangrelor (Kengreal®): IV, reversible inhibitor of P2Y12 receptors

Question 2

Antiplatelets

Answer 2

In general, they are used to prevent arteriothrombosis.

Question 3

Aspirin

Answer 3

Indications:
Acute coronary syndromes & secondary prevention of ACSs (2 antiplatelets)
Stroke & TIA (1 antiplatlet)
Peripheral arterial disease (Aspirin and Cilostazole or Dipyridamole)
Inflammatory arthritis (RA, gout)
Antipyretic
Kawasaki Disease: aspirin reduces the incidence of coronary anuerysms
Essential thrombocythemia: For clotting use aspirin, for bleeding use Hydroxyurea and Anagrelide.

MOA: Aspirin irreversibly inhibits cyclooxygenase enzyme (COX) , which < TXA2, which results in inhibition of platelet aggregation for 7-10 days. thus uf having delicate surgery, need to stop ASA 7-10 days till new platelets are made.

Adverse effects:
Bleeding due to platelet inactivation.
Inhibition of PGE2 causes peptic ulcers and renal insufficiency.
Asthma may result from altering leukotriene synthesis. (Samter’s Triad: is a combination of aspirin intolerance, asthma, and nasal polyps).
Tinnitus: in chronic aspirin use (6-7 days per week).
In toxic amounts aspirin leads to: hyperventilation, metabolic acidosis (with increased anion gap), encephalopathy and renal insufficiency.

Question 4

PAR-1antagonist (Protease-activated receptor) family

Answer 4

Vorapaxar (Zontivity®)
New Class/Drug

Indications: used for persons with a history ofmyocardial infarction or persons withperipheral arterial disease

MOA: It functions by** inhibiting thrombin-related platelet aggregation**. This mechanism works by a different pathway than other anti-platelet medications such as aspirin and P2Y12 inhibitors.

Contraindicated for: people with a history of stroke, transient ischemic attack, or intracerebral hemorrhage

Question 5

phosphodiesterase enzyme (PDE) inhibitor

PDE = platelet enzyme

Answer 5

MOA: It inhibits PDE, thus > CAMP in platelets, which prevents their activation. Inhibitig PDE also > GAMP, in vessel wall, which leads to vasodilation.

Dipyridamole (Persantin®): weak drug, not 1st-line tx. SE: GI bleed (not too much risk). Dizziness and headache because of the vasodilation.

Cilostazol (Pletal®): inhibits phosphodiestarse III. Reversible inhibition of platelet aggregation, vasodilation and inhibition of vascular smooth muscle cell proliferation. Indications: DOC for Symptomatic management of PVD, primarily intermittent claudication (In addition to aspirin or clopidogrel). Side effects: Because of vasodilation it results in headache (most common adverse effect) as well as dizziness and vertigo. The most serious adverse effect is worsening CHF.