Anti-platelets

steps of hemostasis

vasoconstriction, platelet plug, coagulation

vasoconstriction agents

serotonin, thromboxane, endothelin-1

steps of platelet adhesion

GPVI, GPIb bind to collagen and von Willebrand factor

chemical mediators recruit platelets (ADP, Thromboxane 2, serotonin, PAF, thrombin)

activate the fibrinogen binding protein (GP IIb/IIIa)

Name the COX-1 inhibitor (antiplatelet)

Aspirin (ASA)

MOA of aspirin (ASA)

Irreversibly inhibits COX-1 → ↓ thromboxane A2 synthesis

Therapeutic uses of aspirin (ASA)

Primary and secondary prevention of MI, ischemic stroke, prevention of stent occlusion, and TIA prevention

ADEs of aspirin (ASA)

Bleeding; GI irritation/ulceration; bronchospasm (hypersensitivity); angioedema; dyspepsia

Pharmacokinetics / Pearls of aspirin (ASA)

Low dose (75-162 mg) sufficient for antiplatelet effect; effect lasts platelet lifespan (7-10 days); avoid in children with viral illness (Reye); interaction with NSAIDs

Name the P2Y12 ADP receptor inhibitors

Clopidogrel, Prasugrel, Ticagrelor, Cangrelor

MOA of clopidogrel

Irreversible P2Y12 receptor inhibitor

Therapeutic uses of clopidogrel

ACS, post-PCI, secondary prevention after MI/stroke, PAD

ADEs of clopidogrel

Bleeding; bruising; GI upset; rare TTP

BBW for clopidogrel

Reduced effectiveness in CYP2C19 poor metabolizers

Pharmacokinetics / Pearls of clopidogrel

Prodrug activated by CYP2C19 — reduced effectiveness in poor metabolizers; avoid with strong CYP2C19 inhibitors (omeprazole)

MOA of prasugrel

Irreversible P2Y12 receptor inhibitor

Therapeutic uses of prasugrel

Decreasing thrombotic events in ACS

ADEs of prasugrel

Bleeding; hypertension; headache; nausea; rare TTP

BBW for prasugrel

Bleeding

Pharmacokinetics / Pearls of prasugrel

Metabolized by CYP3A4

MOA of ticagrelor

Reversible P2Y12 receptor inhibitor

Therapeutic uses of ticagrelor

Prevention of thromboembolism in patients with unstable angina and acute MI

ADEs of ticagrelor

Bleeding; dyspnea; ventricular pauses; bradycardia; increased uric acid

BBW for ticagrelor

Bleeding risk

Pharmacokinetics / Pearls of ticagrelor

Reversible binding; oral; avoids activation requirement; faster offset than clopidogrel

MOA of cangrelor

Irreversible IV P2Y12 receptor inhibitor

Therapeutic uses of cangrelor

PCI

ADEs of cangrelor

Bleeding; dyspnea

Pharmacokinetics / Pearls of cangrelor

IV only; rapid onset and offset; used when oral agents not feasible

Name the phosphodiesterase inhibitor / adenosine modulator

Dipyridamole

MOA of dipyridamole

Inhibits PDE and adenosine reuptake → ↑ cAMP → platelet inhibition and vasodilation

Therapeutic uses of dipyridamole

With aspirin for stroke prevention (combined), diagnostic agent for CAD

ADEs of dipyridamole

Headache; ischemia; orthostatic hypotension

Pharmacokinetics / Pearls of dipyridamole

Variable oral absorption, highly protein bound, hepatic metabolism

Name the PDE3 inhibitor

Cilostazol

MOA of cilostazol

Inhibits PDE3 → ↑ cAMP → platelet inhibition and vasodilation, lowers TG and increases HDL

Therapeutic uses of cilostazol

Intermittent claudication (PAD)

ADEs of cilostazol

Headache; diarrhea

BBW for cilostazol

Contraindicated in heart failure

Pharmacokinetics / Pearls of cilostazol

Extensively metabolized (CYP3A4, 2C19, 1A2)

Name the GPIIb/IIIa receptor antagonists (IV)

Eptifibatide, Tirofiban

MOA of GPIIb/IIIa receptor antagonists

Block GP IIb/IIIa receptor complex → prevent platelet aggregation

Therapeutic uses of eptifibatide

PCI; given IV with heparin and oral antiplatelet therapy

ADEs of eptifibatide

Hemorrhage

Pharmacokinetics / Pearls of eptifibatide

Given IV as loading dose; agents rapidly cleared when infusion stopped; not routinely used due to limited benefit and bleeding risk

Therapeutic uses of tirofiban

Acute coronary syndrome; given IV with heparin and oral antiplatelet therapy

ADEs of tirofiban

Hemorrhage

Name the PAR-1 antagonist

Vorapaxar

MOA of vorapaxar

Competitive PAR-1 (thrombin receptor) antagonist → inhibits thrombin-induced platelet aggregation

Therapeutic uses of vorapaxar

Reduction of thrombotic CV events in patients with MI or PAD history; given with ASA or clopidogrel

ADEs of vorapaxar

Increased bleeding risk

BBW for vorapaxar

Increased bleeding risk in patients with prior stroke/TIA/intracranial hemorrhage

Pharmacokinetics / Pearls of vorapaxar

Long half-life with persistent effect weeks after stopping; 90% bioavailability; metabolized by CYP3A4; contraindicated in prior stroke/TIA/intracranial hemorrhage