The major cyclooxygenase product of the endothelium causing inhibition of platelet aggregation and vasodilation.

Also called prostaglandin I2 or PGI2.

A member of the family of lipid molecules known as eicosanoids.

It inhibits platelet activation and is also an effective vasodilator.

Known as epoprostenol.

Produced in endothelial cells from prostaglandin H2 (PGH2) by the action of the enzyme prostacyclin synthase.

A member of the prostanoids, with the prostaglandins and thromboxane.

Prevents formation of the platelet plug involved in primary hemostasis, by inhibiting platelet activation.

An effective vasodilator.

Prostacyclin’s interactions in contrast to thromboxane suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage.

Prostacyclin, which has a half-life of 42 seconds.

Is released by healthy endothelial cells.

Functions through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells.

The platelet Gs protein-coupled receptor, the prostacyclin receptor, is activated when it binds to PGI2.

The prostacyclin receptor activation, in turn, signals adenylyl cyclase to produce cAMP.

Prostacyclin is synthesized from arachidonic acid in endothelial cells, sending signals to vascular smooth muscle cells, to increase adenylate cyclase activity, which leads to increased synthesis of cyclic adenosine monophosphate (cAMP), increased cAMP-dependent protein kinase or PKA (protein kinase A) activity, promoting vasodilation and inhibiting cell proliferation. 

Prostacyclin also has anti-thrombotic, anti-fibrotic, and anti-inflammatory effects. 

cAMP inhibits platelet activation and also counteracts any increase in cytosolic calcium levels that would result from thromboxane A2 binding.

Prostaglandin12 also binds to endothelial prostacyclin receptors and in the same manner raise cAMP levels in the cytosol.

cAMP also activates protein kinase A (PKA), which phosphorylates and inhibits myosin light-chain kinase, resulting in smooth muscle relaxation and vasodilation.

PGI2 and TXA2 are physiological antagonists.

Epoprostenol sodium for injectionby continuous infusion at 2 ng/kg/min to start, increased by 2 ng/kg/min every 15 minutes or longer until suitable efficacy/tolerability is achieved.

Treprostinil sodium injection by continuous infusion at 1.25 ng/kg/min to start, increased by up to 1.25 ng/kg/min per week for 4 weeks, then up to 2.5 ng/kg/min per week until efficacy/tolerability is achieved.

Iloprost inhalation solution Inhaled 6–9 times daily at 2.5 mcg, increased to 5.0 mcg 6–9 times daily if well tolerated Synthetic prostacyclin analogues which include iloprost, cisaprost are used intravenously, subcutaneously or by inhalation: as a vasodilator in severe Raynaud’s phenomenon, in pulmonary hypertension, and in primary pulmonary hypertension.

Prostacyclin production is inhibited indirectly by NSAIDs, which inhibit the cyclooxygenase enzymes COX1 and COX2.

Cyclooxygenase enzymes COX1 and COX2 convert arachidonic acid to prostaglandin H2 (PGH2), the immediate precursor of prostacyclin.

Thromboxane, an eicosanoid stimulator of platelet aggregation, is also downstream of COX enzymes.

Prostacyclin concentrations recover much faster than thromboxane levels, so aspirin administration initially has little to no effect but eventually prevents platelet aggregation.

PGI2 is primarily produced in a nucleated endothelial cell, the COX inhibition by NSAID can be overcome with time by increased COX gene activation and subsequent production of more COX enzymes to catalyze the formation of PGI2.

Thromboxane A2 is released primarily by anucleated platelets, which are unable to respond to NSAID COX inhibition with additional transcription of the COX gene because they lack DNA material, allowing NSAIDs to result in PGI2 dominance that promotes circulation and retards thrombosis.

In patients with pulmonary hypertension, inhaled epoprostenol reduces pulmonary pressure, and improves right ventricular stroke work.

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