Prostacyclin
Prostacyclin Uses, Dosage, Side Effects, Food Interaction and all others data.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension.
Prostacyclin has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol.
| Trade Name | Prostacyclin |
| Availability | Prescription only |
| Generic | Epoprostenol |
| Epoprostenol Other Names | Epoprostenol, Prostacyclin, Prostaglandin I2, Prostaglandin X, Vasocyclin |
| Related Drugs | sildenafil, tadalafil, Revatio, Adempas, Opsumit, ambrisentan |
| Type | |
| Formula | C20H32O5 |
| Weight | Average: 352.4651 Monoisotopic: 352.224974134 |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Prostacyclin is a vasodilator and platelet aggregation inhibitor used for the management of primary pulmonary hypertension and pulmonary hypertension in patients with heart failure.
For the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.
Prostacyclin is also used to associated treatment for these conditions: Symptomatic pulmonary arterial hypertension (PAH)
How Prostacyclin works
Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Prostacyclin (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI2) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A2 binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists.
Toxicity
Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of epoprostenol. Single intravenous doses at 10 and 50 mg/kg (2703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
Food Interaction
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Prostacyclin Drug Interaction
Moderate: aspirin, aspirin, arginine, arginine, sotalol, sotalolUnknown: fluticasone / salmeterol, fluticasone / salmeterol, ethanol, ethanol, acetaminophen, acetaminophen, liraglutide, liraglutide, linagliptin, linagliptin, tramadol, tramadol, dulaglutide, dulaglutide
Prostacyclin Disease Interaction
Volume of Distribution
- 357 mL/kg
Half Life
The in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; the in vivo half-life of epoprostenol in humans is therefore expected to be no greater than 6 minutes.
Elimination Route
Prostacyclin is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
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