Iloprost is a medication used to treat pulmonary arterial hypertension (PAH), scleroderma, Raynaud's phenomenon and other diseases in which the blood vessels are constricted and blood cannot flow to the tissues. This damages the tissues and causes high blood pressure. There is ongoing research into using it as a frostbite treatment. Iloprost works by opening (dilating) the blood vessels to allow the blood to flow through again. It was developed by the pharmaceutical company Schering AG and is marketed by Bayer Schering Pharma AG in Europe and Actelion Pharmaceuticals in the USA. Iloprost is given via inhalation, and a therapeautic benefit of the drug is that a very low dose is required because of the deposition in the lung. Iloprost has few systemic side effects for that reason. Clinical pharmacology Iloprost is a synthetic analogue of prostacyclin PGI2. Iloprost dilates systemic and pulmonary arterial vascular beds. It also affects platelet aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer. While Iloprost is an analog of PGI2 that activates PGI2's receptor, the prostacyclin receptor, to stimulate vasodilation, it has little selectivity in that it binds to and activates all four receptors for prostaglandin E2 viz., prostaglandin EP1 receptor, prostaglandin EP2 receptor, prostaglandin EP3 receptor, and prostaglandin EP4 receptor. Activation of the EP2 and EP4 receptors cause vasodilation but activation of the EP3 receptor causes vasoconstriction. Dosage and administration Inhaled In the U.S., iloprost is inhaled specifically using the I-Neb AAD or Prodose AAD delivery systems. In Europe iloprost has been approved for use with two compressed air nebulizers with AAD delivery systems (Halolite and Prodose) as well as with two ultrasonic nebulizers Ventaneb and I-Neb. Ventavis is supplied in 1 mL single-use glass ampules containing either 10 μg/mL or 20 μg/mL. The 20 μg/mL concentration is intended for patients who are maintained at the 5 μg dose and who have repeatedly experienced extended treatment times which could result in incomplete dosing. Transitioning patients to the 20 μg/mL concentration using the I-neb AAD System will decrease treatment times to help maintain patient compliance. The approved dosing regimen for iloprost is 6 to 9 times daily (no more than every 2 hours) during waking hours, according to individual need and tolerability. The significant