Other symptoms include excess sweating, dilation of capillaries, thinning of the skin (which causes easy bruising and dryness, particularly the hands) and mucous membranes, purple or red striae (the weight gain in Cushings syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs, or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or extremely dry and brittle hair. In rare cases, Cushings can cause hypocalcemia. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence in men, and amenorrhoea, oligomenorrhea and infertility in women due to elevations in androgens. Studies have also shown that the resultant amenorrhea is due to hypercortisolism, which feeds back onto the hypothalamus resulting in decreased levels of GnRH release.Many of the features of Cushings are those seen in metabolic syndrome, including insulin resistance, hypertension, obesity, and elevated blood levels of triglycerides.Cognitive conditions, including memory and attention dysfunctions, as well as depression, are commonly associated with elevated cortisol, and may be early indicators of exogenous or endogenous Cushings. Depression and anxiety disorders are also common.Other striking and distressing skin changes that may appear in Cushings syndrome include facial acne, susceptibility to superficial fungus (dermatophyte and malassezia) infections, and the characteristic purplish, atrophic striae on the abdomen.
Because of treprostinils inhibiting effect on platelet aggregation, there is an increased risk of bleeding, especially among patients who are also taking anticoagulants. It is not known whether treprostinil is excreted in breast milk. Caution is advised when administering this medication to nursing women. Caution is advised when administering treprostinil to patients who have impaired kidney or liver function.Common side effects depending on route of administration:

85% of patients report pain or other reaction at the infusion site. Other side effects may include headache, cough, throat irritation, diarrhea, nausea, rash, jaw pain, vasodilatation, dizziness, edema (swelling), pruritus (itching), and hypotension.Warnings:

Abrupt interruption of the treprostinil infusion can lead to worsening of pulmonary hypertension symptoms, and should be avoided. Pharmacology
Mechanism of action
Treprostinil binds to the IP receptor in the lung tissue which will cause G protein activation and lead to three major effects: vasodilation, decreased cell proliferation and inhibition of platelet aggregation. Pharmacokinetics
The pharmacokinetics of continuous subcutaneous treprostinil are linear over the dose range of 1.25 to 125 ng/kg/min (corresponding to plasma concentrations of about 15 pg/mL to 18,250 pg/m) and can be described by a two-compartment model. Dose proportionality at infusion rates greater than 125 ng/kg/min has not been studied. Treprostinil is substantially metabolized by the liver, but the involved enzymes are not currently known. Five metabolites (HU1 through HU5) have been described thus far. Based on the results of in vitro human hepatic cytochrome P450 studies, Remodulin does not inhibit CYP-1A2, 2C9, 2C19, 2D6, 2E1, or 3A. Whether Remodulin induces these enzymes has not been studied.