As a result of this, individuals with this disorder will usually experience a gradual yet predictable delay of sleep onset and waking times. Patients with DSPD may develop this disorder if their condition is untreated. Extrinsic
Shift work sleep disorder (SWSD): Approximately 9% of Americans who work night or irregular work shifts are believed to experience shift work sleep disorder. Night shift work directly opposes the environmental cues that entrain our biological clock, so this disorder arises when an individuals clock is unable to adjust to the socially imposed work schedule. Shift work sleep disorder can lead to severe cases of insomnia as well as excessive daytime sleepiness. Jet lag: Jet lag is best characterized by difficulty falling asleep or staying asleep as a result of misalignment between ones internal circadian system and external, or environmental cues. It is typically associated with rapid travel across multiple time zones. Alzheimers disease
CRSD has been frequently associated with excessive daytime sleepiness and nighttime insomnia in patients diagnosed with Alzheimers disease (AD), representing a common characteristic among AD patients as well as a risk factor of progressive functional impairments. On one hand, it has been stated that people with AD have melatonin alteration and high irregularity in their circadian rhythm that lead to a disrupted sleep-wake cycle, probably due to damage on hypothalamic SCN regions typically observed in AD. On the other hand, disturbed sleep and wakefulness states have been related to worsening of an AD patients cognitive abilities, emotional state and quality of life.
However, it has been shown to have comparable affinity with calcitriol for the vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. The vitamin D receptor belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kidney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes. In mouse studies, topical calcipotriol administration to the ear and dorsal skin led to a dose-dependent increase in the production of the epithelial cell-derived cytokine TSLP by keratinocytes, and triggered atopic dermatitis at high concentrations. This upregulation of TSLP production due to calcipotriol application is thought to be mediated through the coactivation of vitamin D receptor/RXRα and vitamin D receptor/RXRβ heterodimers. As psoriasis is typically thought to be partially driven by Th1/Th17 inflammatory cytokines, calcipotriol treatment at appropriate concentrations may alleviate psoriasis symptoms by repressing Th1/Th17 inflammation through TSLP production, which is linked to a Th2 response. However, it is important to note that this has not yet been confirmed. Pharmacokinetics
After application and systemic uptake, calcipotriol undergoes rapid hepatic metabolism. Calcipotriol is metabolized to MC1046 (the α,β−unsaturated ketone analog), which is subsequently metabolized to its primary metabolite, the saturated ketone analog MC1080.