That route of signalling increases the rate of noradrenergic activity in the locus ceruleus, and the person becomes more alert and attentive to their environment.If a stimulus is perceived as a threat, a more intense and prolonged discharge of the locus ceruleus activates the sympathetic division of the autonomic nervous system. The activation of the sympathetic nervous system leads to the release of norepinephrine from nerve endings acting on the heart, blood vessels, respiratory centres, and other sites. The ensuing physiological changes constitute a major part of the acute stress response. The other major player in the acute stress response is the hypothalamic-pituitary-adrenal axis. Stress activates this axis and produces neuro-biological changes. These chemical changes increase the chances of survival by bringing the physiological system back to homeostasis.The autonomic nervous system controls all automatic functions in the body and contains two subsections within it that aid the response to an acute stress reaction. These two subunits are the sympathetic nervous system and the parasympathetic nervous system. The sympathetic response is colloquially known as the "fight or flight" response, indicated by accelerated pulse and respiration rates, pupil dilation, and a general feeling of anxiety and hyper-awareness. This is caused by the release of epinephrine and norepinephrine from the adrenal glands. The epinephrine and norepinephrine strike the beta receptors of the heart, which feeds the hearts sympathetic nerve fibres to increase the strength of heart muscle contraction; as a result, more blood gets circulated, increasing the heart rate and respiratory rate.
Adverse effects
Voclosporin has a boxed warning for malignancies and serious infections. Patients taking Voclosporin along with other immunosuppressants have an increased risk for developing malignancies and serious infections that may lead to hospitalization or death. The most common adverse reactions of voclosporin were (>3%), glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain(upper), dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue. tremor, acute kidney injury, and decreased appetite. Pharmacology
Voclosporin is a cyclosporin A analog, similar to cyclosporin A with modifications on an amino acid within one region that allows the drug to bind to Calcineurin. Voclosporin inhibits calcineurin, which then blocks the production of IL-2 and T-cell mediated immune responses. As a result of the calcineurin inhibition, podocytes (cells within the kidneys) are stabilized while inflammation is reduced. Reduction of inflammation within the kidneys prevents further renal damage. Pharmacokinetics
When administered on an empty stomach, the median Tmax of voclosporin is 1.5 hours. The AUC is estimated to be 7693 ng/mL and the Cmax  is estimated at 955 ng/mL. The volume of distribution is approximately 2,154 L and distributes within the red blood cells. The distribution between the plasma and whole blood is affected by temperature and concentration. The protein binding of voclosporin is 97%. The average terminal half-life of voclosporin is 63.6 L/h. The drug is mainly metabolized by the CYP3A4 hepatic cytochrome enzyme. Pharmacologic activity is mainly attributed to the parent molecule itself, with the major metabolite being 8-fold less potent than the parent drug.