Binding of an autoreactive antibody to the Fc receptors is mediated through the antibodys N-glycans, which are altered to promote inflammation in people with RA.This contributes to local inflammation in a joint, specifically the synovium with edema, vasodilation and entry of activated T-cells, mainly CD4 in microscopically nodular aggregates and CD8 in microscopically diffuse infiltrates. Synovial macrophages and dendritic cells function as antigen-presenting cells by expressing MHC class II molecules, which establishes the immune reaction in the tissue. Chronic inflammation
The disease progresses by forming granulation tissue at the edges of the synovial lining, pannus with extensive angiogenesis and enzymes causing tissue damage. The fibroblast-like synoviocytes have a prominent role in these pathogenic processes. The synovium thickens, cartilage and underlying bone disintegrate, and the joint deteriorates, with raised calprotectin levels serving as a biomarker of these events. Importantly inflammatory events are not limited to synovium but it appear to be systemic, evidence suggest that alterations in T helper profile favoring inflammation such as inflammatory IL-17A producing T helper cells and pathogenic Th17 cells are come from both memory and effector compartment in RA patients peripheral blood.Cytokines and chemokines attract and accumulate immune cells, i.e. activated T- and B cells, monocytes and macrophages from activated fibroblast-like synoviocytes, in the joint space. By signalling through RANKL and RANK, they eventually trigger osteoclast production, which degrades bone tissue. The fibroblast-like synoviocytes that are present in the synovium during rheumatoid arthritis display altered phenotype compared to the cells present in normal tissues.
Vasopressor
Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable patients with hypotension, especially resulting from septic shock. Such use is common in anesthesia or critical-care practices; it is especially useful in counteracting the hypotensive effect of epidural and subarachnoid anesthetics, as well as the vasodilating effect of bacterial toxins and the inflammatory response in sepsis and systemic inflammatory response syndrome. The elimination half life of phenylephrine is about 2.5 to 3.0 hours. The clinical effects of a single intravenous bolus dose of phenylephrine are short lived and needs to be repeated every 10–15 minutes. Commonly the drug is given as a carefully titrated intravenous infusion with a syringe pump or volumetric pump. Because of its vasoconstrictive effect, phenylephrine can cause severe necrosis if it infiltrates the surrounding tissues. Because of this, it should be given through a central line if at all possible. Damage may be prevented or mitigated by infiltrating the tissue with the alpha blocker phentolamine by subcutaneous injection.Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in some suppository formulations.Recently, Phenylephrine has been used to treat conditions of orthostatic intolerance such as postural orthostatic tachycardia syndrome - where by activation of venous alpha 1 adrenoreceptors increases venous return and stroke volume which improves symptoms. Priapism
Phenylephrine is used to treat priapism. It is diluted with normal saline and injected directly into the corpora cavernosa. The mechanism of action is to cause constriction of the blood vessels entering into the penis, thus causing decreased blood flow and relieving the priapism.