Pathways

Medrysone is a glucocorticoid used in the treatment of various ocular inflammatory or allergic conditions. As medrysone is a glucocorticoid, its mechanism of action is that of the glucocorticoid response element of influencing COX-2/prostaglandin G/H synthase 2 suppression and lipocortin/annexin induction. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. Medrysone also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation.

Metabolites of Medrysone are predicted with biotransformer.

Mefenamic acid (also named Ponstel) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Mefenamic acid can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Since prostaglandin is the messenger molecules in the process of inflammation; hence, inhibition of prostaglandin synthesis can reduce the pain, fever and inflammation.

Mefenamic acid is an NSAID used to treat mild to moderate pain for no more than a week, and primary dysmenorrhea. It has analgesic, anti-inflammatory, and antipyretic properties. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Mefenamic acid inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Inflammatory and infectious diseases trigger fever. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because mefenamic acid decreases PGE2 in the CNS, it has an antipyretic effect. This drug is administered as an oral tablet.

Metabolites of Mefenamic acid are predicted with biotransformer.

Megestrol acetate is a synthetic progestational hormone initially developed as a contraceptive. Nowadays, it is used as a drug to treat anorexia and cachexia (or unexplained weight loss) and as an antineoplastic agent to treat inoperable breast cancer, endometrial cancer, and prostate cancer (palliative treatment). Megestrol has the same physiologic effects as natural progesterone: induction of secretory changes in the endometrium, increase in basal body temperature, and pituitary inhibition. By inhibiting the release of GnRH in the hypothalamus, there is a decrease in LH and FSH synthesis in the anterior pituitary gland. This results in a low level of LH, because the ovaries need a surge of this hormone to release the egg, there is no ovulation. The mechanism of action of megestrol's antianorexic and anticachetic is undetermined. It is thought to act by stimulating the appetite or by its metabolic effects (via interferences with the production or action of mediators like cachectin; inhibition of the adipocyte lipogenic enzymes). This drug is administered as an oral tablet.