Penodex Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. Such actions can include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue and a general suppression in immune response. The degree of clinical effect is normally related to the dose administered. The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use usually depend on the dose administered and the duration of therapy.
Orally inhaled corticosteroid hormones are believed to reduce the immediate and late-phase allergic responses associated with chronic bronchial asthma. Proposed mechanisms of action include decreased IgE synthesis, increased number of beta-adrenergic receptors on leukocytes, and decreased arachidonic acid metabolism, which decreases the amount of prostaglandins and leukotrienes released. Chronic bronchial asthma is associated with increased peribronchial edema and mucus secretions, which can be decreased with corticosteroid therapy. During an immediate allergic reaction, allergens bridge the IgE antibodies on the surface of mast cells, which triggers these cells to release chemotactic substances. Mast cell influx and activation, therefore, is partially responsible for the inflammation and hyperirritability of the oral mucosa in asthmatic patients. This inflammation can be retarded by administration of adrenocorticoids.
Pharmacokinetics: Dexamethasone is administered via oral, intravenous, intramuscular, intra-articular, intravitreal, ophthalmic, otic, and topical routes. Circulating drug binds weakly to plasma proteins, with only the unbound portion of a dose being active. Systemic dexamethasone is quickly distributed into the kidneys, intestines, skin, liver, and muscle. Corticosteroids distribute into breast milk and cross the placenta. Systemic dexamethasone is metabolized by the liver to inactive metabolites. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The plasma elimination half-life of dexamethasone is approximately 1.8-3.5 hours whereas the biological half-life is 36-54 hours.
Affected cytochrome P450 isoenzymes and drug transporter: CYP3A4, P-gp.
Dexamethasone is an inducer of CYP3A4 and is a substrate for both P-glycoprotein (P-gp) and CYP3A4.